Virtual Library

Background
Lung cancer therapies during the last decade are targeting the genome of cancer cells. However, investigating the gene pathways of tumor has the disadvantage so far that mutations are found in a limited number of patients therefore limiting the production of targeting therapies. Novel routes for administering lung cancer therapies have been investigated for decades. Aerosol therapies for several systematic diseases and systemic infections have been introduced in the market for a decade. One of the main issues of aerosol therapies has been the investigation of the deposition of a drug compound throughout the systematic circulation and lymph node circulation. Until now none of the published studies have efficiently displayed the deposition of a chemotherapy pharmaceutical within the lymph node tissue.

Methods
The CytoViva[®] technique can be summarized to the following information. Optical and hyperspectral images along with hyperspectral data were captured utilizing a research grade optical microscope equipped with the CytoViva[®] advanced darkfield illumination system, dual mode fluorescence module and integrated hyperspectral imaging system. This integrated system builds hyperspectral image files via “push broom” method, enabling the creation of a high signal to noise spectral image file. Subsequent image analysis delineates the reflectance spectral response of the sample elements in each nanoscale pixel of the image file.

Results
Figure 1 First picture represents an optical image lymph node station 7 after inhaled cisplatin. Second image represents spectral image of lymph node station 7 red areas represent the cisplatin diffusion within the tissue. Third image spectral library of inhaled cisplatin (90minutes after aerosol cisplatin administration, 40mg) The concentration 90 minutes after the aerosol cisplatin administration (40mg) was 2.09 μg/g Pt. in lymph node station 7 as measured with biochemistry techniques in a second patient.

Conclusion
We have efficiently presented data correlating at the same time local deposition with diffusion of aerosol cisplatin and concentration within lymphnodes. Using an optical technique and a biochemistry technique. Aerosol chemotherapy is an efficient method of treatment and further investigation is warranted with or without additional carriers added to the drug formulation.

Background
Classically the evaluation of response in oncology has been based in comparing pre and post treatment tumour volume by means of studying changes in the diameter lesions. The introduction of new targeted drugs creates the need of a different evaluation of tumours and their response to treatment. Functional imaging techniques that are able to study in vivo physiological processes of tissues and tumours have lately acquired more importance. The dynamic techniques may be more appropriate for assessing response to antiangiogenic drug, such as B, whose mechanism of action appears to focus on the normalization of the tumor vasculature. Preliminary studies have demonstrated significant and very early changes in flow, blood volume and tumor perfusion with therapy. These techniques could be useful to select patients those that are going to respond to drugs with an early evaluation of response by means of functional imaging

Methods
IMPACT is an open-label, single arm phase II study to evaluate the predictive value and early radiologic response or perfusion CT in pts diagnosed with unresectable advanced, metastatic or recurrent nsNSCLC treated with C, G and B. Pts receive B (7.5 mg/kg IV on d1), C (80 mg/m2 on d1) and G (1250 mg/m2 on d1 and 8) up to 6 cycles of 21 d. Pts with no evidence of progression of disease continue to receive single-agent B 7.5 mg/Kg on d1 every 21 d until progression or unacceptable toxicity. Primary endpoint is to assess basal results and early tumour response (at day +7) in terms of blood flow (BF), blood volume (BV), time to enhancement peak (TTEP) and permeability (P) as compared to Objective Response Rate (ORR) in terms of RECIST at d42. Secondary objectives include to assess tumour response (at d42) in terms of BF, BV, TTEP and P as compared to ORR at d42, to assess basal results in terms BF, BV, TTEP and P as compared to PFS and OS, to assess tumour response (at d7 and d42) in terms of BF, BV, TTEP and P to PFS and OS, to describe the safety profile using NCI-CTC AE and efficacy in the subgroup of adenocarcinoma. Planned sample size is 20 pts.

Results
not applicable

Conclusion
not applicable

Background
PET-CT is a standard investigation to stage the mediastinum in non-small cell lung cancer when radical management is planned. The absence or presence of mediastinal lymph node involvement on PET-CT informs surgical selection (with or without further nodal sampling). The clinical utility of PET-CT in carcinoid tumours is uncertain as its test performance at identifying mediastinal lymph node disease in these tumours is as yet undefined with such tumours being rare and FDG avidity often considered to be variable or low. As such, it is argued whether PET-CT serves the same purpose in selecting patients for radical management in carcinoid tumours as it does with other non-small cell lung cancers. The aim of this study was to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours by collating a multicentre database.

Methods
We collated retrospective data from 7 institutions by performing a search on pathological databases for a consecutive series of patients who underwent thoracic surgery for a carcinoid tumour from Nov 1999 - Jan 2013. Preoperative PET-CT staging reports (prior to surgery with lymph node dissection) were obtained from patients’ records and compared against the reference standard of pathologic results obtained from lymph node dissection, and test performance reported using sensitivity and specificity.

Results
From Nov 1999 - Jan 2013, a total of 247 patients from 7 institutions underwent surgery for a carcinoid tumour with a corresponding preoperative PET-CT scan. The mean age of the patients was 61 (SD 15) and 84 were male (34%). The pathologic sub-type was typical carcinoid in 217 patients (88%) and atypical carcinoid in 30 patients (12%). The mean SUV uptake in the primary tumour was 4.8 (SD 4). Results from lymph node dissection were obtained in 213 patients. PET-CT reported uptake at mediastinal lymph nodes in 19 patients, of which only 3 were positive on subsequent pathology. Pathological results, from lymph node dissection carried out in 213 patients at the time of surgery, found 8 patients with mediastinal lymph node positive disease, of which only 3 had been picked up in preoperative PET-CT staging. The calculated sensitivity and specificity of PET-CT to identify mediastinal lymph node disease was 38% (95% CI 8-76%) and 93% (88-96%) respectively.

Conclusion
In non-small cell lung cancer, preoperative PET-CT is used for nodal and distant staging to assist in the selection of patients for radical treatment. British Thoracic Society guidelines for the radical management of patients with lung cancer recommend “radical treatment without further mediastinal lymph node sampling if there is no significant uptake in normal sized mediastinal lymph nodes on PET-CT scanning”. In carcinoid tumours, our results of the largest cohort to date suggest that PET-CT has a poor sensitivity but good specificity for the presence of mediastinal lymph node metastases in the staging of pulmonary carcinoid tumours. Therefore lymph node metastases cannot accurately be ruled out in carcinoid tumours with a negative PET-CT. If treatment decisions are based on the N2 status, invasive mediastinal staging should be undertaken in carcinoid tumours.

Background
Background: Clinical trials for determination of anti-cancer effects of chemotherapeutic agents are key for developing new strategies for cancer treatment. In most trials, primary endpoints are provided by imaging evaluations. Regulatory authorities have been recommending an Independent Central Review (ICR) with several readers to mitigate potential biases resulting from variance between investigator sites in clinical trials. Based on recent publications promoting site -based evaluation as imaging endpoint, they currently investigate an alternative to ICR. The goal of this study is to evaluate a cloud-based paradigm implementing software solutions and services that standardize the imaging evaluations among international investigator sites.

Methods
Methods: Ten lung cancer patients, who received epidermal growth factor receptor-tyrosine kinase inhibitor and for which chest CT scans were available at three time points from baseline to progression, were retrospectively selected. CT scans were evaluated according to the RECIST 1.1 criteria by two oncologists (Saga University) and one radiologist (Nice University Hospital) independently, through a cloud-based software solution named LMS (Lesion Management Solutions, MEDIAN Technologies), which offers reviewing tools and lesion segmentation algorithms. Such system was hosted on the data center (Canon IT Solutions, Japan) and used by readers and data managers (Canon and MEDIAN Technologies) for de-identification, quality control and centralization of the images and their evaluations. The study compared response evaluations between readers and analyzed the reasons for discordances.

Results
Results: Readers with different medical training and education, working at distant locations were able to reliably perform radiological evaluations using the same cloud-based system. Between the oncologists and the radiologist, a discordance rate of 35 % (14/40 evaluations) was observed when considering RECIST overall response (CR, PR, SD, PD) at all time points. Precisely, 6 and 8 evaluations were discordant at time point 1 and 2, respectively. . Half of discordances (7/14) were explained by a difference in the selection of target lesions. There were 3 /14 discordances due to a difference in lesion segmentation. The different segmentations occurred when the lesions were adjacent to mediastinum or pleura, where limits of lesions are not very contrasted.

Conclusion
Conclusion: The study shows the feasibility of imaging evaluation based on cloud services for clinical studies involving multiple international sites. Centralization of data made possible the on-going monitoring of evaluations through specialized services reducing variability among sites. Analysis of discordances between readers identified areas of improvement for cloud-based services such as a consensus process for target selection at baseline and the development of segmentation tools to standardize management of measurable lesions.

Background
Ground-glass opacity (GGO) component in a nodule on thin-section computed tomography (TSCT) often corresponds to a lepidic growth pattern of adenocarcinoma. In contrast, solid attenuation or consolidation on TSCT corresponds to invasive components. Many researchers reported consolidation tumor ratio (CTR; defined as the ratio of the size of solid attenuation to the maximum tumor dimension) was a reliable parameter in predicting tumor invasiveness. However, it has been pointed out that inter-/intra-observer variability in CTR measurement is a major problem in precise and reproducible evaluation of tumor characteristics. The aim of this study was to determine the optimal CT settings to reproducibly diagnose GGO and consolidation areas on TSCT by using an imaging software.

Methods
We reviewed preoperative TSCT images of the patients undergoing surgical resection for T1 lung adenocarcinoma in our institution between 2005 and 2009. The TSCT images were obtained without contrast enhancement and reconstructed in 1.0 or 2 mm thickness, using several CT systems. The imaging software colored GGO areas with cut-off CT levels of -800, -700 and -600 HU. Consolidation areas were colored with cut-off CT levels of -300, -200 and -100 HU. These GGO/consolidations identified by the software were compared with those visually determined by the consensus of the 4 authors (EY, KA, YM, HO). The 4 authors scored the correspondence between visual evaluation and software identification according to the cut-off levels. The scores were summarized to determine the optimal cut-off CT levels.

Results
We have reviewed 20 patients so far. Figure 1 shows a TSCT image and software-yielded image showing good correspondence with each other of GGO and consolidation areas. The best score was obtained when the cut-off level was -700 HU for GGO and -200 HU for consolidation. Figure1. Figure 1

Conclusion
Although based on a small cohort, we found optimal cut-off CT levels to identify GGO and consolidation areas using an imaging software. We need to analyze more cases, but this image analysis method is promising in determining CTR reproducibly.

Background
Pulmonary nodules are detected more frequently than ever in both clinical and screening settings. Timely and correct suspicion of malignancy is of great importance in the subsequent management of the nodules. We present data on pulmonary nodule growth and participants baseline characteristics to determine predictors of malignancy.

Methods
In DLCST, 4,104 current and former smokers, with a history of at least 20 pack years and age between 50-70 years, were randomized to either five annual multi-slice low-dose CT screenings or no screening. All participants had an annual visit to the screening clinic where lung function tests and questionnaires concerning health, lifestyle, smoking habits etc. were performed. The scans were read by two chest radiologists who recorded the location and size of any nodules. Nodules of diameters between 5-15 mm were considered indeterminate, and rescanned after three months. Participants with nodules larger than 15 mm were referred to diagnostic workup, as were those with growing nodules. Lung cancer was diagnosed by pathological evaluation. Using volumetric software solid and nonsolid/partsolid nodules were segmented and followed. Only visually correct segmented nodules that were present more than one year were included. Doubling times of mass, volume and diameter from the first to the last record of the nodule were calculated. We performed logistic regression analysis with malignancy as the outcome and baseline characteristics, nodule type and growth measurements as explanatory variables.

Results
975 nodules in 618 participants were included. 31 nodules (3%) were diagnosed as lung cancers. 10(33%) of the malignant nodules were nonsolid/partsolid. Fig. 1 shows histograms of growth measurements. Fig. 2 show the logistic regression analysis. In both cases FEV1 and Mass Doubling Times predicted malignancy significantly.Figure 1Figure 2

Conclusion
Growth rates measured by volumetric software and FEV1 are powerful predictors for malignancy when a pulmonary nodule is present in a low dose chest CT scan.

Background
Pleural adhesions increase the risk of lung injury and lead consequent prolonged air-leak or conversion to open thoracotomy. We aimed to find the clinical or image predictor for pleural adhesion during video-assisted thoracoscopic surgery (VATS) in lung cancer patients.

Methods
Eighty-nine consecutive patients who underwent VATS for lung cancer were included. We retrospectively investigated operative records and clinical information including age, gender, smoking history, body mass index (BMI), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). Pleural adhesion was categorized into 5 grades; none, minimal, moderate (requiring adhesiolysis during VATS with 30 minute or less), severe (requiring adhesiolysis with 30 minute or longer), and very severe (near total involvement of the hemithorax). Advanced adhesion was defined as the presence of moderate or severe or very severe adhesion. Two radiologists blinded to clinical information performed visual analysis for image characteristics of chest CT in consensus. The presence of parenchymal band or calcified granuloma or pleural retraction around the tumor was determined. Severity of emphysema or interstitial fibrosis was assessed as 5 grades (none, trivial, mild, moderate, and severe). The extent of bronchiectasis or pleural thickening or pleural calcification or extrapleural fat thickening was evaluated as 3 grades (none, localized, and extensive).

Results
Pleural adhesion was found in 51 subjects (57.3 %) including 15 (16.9 %) minimal, 18 (20.2 %) moderate, 16 (18.0 %) severe, 2 (2.2 %) very severe adhesion. Male gender and current smoker was 66 subject (74.2 %) and 60 (67.4 %), respectively. Mean age was 64.6 ± 10.4 years-old. Mean value of FEV1 and FVC was 2.4 ± 0.6 ml (range; 0.7-3.9) and 3.4 ± 0.8 ml (range; 1.3-5.0), respectively. Tumor size was 3.1 ± 1.5 cm. Parenchymal band, calcified granuloma, pleural retraction was found in 41.6 %, 27 %, and 44.9 %, respectively. Most subjects had no (49.4 %) or minimal (23.6 %) emphysema. Mild, moderate, and severe emphysema was found in 18.0 %, 7.9 %, and 1.1 %, respectively. Most patients have no bronchiectasis (86.5 %) and no interstitial fibrosis (89.9 %). Localized and extensive bronchiectasis was found in 12.4 % and 1.1 %, respectively. Trivial and moderate interstitial fibrosis was found in 6.7 % and 3.4 %. Localized and extensive pleural thickening was found in 10.1 % and 1.1 %, respectively. Localized and extensive pleural calcification was found in 4.5 % and 1.1 %, respectively. Both localized and extensive extrapleural fat thickening was found in 5.6 %. In univariate analysis, male gender (P = 0.013), age (P = 0.21), FEV1 (P < 0.001), tumor size (P = 0.003) were significant predictors of advanced adhesion. Among the image characteristics, severity of emphysema was a significant predictor of advanced adhesion in univarite analysis (coeffient of 1.83, P = 0.007). Multivariate analysis revealed that independent predictor for advanced pleural adhesion was only FEV1 (coefficient of 0.13, P < 0.001).

Conclusion
Severity of emphysema and FEV1 might enhance the prediction of pleural adhesion during VATS in lung cancer patients.

Background
Pulmonary pleomorphic carcinoma is rare and aggressive subtype of non-small cell lung cancer, with a dual-cell component of spindle and/or giant cells, and of epithelial cells. The objective of this retrospective study was to assess the clinicoradiological characteristics and surgical outcome of this tumor.

Methods
Data were retrospectively examined for 25 patients who had undergone surgical resection for pulmonary pleomorphic carcinoma. Epithelial components of the pleomorphic carcinoma were as follows: 13 adenocarcinoma (52%), 3 squamous cell carcinoma (12%) and 2 large cell carcinoma (8%). 7 tumors (28%) were composed only of spindle and giant cells.

Results
21 patients (84%) were male. 19 patients (76%) were smokers. Of the 14 symptomatic patients (56%), 7 had cough, 5 had hemoptysis, 1 had back pain and 1 had fatigue. The size of the tumor ranged from 1.9 to 10.1cm (mean 5.2cm). The tumors were located peripherally in 21 patients (84%). Calcification within the tumor was visible in only one patient. The margin of the tumors was well defined in 24 patients (96%). Notch, spiculation and pleural indentation of the tumors were observed in 14, 8 and 6 patients respectively. The tumors were inhomogeneously enhanced in 20 patients (80%) on contrast-enhanced CT. Low attenuation areas on contrast-enhanced CT were found to correspond to areas of necrosis in pathologic specimens. Surrounding area of ground-glass attenuation was seen in 14 patients (56%). Among them, hemorrhagic foci were observed in the pathologic specimens in 5 patients. Invasion of chest wall, diaphragm, other lobes of the lung and SVC was noted in 7, 2, 2, 1 patients, respectively. In addition, 6 patients had pleural invasion. The median length of the follow-up examinations was 46 months (range, 2.3–153.5 months). The 5-year overall survival rate was 30%. Patients with tumors invading the parietal pleura, chest wall, diaphragm, and other lobes of the lung had significantly worse overall survival (P=0.027). The subtype of epithelial components did not affect prognosis. Figure 1

Conclusion
The CT features of pulmonary pleomorphic carcinoma were well-defined and lobulated tumor located peripherally with inhomogeneous enhancement. Peritumoral areas of ground-glass attenuation are associated with tumoral hemorrhage in some cases. Pleomorphic carcinoma carried a poor prognosis, even when completely resected. The lung cancer comprised of at least 10 % of spindle and/or giant cells is suggested to have an aggressive malignant behavior.

Background
Ground-glass opacities (GGOs) on computed tomography (CT) represent a distinctive finding for nodules of bronchioloalveolar carcinoma that are generally stable or growing very slowly due to a low degree of malignancy. Therefore, small GGOs are often followed conservatively. However, some GGO nodules undergo clear enlargement during follow-up. The present study aimed to define the clinical features of GGO with potentially high degree of malignancy.

Methods
Among patients who underwent surgery for non-small cell carcinoma between June 2010 and April 2013 in our hospital, all 28 patients with GGO or mixed GGO nodules who had been prospectively evaluated with high-resolution computed tomography (CT) were enrolled in this study. Immunohistochemical studies using MIB-1 antibody to evaluate cell proliferation were performed using specimens obtained from GGO parts of 6 pure GGO and 22 mixed GGO nodules. A high-proliferation group was defined as cases showing >10% positive cells. The following clinical parameters were assessed: sex; age; smoking history; tumor size; tumor shape; tumor contour; ratio of consolidation area to whole area of tumor; and density of GGO. Correlations between high-proliferation status and clinical parameters were analyzed using Fisher’s exact probability test.

Results
Median frequency of positive cells by immunohistochemistry for MIB-1 was 9% (range, 1-42%) and the high proliferation group comprised 10 cases (35.7%). This group correlated significantly with high-density GGO, defined as showing a difference >400 Hounsfield units between the GGO field and adjacent lung field (P=0.038), and tended to correlate with tumor diameter >20 mm (P=0.095).

Conclusion
Density of GGO lesions correlates with proliferation of tumor cells. This clinical feature appears likely to allow differentiation of high-risk patients with GGO lesions.

Background
The TNM staging system for prognostication in non-small cell lung cancer (NSCLC) is less than satisfactorily accurate. Previous research suggests that FDG-PET-based metabolic tumor volume (MTV) may be an independent prognostic marker in NSCLC when used in Cox-regression models. This study was to determine the potential prognostic utility of FDG-PET-based MTV used in mathematical classifiers for prognostication of NSCLC.

Methods
A consecutive cohort of 328 NSCLC patients (156 males, 172 females) with histologic confirmation and FDG-PET scans was identified for retrospective analysis. MTV measurements were made on baseline 18F-FDG PET/CT scans of the primary tumor (MTV~T~), metastatic lymph nodes (MTV~N~), and metastatic tumors (MTV~M~). Whole-body MTV (MTV~WB~) was defined as the sum of MTVs of primary tumor, metastatic lymph nodes, and metastatic tumors (MTV~WB~ = MTV~T~ + MTV~N~ + MTV~M~). A semi-automated 3D contouring program was used for obtaining the MTVs. Patient survival was determined from cancer registry data, and known survival length of living and lost-to-follow-up (i.e., censored) patients was recorded. Patient survival was determined at one year (189 survived, 129 did not) and two years (127 survived, 186 did not) after baseline FDG-PET scan, and survival status was known for most censored patients except for ten at one year and 15 at two years. Linear discriminant analysis classifiers were constructed on data of patient age, gender, histology, TNM stage, and MTVs. Cross-validation was done as follows: to predict a patient's survival status, a classifier was trained on data of all other patients of known survival status and not on the patient in question. Areas under receiver operating characteristic (ROC) curve (AUC), analogous to C concordance statistics, were compared statistically.

Results
The median patient age was 68.3 years and patient distribution by stage was 46 stage IA, 43 stage IB, 19 stage IIA, 18 stage IIB, 52 stage IIIA, 39 stage IIIB, and 111 stage IV. Median follow-up of living and lost-to-follow-up patients was 58 months and death confirmation was known in 249 (88.4%) patients. For one-year survival, the AUC (± standard error) value of the classifier based on age, gender, histology, and stage was 0.77±0.026 and that of the classifier based on age, gender, histology, stage, and MTVs was 0.82±0.023 (p < 0.01). For two-year survival, the corresponding AUC values were 0.75±0.028 and 0.79±0.026, respectively (p < 0.02). The AUC values were similar for classifiers based on age, gender, histology and MTVs and for classifiers based on age, gender, histology, and stage (p > 0.5). These results were consistent with previous results of statistically significantly better prognostic ability of multivariate Cox-regression models of MTV~WB~ compared with models not including MTV~WB~, after adjusting for age, gender, histology, treatment options, and whole-body tumor SUV~max~.

Conclusion
FDG-PET-based metabolic tumor volume can potentially increase prognostic accuracy for NSCLC patients beyond that of the TNM staging system at one and two years, and mathematical linear classifiers can potentially be used as an alternative to Cox-regression models for estimating survival probability.

Background
The size of the tumor is an important prognostic factor in cancer patient. It is ultimately based on the pathologic measurement of gross specimen from surgical resection. However, the preoperative tumor size could be determined by direct measurement of palpable superficial lesion or radiologic imaging such as chest radiograph or computed tomography (CT) in both lung window setting and mediastinal window setting. To our knowledge, there is no definite method to measure tumor’s size on radiographic imaging, moreover, the correlation between pulmonary tumor size measured by using radiographic imaging and pathologic size has not been studied in Thailand yet. The Northern Thailand Thoracic Group (NT-TOG) would like to determine the correlation between tumor size measured by using chest radiograph and CT chest comparison to the pathological tumor size.

Methods
After institutional review board approval, the retrospectively analytic cross sectional study from pathological records of all patients who underwent surgery in Chiang Mai University Hospital were reviewed. All cases that achieved CT imaging in the department of radiology were included. Finally 60 pulmonary tumors were collected to measure their sizes on chest radiograph and 98 pulmonary tumors were gather to measure their sizes on mediastinal and lung window sets and compared to the pathological sizes. The location of the tumor and histological cell type were recorded. Data analysis was performed using STATA software to find out the correlation between sizes that had been measured on chest radiograph and on CT images comparison to the tissue pathologic size.

Results
The tumor locations were common in the RUL and LUL. Adenocarcinoma was the most common histological type, followed by squamous cell carcinoma and metastasis respectively. The mean radiologic tumor sizes on chest radiograph, CT using mediastinal and lung window settings were 4.8 cm, 4.8 cm and 5.1 cm in maximal diameters, respectively. The mean pathologic tumor size was 4.7 cm in maximal diameter. The mean errors of chest radiographic measurement, CT measurement using mediastinal and lung window settings were 0.25 cm, 0.04 cm and 0.41 cm, respectively. The error of tumor size measured by using CT in mediastinal window setting was statistically significant less than that of using lung window setting (p<0.001). There was a statistically significant difference between tumor size measured by using CT in mediastinal window setting and pathologic tumor size (p<0.001). Predicted tumor size was calculated by using the equation “calculated tumor size (cm) = 1+(0.78xtumor size on CT in mediastinal window (cm)).

Conclusion
Although there is a statistically significant difference between CT measurement and pathologic tumor size, the tumor size measured by using CT in mediastinal window setting is seemly more accurate than in lung window setting or chest radiograph.

Background
The size of consolidation on thin-section computed tomography (CT) has been one of the most important preoperative prognostic factors in resected lung cancer. On the other hand, few reports mentioned the nature of consolidation as prognostic factor.

Methods
A retrospective study was conducted on 617 lung cancers of clinical stage IA which were resected between 2009 and 2012. Thin-section CT scans were available for all cohorts, which were reviewed by authors. Moreover authors divided lung cancers into three categories: ground glass opacity (GGO), part solid and pure solid. 235 cases are part solid nodule. We classified these 235 part solid lung cancers into two groups: homogeneous or heterogenous. The relationship between these consolidation statuses were evaluated using the chi-square test and Fisher’s exact test. The medical record of each patient was examined for investigating following clinicopathological factors: age, gender, smoking status (pack-year smoking), preoperative serum carcinoembryonic antigen (CEA), SUV max of the primary tumor on positron emission tomography (PET), pathological pleural, vascular, and lymphatic invasion. P-value <0.05 was considered statically significant.

Results
Ninety pts (38.3%) had homogeneous consolidation. There were 32 (35.6%) , and 56 (38.6%) men, 6 (14.6%), and tumor having 3 or more SUV max on PET was found in 6 (14.6%), 5 (10.4%), respectively. Based on univariate analysis, age, gender, and pack-year smoking were not statistically significant differences. In homogeneous consolidation group, 2 patients have nodal metastasis, however nodal metastasis were not observed in scattered consolidation group. (P=0.023) Vascular invasive was frequently found in homogeneous consolidation group. (P=0.04)

Conclusion
This result of our study shows that the quality of consolidation in part solid lung cancer could be the prognostic factor.

Background
Bronchial NET:s account for approximately 1% of all lung cancers and usually require surgical removal. Hamartoma is a benign tumor not necessary to treat. The two conditions may have a very similar radiological appearance when studied by chest x-ray or CT, especially when the bronchial NET has a peripheral location. The objective was to assess if integrated FDG PET-CT examination could contribute to the decision-making process.

Methods
The material consists of 119 consecutively operated patients at our Centre during the Period of October 2005 to February 2012, where the Diagnosis (pathologically confirmed) either was Hamartoma or bronchial NET. Retrospective analysis of the Patient Charts and Radiology were performed. Out of these 119 cases, 58 hamartomas and 38 bronchial NET:s had been subject to FDG-PET-CT. All examinations were reviewed by one single radiologist/nuclear medicine physician. SUV-values were measured as well as morphological characteristics were assessed.

Results
Of the 38 Bronchial NET:s, 23 were peripheral and 8 central according to radiological appearance. Mean SUVmax of the Bronchial NET:s was 3.5 ( range 0–7.5). 6 Bronchial NET:s did not show any FDG-uptake. Mean SUVmax of the hamartomas was 0.77 (range 0.0–3.7). 31 of the hamartomas (61%) showed no FDG-uptake.

Conclusion
Although peripheral Bronchial NET:s may be indistinguishable to hamartoma at CT, the two conditions differ in FDG-PET appearance. Thus, it may be possible to avoid unnecessary thoracotomy when a peripheral solid lesion shows absence of FDG-uptake.

Background
The seventh edition of the TNM classification of lung cancer was based on the 67.725 patients from 19 countries treated by all modalities between 1990 and 2000. There was no information about how the c TNM and pTNM was determined and there were probably differences in the preoperative staging methods. At Gentofte University Hospital diagnostic work-up and staging procedures included PET / CT, EUS FNA and EBUS TBNA early on after the introduction of these technologies. The purpose of the project was to evaluate the survival after lung cancer surgery in patients who were diagnosed and staged by PET / CT, EUS FNA and / or EBUS TBNA and to compare survival with the results from the IASLC's staging project.

Methods
All patients in the period 1.1.2005 to 12.1.2012 who had had PET / CT, EUS FNA and / or EBUS TBNA leading to a diagnosis of non small cell lung cancer before surgery were included in the project The date of surgery and the date of death if any were recorded. Survival was measured from the date of surgery and was calculated by the Kaplan-Meier method. cTNM and the methods by which the diagnosis and stage was determined was included in the analysis.

Results
In this period, 4090 lung cancer patients were diagnosed and staged at Gentofte University Hospital.1187 were staged by PET CT, EUS FNA and/or EBUS TBNA and of these 791 were operated. Over all, survival based on cTNM for patients staged at Gentofte University Hospital was on the same level level as found in the the IASLC's analysis for pTNM. In particular, the survival curves for cTNM stage IA, IB and IIIA found in this material appears to be identical with those found in the Stage survicalIASLC's project for the same pTNM stages. For example, the 3-year survival for the cIA in our study was 84% where the IASLC's pIA was 83% and cIIIA in our study was 32% while the IASLC's pIIIA was 37% The cTNM IIIB in our material shows a better survival than IASLC pTNM IIIB (33% vs 14%) There were too few patients in stages IIA and IIB for any meaningful conclusion.

Conclusion
As the treatment regime is based on the cTNM, it is important that it is as accurate as possible. Thus, concordance between cTNM and pTNM should ideally be very high. Using new technologies, the concordance at our institution has increased to the current level of 95%. It is therefore not surprising that the survival of the various cTNM stages in our study are similar to the survival curves from IASLCs staging project.

Background
It is important to identify possible metastatic nodule prior to metastasectomy, in order to perform complete resection. Thin section chest CT (TSCT) can detect small metastatic nodules more accurately than conventional chest CT. Conventional CT is known to miss metastatic nodules that are manually palpable by up to 40%. Reported sensitivity of helical CT cannot exceed 90%, also. We adopted TSCT and applied computer-aided detection (CAD) system for the search of small metastatic nodules to improve the detection power of TSCT.

Methods
From March 2009 to February 2013, 333 patients were referred to thoracic surgeon for pulmonary metastasectomy. TSCT with CAD was performed in every candidate for pulmonary metastasectomy. Every nodule detected by TSCT and CAD was annotated by radiologists and the whole map and annotation numbers of nodules were reported before operation. Intraoperatively, bi-manual palpation in open metastasectomy and finger palpation in video assisted thoracoscopic surgery (VATS) were used to detect the nodules. Only operations with complete available data were included in the study and 251 operations from 239 patients were analyzed.

Results
A total of 1021 nodules were identified by TSCT with CAD, while 115 nodules (11.3%) were additionally detected by CAD. Among the annotated nodules, 742 nodules were palpable during operation. Including intraoperatively detected 49 nodules, a total of 824 nodules were resected. Of 527 pathologically proven malignant nodules, 518 (62.9%) nodules were metastatic lesions. Among metastatic lesions, 496 were detected by TSCT (95.8%), 9 by CAD (1.7%) and 13 by manual palpation (2.5%). Also, 11 metastatic nodules were no palpated during operation but resected according to the annotation on CT. The overall sensitivity of thin section chest CT with CAD was 97.5%. Though overall specificity of TSCT with CAD was very low as 12.1% because that of radiologist’s reading was 14.2%, specificity only for CAD was 45.6%.

Conclusion
TSCT could detect small subcentimetre nodules and CAD enabled detecting additional small nodules. With help of TSCT with CAD, even the metastatic nodules, which were not palpable during operation, could successfully be resected. Furthermore, TSCT with CAD could detect tiny nodules with rather high specificity compare to radiologist’s reading only. Although the number of true metastatic nodules was small and several metastatic nodules were undetected, the TSCT with CAD system increased the detection sensitivity and would be helpful in complete metastasectomy.

Background
The impact of massive early lung cancer detection program on patients` profile and surgical activity of the local thoracic surgery department is analyzed.

Methods
Early lung cancer detection program was conducted in a single city of 400000 inhabitants from 2008 till 2011. Enrollment criteria included both sexes aged 55-65 years with history of 20 pack-years of tobacco smoking. All detected lesions were followed up in accordance with IELCAP protocols. All cases requiring surgery were referred to a single local thoracic surgery department serving for the population of appr. 2 million people. Following data were analyzed: number of NSCLC detected and resected, number of stage I resected patients, histology, type of surgery.

Results
15020 patients were screened (39.5% of the population of people aged 55-65 in our city). 6240 pulmonary lesions were detected, majority (59%) smaller than 5mm. 445 lesions (7.1%) were bigger than 15mm. 182 patients (2.9% of all detected lesions) were referred to the local thoracic surgery. Overall 925 NSCLC were resected at our department in 2008-2011. 232 (25%) of them were stage I. Number of pneumonectomies was 166 (18%). Dominant histology was squamous cell (52%) 247 metastatic lesions were resected in the same period. The early detection group delivered 77 NSCLC resections (8.3% of all resections). 53/77 (69%) were stage I (significant difference versus the entire group). Number of pneumonectomies was 2/77 (2.5%, significant difference vs entire group). Dominant histology was adenoca (50%). 33 metastatic lesions (13.3% of all metastases resections) were treated surgically. 15 small cell lung cancer were diagnosed and referred for chemotherapy. 33 metastatic lesions were resected, too.

Conclusion
The patients with NSCLC detected by the early lung cancer detection programme are treated surgically in earlier stages in comparison to the entire population of patients referred to our department. They require pneumonectomy significantly less frequently than the entire group.

Background
Background: Lung cancer is still the first leading cause of cancer death worldwide, and late diagnosis is a major obstacle to improving lung cancer outcomes. Tumor inflammation and immunology are recently identified as enabling cancer characteristics and play important roles in tumor progression and metastasis. Recently, elevated preoperative or pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio(PLR) and mean platelet volume (MPV) detected in peripheral blood were identified as independent prognostic factors associated with poor survival in various cancers, including colon cancer, esophageal cancer, gastric cancer and breast cancer. These markers are highly repeatable, inexpensive and widely available. The aim of this study is to examine whether MPV, NLR and PLR could be useful inflammatory markers for differentiating lung cancer from healthy controls; also to determine the relation between these markers and other prognostic factors and histopathologic subgroups.

Methods
Methods: Retrospectively eighty-one lung cancer patients and 81 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. The preoperative or pretreatment blood count data was obtained from the recorded computerized database.

Results
Results: NLR and PLR values were significantly higher in lung cancer patients compared to healthy subjects.( NLR: 4.42 vs 2.45 p=0.001, PLR: 245.1 vs. 148.2 p= 0.002) MPV values were similar in two study groups (7.7 vs. 7.8). On the other hand we did not find statistically significant relationship between these markers ( MPV, NLRand PLR) and histopathologic subgroups, TNM stages, grade, OS and PFS (all p>0.05).

Conclusion
Conclusion: Our data suggests that NLR and PLR values may be used as easily and available biomarkers for early diagnosis of lung cancer, but needs more large prospective studies to predict patients outcome.

Background
To evaluate lung cancers detected using low-dose CT screening between February 2004 and March 2012.

Methods
The number of screenees analyzed in the observational study was 12,116. Screenees were classified into three groups based on their smoking index (SI): SI ≥ 600, SI < 600, and never-smokers. Overall, 147 lung cancers in 132 cases treated at the National Cancer Center Hospital and the National Cancer Center Hospital East were evaluated according to the smoking index. Adenocarcinomas were evaluated based on the following classification: group A (adenocarcinoma in situ and minimally invasive adenocarcinoma), and group B (invasive adenocarcinoma). Statistical analyses were performed using the chi-square test.

Results
The ages of the patients with lung cancer ranged between 42 and 85 years (mean, 61 years). Thirty-two of the 2989 male screenees (1.48%) and 2 of the 149 female screenees (1.34%) in the SI≥600 group, 22 of the 2989 male screenees (0.74%) and 10 of the 796 female screenees (1.26%) in the SI<600 group, and 16 of the 2148 male screenees (0.74%) and 50 of the 3878 female screenees (1.29%) in the never-smoker group were diagnosed as having lung cancer. Among the 147 lung cancers, 8 lesions (5.4%) did not present as nodules and instead appeared as a partial thickening of the bulla wall, a funicular-like shadow, a pneumonia-like shadow, etc. Among the remaining 139 lung cancers, 35 lesions (25.2%) presented as pure ground-glass nodules (GGNs), 64 lesions (46%) presented as part-solid nodules, and 40 lesions (28.8%) presented as solid nodules. The histology of the lung cancers was adenocarcinoma in 132 cases (89.8%), squamous cell carcinoma in 8 cases (5.4%), small cell carcinoma in 3 cases (2%), adenosquamous carcinoma in 1 case (0.7%), carcinoid tumor in 2 cases (1.4%), and NSCLC in 1 case (0.7%). The disease stages were as follows: IA, 127 (86.4%); IB, 11 (7.5%); IIA, 2 (1.4%); IIB, 1 (0.7%); IIIA, 3 (2.0%); and IIB, 3 (2.0%). Among the 147 cancers, the number of incident cases was 8 in the SI≥600 group (median follow-up period, 3.1 years), 3 in the SI<600 group (median follow-up period, 2.9 years), and none in the never-smoker group (median follow-up period, 3.0 years). Lung cancer cases in smokers (including ex-smokers) occurred predominantly in men (male, 54; female, 12), while lung cancer cases in never-smokers occurred predominantly in women (female, 50; male, 16) (P < 0.0001). The number of adenocarcinomas in smokers (including ex-smokers) was 29 in group A and 24 in group B, while the number of adenocarcinomas in never-smokers was 42 in group A and 23 in group B (P = 0.274). In the never-smoker group, the number of adenocarcinomas in men was 7 in group A and 9 in group B, while the number of adenocarcinomas in women was 35 in group A and 14 in group B (P < 0.05).

Conclusion
The number of invasive adenocarcinomas was not statistically different between smokers (including ex-smokers) and never-smokers. Never-smokers should also be a target population of CT lung cancer screening. Adenocarcinoma may be overdiagnosed among female never-smokers.

Background
Lung Cancer causes over 35,000 UK deaths per year: early detection by CT screening has been shown to reduce mortality in the USA by 20%.

Methods
UKLS is a pilot randomised controlled trial, screening individuals at a high risk of developing lung cancer (>5% over 5yrs) with low-dose CT. UKLS is population-based, approaching people of 50-75yrs identified through local primary care records and using a validated lung cancer risk prediction model to identify high risk individuals from the target group (Raji Annals of Int. Med 2012). We report observations made from the initial recruitment to the trial. 250,000 individuals were approached in Liverpool and Cambridgeshire, 30% responded positively to the first questionnaire. 4000 individuals were recruited and randomised to receive either a low-dose CT scan or usual care. All CTs were double read according to UKLS protocol. Nodules were reported as category 1, 2, 3 or 4 depending on size and volume (Baldwin et al. Thorax 2011). Participants with category 4 nodules (>500mm3) were referred to the lung cancer multi-disciplinary team (MDT) for further workup. Individuals with a category 3 nodule (50-500 mm3) underwent a repeat CT within 3 months, whereas category 2 nodules (15-50mm3) were followed up at 12 months. The trial is currently in follow-up and some participants are still in the 3 and 12 month phases.

Results
1991 high risk UKLS participants underwent baseline CT by June 2013. 1044/1991(52.4%) individuals had nodules requiring further imaging or work-up. 79/1991 (4.0%) had nodules which required referral to the MDT clinics at the pilot sites for further workup. At this time 31/1991(1.6%) had a prevalent lung cancer. 27/31 lung cancers (87.1%) were non-small cell lung cancer and 25/31 lung cancers (80.6%) were Stage I or II (based on pathological staging or clinical staging where the pathology staging was not available).

Conclusion
UKLS has already demonstrated 1.6% prevalence, utilising the LLP risk prediction model to identify high risk individuals, which compares favourably with the NELSON and other European trials. The Pilot UKLS is due to provide an interim report in 2014.

Background
It is true that treatment in the early stage of lung cancer provides the best benefit, so many researchers have actively sought a good screening test for early detection. Although, chest radiography (CXR) is commonly used for evaluating patient with pulmonary disease. There are some limitations in early detection small nodule. Computed Tomography (CT) can easily solve this problem. However, the disadvantages of the CT are high cost and high radiation dose. Recently, there is a new technique called digital tomosynthesis, which can reconstruct sectional images at arbitrary depths by collecting a number of projection images at different angles using a digital detector. The overlapping anatomy of the section images is much less than the standard projection radiograph. Currently, many articles have presented the benefits of DT. The learning curve for interpretation of the technology is also important. The purpose of this study is to find the detection rate of nodule by using CXR, chest digital tomosynthesis (CDT) and CT examination with phantoms and preliminary clinical application in Maharaj Nakorn Chiang Mai hospital.

Methods
After institutional review broad approval, in-house chest phantom was made from acrylic, plaster and catheters. The plastic beads, diameter size 1-2 mm., 3-4 mm., 5-6 mm., 7-8 mm. and 9-10 mm. were implanted to represent pulmonary nodules in a phantom. None to 20 nodules were randomly embedded in each model and photographed by digital chest radiograph (CXR), chest digital tomosynthesis (CDT) and chest computed tomography (CT). Two thoracic radiologists were blinded to review and label nodules on each image. Percentage of nodular detection in each study was calculated and compared between each other. After gain experience from phantom study, CDT was preliminary applied to the surgical cases for preoperative evaluation.

Results
There were 332 nodules in the 34 phantom-models. Nodule detection rate from each modality was 75.3% of CXR, 91.0% of CDT and 98.8% of CT, respectively. CT could detect all nodules, which were larger than 3 mm in diameter. There were over 90 % of detected nodules from CDT that diameter were larger than 5mm. Percentages of nodular detection of CDT and CT were not statistically significant difference in 5-10 mm sized nodules. Poor nodular detection areas on CXR were mediastinal and hilar regions, while on CDT was costophrenic sulcus. Clinical examinations were shown.

Conclusion
CT showed the highest percentage of nodular detection, followed by CDT and digital CXR, respectively. The percentage of detection in nodules size 5 – 10 mm between CT and CDT was not statistically significant difference.

Background
Cell-CT is a fully-automated, single-cell analysis system that has been developed to enable non-invasive screening for lung cancer. We report the results of a pilot clinical study using Cell-CT for lung cancer detection from patient sputum, including the determination of criteria that define specimen adequacy, the detection of abnormal cells in adequate specimens (sensitivity), and the detection of normal cells (specificity), performed automatically or further enhanced with human evaluation.

Methods
Twenty-seven patients with biopsy-confirmed lung cancer produced spontaneous-cough sputa (three morning-pooled) that were fixed, stained with hematoxylin following mucus dissolution, then enriched for epithelial cells using the method of fluorescence-activated cell sorting. The specimens were analyzed using Cell-CT, which computes 3D digital images of single cells through tomographic reconstruction with isometric, sub-micron resolution (see figure). The 3D cell images were automatically interrogated to measure morphometric biosignatures for lung cancer. 3D feature measurements were combined to produce two probabilistic scores: one that identifies abnormal cell candidates (moderate, marked dysplasia, and cancer) and another that identifies normal bronchial epithelial cells to determine specimen adequacy. 3D images of the abnormal cell candidates were transmitted to a workstation for cytopathologist confirmation and final diagnosis, using a custom computer interface (Surveyor™). Figure 1

Results
Based on a stringent criterion for determining specimen adequacy, 12 of the 27 sputum specimens (or roughly 50%) were deemed adequate. In the adequate specimens, abnormal cells were automatically detected, correctly classified, and confirmed in 11 of the 12 cases. This result is statistically significant and demonstrates that the Cell-CT can achieve an abnormal cell detection rate for lung cancer cells in sputum nearing 92% sensitivity. The area under the receiver operator characteristic curve (aROC) for abnormal cell detection is 0.99 (see figure). We can estimate the specificity for normal specimens by examining the rate of correct normal cell detection and classification. With the detection of 9,683 normal cells, seven were falsely classified as abnormal (false positives). However, following human evaluation using Surveyor, the resulting specimen specificity was essentially 100%.

Conclusion
This first important study of Cell-CT shows there are sufficient abnormal cells in adequate, spontaneous sputa to achieve high-sensitivity lung cancer detection rates without false positives. The power of 3D single-cell morphometry supports the future potential impact of a non-invasive, sputum-based lung cancer screening test.

Background
The benefit of low-dose CT screening was proved by showing reduced mortality from lung cancer in persons at high risk for lung cancer. We evaluated the effect of low-dose CT screening in healthy adults at low risk for lung cancer.

Methods
From January 2006 through December 2008, we retrospectively enrolled 13,085 symptom-free healthy adults who underwent three annual screenings with either low-dose CT (6,256 persons) or chest radiography (6,829) for regular check-ups. They were divided into groups at high risk (≥30 pack-year smoking and ≥ 55 years), intermediate risk (≥20 pack-year smoking and ≥ 50 years), or low risk (<20 pack-year smoking). Data were collected on numbers of screening detected lung cancer and survival from screening detected lung cancer that occurred through December 31, 2012.

Results
The rate of positive screening test was 53.2% with low-dose CT and 13.1% with radiography. A total of 98.2% of the positive screening results in CT group and 97.9% in radiography group were false positive results. CT screening increased the number of screening detected lung cancers in the less than high risk population (multivariable-adjusted odds ratio (OR) 4.75, 95% confidence interval (CI) 2.56 to 8.82, P <.001), but not in high risk population (OR 1.23, CI 0.38 to 3.93, P =.730). In the less than high risk population CT screening detected lung cancers were all adenocarcinomas and were more frequently part-solid or non-solid nodules (P=.008). The stage of CT screening detected lung cancer more commonly in IA disease (76.1% in CT vs. 20% in radiography, P <.001) and the survival of CT screening detected lung cancer was consistently better than radiography screening detected lung cancers in the less than high risk population (multivariable-adjusted hazard ratio (HR) 0.08, CI 0.01 to 0.60, P =.014), in the less than intermediate risk population (HR 0.07, CI 0.01 to 0.66, P =.021), and in the low risk population (HR 0.07, CI 0.01 to 0.69, P =.023).

Conclusion
CT screening in low risk population detected more number of stage IA adenocarcinomas which area more frequently part-solid or nonsolid nodules, as compared with chest radiography or with CT in high risk population. The survival of CT screening detected lung cancer was better than that of chest radiography detected lung cancers in the lower risk population.

Background
Low dose computerized tomography (CT) screening for lung cancer can reduce mortality but it is currently unclear whether CT screening is cost effective. Denmark is a small country (5.3 mio. inhabitants) with a uniform and a public health care system covering all inhabitants. The unique civil registration system allows a linking of all health care expenses to the individual person. The objective of this study is to evaluate the direct healthcare costs generated by a randomized lung cancer CT screening trial in Denmark.

Methods
Methods: A Registry study nested in the Danish lung cancer screening trial (DLCST), involving 4104 participants, current or former heavy smokers, aged 50–70 years. Participants were randomized to five annual low dose CT scans or usual care during 2004 – 2010. Total healthcare costs and utilization data for the primary and the secondary healthcare sector, were retrieved from public registries, covering the period from randomization until September 2011

Results

Table 1. Cumulative relative health care costs in the diagnostic groups compared with the control group in the DLCST, shown as the multiplicative factor the costs on average differ from the costs in the control group.

Annual costs were significantly higher in the screening group compared with the control group (p<0.001), but when cost of CT-scans was excluded, there was no longer a significant difference (p=0.52). Analyses according to diagnostic groups showed that annual costs were 10.57 times higher for the true-positive and 1.67 times higher for the false-positive group compared with the control group (Table 1).

Conclusion
Lung cancer CT screening increases overall healthcare costs compared with no screening, equivalent to the costs of the CT-screening scans. Overall healthcare costs were higher for the true-positive and false-positive groups than for the control group, even when excluding CT-screening scan costs. This increase was outweighed by the larger true-negative group who had reduced, but not statistically significant, costs compared with the control group (Table 1 and Figure 1). .Figure 1

Background
HA concentration is elevated in several cancers, but there is no data regarding its concentration in the sputum of lung cancer patients. In this study, we examined the HA concentrations in tissue and sputum samples and its impact on the screening and diagnosis of lung cancer patients.

Methods
Hyaluronic Acid (HA) was examined in lung cancer tissue of 14 patients through immunohistochemistry using a HA-probe. The analysis was performed using ImageProPlus 7.0. The HA concentration in sputum samples of 90 lung cancer patients, 25 COPD patients and 15 healthy controls was also analyzed. All the patients and healthy controls selected underwent a sputum induction. Sputum samples were incubated with urea 7M at 60[o]C and afterwards incubated with a proteolytic enzyme. The levels of HA were measured by a noncompetitive ELISA-like fluorometric assay.

Results
It was observed a different expression pattern of HA in squamous cell carcinomas vs. adenocarcinomas specimens (p<0.05). In sputum, a significant different concentration pattern of HA was found among lung cancer, COPD and healthy individuals (p<0.001; Fig1A). Equally significant was the difference between HA in the sputum from lung cancer and healthy volunteers (p<0.001), as well as lung cancer and COPD patients (p=0.002). ROC curve between lung cancer and healthy volunteers furnished an area of 0.821 (0.727–0.915). Assuming a cut off value of 31,44ng/mg, the specificity was 100% and the sensitivity was 51% (Fig1B). ROC curve to distinguish COPD patients from lung cancer patients showed an area of 0.698 (0.600-0.797) and the cut off value of 48.3ng/mg presented 100% of specificity and 33% of sensitivity (Fig1C). Figure 1

Conclusion
The results presented suggest a promising role of HA in the developing and progression of lung cancer and its concentration in the sputum as a novel diagnostic marker for differentiating normal from lung cancer patients.

Background
Of all the non-AIDS associated malignancies, lung cancer is the most deadly because of its advanced stage of presentation. Within the HIV population, the incidence of non-small cell lung cancer (NSCLC) is estimated to be 2-4 times that of the general population. Despite this growing burden of NSCLC in HIV-infected smokers, no data exist regarding early detection of lung cancer in this population since screening trials, such as the U.S. National Lung Cancer Screening Trial, excluded HIV-infected participants. Preliminary data have highlighted the ineffectiveness of chest x-rays in diagnosing lung cancer early, and waiting for HIV-positive individuals to develop symptoms is misguided. These facts provide a compelling argument for the use of helical CT as a screening tool for lung cancer in HIV-infected patients.

Methods
From 2006-2013, a prospective feasibility study was conducted to determine the prevalent and incident CT detection rates in HIV-infected smokers of lung cancer. The secondary objective was to determine if CT screening could change the stage distribution of HIV lung cancer to that of an early stage disease. Annual CT screening was conducted for lung cancer in current or former smokers over age 25 years old with ≥20 pack-years history and a confirmed HIV diagnosis. To determine markers of lung cancer risk, we also analyzed from trial participants, clinical data, sera, and CT scans using quantitative, densitometry imaging as an estimate of emphysema, and compared these variables to similar parameters from 130 HIV patients at our institution with known lung cancer.

Results
Of the 224 individuals enrolled, 72% were males, 90% African-Americans, 9.5% Caucasian, and 0.5% Hispanic. The median age was 48 years and the median number of smoking pack-years was 34. No prevalent lung cancers were detected by CT screening and only lung cancer was found on incident screening. There were no interim diagnoses of lung or extrapulmonary cancers. Eighteen deaths occurred but none were cancer-related. Of 29 nodules detected at baseline screening, fifteen were further imaged, five biopsied, but none progressed to cancer at study end. Emphysema was commonly observed and its heterogeneity across the entire lung as measured by CT densitometry was significantly higher in HIV subjects with lung cancer than in those without (p≤0.01). On multivariate regression, increased age, higher smoking pack-years, low CD4 nadir, and increased heterogeneity of emphysema on quantitative CT imaging were all significantly associated with lung cancer in HIV individuals.

Conclusion
This pilot feasibility study is the world’s first reported annual lung cancer CT screening trial in HIV-positive smokers. During 4 years of CT screening of 224 HIV subjects with a median age of 48 years, only one incident lung cancer was found. This suggests that until the median age of the worldwide HIV population increases, the ability of annual CT screening to detect lung cancers in HIV-infected smokers will be low. Immunologic and radiographic differences that exist between HIV patients with and without lung cancer may serve as biomarkers of lung cancer risk.

Background
The lung cancer screening in Japan is only chest radiography now. But in 2011, the national lung screening trial research team was reported reduced lung-cancer mortality with low-dose computed tomographic screening. We studied lung cancer patients about a difference of a screening type, for example radiography and computed tomography.

Methods
From January 2008 through May 2013, we performed the operation of 1344 lung cancer patients. In those patients, 1018 patients were proved the type of screening.

Results

symptom radiography CT pt 146 340 378 age 64±1 64±0.7 67±0.5 cStage IA 50 199 296 IB 22 66 42 IIA 18 25 6 IIB 15 13 8 IIIA 25 21 12 IIIB 6 4 2 IV 7 3 1 pStage IA 35 155 259 IB 18 57 53 IIA 12 31 13 IIB 16 23 11 IIIA 41 50 30 IIIB 6 4 1 IV 12 7 4

The number of patients by symptom, radiography and computed tomography are 146 (14%), 340 (33%) and 378 (37%), respectively. The rate of clinical stage I (789, 78%) are 72 (7%), 265 (26%), 338 (33%), respectively. The rate of pathological stage I (672, 66%) are 53 (5%), 212 (21%), 312 (31%), respectively. On the other hand, the rate of clinical III are 31 (3%), 25(2%), 14 (1%), respectively. The rate of pathological III are 47 (5%), 54 (5%), 31 (3%), respectively. The difference of between clinical stage I and screening type are 0.000, 0.813, and 0.000, respectively. The difference of between pathological stage I and screening are 0.000, 0.081, and 0.000, respectively.

Conclusion
In the group of symptom and radiography, there are a lot of advanced lung cancer patients, while in the group of computed tomography, we can detect a lot of early lung cancer patients. Computed tomography is better than the other screening about the detecting lung cancer. We should use a computed tomography in screening of lung cancer.

Background
The United Kingdom has poorer cancer survival rates than other comparable countries (EUROCARE and International Cancer Benchmarking Partnership studies). Furthermore, for some cancers stage at diagnosis is more advanced; largely explained by differences in one-year survival, a marker of later diagnosis. In 2012, the National Cancer Intelligence Network published a report as part of National Awareness and Early Diagnosis Initiative, Routes to Diagnosis. The key findings were that 24% of newly diagnosed cancer patients in England presented as emergencies. Tumour types most likely to present in this way included lung (39%). Emergency new cancer presentations were more likely in older patients and those from a more deprived background, and the relative one-year survival was significantly lower across nearly all tumour types. However, little is known about the reasons why so many patients present acutely with a potentially delayed diagnosis. Factors that lead to delayed diagnosis have been associated with the patient, the doctor and the healthcare system. Previous research in the area has been restricted by separating primary and secondary care, and data on the patient experience is limited. The CADIAS study is designed to examine the whole diagnostic pathway and consider improvements across all three domains.

Methods
This National Cancer Research Network approved study recruits patients who present to hospital as an emergency with a new diagnosis of lung or colorectal cancer. Data are collected from three sources, the patient, primary care and secondary care. The study aims to understand the whole diagnostic pathway; from first recognising a symptom to emergency presentation in secondary care, including the role of primary care; map the patient, clinical and organisational factors that contribute to an emergency new cancer diagnosis; and suggest ways to improve outcomes by identifying gaps in service provision and any opportunities to diagnose cancer earlier. Six hospitals within the London Cancer Alliance will aim to recruit 250-300 patients into the study (Chelsea and Westminster, Lewisham, Croydon, Hillingdon, St. Georges and Gyus and St. Thomas'). A small pilot study was conducted to confirm the feasibility of the recruitment methods and data collection tools, specifically the use of patient interviews across a relatively large scale and with a group of potentially unwell participants. This part of the study, which included research nurse training, was designed by the Promoting Early Cancer Presentation team at Kings College London.

Results
Data analysis of 9 patients and of the 1st cohort of nurse training demonstrated that the methods used and data collected is of the required quality and standard to open the study to full recruitment. CADIAS is now open across the remaining hospital sites and, at the time of abstract submission, a total of 19 patients had been enrolled.

Conclusion
Understanding the factors which contribute to an estimated 39% of lung cancer patients presenting as an emergency is key to improving cancer services and outcomes. This study brings the patient story together with data from primary care and secondary care to present a rich picture of this type of presentation and identifying any opportunities to diagnose cancer earlier.

Background
The efficacy of EGFR TKIs in EGFR mutation-positive NSCLC patients has led to a need for accurate, timely EGFR mutation testing worldwide. Although EGFR mutation testing has been adopted by many laboratories in Asia, accurate data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods. The objectives are to investigate the practice of EGFR mutation analysis in Asian Pacific countries and document the prevalence of routine testing in this population.

Methods
This is a retrospective database survey of records from NSCLC patients tested for EGFR mutations from 1 January 2011 to 1 January 2012 at participating sites across the Asia Pacific region. The majority of eligible hospitals/laboratories that participated had performed ≥ 100 EGFR mutation tests during that period. Accessible patient records were used to complete an online questionnaire, with data being stored in a central database. Primary objectives were to determine the number of NSCLC patients tested for EGFR mutations and the rate of EGFR mutation positivity: overall, by histological subtype, and by demography. Other variables included the number of NSCLC cases diagnosed, EGFR mutation testing methods used, and tumour sample characteristics and processing. The proportion of EGFR mutation-positive patients and 95% CI were calculated; other variables will be summarized descriptively. An interim analysis has been conducted using data collected from more than 18,000 newly diagnosed NSCLC patients at 29 sites.

Results
The data from surveyed sites indicates that the overall proportion of NSCLC patients tested for EGFR mutations was 31.9% (95% CI 31.2-32.6%), with an EGFR mutation positivity rate of 40.2% (95% CI 39.1-41.4%) overall, ranging from 28.7% to 53.4% (Table). Additional data on demographic and histological subgroups and current testing practices (methods, sample types, sample preparation) will be presented. [*: Wilson score confidence interval. **: Note that the sites from Vietnam (one site) and Philippines (one site) did not test ≥ 100 patients. N.D.: No data.]

Table: Proportion of Patients Tested and EGFR Mutation Rates at Participating Sites

Country	Total number of newly diagnosed NSCLC patients	Proportion of patients tested, % (95% CI*)	EGFR mutation positivity, % (95% CI*)
Total	18,050	31.9 (31.2-32.6)	40.2 (39.1-41.4)
Japan	2,379	64.8 (62.9-66.7)	30.2 (28.0-32.6)
China	12,086	18.3 (17.6-19.0)	38.1 (36.3-39.9)
Taiwan	2,530	52.9 (50.9-54.8)	53.4 (50.7-56.0)
Hong Kong	399	31.1 (26.7-35.8)	49.2 (40.6-57.9)
Malaysia	357	98.6 (96.8-99.4)	45.7 (40.6-51.0)
Thailand	249	57.8 (51.6-63.8)	45.1 (40.6-49.8)
Vietnam**	50	100.0 (92.9-100.0)	36.0 (24.1-49.9)
Philippines**	N.D.	Not Known	38.9 (29.5-49.2)
Indonesia	N.D.	Not Known	28.7 (20.8-38.2)

Conclusion
The data collected in this survey indicate that, in 2011, testing practices varied widely across the region, despite the well-known high incidence of the mutation. The data provide an insight into these practices and provide a reference platform on which to compare and build on for the future of EGFR mutation testing and molecular diagnosis of NSCLC in Asia Pacific.

Background
Lung cancer is the leading cause of cancer related morbidity and mortality in both the sexes in Nepal. It accounts for 15.4 % of total cancer as per hospital based Cancer Registry in Nepal. Patient usually present with stage III (55%) or IV (34%) disease. With the revision of Lung cancer staging system by International Association of the study of Lung Cancer (IASLC) and adoption of this Seventh edition of staging system by American Joint Comitte on Cancer (AJCC) in 2010, we tried to make an attempt and to recognize how many percentages of patients will upstage and downstage with comparison to the sixth edition of staging system.

Methods
This retrospective cross-sectional observational study was conducted at Department of Radiotherapy and Oncology, Bir Hospital and National Hospital and Cancer Research Centre, Nepal. We reviewed the record of the entire registered, histologically diagnosed lung cancer patient in these two centers during the year 2012. Total of 151 patient’s record were analyzed and restaged using both sixth and the seventh edition of staging system. The data were recorded and evaluated.

Results
Male preponderance observed with 63% of the cases and female of 37%. The mean age group was 63.93 years with the youngest being 31 years and the eldest with 83 years of age. The total patients in the different stage with seventh edition observed are IB 2(1%0, IIA 6(4%), IIB (8%), IIIA 59(39%), IIIB 24(16%), and IV 52 (34%. Stage migration was seen in 15.23 % of the total cases. Most prominent was downstage from IIIB to IIIA which accounts for the 7% of all the cases. This downstage is due to the Tumor size >7cm and a separate tumor nodule in the same lobe which elaborates T3 of the seventh edition. Next prominent stage migration noticed was due to categorization of pleural fluid cytology as M1a in seventh edition, which cause a total of 4% of cases to be upstaged from IIIB to IV, which in fact this may further increase. The entire patients presented with pleural effusion have not undergone cytological evaluation because in most of these cases T4 disease was due to invasion and or satellite nodule along with the pleural effusion so effusion was ignored as per 6[th] edition. Rest patient were downstage from T4 to T3 and T3 to T2, which is due to the sub categorization of the tumor by size.

Conclusion
In this cohort of patients, there was downstaging from IIIB to IIIA and upstaging from IIIB to IV because of revised TNM classification. Thus, we feel that a prospective larger study is required as it will further allow us to explain the prognosis and the survival pattern based on the staging system and we strongly recommend to have detailed staging and a routine pleural fluid cytology in the patient with pleural effusion before initiation of the treatment.

Background
The presence of an EGFR mutation in NSCLC provides prognostic and therapeutic information for patients and clinicians. This study investigates the clinical behaviour of EGFR mutant (MT) versus EGFR wild-type (WT) NSCLC in an Irish cohort of patients. Differences in the pattern of presentation, metastasis and diagnostic methods between patients with EGFR-MT and WT tumours are poorly characterised. In this retrospective study, we investigated these parameters, variations in EGFR mutation type and resultant impact on overall survival (OS).

Methods
Patients with EGFR-MT NSCLC were identified from a National Multi-Institutional database. Patient demographics, diagnostic and clinical data were collected by review of medical records. From the database, EGFR-WT controls matched for age, gender and stage were identified and used as a comparator group. Fisher’s exact and Mann-Whitney tests were used to compare variables between groups. Cox model was used to examine the effect of mutation type on OS.

Results
We identified 416 patients with NSCLC. Forty (10%) patients had EGFR-MT positive tumours, of which data were available on 35 (87%) patients. Among patients with EGFR-MT tumours, median age was 64 (range 35-89), 29 (83%) were female, 34 (97%) patients had adenocarcinoma, and 1 (3%) patient had adenosquamous carcinoma. Twelve (34%) patients had resected disease, and 23 (66%) had metastatic disease. At median follow up of 12.8 months, 3 (25%) patients with localised EGFR-MT disease recurred, 0 (0%) of EGFR-WT recurred. There were no significant differences in the pattern of disease between EGFR MT and WT in terms of central/peripheral localisation of primary lesion, or sites of metastasis such as the lung, liver, adrenal gland, bone or brain (p=1.0). Patients with EGFR-MT disease were more likely to be diagnosed via transbronchial biopsy (n=16, 47%) than EGFR-WT (n= 4, 11% p<0.01.) Patients with EGFR-WT disease were more likely to be diagnosed via endobronchial ultrasound/fine needle aspiration (FNA) (n= 21, 58%. p<0.01.) Among those with EGFR-MT disease, 19 (54%) patients had tumours which harboured Exon 19 deletions, and 6 (17%) harboured L858R mutations. The remaining mutations comprised L861Q, V689M and deletions in Exons 18, 20 and 21. Among patients with stage IV disease at diagnosis, the median OS was 20.9 months and 7.3 months for EGFR-MT and EGFR-WT disease respectively (p=0.16.) The median OS for patients who underwent resection was not reached in either group.

Conclusion
There were no significant differences in patterns of presentation and metastasis between patients with EGFR-MT and WT tumours in this cohort. Patients with EGFR mutations were more likely to be detected by transbronchial biopsy compared to patients with WT disease, who were diagnosed more commonly by FNA. Possible explanations for this include institutional preferences or ease of tissue acquisition. In this cohort, the most common mutations in EGFR were Exon 19 deletion or L858R. The likelihood of mutation detection might be improved with the inclusion of a full EGFR mutational analysis.

Background
BACKGROUNDS: The development of multiple synchronous primary malignancies in an individual is uncommon and unfortunate, but the frequency is increasing. The metachronous cancers will appear more commonly as cancer patients live longer lives. OBJECTIVES: The aim of this study was to determine clinical features, organ location, and prognosis in patients with multiple primary malignancies (MPM) including lung cancer.

Methods
METHODS: Following a retrospective review of clinical data, 101 patients with MPM including lung cancer confirmed with a histopathological diagnosis between 2002 and 2012 were enrolled in a tertiary referral hospital.

Results
RESULTS: The median age was 67 years (interquartile range (IQR), 61-73 years) at lung cancer diagnosis, and 66 (65%) patients were male. The most common histologic type of lung cancer was adenocarcinoma (47%), and 5 patients (5%) were diagnosed with triple cancers. In a total 56 metachronous cancer (55%), the median time between lung cancer and other cancer was 47.1 months (IQR 23.6-72.1 months) and 20 had lung cancer diagnosed before the occurrence of other primary cancers. The synchronous tumors were in 45 of 101 (46%). The most frequent cancers accompanying lung cancer were urogenital malignancies (30%) followed by gastrointestinal tract (28%) and thyroid malignancies (17%). Median survival duration calculated from the diagnosis of the first cancer was 33 months in the lung cancer first patients, 11 months in the other cancer first patients and 1.5 months in synchronous patients (p ≤ 0.001) with median follow up of 12.2 months. The factors of significantly associated with the survival of MPM were adenocarcinoma; histologic type of lung cancer (p = 0.010), the initial intensive treatments of lung cancer (p ≤ 0.001), non-smoker (p = 0.045) and operable lung cancer stage (p = 0.049) using Kaplan–Meier method with the log-rank test.

Conclusion
CONCLUSION: The synchronous tumors showed worse outcomes compared with those of the metachronous tumors including lung cancer. Despite multiple primary malignancies in patients with lung cancer, the influence of effective anticancer therapies that improve the survival, and the prognostic factors including the histologic type, staging, and smoking status were similar to the known factors of lung cancer.

Background
To evaluate the usefulness of transbronchial needle biopsy (TBNB) under computed tomography fluoroscopy (CTF) for pulmonary nodule/mass that is invisible at bronchoscopy and not suitable for biopsy using transthoracic approach.

Methods
The study included 23 patients (14 men, 9 women and mean age of 57 years) with pulmonary mass/nodule on computed tomography (CT) scans. In all patients, there was no an endoluminal lesion at bronchoscopy previously carried out and transthoracic biopsy was considered to be inappropriate owing to location of the lesion and/or presence of serious emphysema with abnormal pulmonary function test result. The procedure was done in a CT room with a monitor faced to the radiologist, while performing the broncoscopy by a bronchoscopist. CT fluoroscopic real-time scans were used to confirme that the tip of the bronchoscopic needle was exactly inside of the pulmonary target lesion. After the biopsy performed under CTF guidance, the obtaining samples were examined histopathologically.

Results
Figure 1 CTF-guided transbronchial biopsy samples were adequate for definitive diagnosis in 19 (83%) patients and inadequate in 4 (17%) patients. Inadequate results were caused by inability to reach the lesion as seen on CTF scans. 15 nodules/masses were diagnosed as malignant, 4 as benign. For malignant lesions, the final diagnoses were adenocarcinoma (n=5), small cell lung cancer (NSCLC) (n=4), non-NSCLC of undetermined cell type(n=2), epidermoid carcinoma (n=2), lymphoma (n=1) and sarcoma (n=1). Among the benign lesions, specific diagnoses were obtained in 2 (%50) patients. Mild to moderate hemoptysis occurred in 4 (17%) patients.

Conclusion
CT fluoroscopy-guided transbronchial biopsy is an effective and safe method to obtain the diagnosis of the lung lesion. It seems to be particularly valuable with a real-time guidance in pulmonary nodule/mass which is invisible at bronchoscopy and inappropriate for transthoracic biopsy.

Background
Computed tomography (CT) guided percutaneous transthoracic biopsy is a minimally invasive procedure that has been widely accepted as an effective, safe and feasible alternative for diagnosis of thoracic lesions. It guides therapeutic decisions, avoiding surgical biopsies in many clinical settings. The diagnosis sensitivity rate for malignant lung lesions was high (88-95%). The study was conducted to evaluate the diagnostic accuracy and complications of CT guided percutaneous transthoracic biopsies of suspected malignant pulmonary lesions.

Methods
Retrospective study involving all consecutive patients who underwent diagnostic CT guided percutaneous biopsies of suspected thoracic malignancies on dual slice CT equipment between Jan 2010 and December 2012. Percutaneous core needle biopsies were performed using a 16 / 18 / 20G Temno trucut automatic cutting needle under CT guidance. After the biopsy, a CT slice through the area of biopsy was performed to determine the presence of significant bleeding or pneumothorax. The samples were sent for the histological analysis. Evaluation included clinical data, pathologic results and therapeutic consequences. Statistical analysis of factors related to patient characteristics, lung lesions and biopsy technique was performed to determine possible contribution to the occurrence of pneumothorax.

Results
A total of 204 patients (143 males; 61 females) with mean age of 59.5 ± 14.0 years were included in the study. Mean diameter of lung lesion was 44.4 ± 14.5 mm. Mean depth of lung lesion was 14.4 ± 6.9 mm. Biopsies samples were adequate in 198 patients (97.1%) and inadequate in 6 patients (2.9%). Percutaneous transthoracic biopsy had an overall diagnostic accuracy of 93.6%. For malignant lesions, biopsy was positive in 161 patients (sensitivity of 97.6%) and for benign lesions, in 30 patients (sensitivity of 76.9%). Pneumothorax was observed in 30 patients (14.7%) and only 3 of them (1.5%) required a chest drain. The significant risk factors for pneumothorax were lesion depth >20 mm (p<0.0001), pathology type (malignant; p<0.0001), larger needle size (p<0.0001), number of passes >2 (p=0.001), lesion size <30 mm (p=0.009). There were no haemothoraces or major bleeding complications. However, post-interventional local hemorrhages were observed in 9 patients (4.4%) and hemoptysis was reported in 2 patients.

Conclusion
Percutaneous transthoracic CT guided biopsies of lung lesions were an effective procedure in the diagnosis of malignant lung lesions. Our study also shows that CT-guided needle biopsy is relatively safe, with only 1.5% of pneumothorax requiring chest drain and no major bleeding complications observed.

Background
Accurate staging of NSCLC remains the most important step in predicting outcome. It has been proposed that PET-CT, as an addition to conventional work up, allows for more accurate pre operative detection of stage IIIa and IIIb disease. On the other hand, it appears to have limitations in reliably staging nodal involvement in early stage NSCLC. We aimed to compare pre-operative nodal staging (PET-CT and/or EBUS-TBNA findings) with post-operative histopathological results to determine the accuracy of PET- CT in a multi-disciplinary team setting.

Methods
This was a prospective, observational study of consecutive patients discussed through Nepean Lung Cancer MDT that underwent surgical resection for NSCLC from Jan 2010 until Feb 2013. PET-CT parameters of all patients, including FDG uptake in primary lesion(s) as well as hilar and mediastinal lymph nodes, were compared with post operative histopathology of the primary lesions and resected lymph nodes. Pre-operative nodal staging based on PET-CT +/- EBUS-TBNA was compared with post-operative histopathological staging. A PET-CT SUV (max) of equal or more than 2.5 was considered positive.

Results
74 patients (mean age 69 years, range 47-86, 45 M ) underwent surgical resection with lymph node dissection for NSCLC (65 lobectomies, 5 bi-lobectomies, 2 wedge resections and 2 pneumonectomies). The most common malignancy in this group was Adenocarcinoma (39 [52.7%]) followed by Squamous Cell Carcinoma (25 [33.7%]) and undifferentiated large cell carcinoma (10 [13.5%]). Most patients were post-operatively confirmed to be in early stages (32 stage I and 26 stage II) with other patients in stage III (12 IIIa and 1 IIIb) and stage IV (3). In 47% of cases, PET-CT nodal staging was concordant with final histopathological results. There was discordance in 39/74 cases with PET-CT being more likely to upstage (30/74) than to downstage (9/74) the mediastinum. Symmetrical FDG uptake in hilar lymph nodes was common amongst upstaged cases. Anthracosis/silicosis was reported in lymph node histopathology of 16/74 (%21.6) patients, with 8 upstaged by PET-CT. Overall, sensitivity of PET-CT mediastinal staging in our cohort was 31.25% with a specificity of 70.5%. This translates into accuracy of 70.2%. In 7 cases, EBUS-TBNA was performed to establish nodal staging. One case of micro-metastasis, confirmed on post-operative histopathology, was not detected on EBUS-TBNA.

Conclusion
Nodal staging by PET-CT in early stage NSCLC has reasonable specificity but poor sensitivity, tending to upstage rather than downstage. Benign inflammatory processes affecting intra-thoracic lymph nodes such as anthracosis/silicosis may cause false positive PET-CTs. Nodal staging based only on PET-CT is inadequate and discussion through a multidisciplinary panel as well as minimally invasive investigations such as EBUS-TBNA is recommended. This is consistent with current international guidelines.

Background
In case of mucinous adenocarcinoma (MA), cytologic atypia is usually mild to moderate and can be absent in some cases, creating a diagnostic pitfall in recognizing MA in small tissue biopsy and cytology specimens. Specific diagnosis of mucinous subtype in small tissue n FNA is important because it is considered an invasive neoplasm until proven otherwise, and it carries a worse prognosis for its aggressive behavior with frequent multicentricity and intrapulmonary metastatic spread. The purpose of this study was to evaluate the diagnostic accuracy of transthoracic fine needle aspiration (FNA) or core needle biopsy (CNB) of MA of the lung.

Methods
We retrospectively reviewed a consecutive series of 184 patients who underwent curative operation for MA. Among those patients, 105 patients underwent pre-operative percutaneous FNA (n= 34) or CNB (n= 79). Eight patients underwent both FNA and CNB for the same tumors. Diagnostic accuracies of FNA and CNB for MA were evaluated, and the contribution of various clinicopathologic parameters to subtyping accuracy was analyzed.

Results
Diagnostic accuracies of FNA and CNB in determining malignancy were 67.6% and 87.3%, respectively. 20.6% and 59.5% were successfully diagnosed as MA through FNA and CNB, respectively. Univariate analysis implicated type of procedure and prominent growth pattern of mucinous adenocarcinoma as significant factors for successful pathologic diagnosis. Figure 1

Conclusion
CNB of diagnosis of MA is feasible and accurate. Our data support the suitability of small biopsy specimens for the new therapeutic paradigms even in mucinous adenocarcinoma.

Background
Nickel is one of the most widely distributed and used metals in the world. Exposure to nickel compounds can result in a variety of adverse effects on human health. The China Nickel Workers Cohort Study (Jinchuan cohort) is estimated to include more than 50 000 nickel workers.

Methods
Since 2011, all staff and workers have been eligible for a medical examination every 2 years, and these workers who participated in the medical examination will be in-person interviewed with a standardized and structured questionnaire with trained interviewers and will be included in the Jinchuan cohort study. The medical examination includes a comprehensive physical examination, biochemical examination, epidemiologic survey and collection of biological samples. The Jinchuan cohort has the largest data set from a cohort of nickel exposed workers with both questionnaire and laboratory-based information and the exposure and disease information will be updated every 2 years through the biannual survey and medical examination.

Results
The comprehensive epidemiological and biological data will permit the evaluation of a number of hypotheses concerning the health effects of nickel exposure. The unique repository of blood samples including blood cell, plasma, and serum collected at the time the epidemiology survey will provide a population-based platform to examine biological indicators that closely correlate with nickel exposure and illness by using molecular epidemiologic methods. All of the cryopreserved blood samples are being stored in cryogenic tubes for future studies.

Conclusion
We are conducting the first occupational epidemiological study of nickel exposure in China among over 50 000 workers Comprehensive physical and biochemical examinations, an epidemiologic survey, and collection of biologic samples from workers are being used to evaluate the relationship between nickel exposure, cancer, and other health outcomes The cohort will be followed every two years with a repeat medical examination to update exposure and outcome information

Background
Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. NSCLC is strongly related to age. Its incidence increases with advancing age and the median age at diagnosis is 70 years. Less than 5% of all NSCLC is seen before 40 years of age. Furthermore, young patients have different characteristics compared with older patients. In this study, the clinical features of patients less than 40 years of age were analyzed.

Methods
Medical records of patients diagnosed as having NSCLC between March 2000 and March 2013 were retrospectively examined in 17 institutions of Anatolian Society of Medical Oncology. Epidemiological data such as age, gender and smoking history was collected. Additionally, histological subtype, ECOG performance status, stage, number of organ metastasis, presence of cranial metastases were analyzed.

Results
A total of 210 patients were evaluated. Median age was 35 years (range, 18-40). The majority of the patients were males (148 males and 62 females). There were 120 patients with a history of smoking. Seventy-eight patients were non-smokers and twelve were unknown. Majority of the patients (64%) had stage IV disease at presentation. Most of the patients had good performance status. Half of these patients had two or more organ metastasis (53%). Cranial metastases were detected in 55 patients. Adenocarcinoma was the most common histological subtype (57%). Other subtypes were squamous cell carcinoma (20%) and unclassified (20%). In stage IV disease, adenocarcinoma was more frequent (64%). There was no association between histopathologic subtype and smoking history. Median overall survival (OS) of the entire cohort was 15.1 months. Median OS was similar to the literature data (stage II: 45.8 months, IIIA: 44.4 months, IIIB: 21.1 months and stage IV: 9.9 months).

Conclusion
Adenocarcinoma was more common in the younger patients. These patients had advanced disease and good performance status at presentation. However, survival was not better than older patients based on historical literature data.

Background
Lung cancer incidence and mortality are high in Tasmania; Incidence Mortality Australia (AIHW 2007) 43/100 000 34/100 000 Tasmania (Cancer Registry 2007) 58/100 000 54/100 000 There is limited published data looking at 5 year survival for primary Non-Small Cell Lung Cancer (NSCLC) particularly from Australian cohorts.

Methods
Local clinical practice information was collected in a prospective database. Cases presented at a multidisciplinary lung cancer meeting over a 24 month period (April 2006 -March 2008) were analysed. Patients with NSCLC were identified (n=181). Survival data was obtained for all NSCLC cases (n=181/181) via hospital and general practitioner records as well as the Registry of Births, Deaths and Marriages. Lung cancer stage was based on the 6[th] edition IASLC TNM classification. Mortality data and survival times were calculated according to clinical stage.

Results
Five year survival was 10.5% (19/181) for all stages of NSCLC. Stratified by stage, 5 year survival was: Stage I 25% (13/52), Stage II 25% (3/12), Stage III 6% (3/52), and Stage IV 0% (0/65). Overall median survival was 7 months and when stratified by stage was: 30 months for Stage I, 5.5 months for Stage II, 9.1 months for Stage III and 3 months for stage IV disease. Patients who underwent surgical resection with curative intent had a 60% 5 year survival (13/22) which is in keeping with other published Australian data.

Conclusion
The five year survival rates for Stage II, III and IV NSCLC were comparable with that of internationally published cohorts. In contrast, all-cause mortality rates for Stage I NSCLC appear higher than expected however rates of surgical cure are in keeping with published data.

Background
Lung cancer is the most common cause of cancer-related deaths in the world. In the last decades, the patients with adenocarcinoma histology have been increasing, although we don’t know the exact reason, and now constitute most common histological subgroup of Non-small Lung Carcinoma (NSCLC).Main aim of this study is analysis of histological subgroup of NSCLC, changing of histological subgroupsover time and its effect on survival parameters.

Methods
We analyzed 493 NSCLC patients those who were followed at our department between January 2006 and December 2011. Basic demographic and clinical characteristics such as stage of disease, initial diagnostic tests including invasive procedures, immunohistemochemical methods to clarify the histopathological subgroups, treatment protocols together with survival parameters were recorded retrospectively.

Results
Included were 493 patients with a median age of 60 years (35-102). There were 426 men (86.4%)and 67 women(13.6%)446 (90.5%) patients had a history of cigarette smoking. The percentage of female patients in whole group had been increased over timenonsignificantly(p=0.24). We found that adenocarcinoma was most common histopathological diagnosis (44.9%). Better performance status, early diagnosis, and adenocarcinoma histology exhibit statistically significant effect on overall survival with p values of (p=0.003,p=0.054, p=0.006), respectively. Statistical analysis showed that overall survival and TTF-1 positivity were significantly increased over time in the study with p values of (p=0.011) and (p=0,001) respectively. We also found that TTF-1 positivity was higher in female gender (p=0.005). Additionally,we were not able to show significant effects of basic demographic and clinical characteristicsof the patients such as age, TTF-1 positivity and primary localization of tumor on overall survival (p>0.05).

Conclusion
Our study showed that adenocarcinoma is the dominant histology of NSCLC in Turkey and the percentage of female patients in NSCLC and overall survival in NSCLC had been increased significantly over time.Patient and tumor characteristics, such as histological shifting to adenocarcinoma over time, that we found during our study is compatible with literature.

Background
PIONEER (A molecular ePIdemiOlogy study in Asian patients with advanced NSCLC of adEno histology to assess EGFR mutation status; NCT01185314) was a multinational prospective epidemiological study planned to investigate EGFR mutation frequency in patients from Asia with newly diagnosed advanced lung adenocarcinoma (ADC) and the influence of demographic and clinical factors on EGFR mutation frequency. Here we report analysis results for the subset of patients from China.

Methods
Patients were aged ≥20 years, with treatment naïve stage IIIB/IV lung ADC. The primary objective was assessment of overall EGFR mutation frequency. The secondary endpoints included investigation of the correlation between EGFR mutation status and demographic and clinical factors and attrition rates of EGFR mutation testing. The acquisition, preparation, and processing of tumor material was performed in line with the routine clinical practice of the participating hospital laboratories. Tumor EGFR mutation status was determined in central labs using amplification refractory mutation system (ARMS)-based EGFR mutation detection kit (Scorpion ARMS IVD2, Qiagen, Crawley, UK). 29 mutations were detectable by this method across Exons 18, 19, 20, and 21.

Results
747 patients were registered in 17 investigational sites in China (50.4% of the overall study population). 46.9% of the patients were female, mean age was 58 years (range 17-83), and 56.4% were never-smokers. 72.4% (541/747) of the samples used for mutation testing were primary tumor. Sample locations include lung (73.5%), local lymph nodes (10.3%), distant lymph nodes (6.3%), pleural effusion (2.5%), pleura (2.0%), and others. sample types include image-guided core biopsy (29.7%), bronchoscopic biopsy (24.1%), incisional biopsy(12.7%), cytology and others. The median time interval taken from order to report of mutation test was 16 days with a range from 3 days to 62 days. EGFR mutation status was successfully evaluated in 741 patients: 372 (50.2%) were mutation positive, 369 (49.8%) were mutation negative. Smoking status and pack years had a statistically significant association with presence of EGFR mutation, but even in regular smokers, the mutation frequency was 35.3%. 12 patients provided both histology and cytology samples. Among these 11 had concordant EGFR mutations status and 1 had mutation results that did not match.

Conclusion
Locations and types of the samples used for EGFR mutation testing were various in clinical practice. The overall EGFR mutation frequency in clinically unselected Chinese ADC was 50.2%. Smoking status and pack years had a statistically significant association with presence of EGFR mutation.

Background
Thromboembolic events (TE) are common complication of cancer, may lead to mortality and detoriate quality of life. The most common malignancies associated with TE’s are adenocarcinomas and the mechanism needs to be elucidated.Several studies suggest that increased risk of TE’s with hormonal contraceptives is mediated through the sex hormone-binding globulin levels (SHBG). The aim of this study is to investigate if the SHBG level is associated with TE’s in cancer patients with adenocarcinoma.

Methods
We compared the SHBG levels in 45 patients with TE and 23 patients without TE, all of them cancer with adenocarcinoma histology. A p value of less than 0.05 was considered statistically significant.

Results
Sixty eight patients, aged between 37-80, are evaluated. Thirty five women. There was no statistical significant relationship for age and gender between TE and non-TE groups. AT TE group, 20 (44%) had distal lower extremity (DLE) deep venous thrombosis (DVT), 17 (38%) had PE and the rest includes 4 central/proximal DVT (9%), 4 central venous catheter-related DVT (9%). Frequencies of histopathology for TE and non-TE group were; colorectal cancer 20 (30 %), gastric cancer 13 (20 %), pancreatic cancer 11(16%), breast 10 (%14), Lung 6 (9 %), and other (prostatic 3, hepatobiliary 2, unknown primary 2 and ovarian 1) 8 (%11). There was no difference between SHBG levels with TE group (mean±SD; 59±41) and non-TE group (60±49)( student’s t test; p=0.98).

Conclusion
SHBG levels do not play any role in the mechanism of cancer- related thrombosis in patients with adenocarcinoma.

Background
Epidermal growth factor receptor (EGFR) is a trans-membrane protein it belongs to the ErbB-family, its activity includes transmitting of growth factor signaling from the surface of cells into the cells and activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. EGFR has an impact on malignant cells development in various tumors, affecting their proliferation, apoptosis, motility and angiogenesis. In NSCL cancer EGFR-protein mutations in exons 18–21 results in constant hyper-activation of downstream pro-survival signaling pathways, independent from any external receptor stimulation. Approximately 10% of US patients and 35% in East Asia patients show EGFR mutation of which, almost 90% of these mutations are exon 19 deletions or exon 21 l858r point mutations. EGFR has been identified as an important therapeutic target for the treatment. Purpose: To evaluate the prevalence of EGFR mutations in the diagnosed cases of NSCLC in our hospital, which deals with approximately 80% of lung cancer cases in UAE and to compare it with other geographic and ethnic groups.

Methods
Methods: A retrospective analysis of all non-small non-squamous lung ca cases that had EGFR testing was performed. LAB 21 in UK was used for the EGFR mutation testing. A total of 50 tumor blocks were sent to the laboratory. The test could not be performed on one case. Out of the remaining 49 patients, 13 (26%) were female and 36 (74%) were male. Open biopsy by either lymph node excision, pleuroscopy, open lung biopsy or craniotomy were the tissue source for the EGFR analysis in 23 patients while only 15 had enough tissue from one procedure (bronchoscopy or guided biopsy).

Results
Results: EGFR mutation was identified in 18/49 (37%) patients. of the 18 patient, who had EGFR mutation, 10 (56%) patients had exon 19 mutation, 6 (33%) patients had exon 21 deletion and 2 (11%) patient had double mutation. in those two patients with double mutation, one had mutation in exons 19 and 21 and the other had mutation in exons 18 and 20. No significant difference was observed in EGFR-mutations among the gender of patients, 35% in men and 38% in women. Analysis of ethnicity and prevalence of EGFR-mutation showed a significant difference between Arabs (15 of 32 / 46%) and non-Arabs (3 of 17 / 18%). in the Arabian cohort with EGFR mutations 8 out of 22 patients (36 %) had a smoking history and 7 out of 10 (70%) were documented as non (never)-smoker.

Conclusion
Conclusion: Local prevalence of EGFR mutation was found to be 37% among all the ethnic groups, which is in line with the incidence in Asian population but the Prevalence of EGFR mutations in Arabs was (46%). it is to be stressed here that testing for EGFR mutations should be considered for all patients with non-small non squamous cell lung cancer at diagnosis, regardless of clinical characteristics. This strategy can warrant the prompt use of EGFR tyrosine kinase inhibitors to promote the practice of personalized medicine.

Background
Implementation Science has emerged over the past 20 years to highlight a fundamental problem in health care: that knowledge about optimal care is not applied in clinical practice. A ‘gap analysis’ is an initial research activity undertaken when quantifying the gap between existing knowledge and clinical practice. The purpose of this presentation is to describe outcomes of a gap analysis conducted in lung cancer and priority setting focus groups held with oncology health professionals. This research is being conducted by Sydney Catalyst, a Translational Cancer Research Centre that brings together teams of clinicians and researchers from more than 20 member organisations across NSW, Australia, for the purpose of facilitating rapid translation of scientific evidence into clinical practice and policy.

Methods
A systematic approach was used to examine the evidence across the lung cancer patient journey. Data sources included international and national clinical practice guidelines, systematic reviews and meta-analyses, and research from peer reviewed publications, including population-based patterns of care studies and data linkage studies. We also conducted a descriptive analysis of data from clinical cancer registries and administrative databases used in the local setting of Sydney and regional NSW, Australia, to determine what gaps were locally relevant. All data sources were reviewed and synthesised to create the list of evidence-practice gaps. The gaps are presently being tested in three focus groups in urban and regional cancer services in NSW, Australia. Focus group participants include specialists in lung and thoracic oncology, medical, nursing, allied health and supportive care health professionals. The purpose of these focus groups is to conduct a priority setting exercise, where clinicians can rate the relevance of gaps to the local context and agree on which gaps should first be addressed in any subsequent research projects.

Results
Seven evidence-practice gaps were identified across the patient journey (from initial presentation and diagnosis through to palliative care). We analysed 2008 data from one local hospital for all lung cancer patients (N=329) and found that local patterns of care appear to be consistent with those previously observed in a NSW patterns of care study. This assists in demonstrating that gaps identified at the population level are also present in local health care settings and strengthens a rationale for developing collaborative lung cancer specific research projects that engage clinicians and researchers. The analysis and outcomes of focus groups will be presented, along with a critical appraisal of the gap analysis methodology and show how this approach in lung cancer is relevant to other tumour groups and health conditions.

Conclusion
A gap analysis enables researchers and clinicians to identify where deficiencies exist between published research evidence and optimal patient care. By drawing together and synthesizing data from multiple sources of evidence, identifying gaps and setting priorities with local health professionals, we believe we can address the goal of more rapidly translating evidence into practice.

Background
Australia has the highest incidence rates of malignant mesothelioma in the world. The exact mechanism of mesothelioma development is only partly understood, however it has been linked to occupational and increasingly, non-occupational exposures to asbestos. The Australian Mesothelioma Registry (AMR) was established to collect incidence and mortality data on all cases of mesothelioma in Australia, including detailed information on asbestos exposure. The Australian Mesothelioma Registry completed its second full year of data collection on cases from 1 July 2010.

Methods
The AMR compiles notifications from state/territory cancer registries. Clinicians may be requested to advise if their patients are suitable for recruitment to the asbestos exposure component. Consenting participants are assessed for past asbestos exposure by The Monash Centre for Occupational and Environmental Health, after completing a job and residential history questionnaire and telephone interview using OccIDEAS, an online exposure assessment tool.

Results
More than 600 cases of mesothelioma have been notified to the Registry for 2011. At 30 June 2013, 619 diagnoses of mesothelioma had been reported to the AMR for 2012. Exposure assessments collected within the AMR framework will provide information not previously available. Data will be presented for 2012, the second calendar year of data collection, in addition to results for the exposure assessment component.

Conclusion
AMR information has the potential to provide an accurate assessment of sources of asbestos exposure currently contributing to causing newly diagnosed mesothelioma in Australia. The AMR is a national resource for researchers and may assist in preventing mesothelioma in the future.

Background
Chronic obstructive pulmonary disease (COPD) is a frequent complication seen in 24.9% in patients with lung cancer. In practice, a decreased respiratory function due to COPD influences to decision of treatment. The airway obstruction is assessed by the Global Initiative for obstructive lung disease (GOLD) classification. On the other hand, Goddard classification is a method for evaluating the emphysema using CT images. The respiratory function of an advanced lung cancer has various modifications such as tumor airway obstruction or atelectasis. The hypothesis is that in patient with COPD and advanced lung cancer patients, GOLD classification may not correspond to the Goddard classification. We evaluated the associations of clinical characteristics with Goddard classification as well as GOLD classification.

Methods
Between May 2007 and April 2012, the pre-treatment respiratory function was assessed for patients diagnosed at Osaka City University Hospital as non-small cell lung cancer stage IIIB or IV without EGFR gene active mutations. FEV/FVC% less than 70% were diagnosed for COPD. GOLD and Goddard classification were evaluated. Two doctors independently determined the Goddard classification, and the final score was adopted from the average of two scores. The association of clinical characteristics with Goddard classification as well as GOLD classification was performed by fisher exact test. An univariate analysis was performed to evaluate the prognosis by COX regression method. In multivariate analysis, histology, stage, number of cigarette smoking, and FEV/FVC% were performed to evaluate the prognosis by COX regression selected variable method (stepwise method).

Results
A total of 67 patients were enrolled with median age of 70 (49-81). GOLD classification showed normal (n=32), mild (stage I/II, n=30), and moderate (stage III, n=5) airflow obstructions. There was no severe COPD (stage IV) patient. In GOLD classification, no-significant associations of clinical characteristics were observed such as lobe site of primary lesion (p=0.84), tumor histology (p=0.21), gender (p=0.17), and cigarette smoking (p=0.42). Goddard classification showed non (score zero, n=12), mild (score <8, n=32), and moderate-severe (score 8-20, n=23) emphysema findings. In Goddard classification, there were significant associations of clinical characteristics in tumor histology of squamous cell carcinoma (p=0.010), male (p=0.031), and number of cigarette smoking (p=0.020). Univariate analyses showed neither GOLD nor Goddard classification was associated with overall survival. In multivariate analysis, FEV/FVC% was not associated with overall survival.

Conclusion
As compared with Goddard classification, the distribution of GOLD classification shift relatively mild direction. Therefore, there is no-significant association of clinical characteristics in GOLD classification, and Goddard classification was significant association of squamous cell carcinoma, male, and cigarette smoking. Surprisingly, the FEV/FVC% did not become a prognostic factor for NSCLC received chemotherapy. The severity of COPD might not influence outcome of chemotherapy in advanced NSCLC.

Background
Cigarette smoking, alcohol consumption and presence of co morbidities are important factors that affect health status and mortality in patients diagnosed with lung cancer. While the gold standard for presence or absence of co-morbidities is EPR, the gold standard for obtaining accurate data pertaining to health-related behaviours is by PRS. The purpose of this study is to ascertain, whether in the absence of patient self-reported data, health related behavioural data pertaining to cigarette smoking and alcohol consumption abstracted from EPR provides an accurate and reliable surrogate.

Methods
731 lung cancer patients completed a PRS pertaining to information on their lifetime tobacco use, alcohol consumption and whether or not they had been diagnosed with certain co-morbid conditions. Relevant smoking, alcohol consumption and co-morbidity data was collected independently from EPR. Kappa coefficient analysis was used to assess the agreement.

Results
Results can be seen in Table 1. Ever/never status for smoking showed almost perfect agreement (k=0.95) between PRS and EPR and surpassed all other health behavioural measures and all co-morbidity agreement values. The calculation of pack-years from EPR and PRS showed substantial agreement (k=0.77); However, categorizing the smoking status into current/ former / never, resulted in only moderate agreement (k=0.47). Alcohol ever/ never status agreement was moderate (0.44) with high sensitivity (0.90) but low specificity (0.50). The lung related co-morbidities like emphysema (k=0.41) and chronic bronchitis (k=0.28) showed fair agreement but with substantial missing data through EPR.

Table 1
Health Behaviour	N	Missing Data in EPR	Agreement (k)	95% CI (P value)	Se	Sp
Smoking (E/N)	709	0	0.95	(0.79, 0.89)	0.995	0.94
Smoking (Pkyrs)*	606	81(11%)	0.77	P<0.0001
Smoking (C/F/N)**	705	4(0.5%)	0.47	(0.41, 0.51)
Alcohol (E/N)	575	150(20.5%)	0.44	(0.36, 0.52)	0.9	0.5
Comorbidity
Emphysema	589	126(17.2%)	0.41	(0.33, 0.49)	0.41	0.95
Chronic Bronchitis	601	94(12.8%)	0.28	(0.19, 0.37)	0.39	0.88
*Spearman correlation coefficient
**Weighted kappa

Conclusion
In the absence of PRS data, EPR provides a reliable surrogate for ever/ never smoking status and moderately reliable for lifetime smoking exposure in this lung cancer population. However current/ former/ never smoking status and ever/ never alcohol status cannot be reliably ascertained from medical records. Missing EPR data related to smoking pack years, alcohol consumption and lung co-morbidities is concerning and suggests more systematic or synoptic reporting by physicians would improve opportunities for research

Background
Background: Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for >90% of asbestos used worldwide but its capacity to induce malignant mesothelioma is still controversial.

Methods
Methods: Human mesothelial cells were exposed to crocidolite or chrysotile for a period of 48hr or 5 weeks, either in the presence of TNF–α or human macrophages in a co-culture system mimicking the process of recruitment and activation of inflammatory cells to sites of fiber deposition, which leads to the carcinogenesis of mesothelioma. Functional studies, as well as whole-genome wide expression profiling were performed to compare the molecular mechanisms and the carcinogenic potential of chrysotile and crocidolite.

Results
Results: We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E–cadherin down-regulation and β–catenin phosphorylation followed by nuclear translocation, were induced by chrysotile and crocidolite. Gene expression profiling data detected High-Mobility Group Box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both chrysotile and crocidolite. Crocidolite and chrysotile induced differential expression of 57 out of 28,869 genes interrogated by oligo-nucleotide microarrays and 13 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, while chrysotile effects returned to background levels in five weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks following crocidolite exposure, while returned to background levels eight weeks from chrysotile exposure.

Conclusion
Conclusion: Our results show that chrysotile has the capacity to induce, in HM, molecular changes associated to MM development similar to those induced by crocidolite, but these changes are short lasting. The data suggest that HMGB1 and TNF–α are key mediators of these processes for both crocidolite and chrysotile. However a continuous administration of chrysotile was required for inducing sustained HMGB1 levels. These data support the hypothesis that the different bio-persistence of the two asbestos fibers influences their biological activities.

Background
According to the World Health Organization, one hundred million deaths were caused by tobacco in the 20th century and the expectation for 2030 is equal to 10 million deaths. Lung cancer is the leading cause of cancer death and in the United States cigarette smoking is responsible for an estimated 90% of all lung cancers. About 50% of lung cancer patients are current smokers at the time of diagnosis and 11 to 48% of all smokers continue to smoke. Parsons et al. in a review of 10 studies suggest that smoking cessation after early stage lung cancer diagnosis improves prognostic outcomes and, despite evidences that smoking cessation is related with more effective treatment, reduced chemotherapy and radiotherapy toxicities and a better prognosis, the belief prevails that treating tobacco dependence is less important than the other therapeutic approaches.

Methods
122 lung cancer patients referring to the Thoracic Oncology Unit of the S. Luigi Hospital in Orbassano – Italy (31% of the total number of patients referring to this center in this period of time) were prospectively and sequentially evaluated from 02/01/2013 to 30/05/2013. In order to collect data, a dedicated 15 question-anonymous survey was developed with the aim to understand if smoker or former smoker patients had received information by health professionals, about smoking cessation before or after the diagnosis, which reaction they had and which actions were adopted for quitting smoking.

Results
The median age of participants was 65 years or more, 75% were men, 25% women. 27% were smokers, 73% former smokers. Among active smokers, most patients (87.8%) reduced the number of cigarettes after being diagnosed. 45.4% of patients report not to have received information on smoking cessation by the healthcare professionals and among patients who received it, the majority (84.2%) declared a good or very good ability of health workers to understand the difficulty of quitting smoking. About 76% considers positively the action of health care providers and a little percentage reports a warning and paternalistic attitude of them. 67.7% of patients who attempted to quit smoking, state the sudden termination as the most effective measure, more than the gradual reduction of cigarettes. Analyzing anti-smoking techniques or therapies adopted, most patients declare not to resort to such methods: only 25% started using electronic cigarettes, 5.5% has used a nicotine replacement treatment, 4.1% is attending an antismoking clinic.

Conclusion
The analysis of the study results underline that most lung cancer patients are interested in smoking cessation programs and although many of them receive advice and assistance by healthcare workers, the recourse to the use of techniques, drugs or access to specific clinic is very low. In Italy there are few centers offering counseling for smoking cessation, while in UK, Norway and Netherlands innovative interventions are available and oncology nurses are essential in the identification of and intervention with patients who struggle with this dependence. This is a pivotal experience and other Italian and Spanish centers are already been involved in the questionnaire collection to get more complete and heterogeneous results

Background
Smoking cessation is a highly cost-effective health intervention. Embedding a smoking cessation program within a lung cancer screening program may significantly enhance the cost-effectiveness of screening. Smokers enrolling in Low-dose CT screening studies are motivated to quit but the best strategy to aid smoking cessation is not yet defined.

Methods
Population: smokers enrolled in a LDCT screening study, age 60-74years, with >=30 pack-year smoking history. Smokers could enrol at any time during the LDCT study. Intervention: single face-to-face counselling session on the day of attendance for LDCT screening plus audio cessation advice (on mp3 player) plus written quit materials. The individualised counselling session was given by a thoracic physician using motivational interview techniques. Control: written quit materials only. Outcome: point prevalence self-reported smoking cessation at 1 year, confirmed with exhaled CO measurement (ECO) where available; ≥10ppm level indicating non-abstinence.

Results
Fifty-four participants were randomized (control group n=26, intervention group n=28). There were no statistically significant differences between groups in age, sex, pack-years smoking, baseline CT scan findings, nicotine dependence score, self-belief in ability to quit (on a scale of 1-5, higher score indicating stronger belief) or education level although the intervention group reported a higher number of cigarettes smoked per day (table 1). Baseline LDCT scans were reported as positive if one or more non-calcified nodules >=4mm diameter were detected. The mean duration of interview was 26 minutes. Overall, ten participants (18.6%) reported smoking cessation (five had ECO confirmation and five did not have ECO testing); two patients (3.7%, one from each group) had missing data and were assumed to be continuing smokers; the remainder reported continued smoking. There was no difference in self-reported cessation between the intervention and control groups (17.8% vs 19.2% respectively).

Table 1

		Control	Intervention	p value
	Women	10	10	ns
	Men	16	18	ns
Education	Up to High School	13	13	ns
	Teriary	13	15	ns
	Age, years, mean	64	64	ns
	Age started smoking, years	16	17	ns
	Cigarette consumption per day, n	23	30	0.03
	Pack years smoking, mean	61	64	ns
	FEV1 % predicted, mean	92	90	ns
	Fagerstrom nicotine dependence score, mean	4.9	5.2	ns
Baseline CT Scan report	Negative	12	10	ns
	Positive	14	18	ns
	Self-belief in ability to quit	3.7	3.4	ns

Conclusion
The 18% quit rate in this study is higher than reported background rates however the brief intervention provided did not increase quit rates above that of the control group. Smokers in this study reported moderate to high levels of nicotine dependence with extensive smoking histories, and, although motivated to quit, may require more intensive assistance to support smoking cessation.

Background
Smoking is a public health problem in Mexico and the world, the economic impact in developing countries have not been fully documented. In our country there is a direct relationship between smoking and the 10 leading causes of death in adults. The purpose of this study was to estimate the direct costs of medical care for lung cancer attributable to the tobacco habit in the National Cancer Institute of Mexico (INCan).

Methods
The study was conducted at the National Cancer Institute of Mexico (INCan) during 2009. Costs were estimated from the perspective of services supplier based on the Cost of Illness method. An expert panel developed a diagnostic-therapeutic guide which integrated infrastructure, human resources, technology and health services provided at INCan. Costs were valued in Mexican pesos using an exchange rate of 1USD=13.0659 pesos.

Results
297 incident cases of any type of Non Small Cell Lung Cancer during 2009 were analyzed. The annual average cost attributable to smoking per patient was 84,189 USD regardless of clinical stage. The 96% of the annual cost corresponded to stage IV. The annual total cost of Non Small Cell Lung cancer associated to tobacco habit at the INCan was 18, 807,354.8 USD. Figure 1

Stage [+]	Anual total cost	Anual total cost due to tobacco *
LC I	45,787.2	30,219.5
LC II	76,244.7	50,321.5
LC III	928,261.2	612, 652.4
LC IV	27,445,699.0	18,114,161.3
Total	28,495,992.1	18,807,354.8
Currency: USA dollar, 1 dollar = 13.0659 mexican pesos Exchange according to Banco de México(Banxico) information [+] Estructure established by the Lung Cancer experts of the INCan and the CIE-10 2009. *Obtained with tobacco attributable fraction of LC, calculated for national IMSS; 0.66. Reynales et al.

Conclusion
Health care costs for Non Small Cell Lung Cancer attributable to smoking represent an important and high cost to the INCan and the health sector of Mexico. These costs could be avoided if all the provisions of the Agreement-framework of the World Health Organization for tobacco control were implemented in our country.

Background
Superior vena cava (SVC) syndrome results from great vessel extrinsic compression or intraluminal obstruction resulting in facial erythema, edema, or venous distension. This presentation can escalate into a life threatening condition. The Yale SVC classification system and management algorithm was proposed for tumor-related causes. We hypothesized its inclusion criteria may be limited in scope and not capture common causes and symptoms of SVC. The specific aim was to develop a SVC identification, classification, and management algorithm.

Methods
Retrospective data from Oregon Health & Science University pts diagnosed with ICD-9 code 459.2, compression of vein, between 2008-11 were collected. Pt demographics, vital signs, physical examination findings, hospitalization records, and outcomes were analyzed. ANOVA and Mann-Whitney U tests were utilized to assess significant between genders, p ≤ 0.05.

Results
The study population consisted of 207 pts; 157 were removed due to compression of a vessel other than the SVC. SVC syndrome was secondary to a malignancy (n=30), fibrotic stricture (n=5), or indwelling catheter-related thrombus (n=11). Dyspnea (n=31), facial edema (n=24), and cough (n=18) were the most common physical examination findings. Patients who presented with cough or dyspnea secondary to a malignancy, without facial, neck, or extremity edema (n=7) or those with a post-procedure fibrotic stricture (n=5) or an indwelling catheter-related thrombus (n=11) did not meet the Yale classification system inclusion criteria.

Conclusion
A SVC classification system, which accounts for non-oncologic causes and symptoms due to the mass effect on surrounding tissues (vasculature, trachea, and esophagus) is a more comprehensive approach to SVC treatment.

Background
Cisplatin is a cornerstone of lung cancer treatment and is associated with CINV, which impacts severely quality of life and may cause non-compliance. Palonosetron (PALO) is clinically superior and pharmacologically distinct from old-generation 5-HT3 receptor antagonists. Non-inferiority of 0.50 mg oral PALO (O-PALO) in preventing moderately emetogenic CINV when compared with 0.25 mg intravenous PALO (IV-PALO) has been demonstrated.

Methods
This multicenter, multinational, randomized, double-blind, parallel group study investigated the efficacy and safety of single doses of O-PALO and IV-PALO administered prior to HEC. Adult chemotherapy-naive patients with malignant solid tumors and adequate hepatic, renal and hematological function scheduled to receive cisplatin-based HEC were enrolled. Eligible patients received O-PALO (0.50 mg) or IV-PALO (0.25 mg) with oral dexamethasone (Dex) 20 mg (day 1) followed by Dex 8 mg bid (days 2–4). The primary study objective was to demonstrate the non-inferiority of O-PALO vs IV-PALO (O-vs-IV-PALO) as a percentage of patients with complete response (CR: no emesis and no rescue medication) within the acute phase (0–24 hours after chemotherapy administration). Secondary objectives included the assessment of safety and tolerability of O-vs-IV-PALO and CR in the delayed (25–120 hours) and overall (0–120 hours) phases.

Results
Of 743 patients randomized 1:1 to receive O-vs-IV-PALO, 739 received study medications and 738 were included in the full analysis set. The majority of patients were male (59.3%) and white (86.7%) with a median age of 59 years; 46.5% of patients had lung/respiratory tract cancer. The CR rate in the acute phase was high for both treatment groups (O-PALO 89.4%; IV-PALO 86.2%). The difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21% with two-sided 99% Confidence Interval (CI) from ‑2.74% to 9.17%. Non-inferiority of O-vs-IV-PALO was demonstrated since the lower limit of the 99% CI for the difference in proportions was closer to zero than the pre-defined non-inferiority margin of ‑15%. The same conclusion was obtained in the Per-Protocol population. Furthermore, results were similar with no statistically significant differences between treatment groups for delayed CR (O-PALO 76.2% vs. IV-PALO 74.8%, CMH odds ratio 1.09, 95% CI: 0.77–1.52, p=0.637) and for overall CR phases (O-PALO 73.7% vs. IV-PALO 70.2%, CMH odds ratio 1.20, 95% CI 0.87–1.67, p=0.269). Treatment-emergent adverse events (TEAEs) were reported for approximately half of all patients in each treatment arm. TEAEs related to the study drug were low (3.2% and 6.5% for O-PALO and IV-PALO respectively). Serious TEAEs related to the study drug occurred in 2 (0.5%) patients (O-PALO arm only); abdominal pain and constipation (one patient) and diarrhea and asthenia (one patient). No TEAEs related to study drug leading to discontinuation were reported.

Conclusion
Non-inferiority of O-PALO compared with IV-PALO was demonstrated. The results of the secondary efficacy endpoints supported the demonstration of non-inferiority based on the primary efficacy endpoint. For both O-PALO and IV-PALO the CR rate in the acute phase was >86% in patients undergoing HEC, nearly 50% of whom had lung/respiratory tract tumors. The safety profile of O-PALO and IV-PALO were comparable, with no concerns.

Background
Referrals and diagnostic pathways for people with symptoms of suspected lung cancer vary by where a person lives and ease of accessing services. Lung cancer diagnostic specialist and treatment services are mostly located in major cities, which can make access for people living in regional/rural and remote areas more difficult compared to major cities. Studies have shown that remoteness of residence is associated with an increase of lung cancer incidence and mortality. Hypothesis: The time required for the evaluation of suspected lung cancer is longer for people from regional/rural and remote areas compared to people living in metropolitan Queensland. The aim of the research study is to describe and compare the journey from referral to diagnosis for people with suspected lung cancer from regional/rural and remote areas referred to The Prince Charles Hospital , a tertiary referral center, compared to metropolitan residents.

Methods
A retrospective study of consecutive people with suspected lung cancer referred to The Prince Charles Hospital from December 2010 onwards will be reviewed. Data on patient demographics and referral patterns will be collected from medical records and relevant Queensland Health patient information systems. Information systems include Queensland Oncology Online, Queensland Oncology Analysis System (OASys), The Viewer, Hospital Based Corporate Information System (HBCIS), Practix, Outpatient Services Information Management (OSIM), Picture Archive and Communication System (PACS) and Auscare. The following times will be compared between regional/rural/remote (defined as >50km from TPCH) and metropolitan (<50km from TPCH) patients: (A) from receipt of referral to first specialist appointment (FSA), (B) FSA to first pathological (cytology or histology) diagnosis (FPD), (C) FPD to first multidisiciplinary team discussion (MDT) and (D) MDT to first definitive treatment (FDT). .

Results
Preliminary results show that there are clear differences in times to first specialist appointments, diagnosis and definitive treatment experienced by patients living in more regional and remote areas compared to patients from the metropolitan area. Patients from more regional and remote areas on average waited longer for their first specialist appointments e.g. Non Metro: N= 103 60% of patients seen within 30 days of a written referral and 28% were seen within 7 days. Metro: N= 60 78% patients seen within 30 days of a written referral and 50% were seen within 7 days There was also a pattern of admitting patients from remote areas to have all diagnostic workup and commence treatment as an inpatient. Admitting patients from remote areas for diagnostic workup appears to have decreased time to treatment for this cohort of patients although the cost effectivenss to the health service is unknown.

Conclusion
Lung cancer is a devastating disease and has a poor prognosis. Lung cancer diagnostic and treatment pathways should be developed for patients living in more regional and remote areas of Queensland to ensure times to diagnosis and treatment are optimised. Potentially this will decrease emotional and financial strain suffered by patients and their families as well as being cost effective to health services.

Background
Pulmonary sarcomatoid carcinoma (PSC) is a group of rare tumor .The incidence in previous reports is from 0.1% to 4.7% of all lung malignancies. The recent 2004 WHO classification identified sarcomatoid carcinoma as a group of poorly differentiated non-small cell lung carcinomas that contained a component of sarcoma or sarcoma-like(spindle or giant cell or both) differentiation.There are 5 recognized subgroups: carcinosarcoma, spindle cell carcinoma, pleomorphic carcinoma, giant cell carcinoma, and pulmonary blastoma. Because of its rarity, the actual characteristics and prognosis of PSC is controversial. Some investigations reported PSC having a much more aggressive clinical course and significantly poorer outcome in comparison with other NSCLC, even when disease was diagnosed in early-stage.But others failed to show a poor prognosis for PSC.

Methods
We studied a cohort of 69 patients with PSC who received treatment in Sun Yat-sen University Cancer Center from January 1991 to December 2011 retrospectively.We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor (EGFR) mutation status, K-RAS mutation status, treatments, and prognosis.

Results
PSC mainly occurred in young, male patients with a history of smoking. Eleven patients were stage I, 26 patients were stage Ⅱ, 23 patients were stage Ⅲ, and nine patients were stage IV at the time of initial diagnosis. The pathology of our patients included pleomorphic carcinoma (4 patients), spindle cell carcinoma (11 patients), giant cell carcinoma (10 patients), carcinosarcoma (34 patients), and pulmonary blastoma (10 patients).Most patients received multimodality treatments and the majority had early stage disease. Fifty patients achieved a complete resection while eleven patients achieved only an incomplete resections for a variety of reasones.Eight patients had inoperable disease when they were diagnosed.Among them, 5 received palliative chemotherapy alone.Eleven patients were tested for EGFR mutations, and all were wild type. Two patients tested for K-RAS mutations and identified 1 KRAS mutation.Five patients received EGFR tyrosine kinase inhibitor(EGFR-TKI) Gifitinib or Erlotinib as palliative salvage treatment: three patients maintained stable disease for 2,3,5 months with gefitinib, respectively; and the other two patients developed progressive disease after receiving treatment with erlotinib for 2 ,4 months , respectively. Median survival time (MST) was not reached, and the 5-year survival rate was 17.4%. Neither neo-adjuvant nor adjuvant chemotherapy improved patient survival for those with early stage disease. The patients without distant metastasis, with normal or higher BMI (≥18.5), with normal HGB, with smaller tumor size (≤4cm), and those who received complete resection had significantly better OS (p＜0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a COX regression model, sex, smoking status, BMI, LDH, tumor size, N stage, M stage, pathology and having received a complete resection were independent prognostic factors (p＜0.05).

Conclusion
PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early stage disease. Neither neo-adjuvant nor adjuvant chemotherapy improved patient survival for those with early stage disease. Future multi-center collaborations may be necessary to determine the optimal treatment.

Background
Adenocarcinoma of the lung EML4-ALK-rearranged are about 5-7% of all Non-Small-Cell-Lung Cancer (NSCLC). Treatment for patients affected by metastatic adenocarcinoma of the lung harbouring an EML4-ALK translocation is the oral compound anti-Met, Crizotinib. Crizotinib is considered to be poorly active over cerebral localizations, due to a possible difficult CNS penetration.

Methods
Herein we report a case of a patient with adenocarcinoma of the lung and ALK translocation, with bone and retinal metastases at diagnosis and impressive response to Crizotinib in all those sites.

Results
In August 2012 a 43-year-old man was hospitalized for a severe impairment in his left eye, onset abruptely the day before. In his medical history no trauma had occurred in the days before hospital admission. He had been reporting cephalea for one month, mostly in the left eye area, with metamorphopsias.He underwent a fluoroangiography,showing signs of left retinal detachment due to multiple, non-primitive, retinal neoplasias, mostly in the left eye, but also in the right retina. CT-scan of the brain showed abnormal tissue in the left retina, with important choroidal swelling. A thorax CT-scan revealed a 5-cm nodule in his right lung, median lobe, with enlargement of right mediastinal lymph nodes. Bone scan showed involvement of several bones, cervical and dorsal vertebral bodies, sternum. Biopsy was done through mediastinoscopy and adenocarcinoma of the lung was diagnosed. Genetic characterizazion was: EGFR and KRAS wild type, EML4-ALK translocation, diagnosed by FISH. Clinical TNM at the diagnosis was T2aN2M1, and distant localizations were at the bone and bilateral retinal tissue, mostly on the left.The patient reported pain at his head, neck, dorsal back, severe asthenia; his left eye was off, he had been spending most of his daily time resting at bed since one week. He started to receive Crizotinib 250 mg BID orally at the beginning of October 2012. Treatment was well tolerated, with few G1 episodes of diarrhoea.In few weeks his symptoms improved with resolution of pain and asthenia, the patient returned progressively to a normal life. CT-scan showed a reduction of the main nodule in the right lung and mediastinal lymph nodes, partial response according to RECIST criteria. Surprisingly he reported an improvement in his left eye vision, he could see the light and some objects in the lower left eye field of view. Ophtalmologist reported a reduction of the temporal nodule in the right retina, while in the left retina there was an impressive reduction of the swelling; for that reason at the end of January 2013 the patient underwent surgery to the left eye for the retinal detachment, gaining a complete left eye field of view. He is still on Crizotinib and no progression of disease has been documented up to now.

Conclusion
Crizotinib has induced an impressive response over retinal metastasis from NSCLC; the patient had an eye off at the diagnosis of NSCLC and on treatment gained a complete left eye field of view. Crizotinib is active over cerebral tissue like retina.

Background
The incidence of lung cancer among young people has been increasing in recent years. There are many difficulties in the diagnosis and treatment of this disease in young people, including the need for social support. Therefore, we attempted to clarify the clinical features of lung cancer in young people based on an observation of the clinical course.

Methods
A total of about 600 lung cancer patients visited our hospital during the six-year period from April 2007-March 2013. Out of these, we extracted patients of lung cancer who were under the age of 40, and carried out a retrospective analysis of the data based on the medical records. We summarized the diagnosis, treatment and clinical course of the disease in this study population and then analyzed and discussed the characteristic features.

Results
There were a total of 10 cases of lung cancer among patients who were under the age of 40, of which 80% were male and 20% were female, 80% were smokers and 20% were non-smokers. The reasons for the first hospital visit was the presence of clinical symptoms, e.g., chest pain, bloody sputum, etc., in 70% of the patients. On the other hand, the remaining 30% of the patients were asymptomatic at the first visit and had been referred to our hospital based on the detection of abnormalities on the chest x-ray during periodic medical examination. Their performance status at the time of diagnosis was as follows: “0” in 6 cases (60%), “1” in 2 cases (20%), “2” in 1 case (10%), “3” in 1 case (10%), and “4-5”in 0 case (0%). Histologically, 7 cases (70%) were diagnosed as having adenocarcinoma, and 3 cases (30%) as having other subtypes (including unknown); classified by the disease stage, 70% patients had Stage 3A or more advanced cancer. Therefore, radical surgery could be performed in only 30%, of which one case showed pathological stage3B, and developed recurrence. Chemotherapy was administered in 9 cases, and 6 cases received 3rd or more advanced-line chemotherapy. Radiation therapy was administered in 7 cases. The remaining patients received alternative therapy, such as immunotherapy and local intra-arterial injection therapy, which was performed in 3 cases, at another medical institution. Clinical psychologist intervention was needed in 5 cases, all of which showed progression or recurrence.

Conclusion
Among young patients with lung cancer, the majority were male and smokers. Most of the patients had some symptoms at the first visit, although the performance status was generally good. There were many patients with adenocarcinoma and advanced cancer, and many patients received 3[rd] line or more advanced-line chemotherapy and radiation therapy. Alternative therapy, off-label in respect of insurance coverage, such as immunotherapy was also employed in many cases. In addition, there were many cases needing clinical psychologist intervention. Thus, there were many situations in which the patients required mental care for themselves and/or for their families. In conclusion, among young people with lung cancer, there were many who required a variety of medical and social interventions, including for the diagnosis and treatment, including palliative care.

Background
Phase IV Safety of Avastin in Lung (SAiL) study was conducted to determine the safety and efficacy of first-line bevacizumab plus standard chemotherapy regimens in a broad patient population. Herein, we report a Chinese female patient enrolled in SAiL study who received chemotherapy and subsequent bevacizumab maintenance for 39 months.

Methods
not applicable

Results
A 59-year-old female presented with a cough for 6 months, and was admitted to our hospital on December 2007. CT scan showed multiple patchy shadows in both lungs, multiple nodular shadows in the right pleura, and mediastinal lymph node enlargement. CT-guided biopsy of the lower left lung showed adenocarcinoma, and biopsy of the right supraclavicular lymph nodes confirmed metastasis. The patient was a non-smoker, and was negative for EGFR and KRAS gene mutations, and negative for EML4-ALK rearrangement. From January, 2008, this patient was enrolled in the SAiL study and received bevacizumab(15 mg/kg) plus paclitaxel(175 mg/m[2])/carboplatin(AUC=6) for 6 cycles. Re-examination was performed at cycles 2, 4, and 6, and the results showed the target lesion was reduced by 9.4%, 32.9%, and 22.9%, respectively. The non-target lesions were stable and no new lesions were noted. The therapeutic efficacy was defined as PR, and re-examination was carried out every 6 weeks. After 6 cycles of chemotherapy, maintenance bevacizumab was begun (15 mg/kg) every 3 weeks and continued until March, 2011. A total of 42 cycles of bevacizumab were administered, for a total dose of 44,730 mg. CT in April 2011 showed the target lesion and the non-target lesions had increased, and new metastatic nodules were also found. The therapeutic efficacy was defined as PD. The last follow-up visit was in Apr 2012, PFS was 39 months and OS was 52 months. During maintenance therapy with bevacizumab, the main side effects included proteinuria, secondary hypertension, and pneumothorax. Secondary hypertension was observed after 6 months of bevacizumab, and controlled with nifedipine extended-release tablets. At 7 months from beginning bevacizumab, urinalysis showed proteinuria (++) and bevacizumab maintenance was continued with no dose decrease. According to the protocol, a 24-h urine protein level was obtained every 3 weeks. When the urine protein level was <2,000 mg/24h, bevacizumab maintenance was continued, and if the level was ≥2,000 mg/24h, treatment was discontinued and re-examination of the urine protein level was carried out every 3 weeks. Bevacizumab maintenance was continued when the 24-h urine protein decreased to <2,000 mg/24h. After 19 months of bevacizumab, the patient's urine protein level was >2,000 mg/24h, when treatment was discontinued. Between August 2009 and March 2011, bevacizumab maintenance therapy was stopped several times; the longest duration of discontinuation was 3 months. The maximal 24-h urine protein level was 3,926 mg/24h (grade 3), which was noted 33 months after beginning bevacizumab. It is noteworthy that 12 months after discontinuation of bevacizumab, urinalysis still showed proteinuria (+). Spontaneous pneumothorax of her left lung occurred 36 months after initiation of bevacizumab and chemotherapy. The patient experienced no symptoms, and after 1 month CT showed full expansion of the left lung.

Conclusion
not applicable

Background
Understanding phone calls that patients with lung cancer make after hours is important as it represents an opportunity to provide improved care for patients and their caregivers. Furthermore, better understanding of after- hours phone calls can help to influence ways to reduce healthcare spending. Therefore, we sought to evaluate the nature of after-hours calls initiated by patients and their caregivers to the thoracic oncology clinic from the hours of 5pm-8am and on weekends.

Methods
The study is a retrospective analysis of 4 months of outpatient phone calls made to the Stanford Cancer Institute during the weekends and hours of 5pm until 8am on weekdays. On-call after-hours physicians documented who made the call, chief complaint, age, gender and the advice given. Phone calls were excluded from analysis if there was missing information regarding reason for call or advice given. Differences in proportions were analyzed by Fisher's exact test. A two-sided p value <0.05 was considered significant.

Results
There were a total of 271 phone calls made after hours by patients with lung cancer, however after exclusions, there were 215 phone calls for analysis. The majority of phone calls occurred between the hours of 5pm and 11pm (n = 157; 73%) followed by daytime calls made during the weekend (n = 37; 17%). A majority of the phone calls were made by the patient (50%) with a slightly lower proportion made by a family member (46%). The majority of the patients who called were in their 50’s (29%) and female (54%). A high proportion of patients called for more than one chief complaint (30%) although almost all patients complained of more than one symptom on review of systems (95%). The main symptoms patients called for were cough (28%) followed by shortness of breath (27%). Of the phone calls made, 62% (133) were referred to the emergency room. Of those patients referred to the emergency department, 77% (103/133) resulted in a hospital admission.

Conclusion
Most after-hours phone calls from patients with lung cancer are related to symptoms. A large proportion of patients who were referred to the emergency department subsequently required an admission. Future studies should evaluate whether there are ways to improve patient triage after hours and improve symptom control to prevent hospitalizations for these patient populations.

Background
Hydatid disease, a naturally zoonotic disease, is frequently encountered some region; such as Mediterranean Countries. It is generally occupied on the liver and lung; nevertheless, it can pose on all organs. Primary chest wall origin of the Hydatid disease is very rarely observed.

Methods
In this report; a sixty five years old female patient who has primary chest wall located, having ribs and soft chest wall tissues destruction giant hydatide disease has been presented due to its so many rare observations, atypical localization and mimicking primary chest wall tumor. She has chest and neck pain continuing for about 5 months. In the examination made, a remarkable finding was not encountered in the patient’s medical history and physical examination. In the computerized thorax tomography, it was reported that there were combined but multiple number of tumoral masses in the giant soft tissue density having dimensions of totally approximately 10*15*10 cm (Figure 1). It was reported that the lesions observed in the whole body PET/CT appearance tomography drawn were not active to the highest degree and their SUX max levels were at the level of 3-5 values (Figure 2).

Results
In the exploration, it was observed that the lesions were cystic structures having very high density. Additionally, the thorax wall muscle and soft tissues and the front lateral areas of 2,3 and 4 ribs from above were totally necrotic and destructed. All destructive and necrotic tissues were removed and resected in the operation.

Conclusion
In the postoperative period, no complications developed and the patient was discharged with full recovery after 10 days. Hystopathological examination was reported as necrotic hydatid disease. The patient is still under control in the postoperative 3rd year and she has not symptoms.

Background
Activating mutation in EGFR gene is a predictive marker for treatment response for tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib. These drugs are approved for treatment in any line of advanced stage EGFR-mutated non-small cell lung cancer. The TK domain EGFR mutations are more frequently found in Asian population than Caucasian, and are more prevalent in women than in men. There is scarce data regarding reintroduction of TKI after developing drug resistance during previous treatment.

Methods
We report on the case of 56-years old Caucasian, non-smoking woman diagnosed with cancer of the right lung. In 2004 patient underwent lobectomy of lower right lobe with mediastinal lymph nodes sampling – histopathology showed a grade 2 lung adenocarcinoma, pathological stage was pT2N1; no distant metastases were found. Adjuvant chemotherapy has been applied – patient received 4 cycles of PG regimen (Cisplatin with Gemcitabine); radiotherapy was not used. In March 2008, three and a half years after completion of primary treatment regional recurrence was documented by thoracic CT scan – mediastinal lymph nodes and parietal pleura were involved. Sequential chemoradiotherapy was used – patient received 4 courses of pemetrexed and radiotherapy (RTH) 44 Gy in 22 fractions – partial remission was obtained. Six month after RTH completion, in April 2009, the CT scan demonstrated the progression – large lytic lesion on sternum appeared and mediastinal nodes increased in size.

Results
Because primary tumor was positive for mutation in EGFR exon 19 by polymerase chain reaction, erlotinib treatment in dose 150 mg/d was initiated. The dose has been reduced to 100 mg after 4 courses due to toxicity – persistent and recurrent genitourinary infection. After dose reduction no adverse events were reported. Erlotinib treatment was continued for 18 months until disease progressed in November 2010 - lytic lesion in sternum increased and became symptomatic. Palliative radiotherapy on sternum was applied and third line of systemic treatment was introduced – six cycles of paclitaxel and carboplatin. Result of treatment was stabilization by RECIST 1.0 criteria and bone pain was gone. For the next 12 months CT scans were performed every 12 weeks – during that period there was no need for anticancer treatment. On February 2012 progression was confirmed – dissemination to both lungs. Because of reports in literature suggesting that EGFR-TKI drug resistance may be result of non-mutational, reversible mechanism that can be overcome by temporarily withholding TKI usage (so called “chemotherapy holidays”), decision was made to restart treatment with erlotinib. Treatment with reduced dose of 100 mg/d was initiated in March 2012 and is continued 15 months later. Every three months CT scans are performed – after initial shrinkage there is a tendency to increase tumor size, but progression criteria by RECIST are not met. 60 months after disease recurrence patient is in good condition, fully active and no adverse events were noticed.

Conclusion
Conclusions The intermittent therapy of TKI inhibitors may be beneficial for some patients with lung cancer, given they have reversible TKI-resistance.

Background
Potential beneficial effects of physical exercise for cancer patients remains to be demonstrated for lung cancer patients with advanced disease. Advanced lung cancer is incurable, and is the leading cause of cancer deaths world-wide. The aim of the treatment is to improve QoL and prolong life for these patients; therefore interventions with a focus on VO~2~peak and functional capacity are much needed as physical exercise has shown to have a positive impact on QoL. Kasymjanova et al 2009 has been shown that patients with advanced stage lung cancer significantly lowered their functional capacity after two series of chemotherapy. Moreover, patients with low functional capacity before starting chemotherapy had significantly more disease progression and significantly shorter lifespan, compared to those with a higher functional capacity. Another study from Jones et al 2011 supports this and found that functional capacity is a strong independent predictor of survival in advanced NSCLC that adds to the prediction of survival beyond traditional risk factors, which may improve risk stratification and prognostication in NSCLC. Based on these results this study seeks to examine the effect of a 6-week exercise intervention for advanced lung cancer patients.

Methods
Patients with inoperable NSCLC (IIIb-IV) and SCLC (ED) were screened for eligibility. Aerobic capacity (VO~2peak~), muscle strength (1RM), functional capacity (6MWD), lung capacity (FEV1), HRQOL, cancer related symptoms (FACT-L) and anxiety and depression (HADS) were measured at baseline and 6 weeks.

Results
One-hundred-two patients were included and 72 patients undergoing concurrent systemic treatment were eligible for analysis. There was a significant increase in aerobic capacity - VO~2peak~ (p=0.014) and functional capacity- 6 MWD (p=0.006). There was significant improvement in strength (P<0.001). There was a significant change in the parameter for ‘emotional wellbeing’ (p=0.000) with a moderate effect size of 0.30 and ‘social well-being’ (p=0.000) with a small effect size of 0.23. However, there was no significant improvement or decline in general QOL. Theere was a significant reduction in anxiety (HADS-A) (p=0.008) a significant change in Psychological Morbidity (HADS-T) (p= 0.023). However, there was no significant change in Depression (HADS-D) (p=0.124).

Conclusion
The results from this study shows that it is beneficial for advanced lung cancer patients to participate in a 6 weeks exercise intervention. The significant reduction in anxiety has not been found in other studies with advanced lung cancer patients, further research will show the clinical relevance of these findings.

Background
Research shows that people diagnosed with lung cancer experience high levels of distress and that their unmet physical and emotional needs are greater than those diagnosed with other types of cancer. One significant unmet need for lung cancer patients is social support. An important way for patients to connect and to know they are not alone is through face-to-face support groups. The benefits to cancer patients attending such groups go beyond support and may include increased feelings of control and confidence and a decrease in depression and distress. For many reasons, the majority of lung cancer patients prefer lung cancer-specific support groups rather than those for all cancers. However, facilitators report that starting and maintaining lung cancer groups is often a challenge. As a result, the number of such groups is insufficient to meet the need. Cancer charities play an important role in fostering lung cancer support groups by directly running groups or supporting those who do. Toward the goal of increasing the number and viability of these groups, a study was conducted to understand the challenges related to starting and sustaining lung cancer support groups and the solutions successful facilitators have found to overcome those challenges.

Methods
To understand the challenges of lung cancer specific support groups and how to overcome them, a literature review of research about cancer support groups was conducted. Lung cancer support group faclitators in Australia, the United Kingdom and Australia were surveyed and in-depth interviews were conducted on a sample. Program evaluation data from 37 groups in the UK was also included.

Results
An international guide to lung cancer support groups best practices was developed. The guide provides solutions suitable for all facilitator skill levels and addresses resource constraints that facilitators may face. The solutions presented are designed to assist anyone interested in running a successful lung cancer support group anywhere in the world. A second phase of the research will involve formative research to determine desirability and feasibility of adopting best practices in a sample of control groups in the United States that were not involved in the initial survey and interviews. Those results will be presented at future conferences.

Conclusion
People with lung cancer can benefit from in-person support groups in immeasurable ways but many do not have access due to the lack of available groups. While challenges to initiating and maintaining successful lung cancer specific support groups exist, expert facilitators have found creative ways to advertise their groups, keep participants engaged and their groups thriving. With the information provided, professionals at charities and treatment facilities interested in starting lung cancer support groups will know what to consider as they organize their groups and will have at the ready tried and true techniques for making their groups successful. Charities not able to run their own groups will learn the importance of disseminating this information to facilitators as well as understand how to best support them to reach the goal of increasing the number of lung cancer-specific support groups.

Background
Pulmonary thromboembolism (PTE) is a well-recognized potentially fatal complication after lung cancer surgery. In Japan, PTE had been relatively uncommon. However, it has recently been increasing probably due to changes in lifestyle. In our institution, deep vein thrombosis (DVT) is intensively screened by measuring preoperative D-dimer. Unfractionated heparin (UFH) is routinely administered to the patients having lung cancer surgery in addition to mechanical prophylaxis using elastic stockings(ES) or intermittent pneumatic compression devices(IPC). Here, we retrospectively evaluated efficacy and safety of these strategies to prevent PTE.

Methods
We retrospectively reviewed charts of 531 patients who underwent lung cancer surgery from January 2009 through April 2013. The patients who were deemed high-risk for DVT (those with past history of thrombosis, or those with elevated preoperative D-dimer (>1.0μg/ml), or those with varicose veins in their lower extremities), in principle, underwent venous ultrasonography of lower extremities. Among high-risk patients, those with or without DVT were classified as a group A and B, respectively. Those who failed to undergo venous ultrasonography were referred to as a group C. Those who did not meet above-mentioned criteria for high-risk group were classified as a group D. As perioperative prophylactic measures against PTE, all the patients in the group A wore ES from two days before surgery to one month after surgery. The patients also received continuous intravenous UFH (6000 units per day) immediately after surgery to postoperative day (POD) 1, and then received subcutaneous UFH (5000 units twice daily) from POD 2 until the patients became ambulatory. The patients in groups B, C and D wore ES during and after surgery. In addition, IPC was applied intraoperatively. The patients also received continuous intravenous UFH (6000 units per day) immediately after surgery to POD 1.

Results
Number of patients in each group were 14, 41, 87, and 389 in the group A, B, C, and D, respectively. In the group A, none was diagnosed as having PTE preoperatively. Eleven patients received postoperative UFH. However, two patients with intrathoracic adhesions did not receive UFH to avoid excessive postoperative bleeding. One patient with coronary artery complications underwent perioperative anticoagulation therapy. In this group, one patient without postoperative UFH administration due to adhesion developed symptomatic PTE. One patient was diagnosed asymptomatic exacerbation of DVT by ultrasonography one week after surgery despite UFH administration. In the groups B, C and D, 473 patients received postoperative UFH. Twenty-one patients with intraoperative bleeding or intrathoracic adhesions did not receive UFH. Twenty-three patients with coronary artery complications underwent perioperative anticoagulation therapy. In these groups, none developed symptomatic PTE. In 4 patients of 473 who received UFH, UFH was discontinued before POD 1 due to increase in sanguineous drainage without further complication.

Conclusion
Only one patient of 531(0.19%) developed symptomatic PTE after surgery. This patient had had preoperative DVT. Therefore, we regard that our strategies were effective to prevent PTE at least for patients without preoperative DVT. However, it may be necessary to apply even more intensive prophylactic measures for patients with evidence of preoperative DVT or PTE.

Background
Angiosarcoma is a rare malignant neoplasm of the vascular or lymphatic endothelium that accounts for 2% of all soft-tissue sarcomas.Angiosarcoma in the lung is a rare disorder and is usually attributable to metastasis from primary site such as skin, soft-tissue, heart, breast or liver.We describe a case of pulmonary metastatic angiosarcoma who presented with episodic haemoptysis and severe pain on the back.

Methods
A 21-year-old male was admitted with history of recurrent hemoptysis and pain on the his back for two months.There were no other constitutional symtoms.Thoracic and abdominal computed tomograhy scan revealed left hilar lymphadenopathy and bilateral multiple nodules; the spleen was enlarged and shown multipl hypodense lesions.Hilar lymphadenopathy was sampled by real time convex prob EBUS TBNA and CT guided transthoracic fine needle aspiration was performed.Definitive diagnosis couldnt be obtained with both procedures.PET scan revealed the widespread FDG uptake bone marrow, liver and spleen and lung. The patients underwent bone marrow biopsy and histopathological examination of yields reported angiosarcoma.Immunohistochemistry (CD 31 positivity) confirmed the diagnosis of angiosarcoma.

Results
The patient showed progressive deterioration and anemia and thrombositopenia and hemoperitoneum owing to spontaneous liver rupture appeared.He was managed with repeated blood transfusions but he died twenty-seventh days after admitted hospital.

Conclusion
We presented a rare angiosarcoma case with aggressive clinical course and a fatal prognosis for the patient.

Background
Concurrent chemoradiotherapy (CRT) is standard treatment for patients with stage III non–small cell lung cancer (NSCLC). Myelosuppression can be a significant problem in concurrent CRT, but its risk factors remain largely unkown. The aim of the present study was to assess clinical and biological parameters obtained before concurrent CRT to define the risk factors for myelosuppression in patients with locally advanced NSCLC.

Methods
We retrospectively analyzed 81 patients with NSCLC who received concurrent platinum-based chemoradiotherapy between January 2008 and December 2012. A total of 78 patients (96.2%) received etoposide (50 mg/m2, intravenously (IV) on days 1-5, 29-33) plus cisplatin (50 mg/m2, IV, on days 1,8,29, and 36) and 3 patients (3.8%) treated docetaxel (20 mg/m2/w, IV, on weeks 1-8) plus cisplatin (20 mg/m2/w, IV, on weeks 1-8) concurrently with thoracic radiotherapy to a total dose of 40-66.6 Gy. The risk factors were examined for their association with myelosupression (grade 3 or 4 leukopenia, neutropenia, thrombocytopenia or anemia) by logistic regression analysis.

Results
Grade 3 or higher neutropenia, leukopenia, thrombocytopenia, or anemia occurred in 51.8, 53.0, 8.6, and 7.4 % of the patients, respectively. Multivariate analysis revealed that the risk factors for neutropenia were performance status (odds ratio [OR] , 3,196 ; p=0,032; 95 % confidence interval [CI], 1,104-9,524), white blood cell count (OR, 3,250; p=0,023; 95% CI,1,173-9009 ) and pretreatment creatinine level (OR, 3,325; p=0,018; 95% CI,1,228 - 8,999 ). On multivariate analysis, white blood cell count (OR, 3,311; p=0,027; 95% CI, 1,148-9545 ) was found as significant risk factor for CRT-induced leukopenia. No significant association was found between patient’s characteristics and anemia or thrombocytopenia

Conclusion
This information on grade 3-4 neutropenia and leukopenia is considered to contribute significantly to its safe and effective use of concurrent chemoradiotherapy for treatment of locally advanced NSCLC.

Background
Background: The use of chemotherapy has been shown to increase the effectiveness of best supportive care (BSC) in elderly patients with non-small cell lung cancer (NSCLC). The use of Intravenous chemotherapy ( IV ) has many times been difficult in elderly patients or patients with poor performance status owing to fear of toxicity.We studied the effectiveness of a non toxic regimen with single agent oral chemotherapy with etoposide plus best supportive care versus best supportive care alone in subjects with advanced non small cell lung cancer unfit for IV chemotherapy

Methods
Eighty five cases of advanced non small cell lung cancer and ECOG performance status of 2 to 3 , unfit for IV chemotherapy as per treating physician's discretion were included in the study. Forty three patients received chemotherapy with Tablet Etoposide 50 mg once daily for 14 days along with best supportive care ( BSC )every 21 days for a maximum of 8 cycles in responding patients. Regimen was re challenged on progression. The remaining received BSC only.

Results
We measured at least 1 of the following outcomes: Overall survival ( OS ) or treatment-related mortality. Overall, patients that received chemotherapy plus BSC had significant longer OS than those that received BSC alone (HR 0.75; 95%CI, 0.68–0.82; P,0.001). Additionally, chemotherapy plus BSC as compared to BSC alone resulted in a 24% RR reduction (95%CI: 10–38; P = 0.001) in 6-month mortality, 10% RR reduction (95%CI: 8–15; P,0.001) in 12-month mortality and 6% RR reduction (95%CI: 2–9; P = 0.02) in 2-year mortality. Toxicity was not significantly greater in patients who received chemotherapy plus BSC.

Conclusion
Chemotherapy with single agent oral etoposide plus BSC is a non toxic therapeutic option in infirm and elderly NSCLC patients unfit to receive intravenous chemotherapy.

Background
INTRODUCTION: Oligometastasic pathology has become a usual pathology present in our clinical routine activity.Although invasive treatments are available, SBRT is a non invasive therapy which can be a viable treatment of choice.We introduce our preliminary study of pulmonary lesions treated using a single fraction of 34Gy OBJECTIVES: The main goal of this report is to demonstrate that a fraction of 34Gy is a viable and attainable therapy to treat lesions in oligometastasic patient’s lungs

Methods
Seven patients with 7 pulmonary lesions were treated with single dose of 34Gy. Inclusion criteria were : lesion size smaller than 2 cm , distance from the chest wall and main bronchus tree higher than 2 cm , primary tumor under control in PET scan. Mean Age 61.57y (r39-82), Gender distribution 3 women and 4 men, Histology: 4 cases (57.14% were Metastasic lesions from Colon), 1 metastasic from Adenoid Cystic, 1 Adenocarcinoma from Lung and 1 NSCLC. All patients underwent 4DCT for contouring. Inmobilization was done by thermoplastic mask (Lorca Marin) . Dosimetric characteristics: Mean volume of GTV 1.46cc (r 0.6-4.1), mean volume of PTV 11.29cc (r7.1-22.2), D Max oesophagus 5.06 (r 2.6-8.4), D max Heart 4.05 (r6.86-17.0), D max trachea 5.12 Gy (r 0.3-11.1), Dmax skin 10.98(r7.0-14.4). Patients were treated using True Beam machine. In 6 cases treatments were delivered without flattering filter beams

Results
After 6 months of follow up (r 6-2.19) no toxicity higher than grade 2 was detected. Local control rates and survival are 100%, 100% respectively. To sum up, even this is a preliminary study, seems than long term results can show us a new perspective in these oligometastasic patients.

Conclusion
not applicable

Background
Patients with cancer, especially those with lung cancer have an elevated risk for venous thromboembolism (VTE). Importantly, the adjusted risk of VTE is estimated to be 30 % higher among lung cancer patients undergoing chemotherapy with the majority of VTE events occurring within 6 months of initiation of chemotherapy. The presence of a VTE event is significantly associated with an increased risk of mortality[1] [1]Huang et al, J Thromb Thrombolysis. 2012 Nov;34(4):446-56. This study examines the baseline characteristics of patients with lung cancer with VTE, of the participants enrolled to the CLOT trial - a six month multi-centre study involving 676 cancer patients with acute, symptomatic, proximal deep-vein thrombosis (DVT), pulmonary embolism (PE), or both who were randomly assigned at 1:1 ratio to receive dalteparin sodium subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin sodium alone for six months[2] [2]Lee et al N Engl J Med 2003;349:146-53.

Methods
Post-hoc analysis aimed at interrogating the descriptive fields of the Intention-To-Treat (ITT) CLOT trial population was conducted to determine the quantitative and qualitative base line characteristics of patients with lung cancer at randomisation.

Results
Of the 676 patients with cancer randomised into the CLOT trial, 90 patients had cancer of the lung. Figure 1

Conclusion
Baseline characteristics of patients with lung cancer with VTE as randomised in the CLOT trial indicate they were more likely to be males, under 65 years of age, had no previous VTE to the diagnosis of their lung cancer, were receiving treatment for their lung cancer, with surgical pathology and chronic immobilisation not being a significant risk factor for VTE. Review of published literature also suggests that in comparison to the non cancer population, patients with lung cancer experience significant level of pulmonary embolism[3] [3]Shinagare et al Cancer. 2011 Aug 15;117(16):3860-6

Background
Neurokinin-1 receptor antagonist (NK1RA) in addition to 5-hydroxytryptamine receptor antagonists (5HT3RA) and dexamethasone (Dex) is recommended for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC). It had been also reported that 40-60% of patients receiving HEC had not experienced significant nausea and/or vomiting before NK1RA became available. In 2010 NK1RA aprepitant was introduced for CINV prophylaxis in Japan. However, what proportion of patients receiving emetogenic chemotherapy need NK1RA, and whether all patients undergoing HEC truly need NK1RA remain unknown. Increasing medical costs due to uniform use of NK1RA is another concern. The primary objective of this study is the prevalence of patients who require aprepitant. Therapeutic and preventive effects of aprepitant on CINV induced by HEC or moderately emetogenic chemotherapy (MEC), and quality of life (QOL) regarding CINV are secondary objectives. We conducted this single-institute study before fully introducing aprepitant into clinical practice in our institute.

Methods
From July 2011 to January 2013, 96 consecutive patients receiving HEC or MEC, with age ≥ 20, able to use Japanese language, and with written informed consent, were enrolled onto the study, and 77 patients were analyzed who received ≥ 2 courses in the same chemotherapy regimen. 5-HT3RA and Dex were administered to prevent CINV. Aprepitant was administered to treat CINV in the first course when CINV occurred, or administered to prevent CINV in the second course. All patients who experienced CINV in the first course received prophylactic aprepitant from the second course. QOL regarding CINV was assessed by Functional Living Index of Emesis (FLIE). Numerical rating scale (NRS) was used to assess the severity of nausea. This study was approved by the Institutional Review Board of Aichi Medical University.

Results
Patient characteristics were: median age (range), 67 (38-85); gender (male/female), 64/13; cancer type (lung cancer/thymic tumor/other), 72/3/2; chemotherapy regimen (HEC/MEC), 28/49. Aprepitant was not administered in 57% and 88% of patient who received HEC and MEC, respectively. In patients treated with aprepitant (n=18), therapeutic use of aprepitant after CINV occurred (n=9) decreased average NRS for nausea and average frequency of vomiting per day from 7.44 to 5.44 (p=0.10), and 2.11 to 0.11 (p=0.03), respectively. Prophylactic use of aprepitant in the second course (n=18) increased the proportion of patients with no significant nausea from 6% (first course) to 50% (second course, p=0.007), and those with no vomiting from 33% to 89% (p=0.002). In contrast, in patients who did not require aprepitant (n=59), proportion of patients with no significant nausea and those with no vomiting did not change during the 2 courses (76% to 76% [p=1.00] and 92% to 92% [p=1.00], respectively). In patients who required aprepitant, aprepitant use significantly improved FLIE scores in the second course while these did not change in patients who did not require aprepitant.

Conclusion
More than half of patients receiving HEC and 88% of patients receiving MEC did not require aprepitant. Aprepitant showed significant therapeutic and preventive effects on CINV in patients who truly need it.

Background
Background: Pemetrexed activity is synergistic with both carboplatin and cisplatin in chemonaive NSCLC patients. Two phase II Pem plus carboplatin trials have confirmed the doublet’s activity in NSCLC and response rates were 31% and 24% (Scagliotti and al 2003, Zinner and al 2005). Carboplatin is a good alternative in unfit patients suggesting a balanced benefit/risk profile when combined with Pem.

Methods
Sixty-four patients unfit to receive cisplatin with measurable stage III-B IV NSCLC, received at least one dose of chemotherapy. Pem 500 mg/m2 over 10 min on day 1 with folic acid and vitamin B12 supplementation followed by carboplatin AUC 5 on the same day were given every 21 days for 4- 6 cycles. Primary endpoint was safety and efficacy ( progression free survival)

Results
Sixty four patients received at least one dose of chemotherapy. Median age was: 71.3 yrs (86−44,3), 90,6% of patients presented comorbilities , mainly cardiopathy (73,4%) . Stages IIIb: 15,6%, IV: 84,4%. Non squamous cell carcinoma: 100.% (adenocarcinoma: 92,2%, large cell carcinoma: 7.8% )Male 76,6%, female 23,4%. The median number of administered cycles was 4. Median progresion free survival and overall survival will be presented at the meeting. Grade 3/4 toxicities related to study drugs were: asthenia 6.1%, skin 3.1%, dyspnea 3.1% .Hematological grade 3/4 events were: neutropenia: 6.1%, thrombocytopenia: 1,6%, anemia: 14.1%. 10,9% of patients need dose reduction

Conclusion
In first line NSCLC, the combination of Pem plus carboplatin could be a valuable treatment alternative in unfit patients to recive cisplatin. Anemia is the most frequent toxicity in this combination.

Background
The objective of this study was to evaluate the operative mortality, morbidity, and survival of bronchoplasty and bronchoangioplasty for non-small cell lung cancer. Multivariate analysis was done to determine potential prognostic factors for both procedures based on our 27-year single-center experience.

Methods
Between January 1985 and March 2012, 204 bronchoplastic procedures were done in 1978 patients who underwent lung resections for non-small cell lung cancer at Nagasaki University Hospital. After excluding 18 carino-plasty patients and 13 wedge angioplasty of pulmonary artery, 173 patients (141 bronchoplasty and 32 broncho-angioplasty) were included.

Results
In the bronchoplasty group, the postoperative morbidity was 29% (41/141) and the 90-day postoperative mortality was 5.7% (8/141), while in the broncho-angioplasty group the postoperative morbidity was 28% (9/32) and the postoperative mortality was 15.6% (5/32). Eleven patients (6.4%) experienced bronchopleural fistulas. Multivariate analysis demonstrated that induction therapy (p=0.047) and combined multiple organ resection (p=0.012) were risk factors for postoperative anastomotic complication. The 5-year survival rate for all patients was 46.3%. The 5-year survival rate was 69.5% in patients with pathological stage I disease. In patients with stage II disease, the 5-year survival rate was 34.7%. In patients with stage III-IV disease, the 5-year survival rate was 33.2%. The survival rate in stage I disease was significantly better compared with other stage disease (p<0.0003). Multivariate analysis indicated that the type of operation (bronchoplasty versus bronchoangioplasty), postoperative complications, histologic type (squamous cell carcinoma versus non squamous cell carcinoma), and pN status (N0-1 versus N2-3) were significant factors affecting survival.

Conclusion
Both bronchoplasty and broncho-angioplasty are useful for the treatment of patients with non-small cell lung cancer and should be performed in stage I. However, careful patient selection is mandatory in patients with advanced tumor stages and in those with nonsquamous cell carcinoma, especially if broncho-angioplasty is being considered.

Background
With the rise of technology in health care, the use of electronic or virtual games provides new possibilities for cost effective and individually tailored health care interventions. The advantages of virtual games are the ability and opportunity to incorporate ethnic and cultural diversity and sensitivity, access hard to reach populations, provide motivation and positive feedback for behavior change, and provide information for personalized cancer symptom management. Lung cancer is the leading cause of cancer death in both men and women and is associated with greater levels of psychological distress than any other cancer. Stigma has been found to have a major role in the distress and health outcomes of lung cancer patients. Lung cancer stigma (LCS) is based on the belief that one caused their own cancer (ie, smoking) and negatively impacts patient outcomes. Lung cancer patients report inadequate communication with physicians about important topics such as: symptom experience, prognosis, treatment preferences, practical and financial worries, spiritual concerns, and hospice care. Stigma is a factor that contributes to poor patient-clinician communication and inappropriate referrals. Although palliative care consultation is recommended throughout the trajectory of lung cancer, it is underutilized. Understanding factors that influence communication and referral decisions, such as stigma, can improve integration of symptom assessment and support and palliative care into lung cancer management. Currently there are no interventions to decrease LCS and improve lung cancer patient-clinician communication. The goal of this project was to develop, the mHealth TLC an interactive, immersive 3-dimensional iPad health game that allows individuals to experience first person virtual visits with their clinicians and to conduct initial usability testing.

Methods
Because of the innovative nature of an immersive 3D game for lung cancer patients, iterative development/validation was used. Usability was assessed with participation satisfaction questionnaires and focus groups. Four areas were explored: believability and value; technical issues; transparency of goals; and game outcomes.

Results
Positive usability results for the mHealth TLC included believable game narrative, minimal game experience interference, participant generation of game and intervention goals, and indications that mHealth TLC will be able to influence lung cancer patient outcomes.

Conclusion
mHealth TLC can provide engagement and experiential learning by delivering important information about lung cancer and symptom management and by providing lung cancer patients the opportunity to practice a new communication strategy. Figure 1

Background
Patients with advanced cancer experience various difficulties to communicate and express regarding their wishes, personal values and end-of-life care options. These difficulties could be serious obstacles to initiate early palliative care decision and consequently lead to unwanted and/or futile invasive end-of- life care. There is an urgent need to develop innovative approach to address suffering and distress and improve communication between patients and family members, care givers’ and medical providers.

Methods
“Envoy Service” was designed to assist patients' own words delivered to family members, friends, care givers in processed and edited form. The assigned patients were interviewed by trained dialogist (2 nurses and 3 clinical psychologists), in individualized and narrative style for 30 to 60 minutes per session up to 3 sessions. During the interview, pre-structured questioned regarding palliative care and end-of-life care options. Additionally, patients are offered to speak what matters most to them, things they would most want remembered. The whole interview process could be videotaped, or voice recorded, or writes down by the dialogist, or in combination upon the patients’ own choices. Once interview sessions completed, the dialogues were reshaped into narrative form and carefully edited in the form of video-audio clip recorded in CDs, or letters. The final products were returned to patients to bequeath to a friend or family member. The responses of patients and family members and caregivers’ and medical provider’s opinions were collected and examined.

Results
Twelve patients with advanced cancer (age 40-68, median 57, 5 female, 7 male, 4 lung cancer, 2 head and neck cancer, 5 GI cancer, 1 Gy cancer) received “Envoy service”. It was offered in two hospitals; five patients in Korea University Medical Centre (university Hospital) and seven patients in Seoul Medical Centre (General Hospital) respectively. Interview with dialogist took usually 30-60 minutes (median 40 min) in each session and 1-3 (median 1) sessions. All twelve patients expressed their emotional feeling regarding their illness, fear of death and dying, briefly reviewed their own lives and personal appreciation to their family members and medical providers. Regarding the end-of-life care options, 6 patients choose non-invasive care and 3 patients wished to be chosen by their care giver and physician’s discretion, 3 patients did not evidently spoke about. The edited products, 1 CD, 11 letters were returned to patients to bequeathed to family members. Seven patients reported feeling satisfied. Five patients indicated that the service heightened their physical and psychological well-being. One dialogist reported that completion of services, patients were looked “ready” for dignified end-of-life. Four patients died, 3 without any invasive care, but 1 in ICU.

Conclusion
"Envoy service” a form of dignity therapy, is feasible and could be a novel approach to address distress and suffering of patients with advanced cancer. It might help patients to communicate with family members and caregivers and leads to initiate early palliative care and avoid unnecessary invasive procedure near end-of-life.

Background
To investigate the ‘preoperative CT predictor’ of postoperative acute exacerbation (AE) of lung cancer with underlying idiopathic interstitial pneumonia (IIP) compared to those without AE as control.

Methods
The 78 pulmonary resections for lung cancer with underlying IIP in a single tertiary center, 72 males (92.3%) and 6 females (7.7%), aged from 47 to 80 years old, with a median age of 66 years were retrospectively included. This study was approved by the Institutional Review Board and informed consent was waived. Underlying IIP was retrospectively assessed histological (n=46, 59.0%) and clinico-radiological (n=32, 41.0%) according to ATS/ ERS guidelines. We divided them in two groups, one acute exacerbation (AE group) and the other without acute exacerbation (non AE group) after operation of lung cancer. Records of patients who experienced postoperative acute exacerbation were extracted from the clinical data-base. Two independent expert chest radiologists analyzed CT findings in two times (four data sets) for one month interval. We analyzed age, gender, smoking history and pulmonary function test (PFT) differences between two groups. We analyzed HRCT findings as follows; extent of reticulation, honeycombing, ground-glass opacity, and emphysema in overall extent with area percentage. Fibrotic score (sum of reticulation and honeycombing) was also assessed. We performed the correlation between HRCT findings and presence of acute exacerbation. We used binary logistic regression analysis and student t-test with SPSS 21.0 version as statistics.

Results
Of the 78 lung cancer patients, six patients experienced postoperative acute exacerbation (7.7%). Smoking history and PFT between two groups were not significantly different except age and gender. Inter- and intra-reader correlation coefficient were 0.496~0.928 and 0.667~0.936/0.657~0.949, respectively, good to fair. Honeycombing (p=0.001; OR, 1.243; CI, 1.087~1.422) and fibrotic score (p=0.007; OR, 1.188; CI, 1.047~1.347) and abnormal area (p=0.042; OR, 1.059; CI, 1.002~1.119) were significantly high in AE group.

Conclusion
Physicians should consider the high extent of honeycombing, as well as high fibrotic score in CT, a potential risk factor for acute exacerbation after pulmonary resection for lung cancer.

Background
Sever dyspnea secondary to persistent or recurrent malignant pleural effusion in terminally ill cancer patients offers great challenge to the treating physicians. It has a significant negative impact on the quality of life which is already poor. The main goal of treating physician is symptomatic relief of dyspnea with the least possible tools. A variety of agents can be used to induce pleurodesis. Multiplicity of those agents indicates that none of them is optimal. Whatever the agent used, it should achieve high success rate with no or minimal side effects and tolerability by the patient. Great care should be taken to properly select patients with malignant effusion for pleurodesis to minimize treatment failure. Unsuccessful pleurodesis my be more problematic and difficult to treat due to conversion of the free effusion into encysted one. The aim of this work is to evaluate the success rate of palliative treatment of malignant pleural effusion comparing talc powder ( either through poudrage or slurry) versus Mistletoe preparation (Viscum Fraxini ~2~). To evaluate also the tolerability of both preparations, coast and the complication rate.

Methods
This is a retrospective non randomized study during the period between (Jan. 2008 – Feb 2011). Sixty patients with malignant pleural effusion were included. Patients were divided into 2 groups (30 patients were included in each group) according to the method of pleurodesis used. The first group included patients in whom talc powder ( either through poudrage or slurry) was used for pleurodesis. The second group included patients with Mistletoe preparation (Viscum Fraxini ~2~) used as pleural sclerosant. CT scan of the chest was ordered for all patients prior to treatment. Criteria for potentially successful pleurodesis: There should be no pleural septations or loculation (if present based on CT scan should be lysed pre pleurodesis). The lung should not be entrapped and fully inflated (the presence of residual space will convert the free effusion into encysted one). Response definition : Successful pleurodesis is defined as no recurrence of effusion on clinical and radiologic follow-up 4 weeks after pleurodesis.

Results
There were 34 males and 26 females , the mean age was 59 years, right sided effusion was present in 37 patients (61.6%) and left sided effusion in 23 patients (38.4%) . All patients presented with grade I-III dyspnea and 15% also presented with chest pain. In Group I: Twenty three patients had successful pleurodesis (76.7%), while 7 patients showed treatment failure. Treatment related complications developed in 4 patients. In Group II : Pleurodesis was successful in 19 patients (63.3%)(After 2, 6, 7, 8 injections), treatment failure developed in 11 patients after 6 injections. Four patients developed allergic reactions and two patients suffered empyema.

Conclusion
Both methods used for pleurodesis were well tolerated by the patients with good success rate with minimal complications. Talc offers higher success rate, less coasty and also considered single use therapy while the use of Mistletoe preparation needs repeated injections.

Background
Each year almost 2,000 new cases of lung cancer are diagnosed in Ireland (1). It is the biggest cancer killer for Irish men and women (2) and Irish women rate fifth highest in incidence of lung cancer in Europe (3). In 2011 the Irish Cancer Society (the Society) launched a three year advertising and PR campaign to raise awareness of lung cancer in a novel and engaging way. The Society wished to move away from the grim, grey, tobacco led and often frightening messages and imagery normally associated with lung cancer. The campaign directed people to the Society’s National Cancer Helpline.

Methods
The Society undertook market research in 2011 and 2013 to evaluate the impact of the campaign. The objective of the quantitative survey was to evaluate public awareness of lung cancer as well as prompted awareness of the campaign. This survey was nationally representative and 1,000 interviews were completed. The helpline database was also used to record the number of lung related enquiries during the campaign.

Results
Just under three million adults recall some media attention on the issue of lung cancer in February (2013). This is up considerably on 2011 levels (2.1 million Vs. 2.8 million). Whilst just over six in ten are aware of some media attention in January, this figure rises to seven in ten among smokers. In total 34,342 enquiries about lung cancer were recorded during the two week campaign. This included calls and emails to the National Cancer Helpline (167), walk in enquiries to the daffodil centres in hospital settings (670), unique views of the Society’s lung cancer webpages (2315), direct referrals to the National Smokers Quitline (4), likes/ comments/ shares/views of social media posts (9741) and of a live Q&A via Facebook (21,449). Figure 1

Conclusion
During the campaign, the National Cancer Helpline received more preventative and undiagnosed enquiries about lung cancer than any other cancer. The majority of contacts were female and aged 50-59yrs; our target audience. A sharp rise in webpage views was noted and social media interaction exceeded expectations considering the young audience. Using traditional as well as online advertising mediums, PR and social media platforms also worked well to reach a wide audience and campaign evaluations show traction with both young and old. Delinking lung cancer from tobacco and going with an empowering message meant that more people engaged with the campaign and it was deemed a success.

Background
CT-guided percutaneous needle biopsy is a useful diagnostic procedure that is used for the evaluation of pulmonary nodules, and is regarded as a relatively safe procedure. Although tumor seeding along the biopsy needle tract after CT-guided percutaneous needle biopsy is an extremely rare complication with a reported incidence of 0.06% in Japan, it can lead to unnecessary procedures or fatal outcomes. Most of the reported cases of implantation metastasis after CT-guided percutaneous needle biopsy were about the tumor seeding, which occurred in the chest wall or the pleura; however, we present here a case of intrapulmonary recurrence after CT-guided percutaneous needle biopsy.

Methods
A 70-year-old woman was admitted to our hospital for the evaluation of a growing lung mass. She had undergone a thoracoscopic lobectomy of the right upper lobe 17 months ago, after CT-guided percutaneous needle biopsy, using a 22-gauge needle, which had confirmed the lung mass as an adenocarcinoma. She was discharged uneventfully and had been followed-up without additional treatment because there was no evidence of metastasis to the lymph nodes or to the distant organs. On the follow-up, a CT scan of the chest revealed a small lung nodule (0.5 cm in the longest diameter), which was located in the superior segment of the right lower lobe. Six months later, a repeat CT scan of the chest showed that the nodule had grown up to 1.2 cm.

Results
On admission, we performed successful CT-guided percutaneous needle biopsy of the lesion of the right lower lobe, and pathologic examination revealed an adenocarcinoma, which took the same characteristics as the previous diagnosis from the right upper lobe, which suggested a recurrence. We suspected implantation metastasis, and reviewed the previous biopsy procedures. Finally, we found that the biopsy needle had passed through the superior segment of the right lower lobe to target the right upper lobe lesion, and concluded that the new lesion might be an implantation metastasis, as a result of tumor seeding along the biopsy needle tract. She underwent segmentectomy of the superior segment of the right lower lobe, because there was no evidence of distant metastasis. She recovered well and was followed-up without additional treatment as before.

Conclusion
We present a case of implantation metastasis that occurred in the pulmonary parenchyma, after a CT-guided percutaneous needle biopsy of stage I lung cancer. We also present here a lesson from this case that the biopsy needle should not pass through different anatomical compartments other than the target compartment, and this strategy should be kept in mind, especially, when the lesion is located deeply.

Background
Malignant pleural effusion is common in patients with advanced cancer. Several treatment modalities for malignant pleural effusion have known and of those, chemical pleurodesis can be considered for malignant effusion that do not respond to chemotherapy, radiotherapy, or therapeutic thoracentesis. However, which agent is more effective and safe in chemical pleurodesis is not yet clear.

Methods
This study was designed as a single arm, multicenter, and open-label phase III clinical trial to evaluate efficacy and safety of chemical pleurodesis using ABNOVAviscum[Ⓡ] Injection (Abnoba GmbH. Germany). Reference of other agents in chemical pleurodesis was investigated to compare efficacy and safety, and decide statistical sample size. Of patients who needed pleurodesis for malignant pleural effusion, the patients who had full expansion of lung within 24 hours after pleural drainage, expected life span more than 2 months, and Karnofsky performance scale of more than 50 were enrolled. Efficacy was evaluated by the amount of pleural effusion in chest x ray taken four weeks after pleurodesis (WHO guidelines of response – complete response; few effusion, partial response; lesser than 50% of initial pleural effusion, no response, or not evaluable), and changes of clinical symptoms and karnofsky performance scale. Safety was evaluated by serious adverse event (SAE) and changes of kidney and liver function (AST, ALT, BUN, or creatinine) after pleurodesis. A follow-up period was 4 weeks after last pleurodesis.

Results
A total of 68 patients were enrolled which 7 of them dropped out. Median age of patients was 60 years old [range, 34-80]. The number of male and female was 23 and 38, respectively. 49(80.3%) had complete response, 11(18.0%) had partial response, and one patient had no response. Mean response rate of reference for other agents in chemical pleurodesis was 64%. The mean karnofsky performance scale before the pleurodesis was 79.5 and the mean karnofsky performance scale on fourth week after pleurodesis was 81.9. SAE definitely related to ABNOVAviscum[Ⓡ] Injection was presented in two cases; dyspepsia and generalized muscle weakness. Both of these cases were recovered before the end of this study. SAE probably related to ABNOVAviscum[Ⓡ] Injection was seven cases; dyspepsia, fever (3), constipation, vomiting, and fatigue. These seven cases were recovered before the end of this study as well. No other toxicity related to ABNOVAviscum[Ⓡ] Injection was presented in laboratory findings such as AST, ALT, BUN, or creatinine during a follow-up period.

Conclusion
This study suggests that chemical pleurodesis using ABNOVAviscum[Ⓡ] Injection for malignant pleural effusion might be an effective and safe modality.

Background
Metastectomy for lung cancer had shown varied results some showing survival benefit and in some studies as only palliation. But unlike metastatectomy for lung cancer , lung resection for metastases had shown definitive role atleast in some selected cases like colorectal cancer, renal cell carcinoma, breast cancer , etc. Here we would like to share our experience considering the above mentioned topics.

Methods
Our study was a retrospective analysis of medical records from January 2006 to March 2012 in a single unit in a teritiary care center in India. Clinicopathological features, treatment, prognosis and disease free survival were assessed.

Results
Fourteen patients underwent metastatectomy in lung and five patients underwent metastatectomy for lung cancer (Fig.1). Results were described in Table 1 and 2. Among 14 patients who underwent lung resection for metastases, 5 cases were for osteosarcoma of extremity, 5 for soft tissue sarcoma of extremity, one for pyriform fossa cancer, one for breast cancer, one for gestational trophoblastic neoplasia and one for metastatic gaint cell tumor of bone (Table 1&2). Fig: 2: Clinicopathological features of patients: Figure 1 Figure 2

Conclusion
Stage IV disease in cancer though considered as incurable in adult solid malignancies, a selective group of patients can still be cured. The success of the surgery depends on disease free survival from the detection of primary, number of lesions, grade and stage of initial primary and site of primary. Metastatectomy for lung cancer in our study is done with a palliative intent.

Background
Multiple primary lung tumours can be either synchronous or metachronous. Clarification between synchronous primary tumours and metastatic lesions is vital given the differing prognosis and therapeutic options. We present a case of a patient with a combination of synchronous and metachronous primary lung malignancies, who did well because she had careful multidisciplinary follow-up.

Methods
Not applicable

Results
A 63-year-old female ex-smoker, with history of moderately severe chronic obstructive pulmonary disease but good performance status, was found to have pulmonary nodules in the left upper and lower lobes that increased slightly in size over 2 years on serial thoracic CT scans. On FDG-PET, the lesion in the left upper lobe demonstrated marked FDG-avidity (SUVmax 7.5) while the left lower lobe nodule demonstrated much lower FDG uptake (SUVmax 2.5). These were considered synchronous early-stage lung tumours by consensus of our multidisciplinary lung cancer group. Intra-operatively, frozen sections confirmed malignancy in each lesion and the patient successfully underwent wide local excision of both nodules. Histopathology revealed infiltrating moderately differentiated adenocarcinoma in the left upper lobe (T1N0M0) and infiltrating undifferentiated large cell carcinoma in the left lower lobe with no hilar or mediastinal nodal involvement (T1N0M0). The patient remained disease-free until 6 years later, when new right lung opacities were found incidentally on a chest radiograph. Chest CT confirmed 2 new pulmonary nodules in the right upper lobe, one intensely FDG-avid (SUVmax 11.0) and the other poorly avid (SUVmax 1.2). No other FDG-avid foci suspicious of metastatic disease were detected elsewhere. Following multidisciplinary discussion, wedge resections of both lesions were performed. Histopathology revealed high-grade neuroendocrine carcinoma (small and large cell types) in the intensely FDG-avid lesion and adenocarcinoma in situ in the other lesion. The patient was subsequently offered adjuvant chemotherapy and prophylactic whole brain irradiation.

Conclusion
This rare case of synchronous and metachronous primary lung cancers illustrates the importance of long-term follow up of patients with previously treated non-small cell lung with curative intent. These patients may develop new metachronous early-stage lung tumours that would benefit from aggressive treatment. New lung opacities may not necessarily represent recurrent metastatic disease with poor prognosis.

Background
Limited resections such as wedge resections for ground-glass opacity (GGO) adenocarcinomas have been proposed and widely performed. However there have been reports of cut-end recurrences after wedge resection of those lesions. One of the major obstacles to solve this problem is a lack of method to achieve thorough confirmation of surgical margin during surgery. Here we report a successful confirmation of cut-end using thin slice CT on resected lung specimen.

Methods
A patient with a ground-glass opacity in the right upper lobe underwent a wedge resection under thoracoscopy. The resected specimen was sent for thin slice CT scan, which revealed that there were enough surgical margins from the cut-end to the GGO lesion in any of 0.5mm thick slices. Figure 1 Figure 2

Results
Pathological examination confirmed that the cut-end was free from adenocarcinoma as being consistent with CT findings.

Conclusion
It is feasible and effective to confirm surgical margin of resected lung tumor with GGO during surgery using CT on the resected specimen.

Background
It is well known that old pulmonary tuberculosis (TB) is associated with an increased risk of lung cancer and lung cancer mortality. Malignancy per se and cytotoxic chemotherapy for its treatment both are recognized risk factors for the development of active tuberculosis. Coincidence of tuberculosis and lung cancer at initial diagnosis or development of tuberculosis during the course of lung cancer is a challenge for management of both diseases.

Methods
Herein we analyzed 10 male lung cancer cases (9 NSCLC/ 1 SCLC) coincidentally had tuberculosis.

Results
The ages were ranging between 43-71 years. Only one of these patients had a pulmonary TB history. The sites of TB were lung in 7 patients, mediastinal lymphadenopathy (LAP), cervical LAP, and subcutanous nodules in 1 patient each. Four patients were diagnosed as tuberculosis and lung cancer simultaneously. The diagnosis was confirmed by mediastinoscopic lymph node biopsy in 1, transthoracic biopsy in 1 and sputum smear positivity in 2 patients. In 4 patients the diagnosis of pulmonary TB were confirmed by sputum culture 2-3 months after the diagnosis of lung cancer. All these 4 patients were suspicious for pulmonary TB at the time of lung cancer diagnosis, but sputum smears were negative for acid-fast bacilli. In 2 patients TB were diagnosed later in the follow-up period of the patient. One was diagnosed as TB lymphadenitis by cervical lymph node biopsy, the other was diagnosed as TB by biopsy of subcutaneous nodules on the right leg. One patient who was surgically resected for lung cancer tolerated antituberculosis therapy well. Another patient who was initially staged as T3N2MO lung cancer clinically and radiologically (including PET/CT evaluation) also tolerated the therapy fairly well. After 6 months of antituberculosis therapy, he was restaged as T2aN0M0 and treated with definitive radiotherapy. He died due to venous thromboembolism 1 week after the completion of radiotherapy. Another patient had progressive lung cancer during antituberculosis therapy. Hepatotoxicity was the leading adverse reaction (in 3 patients, 30%) due to antituberculosis therapy.

Conclusion
In conclusion; these cases highlighted the importance of thinking TB in the course of lung cancer especially in countries with high TB prevalence. TB may cause advanced staging of lung cancer at initial diagnosis; chemotherapy may worsen TB course or cause reactivation TB. Reactivation TB may be considered as progression of lung cancer without a tissue diagnosis. The tolerability of antituberculosis therapy is poor in these patients. Guidelines should refer how to manage these patients especially in certain areas with high TB prevalence.

Background
A multiple myeloma (MM) is a malignant disease of plasma cells, which manifests as one or more of lytic bone lesions, monoclonal protein in the blood and/or urine and disease in the bone marrow. The most typical thoracic manifestation of multiple myeloma is bony involvement of the thoracic cage. Other manifestations include pneumonia, intra-parenchymal mass lesions, mediastinal lymphadenopathy, interstitial pattern like reticulonodular shadows and intrapulmonary calcification. The diagnosis of a secondary solid neoplasm in patients with MM is uncommon, and it is debatable whether the MM itself is a risk factor for the incidence of a secondary solid neoplasm.

Methods
62 year-old men, former heavy smoker ,treated pulmonary tuberculosis(1977), autologous bone marrow transplantation (BMT) for MM two years ago.He admitted complaints of fever, cough,sputum and nigth sweats for a month. Physical examination was remarkable moderate pallor. Routıne serum biochemistry parameters were within normal limits except hemoglobin (6.6 gm/dl),ESR was 84 mm in the first hour.Chest xray and computed tomography (CT )showed multiple, bilateral,various size, well-circumscribed pulmonary nodules, containing calcification solid nodul 2 cm in diameter and periferal consolidatıon ın the rigth upper lob . Previous chest radiographs and CT had revealed the presence bilateral multiple nodules and low uptake18F‑fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) ( suv max:2.4).

Results
The patient underwent wedge resectıon rigth upper lobe for evaluating nodules three years ago.Histological examination demonstared weak -granulom formation and nodüles consisting dystrophic calcification ,multifocal hyalinisation and ossification It was considered sequelae of tuberculosis. Follow –up imaging studies increased in size,the number of pulmonary nodules and newly rigth 8th and left 6th rib hypermetabolik uptake in PET.CT -guided transthoracic needle aspiratıon biopsy performed the increasing nodul in the rigth upper lobe diagnosed adenocarcinoma.The patient is still alive and on follow-up.

Conclusion
Studies have shown that people who have had allogeneic transplants have a higher risk of second cancer than people who got a different type of stem cell transplant. In this case it is difficult to conclude whether TB sequelae caused lung cancer or the lung cancer simply associated in a patient with previously known pulmonary TB. Initial diagnosis of tuberculosis in such patients often misleads the physician to abandon further work-up resulting in overlooking or delayed diagnosis of the lung neoplasm,thus affecting their outcome

Background
Cystic and cavitary pulmonary lesions are abnormalities encountered on chest radiography and computed tomography (CT).Malignant lesions, including metastases, rarely present as cystic and cavitary lesions.Due to rarity such cases ,we report here a case of unusual form of pulmonary metastasis of primer lung adenocarcinoma

Methods
A 82-year old female patient admitted to hospital with complaints of dry cough,progressive dsypnea for a month .Her past history was unremarkable. Physical exam was normal.Chest X-ray revealed bilateral diffuse multpil cavitary and cystic lesions In routine laboratory tests, all were normal excepting Hb:10.7 g/dl, CRP:43 The thorax CT showed bilateral diffuse cysticand cavitary lesions in 1-3 cm diameter, with no thoracic lymphadenopathy . As the multiple lung nodules were suspected to be metastatic, 18F‑fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) was conducted, which revealed that the nodules had mild uptake of 18F‑FCG ,a metabolic behaviour consistent with bening aetiologies diseases according to the nuclear medicine report.

Results
Bronchoscopy with bronchial lavage was performed. Cytology was negative for malignancy. Repeat CT scan of chest showed increase in size of lung lesions and new right-sided pleural effusion .CT-guide transthoracic needle aspiratıon biopsy was performed. The pathological examination revealed a metastasis of adenocarcinoma ,however histological differentiation of primary pulmonary adenocarcinoma from metastatic adenocarcinoma is sometimes difficult because of their phenotypic similarities So immunohistochemistry (IHC) was performed, the IHC of lung tumor: cytokeratin 20 (CK20)(-), cytokeratin7(CK7)(+), thyroid transcription factor(TTF)(-)Because of PET CT was no showed extrathoracic uptake,It was considered primary lung adenocarcinoma for final diagnosis.

Conclusion
One of the most important differences in the differential diagnosis of cystic or cavitary lung lesions is the distinction between malignant and benign aetiologies. Primary lung cancer is a common disease, cavitation being detected by CT for up to 22% of primary lung cancers but for near 11% by plain thoracic radiography. However pulmonary metastases can rarely cavitate, with a reported incidence less than 4% on chest radiographs [2]. Even cavitary lung metastases are rare and benign differential diagnosis are more common, clinician should be careful in neoplastic context and investigation should be done In rarity such cases ,we report here a case of unusual form of pulmonary metastasis of primer lung adenocarcinoma

Background
Disparities in cancer survival among rural and urban population is known. Time delay from symptom to presentation for medical attention and treatment in rural lung cancer population is partly responsible for lower survival rates in this population. Identification of specific barriers can help form strategies to improve survival. There are no prospective studies evaluating referral pathways and identifying barriers in lung cancer presentation in rural areas . This study's aim was to analyse time delays in management pathways of rural lung cancer patients and explore the influence of various demographic factors on these times.

Methods
Lung cancer patients presenting to Townsville Cancer Centre, Cairns Base Hospital and Mackay Base Hospital were prospectively recruited over a 36 month period from 2009 to 2012. As per ASGC (Australian Standard Geographical Classification) guidelines of remoteness patients were classified as regional or remote. Fisher’s test was used to identify differences between these two cohorts. Times along referral pathway were divided into symptoms to first presentation, symptoms to diagnosis, symptoms to specialist visit, specialist to treatment and symptoms to treatment. The influence of clinical and socio-demographic factors like gender, ethnic status, education level, income, remoteness of location and stage of disease on these times were analysed using Kruskal-Wallis and Mann-Whitney tests for statistical significance.

Results
A total of 252 lung cancer patients were eligible for recruitment. Of these 180 (71.4%) were classified as urban and rest remote. In remote compared to urban patients there were more males (73.6% vs 60%, p=0.046) and more Caucasians (96.2% vs 90%,p=0.068). Also level of secondary or higher education was significantly more in urban compared to remote cohort (88.5% vs62.7%). Tumour demographics like histology and stage were balanced between the two cohorts. Median time from symptoms to first presentation was significantly affected by ethnicity (indigenous vs non indigenous 92 vs 57 days, p=0.05), older age (<51yr vs >51yr 14 vs 45 days, p= 0.026) and lower level of education (primary/secondary vs tertiary/TAFE 61 vs 23 days, p=0.023). Median time between symptoms to specialist consultation were significantly higher for lower level of education ( primary / secondary vs tertiary/TAFE 140 vs 55 days, p=0.05) and remoteness of location (remote vs urban 113 vs 89 days, p=0.05). Specialist to treatment time was delayed by stage (III vs IV 34 vs 18 days, p=0.021). On multivariate analysis time between symptoms to first presentation was influenced by level of education (primary/secondary vs tertiary/TAFE, p=0.006). For rural compared to urban patients, time between first consultation to specialist visit (p=0.022) and time between symptoms to first treatment (p=0.015) were significantly longer.

Conclusion
The demographic profile of lung cancer patients from remote areas is quite smilar to their regional counterparts. In the five time zones from presentation to treatment, median time from symptoms to first presentation was the most susceptible. In the referral pathways, indigenous ethnicity, level of education, remoteness and stage of disease affected time delays but no impact was found for socio-economic status. On multivariate analysis level of education and remoteness of location emerged as significant barriers to presentation.

Background
Lung cancer in New Zealand is associated with poor survival and regional inequalities. Non-small cell lung cancer (NSCLC) accounts for 80%–85% of all newly diagnosed lung cancer cases. Forty five percent of these patients present with stage III disease (mediastinal node involvement). The Regional Cancer Treatment Service (RCTS), Palmerston North Hospital is using combined modality treatment (CMT) chemotherapy / radiotherapy protocol for inoperable Stage II and Stage III NSCLC since 2006. The chemotherapy regimen employs 3 cycles of Cisplatinum/Vineralbine. This audit reviews the outcomes and side effects of treatment.

Methods
This retrospective study comprises patients with a clinical diagnosis of inoperable NSCLC from the RCTS, Palmerston North Hospital database. Patients confirmed to have stage IIIB and/or inoperable stage II and IIIA NSCLC are included. These patients completed treatment based on the RCTS NSCLC CMT guideline from 1[st] July 2005 to 31[st] May 2012. Information was obtained from Oncology electronic records and paper based clinical notes in RCTS. The treatment protocol includes one neoadjuvant cycle of chemotherapy, given 3 weeks prior to commencing of the radiotherapy. It is followed by further two cycles of Cisplatin/Vinorelbine, given concurrently with radical radiation therapy on day 1 and 22 of the radiotherapy. All patients were treated with 3D conformal radiotherapy to total dose is 60Gy in 30 fractions, over 6 to 7 weeks. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 were applied. Progression free survival (PFS) and median survival were estimated and reviewed.

Results
From 1[st] of July 2005 to 31[st] of May 2012, 39 patients completed CMT. All cases in the study had a history of smoking. Thirty two (82%) patients had inoperable stage III NSCLC (IIIA - 15 cases, IIIB - 17 cases). The remaining seven patients had stage II disease, (IIA - 3 cases, IIB - 4 cases), who were deemed inoperable due to significant medical problems. Protocol doses were maintained in 79% of patients, with dose reduction typically used due to transient renal impairment, ototoxicity and myelosuppression. Neutropenia (ANC <1000/mm3) was documented in 21% of patients. Six patients (15%) had neutropenia on day 14-15 and 2 patients (5%) on day 22-23. One patient had hospital admission for febrile neutropenia. Five other patients developed neutropenia but remained asymptomatic. Grade III anaemia (Hb <80 g/L) was noted in 6 patients - all of them had 2 units of blood transfusion. There were no treatment related deaths. 23 patients developed progression of the disease. At the time this study is completed, 16 patients are remaining progression free. The median progression free survival is 9.4 months (mean 12.4), with a median overall survival of 16.6 months. This study demonstrated a 3-year survival rate of just below 20 %.

Conclusion
These outcomes and toxicities are comparable to the reported international studies and would support continued use of our current protocol. Further studies may be helpful to identify the optimum chemotherapy regimen in concurrent therapy for inoperable NSCLC. The future role of molecular tailored regimens in subgroups of patients undergoing CMT is evolving.

Background
Outcome of advanced NSCLC is poor. Platinum based chemotherapy is standard of care. Addition of antiangiogenic agent such as bevacizumab improves the results.

Methods
Prospectively collected data of patients received bevacizumab, platin and pemetrexed as initial therapy for 6 cycle followed by maintenance pemetrexede and bevacizumab till disease progression or unacceptable toxicity.

Results
We had 18 patients, 14 were males and 4 were females. The age of the patients ranged from 45 to 68 years with a median age of 54 years. About one third of the patients were smokers and most of the patients were of good performance status (ECOG-0/1-94%). The most common symptoms of presentation were, cough in 61% of patients followed by dyspnea in 39% of patients. The chest pain and neck swelling were present in 11% of patients whereas bony pains were present in 39% of patients. Co-morbidities of diabetes and hypertension each were present in 17% of patients. Most of the patients were stage IV(94%). The patients received chemotherapy which comprised of pemetrexed, platin and bevacizumab for 6 cycle followed by pemetrexed and bevacizumab maintenance till progression in responding patients after six cycle. Number of cycle’s received ranged from 2 to 21 with a median of 10 cycles. Response rates achieved were stable disease in 72%, partial remission in 22% with disease stabilization rate of 95%. Grade 3 and 4 toxicities observed were neutropenia 11%,proteinuria 11%, anemia and Hyponatremia were present in 17%.One patient each developed pulmonary thromboembolism and hypertension. Bevacizumab was stopped because of toxicitty in one patint who developed pulmonary throboembolism. Median progression free survival was 7 month and median overall survival for whole group is not reached.

Conclusion
Addition of bevacizumab to standard platin based therapy in both initial and maintenance phase is feasible with acceptable toxicities. Some patients have long term disease control.

Background
Physical activities (PA) induce a positive effect on cardiorespiratory fitness, lung cancer symptoms and quality of life of patients suffering from lung cancer. While 92% of patients are interested in participating in a PA program, only 1/3 of them do sufficient amount of PA to provide important health benefits. The aim of our study was to identify barriers and facilitators to PA in patients with lung cancer receiving chemotherapy.

Methods
Our study provided data from patients diagnosed with primary NSCLC in advanced stages of the disease receiving chemotherapy. We chose a qualitative approach using a semi-structured interview. We conducted an exploratory analysis, using the thematic analysis technique to process the data.

Results
Seven barriers and facilitators to PA were identified (side effects of the disease/cancer-related treatment, other physiological limitation, timing/loss of meaning of projects, kinesiophobia, support/care, social usefulness/useless feeling, nature of the PA) and were grouped into 4 categories: physiological, psychological, social and environmental factors. These factors were identified to have different effects on the barriers to PA. Psychological and social factors mainly have an impact on the willingness and ability to practice PA; while physiological and environmental factors have an impact on the duration, intensity and regularity of PA.

Conclusion
Our study highlighted some of the effects that the barriers to PA have on the practice of PA in patients with NSCLC receiving chemotherapy. Our findings may be used by professionals to design an adapted PA program in this population.

Background
Elderly patients and even more older elderly with stage IV NSCLC are often not optimally treated.

Methods
Not applicable

Results
Between april 1[st] 2010 and february 28th 2013, 25 patients ( aged 84 years or more were referred with a stage IV (11 M1a and 14 M1b) non-small cell lung cancer to our university hospital. There were 11 females and 14 males. There were 11 never-smokers. Median age was 87 years (range : 84-92). Histological subtypes were : 8 squamous cell carcinoma, 14 adenocarcinoma and 3 large cell carcinoma. Molecular analyses was performed in 17 cases among which 2 were impossible due to inappropriate biopsy specimen. EGFR- mutations were found in 4 female patients, 1 with exon 19 deletion and 3 with exon 21 point mutations. There were 3 K-RAS mutations and no ALK translocations. 6 patients received TKIs as first line treatment (5 gefitinib and 1 erlotinib). Two patients with no molecular analysis were treated with first-line TKI (both of them had PS 4, one died after 1.1 month, the other recovered very quickly and is still alive after 15.3 months). The other patients were treated with doublet carboplatine AUC 6 and weekly paclitaxel (90 mg/m², D1, 8, 15), with D1 = D29 (12 patients) or single agent therapy (paclitaxel (2), Gemcitabine (1), vinorelbine(1)). Three patients received only best supportive care (BSC). Doses of TKIs had to be lowered due to toxicity in 1 case. Median overall survival was 8.1 months with a one-year probability of survival of 46%. Survival of the 6 patients treated with first-line TKIs was 1.1, 3.1+, 6.43+, 14, 15.33+, 15.9+ months.

Conclusion
It must be noted that EGFR-mutations were more frequent compared to younger patients (at least 4/25) paralleling the high proportion of never-smokers (44%) and of female patients (44%). In this unselected consecutive series of older elderly patients, only 3 received BSC as sole treatment, while 4 were treated with single agent chemotherapy, 12 with a carboplatine-based doublet and 6 with TKIs as first line therapy, of which only 4 had proven EGF-R mutations. Survival was very similar to what is observed with younger counterparts and thus, nihilism is not appropriate in this category of patients.

Background
With a burgeoning population of elderly patients with lung cancer deemed non-surgical, increasing utilization of minimally-invasive techniques such as CT-guided percutaneous catheter ablation is occurring for the management of solid tumors. However, it is unknown whether a strategy of ablation plus adjuvant chemotherapy improves locoregional and survival outcomes in aged patients with solid lung malignancy. The aim of this study was to compare local tumor recurrence and survival outcomes of ablation plus adjuvant chemotherapy versus ablation alone for management of primary and metastatic solid lung tumors in patients unsuitable for lung resection.

Methods
Searched PubMed, the Cochrane Library, EMBASE, and CANCERLIT databases from January 2000 to December 2012. Blinded duplicate screening was used to extract data from captured clinical studies involving patients with non-surgical solid lung tumors, both primary and/or metastatic. Population was deemed non-surgical, with solid lung tumors, both primary and/or metastatic. Generated aggregate effect estimates from constituent studies for three outcomes (e.g., local tumor progression [LTP], overall survival [OS], and disease-free survival [DFS]) with comparison of pooled fixed effect analyses concerning ablation plus adjuvant chemotherapy versus ablation alone. Data were analyzed using dedicated meta-analysis statistical software (BioStat Inc., NJ, USA).

Results
Ablation + chemotherapy group: 684 patients and 1,314 lung tumors. Ablation only group: 1,874 patients and 2,604 lung tumors. Histology was NSCLC >> mets from colorectal cancer > sarcoma > renal > other. Ablation + chemotherapy versus ablation alone: LTP of 15% over median follow-up of 31 months [range 12 to 59] versus 19% over median follow-up of 21 months [range 12 to 29]; odds ratio (OR) 0.73 (95% CI: 0.61-0.86, p<0.05) at 12 month follow-up. OS was 89% versus 78%, respectively, at 12 month follow-up; OR 1.52 (95% CI: 1.16-2.00, p=0.003). DFS was 90% versus 82%, respectively, at 12 month follow-up; OR 3.18 (95% CI: 2.04-4.96, p<0.05). Forrest plots for the outcomes of LTP, OS, and DFS are shown. Sensitivity analyses were robust, publication bias relatively narrow, and Q statistic <21; p>0.13 for all outcomes.Figure 1

Conclusion
A strategy of CT-guided percutaneous catheter ablation plus adjuvant chemotherapy delivers the benefit of retarding LTP, and expectedly lengthens both OS and DFS. Elderly patients with solid lung tumors who are most likely to benefit from this strategy would be non-surgical candidates with relatively good performance status who could tolerate both catheter ablation and chemotherapy.

Background
Despite improvements in lung cancer treatments, there is little international agreement over the key elements of follow-up; frequency of visits and investigations, and choice of models of care remain controversial. Worldwide there is an emphasis on survivorship in patients who have been treated for lung cancer. Further, there is growing interest in the role of primary care in cancer survivorship and follow-up; primary care has the potential to provide more comprehensive and coordinated care in cancer patients. To date there have been few studies investigating the role of primary care in lung cancer follow-up and survivorship. As a prelude to developing and trialing a primary care-focused package of care for UK patients with lung cancer, we undertook a descriptive study, based on analysis of audit, database and qualitative data.

Methods
Case notes of 183 lung cancer patients from 60 practices in Wales Scotland and England , and data from two Scottish primary care databases (3025 patients) were analysed (attendance patterns in primary care, co-morbidity, investigations, referrals and prescribing). For a subset of database patients, data from control patients, matched for age and sex, were examined. We also interviewed 84 primary and secondary health care professionals from across the UK, and undertook four focus groups of patients and carers. Transcripts were coded thematically using a grounded theory approach; the analysis was conducted inductively, driven by the interview data.

Results
Most (90%) of the patients’ cancers were NSCLC; 57% had received treatment with 'curative intent'; the remainder received essentially palliative treatment. Three-quarters of patients had at least one co-morbidity (32% had two or more). Particularly in the first year post-diagnosis, lung cancer patients had significantly higher primary care consultation rates than matched controls - these differences persisted over time. Approximately 80% of presentations to primary care were for lung cancer-related problems; almost 20% of all primary care consultations led to investigations (predominantly blood tests), and 7% led to a referral. Most prescriptions were for antibiotics, analgesia and antidepressants. There was little evidence of structured approaches to lung cancer follow-up and survivorship. Our qualitative data showed some support amongst key stakeholder groups for an enhanced role for primary care in the follow-up of lung cancer patients. There was, however, a strong perception of 'disaggregation' between secondary and primary care services. Care models involving enhanced roles for primary care were particularly favoured for long-term lung cancer ‘survivors’, with a high burden of psycho-social concerns and unmet need; also, the role of specialist lung cancer nurses was consistently emphasised.

Conclusion
Much of the care provided to lung cancer patients is already based in primary care. Further, specialist nurses provide expert knowledge, familiarity with and access to hospital-based services and engagement with multi-disciplinary team processes. There is, however, limited evidence from our study or the wider literature that the services needed to meet the broad and complex needs of these patients are well-defined or well-integrated. Models which integrate primary care with other lung cancer services offer the prospect of improved continuity, access, care co-ordination and management of co-morbidities.

Background
Video-assisted thoracic surgery (VATS) lobectomy is an accepted oncologic approach for early-stage peripheral typed non-small cell lung cancer (NSCLC).Recently the indication of VATS lobectomy is becoming widely adapted to more complicated cases thanks to development of thoracoscopic instruments and technical aspects.

Methods
We here report a case of patient who underwent VATS lobectomy after induction chemoradiotherapy for locally advanced NSCLC.

Results
A 56-year-old man with a 35 pack-year history of tobacco use presented with productive cough. A computed tomography (CT) revealed a 6-cm hilar mass with consolidation in the right upper lobe and hilar, interlobar,and single mediasitnal lymphnode metastases. There was a significant mass uptake of FDG (standardized uptake value: 16.1 to 19.2) on Positron emission tomography (PET). Bronchofiberscopy showed an intraluminal extension of the tumor centrally to the orifice of the right upper lobe. Bronchofiberscopic biopsy demonstrated squamous cell carcinoma. This patient have a clinical T2bN2M0 IIIA NSCLC. He received two cycles of CDDP+GEM followed by concurrent CDDP+VNR and 40Gy irradiation. Preoperative assessment by CT and PET revealed marked regression of the tumor. A VATS lobectomy was then performed. One utility incision (4 cm) was made over the 4th intercostal and three ports (0.5-1.5 cm each) were placed without rib spreading. By using bipolar scissors, the major vascular structures and the bronchus were safely dissected from the irradiated surrounding tissue similarly to an open procedure. The bronchus could be divided using a stapling device. An anatomic lobectomy with sysytematic mediasitanal lymphnode dissection was fully and safely performed. The chest tube was removed on the postoperative 1st day. He had an uneventful 9-day hospital course. This final pathological finding revealed microscopically residual tumor only in the bronchial wall and lung parenchema andin the single mediastinal lymphnode. This patient have an yield pathological T3N2M0 StageⅢA NSCLC.He received additional 4 cycles of CDDP based chemotherapy postoperatively and is alive with disease free 25 months after surgery.

Conclusion
VATS lobectomy is a feasible approach for selected patients undergoing resection after induction chemoradiotherapy for locally advanced NSCLC.

Background
Lung cancer has the highest cancer-related mortality in the World. In developing countries, mortality rates tend to be higher due to deficits of diagnostic and professional resources, and long time intervals between patient’s symptoms and the initiation of treatment. Multidisciplinary teams improve the care of patients with NSCLC, but this practice is not common in developing countries. In Costa Rica more than 90% of cancer patients are treated in a public hospital where resources are limited. To improve patient care a weekly multidisciplinary thoracic oncology meeting was organized in Hospital San Juan de Dios, one of Costa Rica’s three adult general hospitals. This hospital is responsible for the management of more than 40% of Costa Rica’s cancer patients.

Methods
A multidisciplinary team including Medical Oncology, Pneumology, Pathology, Thoracic Surgery, Radiology and Radiation Oncology started to meet in a weekly basis since November 2011. All patients with a possible lung cancer in the hospital were evaluated by the team and recommendations were given. Data of patients with NSCLC seen by the multidisciplinary team during 2012 was compared to a historic data of NSCLC patients diagnosed in the same hospital between 2003 and 2008 when there was no multidisciplinary team involved in patient care. Exclusion criteria included insufficient clinical information. Epidemiologic data was analyzed and survival curves were obtained.

Results
In the periods 2003-2008 and 2012, 92 and 39 patients respectively with NSCLC were included for analysis. Epidemiologic results are summarized in Table 1 and overall survival is plotted in Figure 1. Figure 1 Figure 2

Conclusion
The inclusion of a multidisciplinary team in the management of NSCLC lead to an earlier diagnosis and increased survival of patients. This approach should be considered in the management of NSCLC patients in a developing country.

Background
In NSCLC, BM are found in 20%-50% overall and 10-18% at initial presentation. Average survival of these patients (pts) is only 3–6 months. The selection of pts who may benefit from surgical resection of BM is challenging. Our goal was to distinguish which pts might benefit from surgical resection of BM.

Methods
We retrospectively reviewed all pts receiving surgical resection of BM from NSCLC at our institution between 2000 and 2011. Survival after Brain surgery was measured.

Results
A total of 52 pts were identified. Median age was 59 years (35-81). ECOG Performance status was 2 or less in 88%.Only 2 were never smokers, and 94% smoked until < 5 years before diagnosis. Nineteen (37%) were women, 29 (56%) had adenocarcinoma (AC), 14 (27%) squamous cell carcinoma (SCC) and 9 (17%) not otherwise specified NSCLC. In 35 pts (67%) single BM was present, 2 in 6 (12%), 3 in 5 (9 %) and 4 or more in 3 (6%) pts. The stage of the primary lung tumor was T1-3 in 40 (78%) and N0-1 in 25 (48%). Synchronous BM were resected within one month of diagnosis in 29 (56%) pts. Twenty-three (44%) had no other distant metastases at the time of diagnosis of the BM. Distribution of distant metastases was adrenal (21%), liver (19%), bone (15%), lung (13%) and other (19%). Median time from lung cancer diagnosis to resection of BM was 7.5 months (0-63 months). WBRT was applied to 45 (87%) pts post brain surgery and once before surgery. The primary tumor was resected in curative intent in 14 (27%) pts at diagnosis. Thirty four (65%) received first line platinum chemotherapy doublets. Second line systemic therapy was given to 19 (37%) pts. Only 8 pts received tyrosine kinase inhibitors, but no one was treated for longer than 4 months. Eight are still alive. Median survival was 9.1 months with only one patient (initially pT2 pN0) surviving more over 5 years. One year survival was 42%. Median survival for males was significantly shorter (6.7 vs. 14 months [p<0.005]). AC was associated with improved survival compared to SCC (10.6 vs. 6.7 months [p<0.05]) with no correlation between gender and histology. In a multivariate analysis, the use of TKI, age and WBRT were not associated with outcome. Thirteen (25%) died within 3 months after surgery including 4 (8%) within 1 month. Six (46%) of them had other metastatic sites involved. New brain lesions post-surgery were documented in 12 (23%) and 4 (8%) had local progression at the resection site.

Conclusion
Resection of BM followed by WBRT lead to good local control. Despite patient selction with almost one third being treated with surgery of the primary tumor "curative intent" as well, only one patient lived > 5 years. The relatively high death rate (25%) within 3 months of surgery indicate the need for further research to better select patients suitable for survery. Female gender and AC histology were associated with better survival after resection of BM. These pts may preferably be considered for resection.

Background
Small-cell lung cancer constitutes 10-15% of lung cancer cases. Although it is sensitive to chemotherapy and radiotherapy, but usually relapsed and recurred with median survival time less than 6 months after second line therapy. Paclitaxel monotherapy had been reported its efficacy with minimal toxicity in relapsed small-cell lung cancer treatment. This presenting case demonstrated activity of paclitaxel in relapsed-refractory small-cell lung cancer in fourth line of treatment.

Methods
This is the case report of paclitaxel monoherapy in fourth line of refractory -relapsed small-cell lung cancer treatment.

Results
A 72-year-old woman with a history of ex-smoker and hypertension presented in September 2007 with weight loss and left- sided chest pain.On physical examination revealed bronchial breathsound at left lung .Computed tomography scan of the thorax showed 5.7 * 4.5 cm mass at left hilar region and occlude left middle part of bronchus. Bronchoscopic biopsy was done and histology showed small-cell lung carcinoma. Staging work up was performed and resulted was limited stage disease. The patients was admininistered chemotherapy with standard cisplatin and etoposide regimen. Concurrent chemoradiotherapy was started on 3rd cycle of chemotherapy . She received first line chemotheapy with total 5 cycles of chemotherapy with good clinical response. Chest imaging showed nearly partial response. Before 6th cycle of chemotherapy she developed relapsed small-cell lung carcinoma and was treated with cisplatin plus irinotecan as second line therapy for 2 cycles and third line with cyclophosphamide/adriamycin/vincristine regimen for 1 cycle with no response and had worse lung symptoms . Fourth line chemotherapy was administered with paclitaxel 175 mg/m2 every 3 weeks for 4 cycle between April and July 2008 . After second cycle of paclitaxel her symptoms and chest imaging were improved. After 4 cycle of paclitaxel monotherapy she was evaluated as stable disease and had long survival since 2008 until now with symptom- free and no relapsed of disease for more than 5 years.She had minimal toxicity from paclitaxel with only mild neuropathy.

Conclusion
In conclusion this case demonstrated that paclitaxel still had benefit with long-term survival and minimal toxicity eventhough in the fourth line therapy of refractory-relapsed small-cell lung cancer.

Background
The progression-free survival and response rate of patients with EGFR-mutant tumors treated with an EGFR TKI has been reported to be superior to standard chemotherapeutic regimens. These mutations, concentrated in the exons 18 to 21 encoding the tyrosine kinase domain of the receptor. However, TKI sensitivity depends upon the nature and location of the mutations. Eighty to 90% of all lung adenocarcinoma-associated EGFR mutations are short, in-frame deletions in exon 19 and the exon 21 point mutation L858R; 70% of tumors with the latter mutations respond to treatment with the EGFR TKIs. The remaining 10 to 20 % of EGFR mutations include several additional point mutations that can be considered as "uncommon mutations". Their identification is problematic for therapeutic decision. Indeed, it remains unclear whether these mutations have benefit upon progression-free or overall survival. Therefore a comprehensive strategy is required to prioritize treatment decisions by physicians in the routine clinical practice.

Methods
By retrospectively analyzing mutational data of 3,200 consecutive patients with metastatic lung adenocarcinomas diagnosed for EGFR mutational status, we have identified those whose tumors had uncommon mutations (mutations that were neither base pair deletion in exon 19 nor the L858R in exon 21). We have contacted the physicians in charge of these patients and asked them the individual therapeutic decision. We have also questioned them about the level of their knowledge on the sensitivity of uncommon mutations to TKIs and how to improve this knowledge.

Results
Out of 3,200 metastatic lung adenocarcinomas, 351 tumors (11%) exhibited abnormalities in the exons 18 to 21. Of these 351 EGFR mutated tumors, 171 (48.7%) were base pair deletions in the exon 19: and 129 (36.7%) were the L868R in the exon 21. The 14.5 % remaining tumors showed "uncommon" mutations. There were G719 to A, C, or S mutations in 18 patients (5%), the L861Q mutation in 14 patients (3%) and only 1 Ins 18 pb in the exon 19. In exon 20, the T790M mutations were found in 4 tumors and in-frame insertions of varying lengths that confer resistance to TKI in 2 patients. Ten additional mutations, most of them being double mutations, were observed in 12 patients (3.4%). Of the 51 patients with uncommon mutations, 15 (29%) have received gefitinib or erlotinib whereas at least 32 patients should have received anti-EGFR therapies. Reasons for this difference were 1) the lack of knowledge of the sensitivity of rare mutations, and mostly double mutations, 2) the difficulty of finding the answer, either on the record or in the scientific literature, 3) the possibility of introducing a platinum-based chemotherapy, 4) the lack of experience of the theranostic which includes many gene mutations.

Conclusion
Opportunities for improvement could be: 1) better information on the medical report when there is scientific evidence suggesting sensitivity or resistance of the rare mutation. 2) in parallel, a more accurate information on the lack of knowledge on the sensitivity or resistance, 3) a website for quick access to this type of information and changes along with the knowledge evolution.

Background
Although primary neurogenic tumors of the lung are very rare, cellular schwannoma is a subtype of the classical schwannoma, which is a tumor of nerve sheath. Despite of pseudosarcomatous appearance, histopathologically, cellular schwannoma is considered as a benign tumor. However, it may carry atypical characteristics and risk of malign degeneration. We are presenting a case of primary pulmonary cellular schwannoma for discussing its clinical presentation and the prognosis.

Methods
A 65 years old male patient applied with the symptoms of cough and sputum production and found to have a 3x2.5 cm mass in the upper lobe of the right lung. At that time, retrospective examination of his available chest radiographs suggested a slowly growing lesion during a 4 years period. The mass was removed by extirpation and the histopathological diagnosis was cellular schwannoma. After surgical treatment no residuel lesion was detectable and he was doing well clinically.

Results
He had been followed up yearly for 5 years. Eight years after the operation a 3x3x4 cm mass was seen at the same site of the previous lesion but the patient refused any surgical or diagnostic intervention. During follow up the lesion was found to be 6x6x5 cm in diameters 12 years after the operation.

Conclusion
In cellular schwannoma the treatment of choice is surgical removal of the mass and the relapse of the disease is very rare. However, in this case the lesion seems to be the relapse of the previous disease. We suggest that in some cases extirpation of the mass may not suffice and surrounding tissue of close contact should also be removed to avoid relapses.

Background
There are limited treatment options for patient with advanced thymic malignancies and the utility of many of the available chemotherapies is restricted by cumulative toxicity such as neuropathy (taxanes) and cardiomyopathy (anthracyclines). We designed this study to look at single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor with minimal cardiac toxicity, in patients with advanced thymic malignancies.

Methods
Eligible patients have confirmed thymic malignancy (thymoma (T) or thymic carcinoma (TC)) with progression or relapse after at least 1 prior chemotherapeutic regimen, and adequate organ function including left ventricular ejection fraction (LVEF) of >50%. The initial treatment plan consisted of amrubicin at 40 mg/m[2] IV days 1-3 repeated in 3-week cycles. The study is a Simon 2-stage design based on a null hypothesis of a true response rate <5%, with 90% power to detect a 20% true response rate and a plan to accrue 12 evaluable patients in stage 1, then if at least 1 response is seen, to add 25 additional evaluable patients in stage 2 for a total of 39 patients.

Results
Enrollment was initiated in July 2011. Here, we report on the first 12 patients, all enrolled at Stanford University over a 19-month period. Of the first 12 patients enrolled, 11 were dosed. All were pre-treated (5 with prior anthracycline). There were 5 women and 7 men; age range of 30-67 years old; 6 were of Asian ethnicity, 5 were non-Hispanic White and 1 was Hispanic. After enrollment of the first 8 patients, of whom 3 were hospitalized with febrile neutropenia (FN) (38%), the study was amended to a starting dose of 35 mg/m[2] days 1-3 repeated in 3-week cycles. Other than FN in the 3 patients mentioned above, G4 thrombocytopenia in 1 patient, and treatment-related G3 fatigue in 2 patients, other toxicities were generally mild and well tolerated. No significant changes in LVEF have been noted on serial echocardiograms. Of the 11 treated patients, there were 3 partial responses (2 T and 1 TC), 7 with stable disease for at least 4 cycles, and 1 with progressive disease (PD) after 2 cycles (TC). Of the 11 treated patients, only 1 patient, with PD after C2, has stopped before completing 6 cycles, and 5 to date have tolerated >10 cycles (with others still on treatment who may receive >10 cycles), with 15 cycles as the highest number to date.

Conclusion
Amrubicin, at 35 mg/m[2] IV days 1-3 on a 3-week cycle, shows promise as a single agent in pre-treated patients with thymoma and thymic carcinoma with a 27% RR in the first 11 treated patients. This exceeded the threshold for proceeding to step 2 and the study will now continue to a total of 39 patients and has expanded to other sites including Indiana University.

Background
Various factors such as age, stage and PS may provide prognostic information in advanced NSCLC; however, a better understanding of a patient’s judgement can help the Physician to make appropriate decisions.Purpose:1- To study the information provided by pts in a questionnaire. 2 To study PS evolution obtained by the doctor (DPS) and by the pts themselves (PPS).3-To evaluate the correlation between some different variables with survival.

Methods
Patients and Method: 224 pts with stages III and IV NSCLC, age range 38 - 74 years, were studied. The study was prospective. Pts underwent chemotherapy and/ or radiotherapy. They determined their own PS through a questionnaire . Some different variables such as age, stage, DPS, PSP, appetite, food intake, amount of solid food, evening meals, average meal per day, serving size, vomiting frequency, daily work activity , activity restrictions, and hours of rest per day were analyzed . DPS and PPS were studied at diagnosis and at 3 months. Statistical methods: Cox Proportional-Hazards Regression, Chi Square Pearson, Irwin-Fisher,Mac Nemar Wilcoxon tests and Kaplan Meier Curves were used.

Results
Results: According to the univariate logrank test applied to the comparison of the Kaplan and Meier survival curves, many factors seem to be related to survival. 9 of all variables studied were statistically significant. There were no complete agreement between DPS and PPS neither at initial evaluation nor at 3 months. Pts’ self assessment showed higher PS score than PS obtained by doctors.(Mac Nemar Test p< 0.0001).The correlation among predictor variables is not taken into account when using the univariate approach, so a Cox hazard model for the proportional risk was adjusted using all the predictor variables available. To eliminate the less prognostic variables a backward regression test was applied It was found that only initial WL and DPS at the third month of evaluation were positively related to the risk of death. However the low correlation between WL as well asDPS provide independent information.there was statistically significant association between response rate with DPS and PPS. Nutritional parameters revealed no significant data.

Conclusion
: Although the univariate approach showed that many factors are related to the survival of pts, the simultaneous analysis of these factors through the Cox model revealed that few of them summarize the most relevant prognostic information. These variables are DPS at the third month of evaluation and initial WL.

Background
Nutritional decline and weight loss are common features in thoracic oncology patients and are independent prognostic indicators for survival in lung cancer. Malnutrition reduces tolerability to treatment and increases both risk of complications and unplanned hospitalisation, all of which lead to increased disability and reduced quality of life (Ravasco et al, 2004). Changes in eating habits and weight loss can also cause significant psychological distress to both patients and carers. Nutritional assessment and support should therefore be an integral component of the lung cancer patient’s care. The UK National Institute for Clinical Excellence recommends that all outpatients are screened for malnutrition at their first visit. We previously reported on a three month nutritional audit which identified that 37% of patients were at risk of malnutrition, confirming the need for dietary intervention (Howell, 2013). Subsequently an online referral system and a weekly dietetic telephone clinic were established to offer interim support to all outpatients. Data is presented here on the first 7 months of our year-long pilot project.

Methods
Between November 2012 and May 2013 all patients presenting to the Papworth Thoracic Oncology Service (PATHOS) with suspected thoracic malignancy were screened for malnutrition using the Malnutrition Universal Screening Tool (MUST) as part of a Holistic Needs Assessment. Patients at high risk of malnutrition (i.e. MUST score ≥2) received written and verbal advice on first line nutritional support, were commenced on oral dietary supplements and referred to the dietetic telephone clinic.

Results
26 patients were referred to the dietetic telephone clinic. Assessment calls took approximately 30 minutes, whilst follow-up calls took 10-15 minutes. All patients received an initial assessment call, and the majority of patients received at least one additional follow-up call. 13 (50%) patients were subsequently referred to a community dietician for further management. The following comments are examples of the feedback received. Patient A “it was helpful to have confirmation of what I should be eating and the types of foods to focus on”. Patient B “the information I received on food consistency and the different products available really helped”.

Conclusion
A multi-disciplinary team approach has been established to support and educate thoracic oncology outpatients about their nutritional requirements. Although the numbers are small, the new service has been well received by both patients and staff. The online referral system is easy to use and the written information leaflet contains details of the referral and when patients will be contacted. Developments: Modify the online referral system to include likely diagnosis and future plans. Maintain continuous audit, also collect data on: Diagnosis and stage of disease Eventual treatment plan Outcome of community referral Introduce an anonymous patient satisfaction questionnaire. Consider using a nutritional screening tool specific to oncology patients. References: Ravasco P. Monteiro-Grillo I. Marques Vidal P. & Camilo ME. (2004) Cancer: disease and nutrition are key determinants of patient's quality of life. Supportive Care in Cancer. 12: 246-252 Howell G. (2013) Nutritional reassessment and dietary support of thoracic oncology patients is a "MUST". Lung Cancer. 79 (suppl 1): S42

Background
Angiosarcoma is a rare (1-2% of all soft-tissue tumors) but highly-malignant tumor deriving from the endothelia of small vessels. It primarily affects the skin, mamma, liver and spleen and the lung is the predominant organ of metastatic spread. Symptoms as well as radiologic characteristics are unspecific and diagnosis is made by biopsy and histopathological assessment.

Methods
Single-center case series focusing on the role of VATS in diagnosis and (palliative) therapy of primary and secondary pleuro-pulmonary angiosarcoma.

Results
From 11/2012 to 04/2013 three male patients (77 (74-78) y/o) underwent VATS for diagnosis and therapy of primary disseminated pleuro-pulmonary angiosarcoma (n=2) or bilateral pulmonary metastases of a cutan angiosarcoma. All patients presented with unspecific symptoms like dyspnoea and chest pain. Primary angiosarcoma was associated with severe and recurrent hemorrhagic pleural effusion, while bilateral pulmonary angiosarcoma metastases led to a bilateral pneumothorax under systemic chemotherapy. Two patients suffered from recurrent hemoptysis. Indication for VATS was diagnosis (pleural biopsies, n=3) and palliative therapy (talcum pleurodesis [n=3] and apical wedge resection with pleurectomy [n=1]). Mean operating time was 62 (31-117) min. Following VATS (and diagnosis) all patient received chemotherapy. One patient died 4 month after primary diagnosis, the two others are alive with stable disease.

Conclusion
Multiple unspecific pleural lesions on CT in patients presenting with hemoptysis and recurrent hemothorax may indicate a primary or secondary pleuro-pulmonary angiosarcoma. VATS is a safe minimally invasive single step procedure for both diagnosis and palliative therapy in this highly malignant soft tissue tumor.

Background
In the UK, the 5-year survival for lung cancer patients is less than 10%. One of the reasons contributing to this poor survival is the late stage at diagnosis, with approximately 80% of patients presenting with unresectable disease. CT screening of high risk patients may be effective but is expensive and still under investigation in clinical trials. Symptom-driven investigations may be more likely to detect advanced than early disease. We present data of the presenting symptom type and duration in patients diagnosed at an early, potentially curable stage.

Methods
Data from available casenotes of patients with resected non-small cell lung cancer were extracted by one data manager (NP) to study the main presenting symptom, other tumour-related symptoms, duration (where documented), smoking history and stage of disease. All patients were treated in a single institution between 2003 and 2008.

Results
105 patients’ details are included. 54 were male; age range 40-83 years, mean 67 years. Chest X-ray was abnormal in 103/105 patients. Smoking status was recorded in 83 (79%) cases. Three were never smokers. At time of diagnosis, 32 patients were still smoking and 17 had just quit. Of those who had stopped previously, 7 did so < 5 years before diagnosis, 5 at >5 < 10 years and 19 > 10 years before diagnosis. Pack year estimates were available in 91 patients and ranged from 5 to 180 (mean 40). Tumour stage at resection was 1a in 28, 1b in 29, IIa in 19, IIb in 15 and IIIa in 14. 25 patients had no symptoms (25%). The most common major presenting symptoms are in Table 1. Pre-diagnosis duration of symptoms was recorded in 67 patients (84%). 31 (39%) had >1 symptom.

Dominant symptom	No of patients	Duration in months (mean)
Cough	25	1-24 (3)
+haemoptysis	10	0.5-6 (1)
Lower respiratory infections	10	0.5-36 (3)
Dyspnoea	10	0.25-12 (1)
Chest/arm pain	9	2 hours – 4months (1)
Weight loss	4	3-6
Other	12	1-12 (2)
None	25	-

Conclusion
CXR was abnormal in the majority of these patients with early tumours. The mean time to presentation with a dominant symptom was short. Almost a quarter of patients were asymptomatic and picked up as an icidental finding.The challenge to identify lung cancer patients early, at a curable stage, continues.

Background
Repeated pulmonary resections there are predominantly used in sarcomas and colorectal cancers and in young age. Bad prognosis is in patients with reccurency of pulmonary metastases in period to six months. There are exist four prognostic groups according present risk factors (short disease free interval, multiple metastases).

Methods
We performed in period I/1997 to XII/2011 165 operations in 149 patients. 10patients had multiple pulmonary resections. According origin histology were – 6x sarcomas. 2x tu Grawitz, 1x Schwannoma malignum, 1x ca laryngis. There are synovialosarcoma, osteosarcoma, rhabdomyosarcoma, alveolar sarcoma and sarcoma uteri in group of sarcomas.

Results
As approach we used VATS 2x, clamshel thoracotomy 2x, muscle sparing vertical thoracotomy 7x and posterolateral thoracotomy 6x. We performed extraanatomic resection 13x, lobectomy 4x and completion pneumonectomy 1x. We observed 6x complications (3x small air leak, 3x wound infection) in postoperative period. No necessary rethoracotomy for complications, letality 0.

Conclusion
Surgery is part of complex therapy. There are very necessary strict selection of candidates for surgery and experienced team of thoracic surgeons. Surgery is safe and useful procedure at pulmonary metastases surgery.

Background
Lung cancer affects nearly 40,000 patients per year in the UK and despite recent improvements in treatments, outcomes remain poor (NCIN 2012). Therefore the delivery of high quality care is vital. Lung Cancer Nurse specialists (LCNS) are well placed to provide holistic care, ensuring needs are addressed throughout the pathway, and there is an improvement in outcomes and experience for patients. The National Lung Cancer Forum for Nurses (NLCFN) was established in 1999 and is a national organisation in the United Kingdom (UK) developed to support lung cancer nurses through education, sharing best practice and peer support through a national network. The Forum has grown inexplicably and its success can be measured by the links and networks for nurses involved in caring for people with lung cancer as well as the strategic groups it is involved with nationally and internationally. The members are from diverse backgrounds of palliative care, respiratory medicine and thoracic oncology which results in a wealth of experience and knowledge. The NLCFN has approximately 280 members.

Methods
The NLCFN runs a Research Interest Group (RIG) and a Thoracic Nurses Subgroup (TNS) and both groups are active in improving practice and initiating research projects in lung cancer. The NLCFN proactively supports nursing research and offers a small grant award scheme each year to support lung or thoracic nurses who wish to develop a research project. Collaboration between the Forum and Sheffield Hallam University has led to the development of funding for a part-time PhD studentship. The RIG has been successful in obtaining a research grant to explore in more detail the evaluation of the LCNS role in treatment access. The NLCFN also hosts a website where patients, carers and clinicians can assess up-to-date information on lung cancer management, treatments and interventions and find out about local and national services for lung cancer patients. There is a NLCFN members section which houses guidelines and relevant documents

Results
Over the last 10 years the NLCFN has developed into a national voice on clinical and strategic issues and as such is represented on all lung cancer improvement and strategic groups in the UK. The NLCFN have produced several documents and guidelines which are available to all health care professionals.

Conclusion
The number of Lung Cancer Nurse Specialists has increased since the introduction of the role in 1995. They play a vital role in supporting patients and carers throughout their pathway from pre-diagnosis to end of life care and ensuring that all their needs are addressed. The NLCFN aims to provide the LCNS with a good infrastructure for networking and support as well as continually striving for better care for their patients.

Background
To develop adequate self-care strategies, patients with lung cancer and their families are in need of emotional, informational and behavioural supportive care. Supportive care in cancer can reduce symptom burden and improve patients and their families self-management skills. As lung cancer incidence continues to rise, and increased attention is given to early diagnosis, research on early involvement of lung cancer nurse (LCN) in care, the feasibility and impact on patient outcomes is needed. The primary aim of this study is to assess the feasibility and acceptability of a LCN model of care commenced during first line of chemotherapy, and the impact on patient self-reported changes in self-efficacy, symptoms and supportive care needs. In addition perceived barriers and facilitators for the application of the LCN model will be examined.

Methods
An exact single-stage phase II design will be conducted. Lung cancer patients with planned chemotherapy with or without radiotherapy will be recruited at the thoracic cancer center in a Swiss University Hospital. The LCN model of care consists of two face-to-face consultations alternating with two telephone consultations during first line of chemotherapy. LCN consultations will comprise focused assessment of physical and psychological symptoms, information (printed and oral) about disease and its treatment, therapeutic education concerning strategies to manage physical and psychosocial symptoms and review of available support resources. Participants will be invited to complete the validated patient reported Lung Cancer Symptom Scale, Supportive Care Needs Screening Tool 9 and Self-Efficacy Scale for Lung Cancer. Study data will be collected at baseline (day 1 of 1[st] chemotherapy cycle), time 1 (week 3 of 2[nd] cycle) and time 2 (week 3 of 3[rd] cycle). Participants will be categorized as compliant if they complete all their scheduled LCN consultations and questionnaires. For a 5% probability of accepting a poor feasibility (alpha) and a 20% probability of rejecting an acceptable feasibility (beta) we then need to enroll 71 patients. Feasibility will be considered as acceptable for further studies if at least 36 patients will be compliant. Secondary outcomes will be analyzed descriptively for each variable (self-efficacy, symptoms and supportive care needs) across each time point. At the end of quantitative data collection, a focus group will be conducted to explore acceptability of the new role among health professionals working with the LCN in order to identify perceived barriers and facilitators for collaborative work with the new role.

Results
N.A.

Conclusion
This project is expected to have direct impact on enhancing the quality of supportive care for patients with lung cancer. Findings will provide evidence for refining the LCN model prior to embarking on a full-scale evaluation using a comparative experimental design. Furthermore, phase II designs have rarely been applied to psycho-social interventions. This method could give new insights to the nursing and allied health professionals how to investigate the efficacy and feasibility as well as the needed intensity of newly developed interventions in order to improving supportive care in oncology.

Background
Unplanned hospital admissions (UHAs) are frequent in lung cancer patients, but literature on this topic is scarce. The aim of this study is to get better insight in the demographics, patterns of referral, presenting symptoms, and outcome of lung cancer patients with UHA.

Methods
Data of all consecutive events of UHA between July 1 and December 31, 2012 were reviewed. Details on the factors listed above were examined.

Results
There were 247 UHA events during the 6 month study period. Male/female ratio was 185/62, mean age was 66 years (range 40-90), PS on admission was 0-1 in 79 (32%), 2 in 92 (37%), and 3-4 in 76 (31%). Two thirds were stage IV, and 57% did not have ongoing oncological treatment. On 83 occasions (34%), referral was by the general practitioner (GP-REF), for 101 (41%) own initiative (SELF-REF), and for 63 (26%) specialist advice. The most frequent main presenting symptoms were respiratory (21%), infection (15%), general weakness (15%), and pain (13%). The mean hospitalization duration was 9.5 days, shorter and with more same-day-return in SELF-REF patients (Table). Final diagnoses were categorized in nine groups: infection (22%), respiratory problems (17%), lab abnormalities (13%), pain (12%), abdominal problems (11%), cardiovascular problems, neurological events, general weakness and other (6% each). This differed from the problem as recorded in the ER in one third of the events. Final grading (CTC AE v3.0) of the main event was 1-2 in 38%, 3 in 51%, 4 in 8% and 5 in 2%. Causality was decided as therapy-related (THER-REL) in 59, cancer-related (CANC-REL) in 117, unrelated in 48, and unclear in 23. In the THER-REL events, lab abnormalities (36%), infection (34%) and abdominal complaints (22%) were most common, while this was respiratory problems (23%), pain (18%) and infection (16 %) for CANC-REL events. On subgroup analysis (Table), length of stay was higher in CANC-REL events. Nearly all THER-REL events had medical therapy, while for CANC-REL events this was medical 50%, interventional 33% and supportive only 17%. Figure 1

Conclusion
UHA in lung cancer are predominantly cancer- rather than therapy-related, with a variety of symptoms. More than half of the events are not seen by the GP first, and the majority results in hospital stay of 9.5 days on average . Our work is a first step in identifying specific groups of events, where better interaction with GPs and education of patients might reduce the incidence of UHAs.

Background
not applicable

Methods
During November 2010 to October 2011, 160 elderly bedridden patients after major surgery were divided into the conventional care group, “invigorating qi and promoting qi” group, “Blood-activating and Dampness-eliminating” group and acupoint-combination stimulation group. Whole blood viscosity, plasma viscosity, D-dimer, lower limb skin temperature, lower limb circumference and flow velocities of the external iliac vein, the femoral vein, the popliteal vein and the calf deep veins in all patients were documented and compared as four individual groups.

Results
Whole blood viscosity, plasma viscosity, D-dimer and lower limb circumference were significant reduced in “Blood-activating and Dampness-eliminating” group compared to conventional care group (P<0.05) and almost equal to the results in acupoint-combination stimulation group (P>0.05). Lower limb venous flow velocities were accelerated in“invigorating qi and promoting qi” group compared to groups other than the acupoint-combination stimulation group (P<0.05).

Conclusion
Hemorheological indexes in postoperative bedridden elderly patients were improved after electrical stimulations of Yinlingquan (SP 9) and Sanyinjiao (SP 6) in combination. Electrical stimulations of Zusanli (ST 36) and Taichong (LR 3) in combination, on the other hand, accelerated the lower limb venous flow.

Background
With recent progresses and advances in technology, the number of oral cancer treatment is on the rise. Treatment for NSCLC was once chosen only according to the stage of disease and its histologic classification. Though these are important , but discovery of tumor markers and identification of biomarkers and genetic profiling in lung cancer have led to an added layer of classification. This new evolution have improved lung cancer treatment by providing information that helps oncologist match the right patient with the right treatment which will move majority of these patients from infusion centres to their homes. The concern will show up about how the medication adherence affects the outcomes of cancer treatment and quality of life of people with cancer.

Methods
Not applicable

Results
Not applicable

Conclusion
In this presentation we will discuss the role of tumor biomarkers in designing personalized therapy Identify different oral cancer therapies and how they are named Define adherence Discuss different factors impacting patient adherence and Implications for clinical practice

Background
Li and Girgis (2006) note patients with lung cancer have a higher level of unmet needs than patients with other types of cancer. Wilder et al (2008) found cancer patients report significantly more comorbid conditions, poorer physical and mental health compared to the general population. Lung Cancer Nurses utilise a community wide approach to optimise cancer care for patients, provide patient centred care and promote multidisciplinary care. The implications of lung cancer patients having the presence of multiple comorbidities at diagnosis include; an increased need for nursing education surrounding the more common comorbidities, poly-pharmacy issues, increased clinical needs, increased community supports and psychosocial support. Also the financial implications of increased care needs both to the patient and the community. Data is being collected from two different hospitals, one regional and one urban, from two different states within Australia. Although geography and resources determine the fine tuning of the Lung Cancer Nurse role to individual hospitals, essentially both models of care promote improved patient outcomes.

Methods
All new patients presented in the Lung cancer Multidisciplinary team meeting for a twelve monthe period from September 2012 to end of August 2013 will have their comorbidity data collected. Including associated pharmacy, performance status, main carer and smoking status. The same data is being collected at both sites in this study.

Results
Results and their implications will be discussed once data collection completed at end of August 2013.

Conclusion
Preliminary data is showing that the majority of our patients with lung cancer have multiple comorbidities and thus, poly pharmacy and increased needs. The data between the urban and regional hospitals will be compared and the implications, differences, simliarties and the impact this has on the Lung Cancer Nurse's role at each site will be discussed as well as future directions and what regional and urban areas can learn from each other.

Background
Serum levels of the potent immune-modulatory cytokine interleukin (IL)-6, which signals via the shared gp130 co-receptor, are elevated in smokers, and are higher still in those with lung cancer, the leading cause of cancer death worldwide. However, the precise role that IL-6 plays in the pathogenesis of lung cancer remains to be elucidated. To utilize in vivo molecular dissection of gp130 signaling to identify specific molecular components of the IL-6 cytokine family network which facilitate tobacco-related lung carcinogenesis.

Methods
Nicotine-derived Nitrosamine Ketone (NNK) is a potent tobacco carcinogen and reliably induces lung tumours in mice. We therefore examined the effect of deregulated IL-6 signaling on NNK-induced lung carcinogenesis by using gp130[F/F] mice which carry a knock-in mutation in the endogenous gene for gp130, the critical co-receptor for the IL-6 cytokine family.

Results
The lungs of these mice display IL-6-induced hyperactivation of the latent transcription factor Stat3 via gp130 in the absence of gp130-mediated PI3K/Akt and Mapk signaling. The gp130[F/F] and control gp130[+/+] (wild-type) mice were injected with NNK or PBS and observed over 16 weeks prior to the evaluation of lung tumourigenesis at the cellular (immunohistochemistry, histology) and molecular (qPCR) levels. In response to NNK, the absolute number of lung lesions in gp130[F/F] mice (3.81 ± 0.84; mean ± SEM) was significantly reduced compared to gp130[+/+ ](6.43 ± 1.72; p<0.05) mice. In addition, we also observed a significant reduction in the size of lesions in gp130[F/F] compared to gp130[+/+] mice (1.00 ± 0.05mm vs 0.69 ± 0.05; p<0.0001). Notably, the number and size of lesions in the lungs of NNK-treated gp130[F/F]:Stat3[-/+] mice displaying genetically-reduced Stat3 hyperactivation were comparable to gp130[F/F] mice.

Conclusion
Collectively, our data suggest that IL-6/gp130-mediated activation of the PI3K/Akt and/or Mapk pathways, but not Stat3, plays an important role in promoting NNK-induced lung carcinogenesis.

Background
Development of new methods for selective chemosensitization and radiosensitization of human lung tumors is acutely needed. We propose to combine inhibitors of the chaperone activity along with inhibitors of chaperone expression to treat lung cancer. Our approach is based on such facts: (i) cancer cells are addicted to the chaperone activity of heat-shock protein 90 (Hsp90) because it is required for their survival and proliferation, (ii) inhibitors of the Hsp90 chaperone activity (e.g. 17AAG) may have a 100-fold higher affinity to Hsp90 in malignant cells than in normal cells and (iii) these Hsp90 inhibitors cause undesirable induction of cytoprotective chaperones Hsp70 and Hsp27 that can impair antitumor effects of the Hsp90 inhibition.

Methods
Cultured cells of human lung cancer cell lines SQ-5, H460 and A549, and, for comparison, human normal lung-derived alveolar epithelium or fibroblasts were subjected to 17AAG and known inhibitors of the Hsp induction (quercetin, triptolide, NZ28) and conventional drugs (carboplatin, doxorubicin, paclitaxel) or clinically relevant doses (3-5 Gy) of gamma-photon irradiation. Inhibition of the intracellular Hsp90 chaperone activity was detected on a delay in the Hsp90-dependent reactivation of thermally denatured luciferase in the heat-stressed transfectants. The cell death or survival was assessed in annexin V-staining and clonogenic assays. The angiogenic potential of lung cancer cells was tested in cell-proliferation assays with cultured human vascular endothelial cells (EC). The cellular levels of cell survival- and angiogenesis-related proteins were analyzed by Western blotting.

Results
It was found that 10-100 nM 17AAG significantly retarded proliferation in all the three lung cancer cell lines studied. As biomarkers of the Hsp90 activity inhibition, the specific depletion of Akt, survivin and HIF-1alpha as well as up-regulation of Hsp70 and Hsp27 were revealed in those cell samples. In parallel, co-treatment with 10-30 uM quercetin or 2-4 nM triptolide, or 0.3-1 uM NZ28 fully prevented the Hsp up-regulation in the 17AAG-treated lung cancer cells and rendered them much more sensitive to carboplatin, doxorubicin and paclitaxel, and to gamma-radiation exposure. Importantly, no enhanced cytotoxicity was observed in cultures of normal human fibroblasts and epithelial cells co-treated by the same way. The enhanced chemo- and radiosensitization of lung cancer cells appears to be due to simultaneous blockade of both the Hsp90-dependent antiapoptotic pathways and the 17AAG-induced up-regulation of cytoprotective Hsp70 and Hsp27. Besides the sensitizing effects on the lung cancer cells, the double-inhibitor combination considerably reduced their angiogenicity that was manifested in down-regulation of the HIF-1alpha and VEGF expression levels, and also in the clearly impaired proliferative response of EC stimulated with lung cancer cell culture-conditioned growth medium.

Conclusion
Combined use of the Hsp90 chaperone activity inhibitors and blockers of the concomitant induction of inducible chaperones Hsp70 and Hsp27 enables to selectively sensitize human lung cancer cells to chemo- and radiotherapy, and to suppress the lung cancer-associated angiogenesis. In perspective, such an approach may be developed into a new, effectual strategy for lung cancer treatment.

Background
Non-small-cell lung cancers (NSCLCs) constitute about 85% of lung cancers and have been associated with a poor prognosis, despite the introduction in clinical practice of targeted therapies. The majority of patients are still treated in first-line with a cisplatin containing doublet. New molecular predictors should be discovered. Our attention has been focused on KRAS. Mutations in the KRAS gene have been found in 17% of NSCLC patients mostly at codon 12. It has been observed that a pool of mutations, responsible for different aminoacid substitutions, occured at this position. In NSCLC these mutations are present at a different frequency compared to colon and pancreatic cancer. It has been supposed that different aminoacids in the same position of KRAS protein could differently impact on tumor progression and drug resistance. To test this hypothesis, KRAS overexpressing clones with the three most common mutations found in NSCLC patients (G12C, G12D and G12V) have been generated in NCI-H1299 cell line. The clones showed a different response in vitro to cisplatin (Garassino MC et al, Annals of Oncology, 2011).

Methods
The clones were xenografted in nude mice to determine the antitumor activity of cisplatin in vivo. The effect of cisplatin on signalling pathways and DNA damage response was determined by western blotting, immunofluorescence and Real-Time PCR. Platinum adducts on DNA were revealed by DRC-ICP-MS.

Results
The resistance induced by the presence of G12C KRAS was still present compared to wild-type KRAS clone when these clones were transplanted in nude mice and treated with cisplatin. Some of the logic pathways functionally linked to KRAS, such as MAPK and PI3K, did not seem to account for the different cisplatin sensitivity observed. Factors previously reported to be associated to cisplatin resistance, such as the levels of cisplatin transporter CTR-1, of GSH and GST enzyme, and the total intracellular platinum levels were comparable among the clones. Several concordant results seem to indicate that, with a similar ability to enter the cells and to reach the DNA, an increased removal of platinum bound to DNA might account for the resistance of G12C clone: i) the cell cycle perturbation induced by cisplatin indicated that a reduced G2/M cell cycle phase block was observed in the G12C clone compared to all the others; ii) H2AX foci and ATM phosphorylations following treatment were barely detectable in the resistant clone; iii) the levels of platinum bound to DNA were much faster declining in G12C cells. The involvement in the resistance of G12C clone of Nucleotide Excision Repair and Fanconi Anemia repair mechanisms, which have been associated to the removal of adducts from DNA, was excluded by our experiments.

Conclusion
Altogether these data reveal the possibility that the presence of G12C KRAS mutation stimulates a DNA repair mechanism, not yet identified, able to faster remove platinum from DNA before the formation of double strand cross-links. Studies are ongoing to specifically address this point. Understanding why the different KRAS mutations influence the response to cisplatin could be useful in the clinical setting to tailor therapies for patients.

Background
p53 mutations have been categorized as type I (contact) and type II (conformational) mutations. Differential effects of type I vs. type II p53 mutations in spontaneous lung tumor formation, and their relationship with secondary genetic alterations have not been previously reported. .

Methods
We evaluated the potential of two common type I (273H) and type II (175H) mutations under the transcriptional control of the human surfactant protein C (SP-C) promoter to induce lung tumors in transgenic mice. Necropsies of 138 non-transgenic, 207 SP-C-p53-273H and 171 SPC-p53-175H transgenic mice in progressive age cohorts were performed.

Results
Ninety-one tumors, all adenocarcinomas, were observed; 8 (5.8%), 37 (17.9%) and 46 (26.9%) in non-transgenics, p53-273H and p53-175H, respectively (non-transgenic vs. 273H, p=0.010; non-transgenic vs. 175H, p= 0.0003; logistic regression). Type II p53 mutants had an earlier onset of tumors; 23 of 98 p53-175H mice developed tumors before the age of 13 months, compared to 7 of 108 p53-273H mice (p=0.012, logistic regression). K-ras mutations occurred in a substantial proportion (21 of 50, 42%) of murine lung tumors sequenced. For both the non-transgenic and the p53-273H transgenics, tumor K-ras codon 12-13 mutations occurred after 13 months with a peak incidence at 16–18 months. However, for the p53-175H transgenics K-ras codon 12-13 mutations were observed as early as six months, with a peak incidence between the ages of 10-12 months. Codons 12-13 were the predominant location in p53-175H transgenics (6 of 7), whereas codon 61 (6 of 10) was more common in p53-273H transgenics.

Conclusion
The observation of accelerated tumor onset, early appearance and high frequency of K-ras codon 12-13 mutations in type II p53-175H mice confirms the enhanced oncogenic function of conformational p53 mutations, and the gains in early genetic instability for tumors containing these mutations compared to contact mutations. These data would suggest that not only the presence, but also the type of p53 mutations in human lung cancer should be considered when evaluating prognosis and developing treatment strategies for this malignancy. These mice develop a single-lung tumor that is easy to follow with CT imaging. Thus, these animal models provide a framework for evaluation of the effects of these mutations on response to standard and novel anticancer treatment interventions.

Background
Background: Detection of homozygous deletion of the 9p21 locus, the site of the CDKN2A/p16 gene, is useful in differentiating reactive mesothelial hyperplasia (RMH) from malignant pleural mesothelioma (MPM) in pleural effusion cytology, biopsy specimens, and surgical specimens. However, the cutoff value for 9p21 FISH varies. Furthermore, 9p21 FISH reveals not only homozygous deletion, but also heterozygous deletion, in MPM tissue samples, and only two studies have evaluated heterozygous deletion. The aim of this study was to establish a FISH cutoff value for 9p21 homozygous deletion and apply it to a clinical diagnosis. In addition, we investigated the significance of 9p21 heterozygous deletion in MPM.

Methods
Design: Ninety-five histopathological (49 MPM + 47 RMH) and 35 cytological (15 MPM + 20 RMH) cases were studied. Cutoff values were evaluated as mean + 3SD based on the results of RMH 9p21 FISH. The copy number of the p16 gene was analyzed in 22 MPM tissue samples and 17 RMH by real-time PCR, using RSP6 as a control gene, and samples were divided into three groups (1.0: no deletion, 0.5: one allele deletion, and 0: two allele deletions). Methylation-specific PCR (MSP) was performed in two heterozygous deletion dominant cases. Overall survival was evaluated using Kaplan-Meier survival analysis and log-rank test.

Results
Results: In MPM, 44/49 (90%) cases were homozygous deletion-positive (>10% cutoff value), and 12/49 (24%) cases were heterozygous deletion-positive (>46.6% cutoff value) by p16 FISH. None of RMH cases were deletion-positive in tissue samples. Real-time PCR was performed for 22 cases of MPM and 17 cases of RMH. The p16 copy number in RMH was 0.83-1.28 (average 1.06). In MPM, 16/22 (73%) revealed a two-allele deletion pattern for p16. Two cases of homozygous deletion-negative MPM by FISH also had no deletion pattern by real-time PCR. One case of heterozygous deletion-dominant MPM (over 55%) revealed a two-allele deletion of p16 by real-time PCR, and two cases showed a one-allele deletion of p16. These cases had no methylation by MSP. In 25 cases of MPM for which follow-up was available, the overall survival rate was significantly lower in homozygous deletion-positive MPM (21/25 cases) than homozygous deletion-negative MPM (4/25 cases) (p= 0.01).

Conclusion
Conclusion: 9p21 FISH was useful for differentiating MPM from RMH, and p16 homozygous deletion in MPM has the potential to be a prognostic factor. Moreover, a combination of p16 FISH, p16 real-time PCR and MSP is useful for discriminating heterozygous deletion from homozygous deletion in MPM. The presence of heterozygous deletion suggest the possibility of a p16-independent tumorgenesis pathway in MPM.

Background
Platinum-based combination chemotherapy is the first-line treatment for advanced non-small cell lung cancer, but tumor recurrence occurs in most of patients who have received this treatment. Recent evidences suggested existence of CD133+ cancer stem cells is the cause of drug resistance and tumor recurrence. However, there is no efficient way to eliminate CD133+ cancer stem cells. Accordingly, the goal of this study is to identify novel compounds that targeting CD133+ CSCs of non-small cell lung cancer.

Methods
A hCD133 promoter-driven GFP reporter construct was used to identify CD133+ cells. CD133+ cells were FACS sorted from H460 cell line. The stemness and drug resistance of CD133+ cells were characterized according to their sphere formation, differentiation, gene expression, and chemo-response. IC~50~ of each novel compound was determined using MTT assay.

Results
CD133+ lung cancer cells identified by a human CD133 promoter- driven GFP reporter exhibited drug resistance and expressed stem-cell characteristics. Treatment of lung cancer cells with cisplatin was sufficient to result in enrichment of CD133+ cells, to induce DNA damage responses, to up-regulate levels of ABCG2 and ABCB1 which therefore increased resistance to doxorubicin and paclitaxel. We further found that cisplatin-induced enrichment of CD133+ cells was mediated by activation of notch signaling as judge by increased levels of NICD. Pre-treatment of cells with g-secretase inhibitor, DAPT, remarkably reduced cisplatin-induced enrichment of CD133+ cells and increased the sensitivity to doxorubicin and paclitaxol. Ectopic expression of NICD reversed the function of DAPT on drug sensitivity. The similar effect was also observed in tumor-engraft experiments as cisplatin treatment significantly increased the number of CD133+ cells in tumor-engraft in nude mice. In contrast, intra-tumor injection of DAPT together cisplatin was able to significant decrease the number of CD133+ cells in the tumor-engraft of mice. To identify novel compounds that may target CSC and cancer cells, we tested the cytotoxic effect 30 synthesized small compounds. Among of these compounds, 4 compounds, NCKU-44, NCKU-291, NCKU487 and NCKU-570, effectively killed both CD133+ CSCs and parental cancer cells. Three compounds, NCKU-46, NCKU-mo and NCKU-ts, specifically targeted to CD133+ CSCs.

Conclusion
In our study, we developed a drug-screening platform of CD133+ CSC of non-small cell lung cancer. At least 7 novel compounds were identified as potential CSC-targeting agents, which could be used in the future pre-clinical trials.

Background
We previously reported that SCLC distinct characteristics by primary tumor location (central type or peripheral type) and TTF-1 expression. Peripheral type and/or TTF-1 expression were predictive factors of poor prognosis in SCLC. In this study, we examined whether or not SCLC distinct characteristics of gene expression by primary tumor location, using microarray analysis of snap frozen tissue samples.

Methods
Fourteen SCLC, diagnosed from biopsies and/or surgical materials, for which snap frozen tissue samples were available, were collected during 2004-2011 from Japanese patients. We evaluated the location of primary tumor (central or peripheral) by CT at diagnosis. Total RNAs from the snap frozen fresh tissue sample of the surgically resected SCLC (n=14, central type:3, peripheral type:11) were used to prepare cDNAs, which were hybridized to the Whole genome Human 60K Microarray chips (Agilent Technologies Inc, Tokyo, Japan). Data normalization, log transformation, statistical analysis, gene ontology (GO) analysis, and pattern study were performed with GeneSpring GX12 (Agilent Technologies Inc, Tokyo, Japan) and Ingenuity Pathway Analysis software, with the stringency of P < 0.01 and a < 2-fold change by moderated t-test corrected with Bonferroni multiple testing.

Results
There were a total of 31551 genes scored as differentially expressed between groups. A total of 833 genes were identified that differed significantly in expression: 424 genes were upregulated and 409 genes were downregulated in peripheral type compared with central type. Interestingly, upregulated gene analysis revealed that peripheral type SCLC had increased levels of neuroendocrine genes such as NCAM, Synaptophysin (SYN), Chromogranin A (CGA), Gastrin-releasing peptide (GRP), ASCL1, and TTF-1. Subsequently, GO and network analysis revealed that most of upregulated genes in peripheral group were related to neuron functions. Hierarchical cluster analysis clearly distinguished between central type and peripheral type.

Conclusion
SCLC had a distinct gene expression profile from tumor location and had higher expression of genes associated with neural function in peripheral SCLC. Defining gene expression profiles by tumor location may help elucidate distinct characteristics of SCLC between central type and peripheral type.

Background
Cancer-associated fibroblasts (CAFs) contribute to cancer progression through multiple pathways.

Methods
Here we comprehensively compared gene expression in lung cancer cells cultured with conditioned medium from lung CAFs and normal lung fibroblasts by cDNA microarray analysis.

Results
The expression of many genes was up-regulated in cancer cells by CAFs’ conditioned medium, particularly cell adhesion molecules integrins and anti-apoptotic protein Bcl-2. Additional analysis indicated that the expression of integrins seems to be upstream of that of Bcl-2. We identified transforming growth factor-β as a candidate factor that induces the expression of those genes in cancer cells. Immunohistochemical studies on clinical lung cancer tissues revealed that integrins and Bcl-2 are more highly expressed in the leading cells, but not the following cells, at the invasive front of cancer nests, which are adjacent to or in proximity to the stroma. Furthermore, the expression of integrins and Bcl-2 in the leading cells was correlated with the clinical stages of cancer progression including lymph node metastasis.

Conclusion
In conclusion, our results suggest that CAFs promote lung cancer progression partly through the direct regulation of gene expression in the leading cells of invasive cancer nests.

Background
Many early-stage NSCLCs in spite of treating with surgical resection and adjuvant therapy relapse, occur metastasis and become fatal. Therefore there is an urgent need for research the key molecular events driving lung cancer invasion and metastasis that could lead to achieve effective prevention, reliable diagnosis, preparing useful prognostic indicator and treatment. Atypical protein kinase C lambda/iota (aPKCλ/℩), Partitioning defective-3 (Par3), Partitioning defective-6 (Par6) and Drosophila Lethal giant larvae mammalian homologue (Lgl2) are implicated in cell growth and apoptosis, and the maintenance of epithelial cell polarity. Loss of apical-basal polarity in epithelial cells is one of the hallmarks of aggressive and invasive cancer. This study was designed to investigate the correlation of expression of aPKCλ/℩ and Lgl2 with the clinicopathological characteristics and prognosis of lung adenocarcinoma, and to analyze the molecular mechanisms of invasion and metastasis of the tumor.

Methods
This study included 107 patients who underwent resection of lung tumor and diagnosed as lung adenocarcinoma at the Tokai University Hospital between 2002 and 2005. The expression of aPKCλ/℩ and Lgl2 was examined by immunohistochemistry. E-cadherin-mediated cell-cell adhesion is considered a suppressor of cancer cell invasion. Low E-cadherin expression in NSCLC tumors has been reported in several studies to be associated with a more aggressive behavior of tumor cells and a worse prognosis. In this study, the colocalization of aPKCλ/℩ and E-cadherin was observed by double-immunohistochemistry. Furthermore, we also analyzed the interaction of aPKCλ/℩, Par3 and Lgl2 by immunoprecipitation-Western blot assays.

Results
Immunohistochemical analysis showed that aPKCλ/℩ and Lgl2 were expressed in lung adenocarcinoma and correlated with lymphatic invasion and metastasis. Kaplan-Meier regression analysis showed that patients with　increased aPKCλ/℩　expression had significantly shorter overall survival than those with lower aPKCλ/℩ expression. Double-immunohistochemistry showed E-cadherin decreased in highly expressed aPKCλ/℩ of tumor cells. Furthermore, immunoprecipitation-Western blot assays showed that aPKCλ/℩-Lgl2-Par6 complex and　aPKCλ/℩-Par3-Par6 complex increased in lung adenocarcinoma tissue.

Conclusion
These results suggested that aberrant formation of both aPKCλ/℩-Lgl2-Par6 complex and aPKCλ/℩-Par3-Par6 complex could induce lung cancer progression by loss of cell-cell adhesion in lung adenocarcinoma.

Background
Acute inflammation is usually a rapid and self-limiting process, however it does not always resolve. This leads to the establishment of a chronic inflammatory state and provides the perfect environment for the transformation process. It has been estimated that approximately 25% of all malignancies are initiated or exacerbated by inflammation caused by infectious agents. Furthermore, inflammation is linked to all of the six hallmarks of cancer (evasion of apoptosis, insensitivity to anti-growth signals, unlimited replicative potential, angiogenesis, increase in survival factors and invasion and metastasis). It is thought that inflammation may play a critical role in lung carcinogenesis given that individuals with inflammatory lung conditions have an increased risk of lung cancer development. This study focuses on inflammation as a contributory factor in non small cell lung cancer (NSCLC), concentrating primarily on the pathological involvement of the pro-inflammatory cytokines, TNF-α, IL-1β, and hypoxia.

Methods
A normal bronchial epithelial cell line (HBEC4) was modified to stably and functionally over-express TNF-α and IL-1β (alone or in combination) and were continuously cultured for three months under normoxic or hypoxic (Invivo~2~ Hypoxia Workstation - 0.5% oxygen) conditions. Subsequently a range of experimental assays were carried out to assess functional cell change. These included: transformation assay (soft agar), proliferation (BrdU ELISA), invasion (Cell Invasion assay), migration (Scratch assay) and angiogenesis (Endothelial tube formation). Gene expression changes were also assessed using qPCR Cancer PathwayFinder arrays.

Results
Although transformation was not evident by soft agar, the adhesion potential (ICAM and VCAM levels) of normoxic and hypoxic clones has amplified and the growth rate has increased over time. Under normoxia the IL-1β and the TNF-α/IL-1β clones displayed an increased invasive capacity compared with the empty vector control (p<0.05). Differences were also detected in the gene expression profile implicated in the pathways involved in the hallmarks of cancer - cell signalling (FOS, JUN), apoptosis (BAD, BAX, BCL2), angiogenesis (CXCL8), adhesion (ITGB3), invasion (S100A4, TIMP1) and cell cycle regulation (p53, c-myc). A number of these targets are currently undergoing validation.

Conclusion
This study provides a valuable isogenic cell line model in which to study the effect of prolonged chronic inflammation. Although the cells have not developed anchorage independent growth as assessed by soft agar, there are distinct indications that phenotypic changes occurred within the three month time frame. As pro-longed chronic exposure to inflammation is a pre-requisite for many disease states, these results warrant extended growth studies to further delineate the complex roles of TNF-α, IL-1β and hypoxia in the process of carcinogenesis. This will assist in the development of novel cancer target therapeutics and chemo-preventive agents in lung cancer.

Background
IL-23A is a member of the IL-6 super-family and is composed of covalently bound IL-12p40 and IL-23p19 (IL-23A) subunits. The functional IL-23R is composed of the IL-23R and IL-12Rβ1 subunits and once activated can promote the STAT3 signalling pathway. IL-23A plays a key role in chronic inflammation through the promotion of IL-17 production by T helper 17 cells (Th 17). Stimulation of IL-23A associated pathways produces pro and anti oncogenic effects which are cell type dependant. We have previously identified IL-23A axis as deregulated in NSCLC and sought to examine the family in greater detail.

Methods
The expression of IL-23A/IL-23R was examined in a series of resected fresh frozen NSCLC tumours and in a panel of normal (HBEC) and NSCLC cell lines. Epigenetic regulation of IL-23A/IL-23R was determined in NSCLC cell lines using histone deacetylase (HDi) and DNA methyltransferase (DNMTi) inhibitors. A ChIP assay was performed to investigate the direct effect of Trichostatin A (TSA) on the IL-23A/IL-23R promoter regions. Additionally, the effect of Gemcitabine on IL-23A/IL-23R expression was examined. Finally, the effect of recombinant IL-23 treatment and Apilimod (STA 5326) (a small molecule which blocks the expression of IL-23 and IL-12) on NSCLC cell line proliferation was examined. IL-23 expression was also studied in a panel of NSCLC cisplatin sensitive and resistant cell lines. Furthermore due to its role in immune regulation, we are currently studying the effect of IL-23 on innate immune cell function.

Results
IL-23A expression was significantly elevated in a cohort of NSCLC patient tumour samples (p<0.05). Differential IL-23R expression was evident in a panel of NSCLC normal/tumour matched pairs (n=20), with no expression in 25%, reduced levels in 20% and increased levels in 55% of tumour samples compared with matched normal. In addition, IL-23A/IL-23R was found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation in the A549 cell line (p<0.05), with associated chromatin remodelling at both promoters. Gemcitabine, also induced IL-23A/IL-23R expression in this cell line (p<0.05). Furthermore, treatment with recombinant IL-23 resulted in increased cellular proliferation in the A549 cell line, while Apilimod reduced cellular proliferation. Preliminary results indicate that IL-23 can potentially affect the function of innate γδ T cells. In a panel of cisplatin resistant and sensitive cell lines, IL-23A was up-regulated in 3/5 resistant cell lines. Work is ongoing to assess the IL-23R expression in CisR and Parent cells lines and the effect of co-treating cells with HDi and Apilimod and to determine whether these compounds can re-sensitise cells to cisplatin therapy.

Conclusion
Based on our results the IL-23A/IL-23R axis is dysregulated in NSCLC. The IL-23 family is subject to epigenetic regulation through HDAC modifications and CpG island methylation. Gemcitabine treatment also affected the expression of this family. Recombinant IL-23 was pro-proliferative in NSCLC and blocking IL-23 with Apilimod reduced the proliferative capacity of the cells. Levels of IL-23A are differentially expressed between cisplatin sensitive and resistant cell lines. Apilimod may be a novel therapeutic drug in the treatment of NSCLC.

Background
Pequi (Caryocar brasiliense Camb) is a Brazilian fruit that has high concentrations of antioxidants, such as vitamin C and E, carotenoids, phenolic compounds and essential oils. Consumption of foods high in antioxidants, particularly carotenoids and phenolic compounds have been associated in the prevention of oxidative damage caused by reactive species (ROS), including DNA damage, and can reduce the risk of cancer, atherosclerosis and other degenerative diseases. The aim of this study was to estimate the antioxidant enzyme activity of catalase, superoxide dismutase and glutathione peroxidase and to evaluate the antioxidant activity of the pequi oil, measuring lipid peroxidation, DNA damage and nitric oxid synthases expression.

Methods
The study was performed in 40 male BALB/c mices: 35 animals were submitted to two doses of 1,5g/kg intraperitoneal of urethane (U=5), 10 of these mices received by gavage 15μL of pequi pulp oil (U+O), 10 animals received by gavage 15μL of ethanolic extract of pequi pulp (U+E=10) and the other 10 animals received by gavage 3μg/kg of betacarotene (U+B). 5 mices didn’t receive the urethane doses neither the gavage (C=5). After 60 days, the groups were sacrificed. The enzymatic antioxidant defense was measured by biochemical test. The antioxidant activity of pequi oil was evaluated in the lung tissues by the biochemical TBARS test (Thiobarbituric acid-reactive substances) and the DNA damage by the comet test method. Nitric Synthase expression was analyzed by imunohistochemestry.

Results
The lung parenchyma from the Urethane groups that received and didn’t receive gavage, showed neoplasic formations induced by the chemical carcinogenesis in contrast with control group (C). The results of the TBARS test showed a significant decreased of the lipid peroxidation in the groups that were treated by gavage (U+O)(U+E)(U+B), when compared with Urethane group (U) (p<0,05). In the same way, the image analysis of the comet assay showed a statistical significant decreased of the DNA damage cells in the groups that received treatment by gavage (U+O)(U+E)(U+B) when compared with urethane group (p<0.001). The nitric oxid synthases expression was higher in the urethane group (U), but showed a significant decrease in groups that received the gavage (p<0,05). The catalase, glutathione peroxidase and superoxide dismutase test, as well as the ratio between then, didn’t show a significant difference.

Conclusion
We conclude that because of its composition, high in antioxidants, pequi fruit is efficient to diminish the oxidative stress status (DNA damage and lipid peroxidation) and the nitric oxid synthases expression in chemical carcinogenesis induced by urethane. Our results also suggest that the antioxidant enzyme defense are not envolved in this process, suggesting that antioxidants present in pequi fruit may have a greater impact in lung cancer treatment.

Background
Lung adenocarcinomas can be classified into two major subtypes, terminal respiratory unit (TRU) type and non-TRU type. We previously reported that non-TRU type adenocarcinoma has unique clinical and morphological features compared with TRU type adenocarcinoma. In brief, among 36 cases of non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF-1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma. We investigated whether microRNA (miRNA) expression profiles can differentiate between non-TRU type and TRU type lung adenocarcinoma.

Methods
MiRNA expression in lung adenocarcinoma with non-TRU and TRU type was analyzed by microarray analysis with 1205 human and 144 human viral miRNAs.

Results
Eight pairs of lung adenocarcinomas and corresponding noncancerous lung tissues (4 for non-TRU type and 4 for TRU type) were analyzed by microarray analysis. Initially, 44 miRNAs showed statistical differences in expression between lung cancer tissues and corresponding noncancerous tissues. Comparison analyses between non-TRU type and TRU type revealed 30 miRNAs with statistically different expression. Particularly, hsa-mir-494 and ebv-mir-BART19 were upregulated with more than 5-fold difference as compared with TRU type adenocarcinoma. Similarly, hsa-mir-551b was downregulated at more than 4-fold as compared with TRU type adenocarcinoma. Only 2 miRNAs (hsa-mir-1 and hsa-mir-133b) were shared in both non-TRU and TRU type of adenocarcinoma.

Conclusion
We demonstrated that non-TRU type adenocarcinoma showed different miRNAs expression patterns compared with TRU type adenocarcinoma, suggesting different carcinogenic pathways for these tumors. Further studies are required for validation the results from microarray analysis.

Background
Cancer stem-like cells (CSCs) / Cancer-initiating cells (CICs) have been described as a small population that have (i) tumor initiating ability, (ii) differentiation ability and (iii) self-renewal ability and regarded as major causes of cancer recurrence, distant metastasis and treatment resistance. CSCs/CICs have been thought to have similar molecular mechanisms to normal stem cells and keep undifferentiated state. And we thought that Lung CSCs/CICs constantly exchange the state of differentiation and dedifferentiation. Previously we showed that SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma cell lines. And so, we think SOX2 is important for the sustention of CSCs/CICs. In this study, we examined the differentiation and dedifferentiation of Lung CSCs/CICs in single-cell level and investigated the regulation of SOX2 expression in Lung CSCs/CICs.

Methods
Lung adenocarcinoma cell lines LHK2 were stained with Hoechst33342 dye and CSCs/CICs were isolated as Side population (SP) cells and non-CSCs/CICs were isolated as Main population (MP) cells using a FACS Aria II cell sorter. Many single cell clones (SP clones, MP clones) were established from SP cells and MP cells respectively. SOX2 expression was addressed by qPCR. LHK2 were treated with HDAC inhibitor Trichostatin A (TSA).

Results
SP cells and MP cells were generated from each SP clones and MP clones. The SOX2 expression of SP clones were higher than that of MP clones. TSA treatment enhanced the expression of SOX2 and increased the rate of SP cells.

Conclusion
It was indicated that the differentiated Lung carcinoma fractions were dedifferentiated into CSCs/CICs and SOX2 expression was important for the mechanisms. It was considered that the differentiation and dedifferentiation occurred with comparative ease in Lung carcinoma, so we thought that the mechanisms related to the epigenetic regulation. In this study, it was indicated that SOX2 expression in Lung cancer cells were regulated by histone acetylation. Therefore, Lung CSCs/CICs phenotype might be regulated by epigenetic mechanisms.

Background
The MAGE-A3 and PRAME tumor antigens are potential targets for cancer immunotherapy. In patients with non-small cell lung cancer (NSCLC), specific mutations of the epidermal growth factor receptor (EGFR) gene are associated with improved therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs); mutations in the KRAS gene confer resistance to EGFR-TKIs. In NSCLC, EGFR and KRAS mutations are predominantly found in adenocarcinomas. The relationship between MAGE-A3 or PRAME expression and EGFR/KRAS mutational status is unknown. The presence of specific EGFR mutations determines the selection of patients for EGFR-TKIs therapy. With cancer immunotherapeutics and EGFR-TKIs potentially moving on to the same treatment stages, it is important to determine whether patients eligible for EGFR-TKI therapies might be also eligible for treatment with MAGE-A3 or PRAME cancer immunotherapeutics. We have previously reported that MAGE-A3 and PRAME were expressed in 36% and 66% of NSCLC tumor samples, and in 27% and 44% of adenocarcinoma samples, respectively (Linder et al. ASCO 2012). Here we report the MAGE-A3 and PRAME expression rates and mutational status of EGFR and KRAS in NSCLC adenocarcinoma.

Methods
This was a single-center, non-interventional, retrospective study conducted at the Lungenklinik Hemer (Germany). MAGE-A3 and PRAME mRNA expression patterns in patients with pathologically proven stage I, II or III NSCLC were determined by quantitative real-time PCR on formalin-fixed paraffin-embedded (FFPE) tumor samples. EGFR and KRAS mutational status was analyzed on DNA extracted from FFPE samples using laboratory-developed PCR-based assays. Samples from patients with adenocarcinoma i.e. adenocarcinoma, bronchoalveolar adenocarcinoma, adenosquamous carcinoma, for which MAGE-A3 and/or PRAME expression results were available were selected for this analysis.

Results
Out of 311 samples, 277 and 287 produced valid results for EGFR and KRAS mutational status, respectively. EGFR mutations were found in 10.1%, and KRAS mutations in 33.8% of samples. The association between MAGE-A3 or PRAME expression and EGFR mutational status is shown (table). Figure 1 EGFR mutational status was not associated with MAGE-A3 expression but was significantly associated with PRAME expression (table). There was no association between KRAS mutational status and MAGE-A3 (P=0.6109) or PRAME (P=0.8983) expression.

Conclusion
In this study, tumor samples expressing PRAME tended to be associated with wild-type EGFR status. Thus, among patients with PRAME-positive tumors, only very few would be eligible for EGFR-TKI therapy. This indicates a potentially straightforward treatment choice for patients and physicians, should EGFR-TKIs and PRAME cancer immunotherapeutics become available for similar indications. Funding: GlaxoSmithKline Biologicals SA.

Background
Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality in the Western world with a poor overall 5 year survival of <15%. The most effective systemic chemotherapy for NSCLC is cisplatin-based combination treatment. However, chemoresistance is a major therapeutic problem and understanding the mechanisms involved is critical to the development of new therapeutic intervention strategies. The PI3K pathway plays an important role in NSCLC and we and others have shown increased PI3K signaling to be associated with a more aggressive disease with poor prognosis. Several proteins in this pathway have been indicated as potential mediators of cisplatin resistance in other cancers, and our group has previously identified the PI3K-activated transcription factor NFκB as a key player in this setting. In this study, targeted inhibition of three strategic points of the PI3K pathway was carried out with the aim of overcoming acquired resistance to cisplatin in these cell lines.

Methods
A panel of cisplatin resistant cell lines was previously generated in our laboratory through prolonged exposure to the drug. Expression of PI3K pathway related genes was compared between H460 parent (H460PT) and H460 cisplatin resistant (H460CR) cells using a PI3K pathway SABiosciences RTPCR array. Identified genes of interested were further investigated via PCR and Western blot in these cells as well as A549 parent (A549PT) and A549 cisplatin resistant (A549CR) cells. Three strategic points of the pathway were inhibited using GDC-0980, a dual PI3K-mTOR inhibitor currently in Phase II clinical trials in NSCLC, and DHMEQ, an inhibitor of NFkB translocation which has been used extensively both in vitro and in vivo. Effects of the two inhibitors on the parent & cisplatin resistant cell lines both with and without cisplatin were assessed by BrdU proliferation assay and multiparameter apoptosis assay (High Content Analysis).

Results
One of the most notable targets to emerge from the PI3K pathway RTPCR array screen was NFKBIA; the gene which codes for NFκB inhibitor IκBα. This gene was shown to be 12 fold overexpressed in H460CR compared to H460PT. This finding was validated at both the RNA and protein level by PCR and Western blot. NFκB was also found to be overexpressed in cisplatin resistant cells compared to their respective parent cells. Inhibition of NFκB by DHMEQ led to significantly improved inhibition of proliferation and induction of apoptosis in cisplatin resistant cells compared to parent cells. Preliminary data indicates that inhibition of PI3K and mTOR by GDC-0980 did not offer as significant a benefit as inhibition of NFκB in the cisplatin resistance setting, though further data from combination studies will be presented.

Conclusion
We conclude that the PI3K pathway plays an important role in resistance to cisplatin in NSCLC, particularly when signaling proceeds through the transcription factor NFκB. Targeting this pathway may be of benefit in re-sensitizing cisplatin resistant tumours to the drug.

Background
The MAGE-A3 tumor antigen is expressed in non-small cell lung cancer (NSCLC), and is a potential target for cancer immunotherapy. NSCLC patients may also have specific epidermal growth factor receptor (EGFR) gene mutations, which are responsible for sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in metastatic NSCLC patients. In Asian populations, a relatively low MAGE-A3 expression (Therasse et al. ASCO 2012) and a relatively high frequency of EGFR mutations (An et al. 2012) have been reported compared to Caucasian populations. Three phase III studies, one with MAGE-A3 cancer immunotherapeutic and two with EGFR-TKIs, are ongoing in patients with early-stage, resected NSCLC. However, to date, a direct association between MAGE-A3 expression pattern and EGFR mutational status has not been investigated. Here, we evaluate a potential link between MAGE-A3 expression and frequency of EGFR mutations in Chinese NSCLC patients.

Methods
This single-center, non-interventional, retrospective study was conducted at Guandong Lung Cancer Institute, China. Adenocarcinoma and squamous cell carcinoma (SCC) fresh frozen (FF) stage IB, II or IIIA NSCLC tumor samples were collected. MAGE-A3 transcript levels were determined using quantitative real-time PCR. The presence of EGFR mutations was detected using bidirectional Sanger sequencing on genomic DNA extracted from the same FF tumor samples.

Results
MAGE-A3 was expressed in 15.6% of adenocarcinoma (N=96) and 31.6% of SCC (N=95) samples. EGFR mutations were found in 43.8% of adenocarcinoma and 5.3% of SCC samples. MAGE-A3 expression rates and EGFR mutational status are shown (table). Figure 1

Conclusion
In this study, mutated EGFR status was observed in more than half of MAGE-A3-positive adenocarcinoma samples. However, due to a small number of samples analyzed, no statistical association could be concluded. Additional larger studies, especially in Asian patients with adenocarcinoma, are needed to confirm the findings. This study was funded by GlaxoSmithKline Biologicals SA.

Background
The new lifestyle adaptations in the developing countries altered the environment and these contribute in the development of various respiratory diseases like asthma, COPD, etc. Though it is well known that COPD may lead to development of lung cancer, the effect of asthma on lung cancer development is not well studied. Lung cancer is a leading cause of mortality worldwide as more than a million people die every year. Few recent meta-analytic studies showed a positive correlation between asthma and lung cancer. But, there are no reports to demonstrate the status of DNA damage in asthma.

Methods
8-hydroxydeoxyguanosine, DNA damage marker, was measured in BAL fluids and sera samples of human asthmatics. To see the gene expression related to DNA damage response, we performed the quantitative Real Time PCR array in human normal and asthmatic lungs. Significantly altered genes were validated at mRNA as well as in protein levels by using western blotting and immunohistochemistry.

Results
Increased levels of 8-hydroxydeoxyguanosine was observed in BAL fluids and sera of human asthmatics. Human and murine asthmatic lungs show an increase in the expression of 8-hydroxy-2'-deoxyguanosine. In comparison to normal, human asthmatics showed a decrease in the expression of key DNA damage response proteins like gamma-H2AX, Atm, chk2, Mre11 and DNA-pkcs.

Conclusion
For the first time, we have shown that there may be defective DNA damage response in asthmatics which might link asthma to lung cancer. As various meta-analysis studies indicate a positive correlation between asthma and lung cancer, it is necessary to delineate the mechanisms underlying this.

Background
Epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show incredible response rate up to around 80 % to non-small cell lung cancer patients with EGFR sensitive mutations, and also contribute to improve overall survival time of such patients. However, it is no doubt that almost all patients have recurrences in time. Some genetic aberrant changes such as the secondary mutation T790M in exon 20 of EGFR are known to have influence on drug resistance, but most mechanisms of drug resistance are still unclear. Recently, Some studies suggested that heterogeneous distribution of EGFR mutations seemed to have correlations with treatment failure of EGFR-TKIs, but others reported that heterogeneity was extremely rare. Heterogeneity of EGFR is still remains to be controversial. In this study, we reported one rare case that resected lung after chemotherapy with gefitinib showed heterogeneous distribution of L858R point mutations and it’s correlation with effects of EGFR-TKIs.

Methods
A 68-year-old woman was diagnosed as lung adenocarcinoma (T3N1M0 stageⅢa) with the L858R point mutation. Unilateral Pulmonary Artery Occlusion test before operation showed a high probability that patient’s oxygenation would decrease to near the tolerance limit by right peumonectomy. For the purpose of reducing the tumor volume to avoid the pneumonectomy, she received gefinitib (250mg/body/day) as neo-adjuvant chemotherapy for three months and succeeded. Continuously, she underwent right middle and lower lobectomy and lymph node dissection (ND2a). Pathological examinations of resected lung specimens were done using H&E staining and immunohistochemistry with L858R Mutant Specific Rabbit monoclonal antibody for EGF Receptor. Two different tissue parts were respectively macrodissected from Formalin-Fixed Paraffin-Embedded tissue slides and analyzed genetically by direct sequencing analysis.

Results
H&E and immunohistochemical staining specimens showed that this resected identical tumor was divided into two areas. One area consisted of necrotizing and degenerating cell population and was stained with L858R specific antibody. The other area consisted of viable cell population with relatively low nuclear grade and was not stained with L858R specific antibody. Additionally, direct sequencing analysis of each extracted DNA from these two different areas revealed that the former area contained only wild type base sequence in exon 21 of EGFR, but the latter contained a mixture of point mutation of L858R and wild type base sequence in exon21. Secondary T790M mutations were not detected in both areas. The result of direct sequencing analysis supported heterogeneous distribution of L858R point mutations which was found on immunohistchemical staining. Comparing with pathological finding of HE staining, it was implied that therapeutic effect of gefitinib was limited only to the tissue area having L858R point mutation and cells of non-mutated tissue area survived.

Conclusion
This study suggested that there may be intratumoral heterogeneity of EGFR mutation and therapeutic effect of EGFR-TKIs could be limited only to mutant cells. As a result, wild-type cells would survive and develop drug resistance against EGFR-TKIs, even if tumors had no secondary T790M mutations in exon 20 of EGFR.

Background
Somatostatin receptors (SSTRs) have been shown to be overexpressed in 80-90% of all neuroendocrine tumors, including SCLCs. Previous reports have shown that SSTR2 activation modulates cell proliferation by acting through the ERK signaling cascade. We hypothesized that down regulation of SSTR2 will inhibit cell proliferation in lung cancer cell lines that overexpresses this receptor.

Methods
SSTR2 expression was assessed by western blot analysis in 28 lung cancer cell lines. H520 (SCC) and H727 (Carcinoid) were used as an in vitro model for studying the effects of targeted down-regulation of SSTR2 by shRNA. Several SSTR2 null-colonies of these cell lines were generated by antibiotic selection. Cell proliferation was measured at four different time points using MTS metabolic assay. In addition, we evaluated the effect of SSTR2 down regulation in colony formation potential of our lung cancer cell lines.

Results
Western blot analysis of 28 lung cancer cell lines showed expression of SSTR2 in 17/18 (94%) of SCLCs including carcinoids, 3/6 (50%) of NSCLCs, and 0/4 (0%) of non-immortalized human bronchial cells. Post transfection analysis by western blot revealed a significant decrease in SSTR2 protein expression in multiple SSTR2 null-colonies. We observed a 37% decrease in cell growth in H520 and a 38% decrease in H727 by day 6 with p values of 0.007 and 0.002 respectively. In addition, down regulation of SSTR2 resulted in reduction in the number of colonies formed by both cell lines.

Conclusion
These results demonstrate that that knocking down SSTR2 in lung cancer cells induces a marked decrease in cell proliferation. Ongoing studies are focused on understanding the effect of knocking down SSTR2 on oncogenic traits of lung cancer cells including cell survival, apoptosis, migration and invasion and the cellular mechanisms underpinning our original observation.

Background
The present study investigated adenosine-induced apoptosis in human malignant pleural mesothelioma cells.

Methods
MTT assay, TUNEL staining, flow cytometry using propidium iodide and annexin V-FITC, real-time RT-PCR, Western blotting, and assay of caspase-3, -8, and -9 activities were carried out using malignant pleural mesothelioma cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells, and P53 or A3 adenosine receptor was knocked-down by transfecting each siRNA into cells.

Results
Adenosine induced apoptosis in all the malignant pleural mesothelioma cells used here, independently of caspase activation. The adenosine effect was prevented by the adenosine transporter inhibitor dipyridamole, the adenosine kinase inhibitor ABT-702, or the A3 adenosine receptor inhibitor MRS1191. Adenosine upregulated expression of the p53 mRNA and protein, that is abolished by ABT-702, but not by knocking-down A3 adenosine receptor. Adenosine-induced apoptosis in NCI-H28 cells was significantly inhibited by knocking-down p53 and in part by knocking-down A3 adenosine receptor.

Conclusion
The results of the present study show that AMP converted from intracellularly transported adenosine upregulates p53 expression to induce caspase-independent apoptosis in malignant pleural mesothelioma cells and that A3 adenosine receptor also participates partially in the apoptosis by the different mechanism.

Background
Microvasculature and microenvironment play important roles in proliferation, invasion, metastasis and prognosis in non-small cell lung cancer (NSCLC), which might be altered by many anti-angiogenic drugs. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors, such as endothelial growth factor (VEGF) and angiopoietins (ANGs). Hypothesizing that EGCG might regulate microvasculature and microenvironment in NSCLC, the effects of EGCG on microvessel density (MVD), expression of Ang-1 and Ang-2, interstitial fluid pressure (IFP), tumor hypoxia, and chemotherapy sensitivity were examined.

Methods
Build nude mice xenograft tumor model(A549 cell line). Treat them with EGCG(i.p.), Counting MVD labeled by CD31, observing Ang-1 and Ang-2 expressions detected by quantum dots double-label immunofluorescence assessment. interstitial fluid pressure (IFP) was measured by the Wink-in-needle method, while hypoxia was assessed by polarographic electrode and pimonidazole (PIMO) immunohistochemistry. Assuming that these changes would increase response to chemotherapy, tumor growth studies were performed in nude mice with xenografts, which were then treated with EGCG and the chemotherapeutic agent.

Results
EGCG treatment led to a significant decrease of MVD, and of Ang-2 expression, while Ang-1 decreased with no significance. Both IFP and hypoxia were decreased. Tumor growth studies show that EGCG therapy combined with cisplatin led to synergistic inhibition of tumor growth, compared with administration of each treatment separately (P < 0.001). According to linear regression analysis, IFP was positively correlated with PIMO staining (R2 = 0.618, P = 0.002), Ang-2 was correlated with MVD (R2 = 0.423, P = 0.022), IFP (R2 = 0.663, P = 0.01) and PIMO staining (R2 = 0.694, P = 0.01).

Conclusion
IFP and delivery of oxygen might be improved by rebalance of Ang-1/Ang-2 under the treatment of EGCG in NSCLC, which also acts as a sensitizer of chemotherapy. These studies established a new mechanism for using EGCG as an adjuvant chemotherapy agent through modifying microvasculature and microenvironment.

Background
Lung cancer remains the most common cause of cancer-related death in the world for which novel systemic treatments are urgently needed. Protein homeostasis that regulates protein levels and their fold is critical for cancer cell proliferation and survival. A complex network of cellular organelles and signaling cascades is involved in control of protein homeostasis including endoplasmatic reticulum (ER). Thus, proteins in control of ER homeostasis are increasingly recognized as potential therapeutic targets. Molecular chaperone heat shock protein 90 (Hsp90) and histone deacetylase (HDAC) play an important role in ER homeostasis. Previous studies demonstrate that Hsp90 and HDAC inhibitors are individually functional against lung cancer. In this work we suggested that combined Hsp90 and HDAC inhibitors may elevate ER stress thereby enhancing the anti non small lung cancer (NSCLC) activity.

Methods
NSCLC cell lines (A549, H1299, H460) were treated with 17-DMAG (Hsp90 inhibitor), PTACH (HDAC inhibitor) and both drugs simultaneously for 24 hours. Cells were harvested and analyzed for ER stress markers (Immunoblot), viability (WST1 assay), motility (Scratch assay), and death (Flow cytometer).

Results
Using an in vitro cell line model we demonstrated that 17-DMAG co-administration with PTACH caused elevated ER stress (more than 110%, p<0.05) accompanied by apoptotic cell death (Annexin V) (7-21%, p<0.05). Moreover, 17-DMAG/PTACH treated cells lost the ability to migrate (57-85% of scratch closure, p<0.05).

Conclusion
Our findings provide proof-of-concept that targeting ER homeostasis is therapeutically beneficial in lung cancer cell lines. Indeed, the elevated ER stress caused by 17-DMAG/PTACH combined treatment leads to increased cell death of NSCLC cell lines compared to the application of the drugs separately.

Background
To evaluate and compare quantitatively aberrant methylation in the promoter area of EGFR gene in patients (p) with in non small cell lung cancer (NSCLC) lung tumor tissue (TT), lung normal tissue (NT), blood (B), bronchial aspirate (BA) and sputum (S). Correlate these methylation patterns with clinical variables.

Methods
DNA was extracted from samples of B, S and BA from patients with NSCLC prior to surgery and resected TT and NT. Methylation patterns were analyzed by the bisulfite conversion and subsequent pyrosequencing (QIagen PyroMark System). We analyzed three CpG islands in the promoter region of EGFR gene.

Results
43p were included, median age 66 years (range 46-79), 35 men and 8 women. Histology: 26p adenocarcinoma, 14 squamous and 3 others. 2p had EGFR mutation. Smoking status: 4p never smokers, 21p former smokers, 18p smokers. Significant differences in methylation percentage (%Mth) were observed between TT and S in the following islands: CpG2 (11.8vs7.1, p = 0.008), CpG3 (10vs7.4, p = 0.037) and in overall promoter area (10.6vs7. 6, p = 0.034). The %Mth was higher in women vs men in TT CpG1 island (16.2vs24.9, p = 0.042) and TT CpG2 island (15.8vs26.5, p = 0.013). The %Mth was higher in squamous histology compared to adenocarcinoma in NT CpG2 island (22.6vs14.1, p = 0.017) and S CpG1 island (13.7vs8.2, p = 0.047). However, the %Mth was higher in the overall promoter area of adenocarcinoma respect to squamous histology (19.7vs12.8 TT, p = 0.042). The %Mth was higher in overall promoter area of NT respect Stage I vs II vs III (22.3 vs 13 vs 17.5, p = 0.03). The %Mth was higher in former smokers compared to current smokers and non smokers in NT CpG3 (22.8 vs 13 vs 14.1, p = 0.032). The %Mth in NT CpG3 was higher in never smokers and former smokers > 5 years, respect to current smokers and former smokers <5 years, (23.3 vs 15.8, p = 0.05).

Conclusion
EGFR aberrant hypermethylation was higher in tumor tissue respect to sputum, with no correlation with EGFR mutation. The %Mth in normal tissue was higher in never smoker and former smokers > 5 years patients. * This study was funded by the Carlos III Health Institute (PS09/00308), Spain

Background
Four neuroendocrine subtypes are distinguishable which differ in the extent of differentiation and grade of biological aggressiveness. Therefore the differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. However, for pathologists it is often a challenge to establish a faithful differential diagnosis with an accurate prognosis which is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts. Thus we investigated two types of miRNAs as an additional tool for differential diagnosis and possible molecular targets.

Methods
A collective of 38 patients suffering from well to poorly differentiated neuroendocrine lung tumours were examined. Two different miRNAs (miR-21, miR-34a) were investigated in four distinct subtypes of pulmonary neuroendocrine tumours by comparative gene expression analysis.

Results
miRNA 21 was upregulated in G3-neuroendocrine tumors (Mean rank: 26.8; 28.75) as compared to carcinoids (mean rank: 12.33; 12.07) with a significance of 0.00033. High-expression level of miRNA 34a was associated with atypical carcinoids (p = 0.010).

Conclusion
miRNAs are suitable candidates for differential neuroendocrine lung cancer diagnosis. A close association is implicated between the elevated miR-21 in high-grade and miR-34a in low grade atypical neuroendocrine lung carcinomas which could potentially be exploited as practical supportive markers for differential lung cancer diagnosis in routine. However, some additional research and validation studies are needed to utilize them as routine markers or potential molecular targets for personalized medicine.

Background
Molecular targeted therapy based on TKIs, directed at the Epidural growth factor receptor (EGFR) is one of the recent option for the management of advanced Non-Small Cell Lung Cancer (NSCLCs). EGFR gene mutations, exon 19 deletions (E19 del (LREA deletions)) and exon 21(L858R) are most common and good predictions of response to EGFR-TKI treatment. EGFR gene mutations are found in approx. 10% of Caucasian patients and up to 50% of Asian populations[(1)] .Recent studies have endorsed these incidences in European and Asian populations. The frequency of EGFR mutation is higher in non-smokers and in women[(2,3) ].The aim of the study was to determine the frequency of EGFR gene mutation in advanced non small cell lung cancer patients presenting to SKMCH & RC.

Methods
Between Sep 2011 to Sep 2012, we have sent EGFR Mutation testing for 15 patients with proven histology of TTF-1 positive adenocarcinoma lung. EGFR gene mutations in exons 18, 19,20 and 21 were carried out by National University Hospital Singapore and Singapore General Hospital. Data was collected and analysed. Frequencies were determined.

Results
10 (66.6 %) patients were male and 5 (33.3 %) were females. Eight (53.3 %) were smokers and 7 (46.6 %) were non smokers.Three (20 %) patients were having EGFR mutation +ve . One with +ve mutation on exon 19, one with +ve mutation on exon 21 and one with +ve EGFR mutation on exon 20. Two of these three( 66.6%) patients were smoker and one ( 33.3%)out of them was non smoker. All three patients were male. One (6.6%) patient has insufficient biopsy material to carry out the test. While 8 (53.3 %) patients have –ve EGFR mutation on all exons and 3 (20%) patients have unsatisfactory results on few exons and –ve mutation on other exons.

Conclusion
The frequency of EGFR mutation in our institution was 20 % and all these patients were male, two third patients were smokers. This trend is not in accordance with literature, needs more number of patients to find out the real trend.

Background
MED12 negatively regulates TGF-b receptor signaling. Loss of MED12 induces an EMT-like phenotype associated with chemotherapy resistance. IDO and IL6 activate the JAK2/STAT3 signaling pathway, which – together with NFkB (RelA) signaling – is often altered in lung cancer. BIM could influence response to chemotherapy. We have examined these components and KRAS mutations in NSCLC tumor samples and correlated results with progression-free survival (PFS).

Methods
The mRNA expression of MED12, IDO, JAK2, STAT3, RelA and BIM was examined in microdissected tumor samples from p with stage IV NSCLC. mRNA levels were assessed by RT-PCR and categorized by terciles (high vs low/intermediate). KRAS mutations were assessed by high resolution melting.

Results
A total of 55 p with performance status (PS) 0-1, treated with platinum plus either gemcitabine or pemetrexed: median age, 62 years; 27.6% females; 84.2% smokers; 66% adenocarcinoma; 16% with KRAS mutations. There was no correlation between gene expression levels and KRAS mutation status. In the multivariate analysis, including gene expression levels, histology and PS, only MED12 and STAT3 were associated with PFS (low MED12: HR=11.6, P=0.005; high STAT3: HR=6.5, P=0.01). HR for low BIM expression was 2.4 (P=0.16). None of the markers were associated with overall survival.

Conclusion
To the best of our knowledge, this is the first time that low expression of MED12 with significantly shorter PFS in NSCLC p receiving platinum-based chemotherapy. MED12 could be a new biomarker of chemoresistance and inhibition of TGF-bR signaling can restore chemotherapy response in patients with low MED12.

Background
Adenocarcinoma in situ (AIS) of the lung shows a very favorable prognosis, with a 5-year survival rate of 100%. However, early but invasive adenocarcinoma (eIA) sometimes has a fatal outcome. In order to elucidate the key molecule that affects the malignant progression of adenocarcinoma at an early stage, we previously compared the expression profiles of AIS with those of eIA, and found that stratifin (SFN, 14-3-3 sigma) is one of the differentially expressed genes related to tumor progression (Aya Shiba-Ishii, IJC. 2011). Immunohistochemistry (IHC) with anti-SFN antibody revealed that more than 95% of eIAs were SFN-positive, in comparison with only 13% of AISs. We also found that promoter demethylation triggered aberrant SFN overexpression in eIAs (Aya Shiba-Ishii, AJP. 2012). Here, we performed functional analysis of SFN and identification of SFN binding protein (SBP) to clarify how SFN affects the progression of lung adenocarcinoma.

Methods
For in vitro functional analysis, we performed RNA interference and expression vector transfection analyses and subsequent cell proliferation assays or cell cycle phase assay using a lung adenocarcinoma cell line (A549). An in vivo animal study was also performed using siSFN-transfected A549. Additionally, in order to identify SBP, SFN vector-transfected A549 was subjected to pull-down assay and subsequent LC-MS analysis. Interaction of SFN and SBP was examined using co-IP and western western blotting.

Results
Suppression of SFN expression by siSFN significantly reduced cell proliferation activity and the S-phase subpopulation. Transfection of the SFN expression vector led to a significant increase in cell proliferation. A549 treated with siSFN showed reduced tumor development relative to the controls. Pull-down assay and LC-MS analysis revealed that SKP1 is one of the SBPs. SKP1 is a component of the SKP1-Cullin1-F-box containing complex (SCF complex). We found that Fbw7, one of the substrate recognition subunits of SCF complex, also binds to the SFN-SKP1 complex, resulting in up-regulation of cyclin E1 phosphorylation by SFN.

Conclusion
Although SFN was originally identified as a negative regulator of the cell cycle, especially in response to p53-sensitive DNA damage, subsequent reports indicated that it is a positive mediator of cell proliferation. In breast cancer, SFN induces G1/S progression by increasing the expression of cyclin D1. Here, we demonstrated that SFN enhanced the proliferative capacity of lung adenocarcinoma cells both in vitro and in vivo. We also revealed that SFN down-regulated expression of the SCF[Fbw7] complex. As cyclin E1 is a common target of SCF[Fbw7] ubiquitination, we predict that SCF[Fbw7] down-regulation by SFN might induce stabilization of cyclin E1. Since we also found that the S-phase subpopulation was decreased after siSFN treatment, SFN might induce G1/S progression through an increase of cyclin E1 phosphorylation in lung adenocarcinoma. In conclusion, SFN facilitates cell proliferation and malignant progression of lung adenocarcinoma, and its mechanism of action is thought to be associated with inhibition of SCF[Fbw7] ubiquitination and degradation.

Background
Lung cancer occurs in a significant number of never-smokers. Epigenetic changes in lung cancer potentially represent important diagnostic, prognostic and therapeutic targets. Accordingly, we sought to determine if there are differences in DNA methylation between lung adenocarcinomas and adjacent non-malignant lung tissue in never-smokers.

Methods
Using the Illumina Infinium HumanMethylation27 BeadChip we compared the DNA methylation profiles of 28 adenocarcinomas of the lung of never-smokers with their paired adjacent non-malignant lung tissue. The β value represents each methylation data point as the ratio of fluorescent signals between the methylated sites and the sum of methylated and unmethylated sites, which ranges continuously from 0 (unmethylated) to 1 (fully methylated). We used the Mann Whitney U test to compare β values between groups using JMP (SAS Institute Inc. Cary, NC USA). Then, using the Illumina Human WG DASL beadchip, we correlated differential methylation changes with gene expression changes from the same 28 samples. We validated our findings with 24 samples of lung adenocarcinomas and paired non-malignant tissue from The Cancer Genome Atlas (TCGA). Database for Annotation, Visualization, and Integrated Discovery was used to determine gene enrichment.

Results
We observed a distinct separation in methylation profiles between tumor and adjacent nonmalignant lung tissue using principal component analysis. Tumors were generally hypomethylated (β=0.15) when compared to adjacent non-malignant tissue (β=0.17; p=0.02). There were 1906 differentially methylated (Bonferroni corrected p value <0.05) CpG sites between tumor and adjacent non-malignant lung tissue. Of these sites, 1198 were within classically defined CpG islands where tumors (median β=0.38) were hypermethylated compared to adjacent non-malignant tissue (median β=0.22; p<0.0001), and 708 sites were outside of CpG islands where tumors (β=0.49) were hypomethylated compared to adjacent non-malignant tissue (β=0.56; p<0.0001). When compared to a dataset of 24 lung adenocarcinomas and paired non-malignant tissue from TCGA, 1841 of these 1906 (96.6%) sites were also differentially methylated with the same direction of change between tumor and non-tumor lung tissue. We matched 1483 genes with the differentially methylated CpG sites and found that these genes were enriched with the terms glycoprotein, signal, plasma membrane part, homeobox in addition to a few other terms. There were significant differences in expression of 376 genes (Bonferroni corrected p<0.05) of the 1483 (25.4%) differentially methylated CpG sites. There was an inverse correlation between methylation and gene expression in 80% of these genes. Genes that were not significantly differentially expressed and were hypermethylated within CpG sites were enriched for homeobox genes (false discovery rate = 1.2E-27).

Conclusion
The methylation profiles of lung adenocarcinomas of never-smokers and their adjacent non-malignant lung tissue are significantly different. Differential methylation of a CpG site was associated with altered gene expression in approximately 25% of cases. Despite the differential methylation of homeobox genes, no significant changes in expression of these genes were detected.

Background
Neuroendocrine differentiation (NED) has been observed in approximately 25-33% of all lung tumors. Essentially all small cell lung cancer (SCLC) and carcinoid tumors show distinct histological morphology and stain positive to neuroendocrine markers such as neuroamines, neuropeptides, dense core secretory granules, chromogranin A, neuroendocrine specific protein (NSP), and neuron-specific enolase (NSE). It was later recognized that NED was not limited to SCLC and carcinoid, and it could involve non-small cell lung cancer (NSCLC) such as large cell neuroendocrine carcinoma (LCNEC). Subsequently, it was found that about 10-20% of NSCLC, including adenocarcinomas and squamous cell carcinomas, also exhibit some neuroendocrine properties despite being considered non-neuroendocrine types. It has been postulated that NED of NSCLC represents an intermediary transition between SCLC and NSCLC, or that NED may be a predictor of the response to chemotherapy or radiotherapy, as well as a predictor of shorter survival in patients with stage I adenocarcinoma of the lung. Irrespective of these observations, the clinical significance of NED of NSCLC remains unclear.

Methods
We hypothesize that the investigation of the intracellular signal transduction pathway involved with NED of NSCLC cells may reveal potential molecular targets for the treatment of NSCLC with NED. We explore the potential molecular pathway involved in NED of NSCLC and its clinical association, through the induction of NED of a NSCLC cell line NCI –H157 in vitro. We further confirmed our findings using activators vs. inhibitors to these signal transduction pathways in vitro. We conducted immunochemical stains for phopsphorylated ERK1/2 expression of lung tumors know to have NED. ERK1/2 positivity was defined by 5% or more tumor cells stained positive with phospho-Erk½.

Results
We discovered that NED of NSCLC was associated with the activation of Erk1/2-MAPK signal transduction pathway, and the inhibition of the Akt signal transduction pathway. Using specific activator (Pb[2+]) and inhibitors (siRNA-Erk1/2, and U0126) to the Erk1/2 /MAP-kinase pathway, as well as the inhibitor (LY294002) to the Akt pathway, we found that Erk1/2/MAP-kinase activation was essential for NED of NCI-H157 cells. Staining of Erk1/2/MAP-kinase pathway reveals a high rate of positivity in NSCLC tumors with NED when compared with other neuroendocrine lung tumors. The positive rate of IHC was 0/10 (0%) for typical carcinoid; 2/10 (20%) for atypical carcinoid; 4/9 (44.4%) for small cell lung carcinoma; and was 7/10 (70%) for large cell neuroendocrine lung carcinoma.The ERK1/2 activation was statistically different (**p<0.01 by two tailed Fisher exact test) comparing all carcinoid tumors (2/20, typical plus atypical) with high-grade neuroendocrine carcinoma (11/19, SCLC plus NSCLC) .

Conclusion
Through the in vitro NED induction of NSCLC cell line NCI-H157, and in vivo correlative investigations in lung tumors with NEC, we discovered that NED of NSCLC was associated with the activation of Erk1/2-MAPK signal transduction pathway. To our knowledge, our findings are the first to describe the potential involvement of Erk/MAPK signal transduction pathway of NSCLC in the association with NED. Further investigation of the Erk/MAPK signal transduction pathway of NSCLC may yield discoveries in identifying specific molecular targets for the treatment of NSCLC with NED.

Background
Fibroblast growth factor (FGF) family consists of at least 23 polypeptides which have important functions in embryonic development, tissue repair, and tumorigenesis. Recent studies have shown that the activation of FGF9 is associated with pathogenesis of several cancers. In the lungs, FGF9 was highly expressed in adenocarcinoma by immunohistochemistry, and disturbing FGF9 function reduced the proliferation of lung adenocarcinoma. However, its clinicopathological and biological significance in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study is to clarify the characteristics of FGF9-expressing NSCLC.

Methods
Using a cDNA microarray data set for 90 surgically resected NSCLC and corresponding non-tumorous lung tissue samples, we analyzed the relationship between the expression of FGF9 and their clinicopathological characterisitics. Also, we validated FGF9 expression by quantitative RT-PCR, and immunohistochemistry at protein level. Associations between FGF9 expression and clinicopathological factors were assessed by the χ2 test and Mann-Whitney U-test. Log-rank test was applied for survival analysis, and Kaplan-Meyer curve (Fig.1) was drawn. Multivariate analyses of the influence of variables on overall survival were performed with using Cox proportional hazards model.

Results
Nine out of 90 (10%) NSCLC had “high” FGF9 expression compared with corresponding non-cancerous lung tissues. Histologically, 5 out of 9 FGF9-high NSCLC were adenocarcinoma, and there was no squamous cell carcinoma. The correlations between FGF9 expression and sex, smoking history or clinical stage were not observed. On the other hand, postoperative recurrence rates and 3-year survival rates were 56% vs. 36% (p=0.033) and 44% vs. 88% (p=0.001) for FGF9-high vs. -low NSCLC patients, respectively. The overall survival of the patients with high-FGF9 expression was significantly worse compared that with FGF9-low NSCLC patients (p<0.001). At protein level, FGF9 expression (immunohistochemistry) was significantly higher in FGF9-high mRNA group compared with FGF9-low group. FGF9 was confirmed to be expressed in cancer cells in these resected NSCLC tissues, and localized in cytoplasm of the cells. Figure 1

Conclusion
FGF9 is highly expressed in a subset of lung adenocarcinoma, and is associated with poor prognosis.

Background
Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are response predictive markers for the treatment of lung adenocarcinoma by using EGFR tyrosine kinase inhibitors. The stability of EGFR is dependent on its interaction with heat shock protein 90 (Hsp90), and Hsp90 inhibition may induce ubiquitin-mediated degradation of EGFR proteins. However, the mechanism of EGFR downregulation by HSP90 inhibition remains unclear. Here, we report a novel interaction between EGFR mutants and the E3 ubiquitin ligase C-terminus of Hsp70-interacting protein (CHIP), which can ubiquitinate and destabilize EGFR mutants

Methods
Cell culture, transfection and drug treatments NSCLC (A549, H358, H827, and PC9 cells) and Chinese hamster ovarian (CHO) cell lines used in the study were obtained from ATCC. Transfections of different DNA constructs were performed using Lipofectamine 2000 or PolyJet Western blot and immunoprecipitation Cells were then chilled on ice, washed twice with ice-cold PBS, and lysed in a buffer. Protein concentrations were determined using a Bradford assay kit. Equal amounts of protein (20 μg) in cell lysates were separated by SDS-PAGE, transferred to membranes, immunoblotted with specific primary and secondary antibodies, and detected by chemiluminescence with the enhanced chemiluminescence detection reagents. Cell viability assay After trasnfection with or without CHIP, cell metabolic activity was determined every 24 hours by using the CCK-8 (Dojindo, Gaithersburg, MD) colorimetric assay according to the manufacturer’s instructions. Cell cycle analysis by FACS Cells were seeded in 6-well plate and incubated overnight before transfection. After harvest at 48 h following transfection, cells were washed twice with pre-chilled PBS and resuspended in PBS (100 μL) at a concentration of 1 × 106 cells/mL. Cell cycle analysis was performed using the Coulter DNA PrepTM Reagents Kit. Xenograft studies A549 and PC9 cells were cultured as monolayers, trypsinized and resuspended in an equal volume of PBS at 5 × 107 per ml, respectively. BALB/c female nu/nu mice (5 weeks of age) were given bilateral subcutaneous injections of 5 × 106 (0.1 ml). Tumor growth was monitored twice each week by measuring the tumor size using calipers

Results
In CHO cells expressing either WT or mutant EGFR, the expression of the EGFR mutants L858R, G719S, and L747_E749del A750P was inhibited following overexpression of CHIP, whereas WT EGFR expression was not diminished in CHIP transfected cells. In a pull-down assay, CHIP interacted with G719S and del L747_E749del A750P, but not L858R, and simultaneously induced the ubiquitination and proteasomal degradation of its proteins. Similarly, the expression of mutant EGFR proteins in the non-small cell lung cancer cell line PC9 was also diminished by CHIP-mediated ubiquitination and degradation relative to WT EGFR. In EGFR mutant cell lines, CHIP inhibited cell proliferation as well as the depletion of phosphorylated Akt. In addition, CHIP inhibited the tumor growth of PC9 cells in xenografts of CHIP-overexpressing stable cell lines.

Conclusion
These data suggest that CHIP-induced ubiquitination of EGFR mutants may be responsible for EGFR regulation in lung adenocarcinoma and provide evidence that CHIP could be a novel E3 ligase for EGFR mutants.

Background
Our recent studies revealed that hepatoma-derived growth factor (HDGF) was highly expressed in non-small cell lung cancer (NSCLC) cells, when HDGF targeted-silenced by siRNA strategy, anchorage-independent growth of NSCLC cells can be significantly inhibited, the ability of NSCLC cells to invade across BD Matrigel membrane barrier can also be significantly inhibited, clearly suggested HDGF’s important role in cell growth, invasion and metastasis of NSCLC. However, the molecular mechanism is still undiscovered. Here, we reported that HDGF-ADAM9…may be the novel pathway for HDGF promotes growth and invasion of NSCLC cells. The expression of HDGF, ADAM9 in human resected NSCLC tissues will be detected, and the co-relationship, coordination of HDGF and ADAM9 will be evaluated to provide evidence, to elucidate the logic possibility of the HDGF-ADAM9…pathway.

Methods
siRNAs targeting HDGF were designed, used for specifically silencing HDGF in NSCLC cells. In vitro and in vivo cell growth and invasion assay were conducted. cDNA microarray and Western blot were used to explore the novel pathway, the possible molecular mechanism, by which HDGF promotes growth and invasion of NSCLC cells. Immunohistochemical SP method was used to detect the expression of HDGF and down-stream modulated genes in NSCLC tissues. Multivariate analysis and survival analysis were conducted to evaluate the clinical significance, the co-relationship, the possible coordination of HDGF and down-stream genes.

Results
Western blot revealed that HDGF protein expression in NSCLC cells were down-regulated more than 90% after silenced by targeted siRNA; anchorage-independent growth of A549 and H226 cells were inhibited significantly (P=0.000, 0.003, respectively); the ability of invading across BD Matrigel membrane barrier were inhibited significantly (P=0.004, 0.000, respectively). cDNA microarray revealed that a panel of genes, including AXL, GLO1, and ADAM9, were significantly down-regulated when HDGF was silenced by siRNA, suggested the possible pathways in which HDGF was involved. The expression of HDGF and ADAM9 were Immunohistochemically detected in 63 cases of completely resected stage Ⅰ NSCLC, found highly expressed in NSCLC when compared with normal control lung tissues (P=0.003, 0.001, respectively); highly expressed HDGF and ADAM9 were found correlated with significantly declined 5-year survival rates (P=0.009, 0.015, respectively). HDGF expression was revealed correlated positively and significantly with ADAM9 expression in these resected stage Ⅰ NSCLC (Pearson r=0.547, P=0.000).

Conclusion
These results clearly revealed that HDGF may promote cell growth and invasion of NSCLC cells via ADAM9 pathway, HDGF-ADAM9…should be a novel pathway of lung cancer invasion and metastasis. High expression of HDGF and ADAM9 correlate with shortened survival time, predict lower 5-year survival rates, suggesting that HDGF and ADAM9 are novel biomarkers for predicting prognosis in resected stage Ⅰ NSCLC, revealing their significance as novel molecular staging biomarkers. HDGF and ADAM9 may also become useful predictive biomarkers for the selection of adjuvant chemotherapy treatment of NSCLC to improve personalized postoperative treatment in resected stage Ⅰ non-small cell lung cancer. (This study was partly supported by grant from the Nature Science Foundation of Liaoning Province, China, No.20102285; and the Fund for Scientific Research of The First Hospital of China Medical University, No.FSFH1210).

Background
Microsatellite instability (MSI) can be analyzed by microsatellite markers consisting of mono-, di- and trinucleotide repeat sequences. In primary lung cancer, chromosomal instability including loss of heterozygosity (LOH) has been thought to play an important role in carcinogenesis. Although MSI was thought to be unrelated to lung carcinogenesis, recent findings suggest the role of tetranucleotide repeat sequence instability in prostate, skin, bladder and lung cancers. Unlike Bethesda panel markers (D17S250, D2S123, D5S346, BAT25 and BAT26) for Lynch syndrome, these tetranucleotide markers are not unified. Moreover, there are frequent elevated microsatellite alterations at selected tetranucleotides (EMAST) that are distinct from traditional MSI in several tumor types. EMAST in lung cancer has not been reported to date. We investigated EMAST in non-small cell lung cancers (NSCLCs) using selected tetranucleotide repeat markers (EMAST markers: D8S321, D20S82, UT5037, D8S348, D2S443, D21S1436, D9S747, D9S303, D9S304 and MYCL1) based on previous reports and analyzed their correlation to clinicopathological factors.

Methods
Sixty-five NSCLC tissue samples (19 squamous cell carcinomas, 39 adenocarcinomas, one adenosquamous cell carcinoma and six large cell carcinomas) without lymph node metastasis and preoperative chemotherapy or radiation therapy were obtained after resection from Yokohama City University Medical Center. Tumorous DNA was extracted by laser captured microdissection, and paired normal DNA was extracted from non-tumorous tissue or normal lymph nodes. Genotyping for EMAST determination was carried out using ten tetranucleotide repeat markers and five Bethesda panel markers.

Results
Using the ten tetranucleotide repeat markers, MSI was detected in 42 of 65 (64.9%) of the tissue samples. There was a higher rate of MSI at selected tetranucleotide markers than at Bethesda panel markers in the tissue samples (12.3%). The high EMAST group (MSI found at two or more markers) was significantly correlated to the presence of multiple malignant neoplasms (p=0.021) compared to the low EMAST group (MSI at none or one marker). We also examined a representative malignant neoplasm (renal pelvic carcinoma) complicated with NSCLC using EMAST markers. The tumor showed EMAST in the two markers (D2S443 and D21S1436).

Conclusion
Our results suggest that EMAST could participate in carcinogenesis of NSCLCs and lead to other malignant neoplasms.

Background
CADM1, a member of the immunoglobulin superfamily cell adhesion molecules, acts as a tumor suppressor in a variety of human cancers. CADM1 expression is frequently lost in various cancers and CADM1 inactivation by promoter methylation was observed in 44% of non-small cell lung cancer (NSCLC). In contrast, CADM1 is ectopically expressed in adult T-cell leukemia (ATL), conferring an invasive phenotype characteristic to ATL. Therefore, CADM1 plays dual roles in human oncogenesis: as a tumor suppressor in epithelial cancers and as an oncoprotein that promotes invasion in ATL cells. Here, we investigate the roles of CADM1 in small cell lung cancer (SCLC).

Methods
We studied splicing variant of CADM1 in 5 primary NSCLC tumors and a primary SCLC tumor, as well as 16 SCLC and 10 NSCLC cell lines. Expresssion and splicing variant of CADM1 was examined by RT-PCR, Western blotting, immunohistochemistry, and SSCP, respectively.

Results
Immunohistochemistry demonstrates that 10 of 35 (29%) primary SCLC tumors express CADM1 protein. Western blotting and RT-PCR analyses have revealed that CADM1 is significantly expressed in 11 of 14 SCLC cells growing in suspension cultures but in neither of 2 SCLC cells showing attached growth to plastic dishes, suggesting that CADM1 is involved in anchorage-independent growth in SCLC. Then, we demonstrate that SCLC expresses a unique splicing variant of CADM1 (variant 8/9) containing additional extracellular fragments corresponding to exon 9 in addition to variant 8, a common isoform in epithelia. Variant 8/9 of CADM1 is almost exclusively observed in SCLC and testis, although this variant protein localizes along the membrane and shows similar cell aggregation activity to variant 8. Interestingly, both variant 8/9 and variant 8 of CADM1 show enhanced tumorigenicity in nude mice when transfected into SBC5, a SCLC cell lacking CADM1. Inversely, suppression of CADM1 expression by shRNA reduced spheroid-like cell aggregation of NCI-H69, a SCLC cell expressing a high amount of CADM1. These findings suggest that CADM1 enhances the malignant features of SCLC, as is observed in ATL.

Conclusion
CADM1 could provide a novel molecular target for the diagnosis and growth suppression of SCLC cells.

Background
Lung carcinoma is the fifth common cancer affecting Saudi men. Recently, translocation of the anaplastic lymphoma kinase (ALK) gene is found to play a predictive role in adenocarcinoma tumor genesis. ALK gene rearrangement can identify patients with adenocarcinoma who are sensitive to ALK inhibitors. However, no data are available on the prevalence of ALK rearrangements changes in Middle Eastern population. Therefore, we carried out this study to evaluate the prevalence of ALK rearrangements in lung adenocarcinoma of Saudi patients.

Methods
ALK gene rearrangements were studied using fluorescence in situ hybridization (FISH) on 97 adenocarcinoma samples utilizing tissue microarray format. ALK gene translocations identified by BAC clone RP11-328L16 were studied by the break part probe from Vysis (Abott Molecular, Il, USA).

Results
Ninety seven (97) lung adenocarcinoma cases were evaluated. There were 3 cases exhibited ALK gene rearrangement (3%). All of these 3 cases was moderately differentiated adenocarcinoma. None of our cases showed signet cells or abundant intracellular mucin.

Conclusion
This is the first study that reveals frequency of ALK translocation in a ethically unique cohort of Saudi lung cancer patients. The findings of this study show that incidence of ALK adenocarcinoma is similar to the published western data and these patients can benefit from targeted therapy like Crizotinib- a dual ALK and MET inhibitor that has shown promising results in clinical trials.

Background
Epidermal growth factor receptor (EGFR) activating mutation is an important predictive biomarker of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), while family history of cancer also plays an important role in the neoplasia of lung cancer. This study aimed to investigate the association between family history of cancer and EGFR mutation status in NSCLC population.

Methods
From February 2008 to May 2012, 538 consecutive NSCLC patients with known EGFR mutation status were included into this study. Amplification refractory mutation system (ARMS) method was used to detect EGFR mutation. The associations between EGFR mutation and family history of cancer were evaluated using logistic regression models.

Results
EGFR activating mutation was found in 220 patients and 117 patients had family cancer histories among first-degree relatives. EGFR mutation was more frequently detected in adenocarcinoma patients (p<0.001), never-smoker (p<0.001) and with family history of cancer (p=0.031), especially who had family history of lung cancer (p=0.008). In multivariate analysis, the association of EGFR mutation with family history of cancer also existed (p=0.027).

Conclusion
NSCLC Patients with family history of cancer, especially family history of lung cancer, might have a significantly higher incidence of EGFR activating mutation.

Background
Limited information exists regarding long non-coding RNAs (lncRNAs) which regulate gene expression during initiation and progression of human lung cancers. The present study was undertaken to utilize a novel in vitro model system to examine long non-coding RNA alterations mediated by cigarette smoke in normal respiratory epithelia and lung cancer cells.

Methods
Normal human small airway epithelial cells (SAEC) and cdk-4/h-TERT immortalized human bronchial epithelial cells (HBEC), as well as Calu-6 and H-841 lung cancer cells were cultured in the presence or absence of cigarette smoke condensate (CSC). Array and qRT-PCR techniques were used to assess lncRNA and gene expression profiles in CSC-treated or control cells. qRT-PCR techniques were used to evaluate expression levels of BC070487 and its target gene, ZNFX1 in primary lung cancers relative to paired normal lung tissues. Chromatin immunoprecipitation (ChIP), RNA-crosslink immunoprecipitation (CLIP), and methyl DNA immunoprecipitation (MeDIP) techniques were used to evaluate chromatin alterations within the ZNFX1 promoter region mediated by BC070487. MTS, invasion, and murine xenograft experiments were performed to examine proliferation, invasion and tumorigenicity of lung cancer cells following manipulation of BC070487 or ZNFX1 expression.

Results
Under relevant exposure conditions, CSC mediated a 4-7 fold up-regulation of BC070487, with a 4-8 fold down-regulation of ZNFX1 in normal respiratory epithelia and lung cancer cells. BC070487 epression correlated inversely with expression of ZNFX1 (BC070487: 1.38-10.31 fold up vs ZNFX1: 2.26-26.29 fold down) in primary lung cancers relative to adjacent normal lung tissues. Over-expression or depletion of BC070487 inhibited or enhanced expression, respectively, of ZNFX1 in normal respiratory epithelia and lung cancer cells. CSC as well as BC070487-mediated repression of ZNFX1 coincided with increased occupancy of EZH2, SUZ12 and BMI1, as well as increased H3K27Me3 and decreased H3K4Me3 levels within the ZNFX1 promoter region. CSC or over-expression of BC070487 enhanced binding of BC070487 with EZH2, SUZ12 and BMI1 proteins in SAEC and Calu-6 cells. CSC exposure mediated a significant increase in DNA methylation in one of two CpG islands spanning the ZNFX1 regulatory region in SAEC and Calu-6 cells; this phenomenon coincided with enhanced binding of BC070487 with DNMT3a and 3b, and recruitment of these de-novo DNA methyltransferases to the ZNFX1 regulatory region in these cells. Over-expression of BC070487 increased proliferation and invasion potential of lung cancer cells in-vitro, and enhanced growth of lung cancer xenografts in nude mice. Consistent with these findings, ZNFX1 depletion enhanced, whereas constitutive over-expression of ZNFX1 inhibited growth and tumorigenicity of lung cancer cells.

Conclusion
Cigarette smoke induces expression of LncRNA BC070487, which in turn represses ZNFX1 in normal respiratory epithelia and lung cancer cells. These findings provide a novel mechanism by which cigarette smoke mediates initiation and progression of lung cancers, and highlight the potential implications of smoking status of lung cancer patients at diagnosis or during therapy.

Background
In non small cell lung cancer (NSCLC) it is of vital importance to develop biomarkers that allow us to assign a more accurate prognosis for patients in early stages, so we can apply the right treatment at the right time, preventing that the cancer reaches advanced stages when the cure rate is close to zero.

Methods
In this study we have selected a set of 9 genes related to immunoregulation and inflammation processes to analyze their relative expression on mRNA by qPCR in lung tissue samples from patients with NSCLC and resectable stage. CCL2 and CD1c genes showed a significantly lower expression in tumor tissue versus healthy tissue. After that, we analyzed the correlation between expression levels of these genes and relevant clinicopathological variables in the patients. Poorly differentiated tumors showed higher expression levels of CD209, CCL2, LGALS1 and LGALS2, whereas in smokers an increased expression of galectin LGALS1 was documented. Finally, survival analysis was performed using the Kaplan-Meier method to assess the utility of genes as prognostic biomarkers in this disease.

Results
In the subgroup of patients with squamous cell histology, those with lower levels of expression of CCL22 showed a significant increase in overall survival (OS) and progression-free survival (PFS). In our cohort of patients with resectable NSCLC, survival analyses showed that elevated levels of galectin LGALS2 and CCL2 chemokine are associated with a better prognosis in overall survival (OS) and progression-free survival (PFS).

Conclusion
The data obtained in our study provide further evidence about the necessity of tumors to manipulate the microenvironment around them as a prelude to progress and invade tissues.

Background
Endobronchial dysplasia is a premalignant lesion commonly found in current and former smokers. Identifying and treating these lesions before they progress to lung cancer may improve survival. The iloprost chemoprevention trial demonstrated that supplementation with the prostacyclin analog, iloprost, reduced histologic dysplasia in former smokers (Keith et al. Cancer Prev Res. 2011). However, accurate detection of dysplasia requires invasive bronchoscopy to collect multiple endobronchial biopsy samples. This study is the first step in generating blood-based markers of dysplasia to identify individuals at high risk for developing lung cancer and who could benefit from chemoprevention treatment.

Methods
Baseline serum samples (n=70) collected from current and former smokers enrolled in the iloprost chemoprevention trial were analyzed with the SOMAscan proteomic platform, which measures 1129 proteins with a median limit of detection of 40 fM and 5% CV. To characterize dysplasia, 6 standardized endobronchial sites, as well as any others that appeared suspicious by either white light or autofluorescence visualization, were biopsied from each study participant and scored by expert pathologists. Samples were stratified by worst biopsy score (Max) for proteomic analysis. Biomarkers correlating with Max pathology score were identified using principal component analysis (PCA), a multivariate technique to identify correlated variables, and the univariate, non-parametric Kolmogorov-Smirnov test (KS test). Serum proteins correlating with pulmonary function were also analyzed.

Results
Six proteins correlated with the progression of Max pathology. The change in serum level of these proteins ranged from 14-50% when comparing the lowest (n=16) and highest (n=39) Max pathology score groups. The proteins function in neoplastic progression, cell adhesion, inflammation and metabolic regulation. The protein with the most significant change (FDR correct p value = 0.05) regulates plasma clearance of steroid hormones. The serum protein most strongly correlated with lung function in our study was VEGFR2, which mediates VEGF induced endothelial proliferation and is known to be reduced in the lungs of smokers and patients with COPD and emphysema.

Conclusion
Our preliminary results of serum biomarkers associated with preneoplastic dysplasia warrant further study. If validated, this serum-based test to identify individuals who may benefit from chemopreventive intervention could impact lung cancer survival. This work was supported by NCI grants CA 58187 and CA165780.

Background
Proteomic analysis of blood and tissue can reveal essential connections between the biochemical pathways altered in malignancy and tools for cancer diagnosis and treatment. The two major histologic subtypes of non-small cell lung cancer (NSCLC), adenocarcinoma (AD) and squamous cell carcinoma (SQ) differ in prognosis and optimal treatment. Targeting molecular pathways that drive malignancy has led to a paradigm shift in the development of specific treatments for patients based on their tumor mutation profile. We have conducted a comparative proteomic analysis of lung tumor histologic and driver mutation subsets to reveal biomarkers that link critical pathways for cell growth and survival to specific tumor phenotypes and genotypes.

Methods
We analyzed 68 NSCLC tumor and matched non-tumor tissue lysates (2 ug total protein/sample) with the SOMAscan proteomic platform, which measures 1129 proteins with a median limit of detection of 40 fM and 5% CV. The study consisted of 49 AD and 19 SQ tumors, 88% of which were Stage I or II. Somatic driver mutations were identified with multiplex PCR (SnapShot genotyping). Pairwise proteomic comparisons of tumor/non-tumor or AD/SQ tissue samples were performed using the Mann-Whitney test. The non-parametric Kruskal-Wallis test was used to discover differences among multiple pairwise driver mutation comparisons. Dependency network analysis was used to explore correlations enriched in tumor tissue vs non-tumor tissue. The statistical significance of the results was adjusted for multiple comparisons using false discovery rate (FDR) correction.

Results
Differences between tumor and non-tumor tissue were dominated by inflammatory, apoptotic and cell proliferation proteins. A total of 79 proteins were significantly different between AD and SQ at a 15% FDR. When compared to non-tumor levels, these proteins divided into 3 phenotypes: AD only (9 proteins), SQ only (19 proteins) or Both (51 proteins). Both refers to proteins that are tumor biomarkers in both AD and SQ and the protein levels are different between AD and SQ. The most common pattern was a progression in protein levels from non-tumor to AD to SQ, whether the pattern was higher or lower in tumor tissue. These proteins are members of cell proliferation and inflammatory pathways. This observation is consistent with the SQ only proteins, which are enriched for angiogenesis, cell proliferation and cell adhesion proteins. Driver mutation analysis revealed 5 inflammatory proteins that were higher in KRAS vs EGFR mutations and a TNF-alpha antagonist that was suppressed in EGFR mutants.

Conclusion
Unexpected findings that the AD proteome is closer to non-tumor lung tissue than SQ were revealed through broad proteomic profiling. Alteration in cell proliferation and inflammation pathways discovered in this study may lead to new insights in tumor biology and targeted therapeutics. This work was supported by a grant from the LUNGevity Foundation, NCI grant CA 58187 and Cancer Center Support Grant (P30CA046934).

Background
PRMT5 is an arginine methyltransferase that regulates cellular events by methylation of Arginine residues on histone and non-histone proteins. PRMT5 cooperates with chromatin remodelers and co-repressors to induce epigenetic silencing, and is overexpressed in several human cancers. It also has impact on cell growth and transformation pathways by modulation of E2F1, p53, EGFR and CRAF. We investigated the role of PRMT5 in lung cancer.

Methods
The expression pattern of PRMT5 using immunohistochemistry from resection specimens obtained with an IRB approved protocol. Immortalized lung cancer cells (A549, H719, H520 and H1299) were obtained from ATCC and normal bronchial airway cells (HPAEpiC, HBEpiC) were obtained from ScienCell. Western immunoblot and cell cycle analysis by flow cytometry was performed using standard techniques. A novel and specific inhibitor of PRMT5 developed by colleagues at OSU was applied to in vitro culture systems.

Results
The expression of PRMT5 was analyzed in 9 lung cancer resection specimens (3 adenocarcinoma, 3 squamous, 2 small cell and 1 large cell neuroendocrine cancer). All 9 showed diffuse cytoplasmic and variable nuclear PRMT5 expression. PRMT5 was also seen in reactive type 2 pneumocytes and respiratory epithelium adjacent to the tumors but not in alveolar parenchyma, fibroblasts or endothelial cells. Using Western immunoblot, PRMT5 is highly expressed in A549, H719, H1299 and H520 cells compared with normal cells such as HPAEpiC and HBEpiC. We knockdowned the expression of PRMT5 by lentiviral shRNAs and identified several clones with effective PRMT5 inhibition. Inhibition of PRMT5 was associated with slow cell growth. The cell proliferation decreased 58.4% and 62.3% in H1299 and A549 knockdown cells respectively. Interestingly, while H4R3 methylation was decreased with PRMT5 knockdown in A549 it was not in H1299 cells. We further analyzed the role of PRMT5 by using a specific inhibitor developed by researchers at OSU, CPD5. One of the PRMT5 specific marks of histone H4R3 methylation was inhibited and significant cell cycle changes were observed in A549 and H1299 cells treated for 24 hr and 48 hr. At 24 hours, the percentage of cells in G0/G1 was 57.1% (control) compared with 66.4% in CPD5 treated A549 cells, and 52.5% (control) compared with 70.9% in CPD5 treated H1299 cells. The expression of p21 was increased while cyclin E1 was decreased in A549 cells treated with CPD5. In contrast, the expression of cell cycle related proteins were not found in PRMT5 knock-down cells. Immunoprecipitation and other protein interaction techniques are in process to identify new PRMT5 targets.

Conclusion
In summary, PRMT5 is highly expressed in lung cancer cells compared to normal lung. A novel PRMT5 inhibitor and shRNAs can inhibit cell proliferation. Although PRMT5 inhibitor could induce cell death by cell cycle regulation and apoptosis, different pathways may be involved in PRMT5 knock-down cells and speaks to the complexity regulating mechanisms in different histological lung cancer patients. The differences in H4R3 methylation suggest that epigenetic repression may be dominant in some cancers, but that non-epigenetic mechanisms may be relevant in others. Further exploring of PRMT5 targets are ongoing.

Background
Although p53 alterations have been studied in pulmonary neuroendocrine tumors, these studies have only tested immunochemistry. Typical (TC) and atypical (AC) carcinoids manifest a heterogeneous Rb-protein pattern. Other markers (c-kit, c-met, and PDGFa/b) have unknown functions on pulmonary carcinoids.

Methods
We have evaluated 60 consecutive lung carcinoid samples, referred between 1989 to 2011 for surgical treatment with respect to assessed the profile markers involved in lung carcinoids (AC and TC) using qRT-PCR.

Results
All genes studied were positives in both TC and AC samples. When we compared TC and AC results, we found differences as follow: p53 was positive in 72.72% AC and 50% TC; Rb positivity was found in 63.64% AC and 70.45% TC; 81.82% AC and 59.1% TC were positive for c-met; c-kit was positive in 27.27% AC and 22.73% TC; 36.36% AC and 25% were positive for PDGFa; PDGFb was positive in 72.73% AC and 50% TC.Figure 1

Conclusion
From these results, it can be hypothetized that a progressive higher degree of malignancy from TC to AC is paralleled by alterations in profile markers of proliferation, apoptosis, and angiogenesis. The regarding markers (c-met, c-kit, and PDGFa/b) have unknown functions on lung carcinoids. Thus, our results are added to the evidence that the expression of neuroendocrine differentiation in pulmonary carcinoid tumors is controlled by multiple genetic determinants.

Background
Neuroendocrine (NE) lung tumors display a broad spectrum of morphological types, ranging from typical carcinoids (TC), with low malignant potential, to small cell lung carcinoma (SCLC) with the most rapid and disseminated growth. Two new additional NE forms are recognized: the intermediate grade, atypical carcinoid (AC), and high-grade large cell neuroendocrine carcinoma (LCNEC). It is believed that lung carcinoid tumors are derived from endocrine cells (PNECs/NEBs), regulated by ASCL-1, of the airway tract. Active Notch-1 signaling in the developing endoderm inhibits endocrine differentiation via supression of ASCL-1. The aim of this study was to evaluate expression of developmental transcription factors and Notch signaling components in human lung carcinoids samples.

Methods
Sixty formalin-fixed paraffin embedded human lung carcinoid tumor (typical and atypical) samples were analyzed by IHQ and qRT-PCR. Tissue arrays were used in order to perform the IHQ. We assessed the profile of markers involved in lung carcinoid tumors using qRT-PCR with SYBR Green.

Results
In the present work we found that Notch pathway components have variable levels when we compare typical vs atypical histology in a set of human lung carcinoids. The heatmap (Figure) shows the presence of a group of genes with low expression by IHQ in almost all samples analyzed (NOTCH1, NOTCH4, DLL3 and DLL4). The remaining genes (NOTCH2, NOTCH3, JAG1, DLL1 and HES5) show clear differences in expression between samples.Figure 1

Conclusion
The molecular studies on human lung carcinoid samples indicate that the Notch signaling pathway, and the basic Helix-Loop-Helix (bHLH) transcription factors, including ASCL1, might regulate the neuroendocrine phenotype in human lung carcinoids. The Notch signaling pathway components and their transcription factors may be significant regulators of neuroendocrine indifferentiation in human lung carcinoid tumors.

Background
Although p53 alterations have been studied in pulmonary neuroendocrine tumors, these studies have only tested immunochemistry. Typical (TC) and atypical (AC) carcinoids manifest a heterogeneous Rb-protein pattern. Other markers (c-kit, c-met, and PDGFa/b) have unknown functions on pulmonary carcinoids.

Methods
We have evaluated 60 consecutive lung carcinoid samples, referred between 1989 to 2011 for surgical treatment with respect to assessed the profile markers involved in lung carcinoids (AC and TC) using qRT-PCR.

Results
All genes studied were positives in both TC and AC samples. When we compared TC and AC results, we found differences as follow: p53 was positive in 72.72% AC and 50% TC; Rb positivity was found in 63.64% AC and 70.45% TC; 81.82% AC and 59.1% TC were positive for c-met; c-kit was positive in 27.27% AC and 22.73% TC; 36.36% AC and 25% were positive for PDGFa; PDGFb was positive in 72.73% AC and 50% TC.Figure 1

Conclusion
From these results, it can be hypothetized that a progressive higher degree of malignancy from TC to AC is paralleled by alterations in profile markers of proliferation, apoptosis, and angiogenesis. The regarding markers (c-met, c-kit, and PDGFa/b) have unknown functions on lung carcinoids. Thus, our results are added to the evidence that the expression of neuroendocrine differentiation in pulmonary carcinoid tumors is controlled by multiple genetic determinants.

Background
Lung cancer is the leading cause of cancer-related deaths worldwide, with poor survival largely attributed to late stage of disease at diagnosis and frequent metastasis. Typically, tumor cells colonize the regional lymph nodes before spreading to distant sites, significantly dampening prognosis. The presence and number of affected nodes can be detected by routine imaging procedures, but occasionally, additional affected nodes are not detected until time of surgery, which impacts staging. The identification of biomarkers that stratify node positive (NP) and node negative (NN) patients could improve detection of aggressive disease, while a deeper understanding of the underlying biology of NP lung cancer could lead to the design of novel therapeutic interventions. MicroRNAs (miRNAs) are major regulators of gene expression that control a wide range of cellular processes, and have been shown to be excellent biomarker candidates due to their stability in biofluids. The role of miRNA deregulation in NP lung cancer is poorly understood; therefore, we sought to compare miRNA expression levels of lung adenocarcinoma (AC) cases with and without nodal involvement in order to identify miRNAs associated with tumor aggressiveness. We hypothesize that a subset of miRNAs are specifically deregulated in NP AC, representing potential biomarkers, and that identification of miRNA-mRNA interaction networks will shed light on the biological mechanisms of tumor spread that may be therapeutically exploited.

Methods
A panel of 45 NN and 28 NP primary AC tumors were collected along with paired adjacent non-malignant tissues. All samples underwent expression profiling of miRNA (Illumina GAIIx small RNA sequencing) and mRNA (Illumina microarray). NN and NP groups were analyzed separately as follows: matched tumor and normal miRNA normalized read count comparisons were performed (Wilcoxon Signed-Rank test, Bejamini-Hochberg corrected p<0.05), and miRNAs that were significantly deregulated in tumors were further investigated. miRNA fold changes (FC) were calculated on a case by case basis, and FC values were then compared between groups (Mann Whitney U Test p<0.05). miRNAs that (i) displayed a minimum 2-fold frequency of disruption >50% of NP cases, (ii) had a median FC>2 in the NP group, (iii) had a Signed-Rank corrected p<0.05, and (iv) had a MWU p<0.05 were considered to be NP-specific. Target prediction analysis of these miRNAs was then performed, and mRNA expression data was utilized to ensure predicted target expression was anti-correlated with miRNA expression. Candidate targets were input into Ingenuity Pathway Analysis to determine pathways implicated in NP AC.

Results
Fourteen miRNAs were NP-specific according to our criteria. These miRNAs included those previously associated with biology and metastasis of epithelial cancers, as well as miRNAs novel to lung AC. Target analysis implicated several pathways and functions previously associated with a metastatic phenotype such as the TGFβ pathway.

Conclusion
These results indicate that miRNA expression differs between NP and NN lung AC, further demonstrating the involvement of miRNAs in the regulation of the metastatic process. The role of these miRNAs as prognostic markers and serum biomarkers, as well as the mechanism of action of these miRNAs in AC biology must be further explored.

Background
CXCR4 is a chemokine receptor that activates signaling pathways responsible for trafficking of cells to sites of inflammation, retention of stem cells in the bone marrow and plays a role in migration and metastatic processes in tumour cells. Previous work by the Bebb lab demonstrated that female stage IV NSCLC patients with high CXCR4 expression have significantly worse survival compared to their low CXCR4 expressing counterparts. Recently, a positive regulatory loop was discovered linking CXCR4 and ER signaling pathways leading to increased gene expression of SDF-1 and other ER dependent genes. We explored the relationship between CXCR4 and ER/PR signaling in NSCLC cell lines, and assessed the expression of ER/PR in stage IV tissue samples to determine if ER/PR could be contributing to the observed gender dependent difference in clinical outcome seen in CXCR4 high expressers.

Methods
Two male and two female NSCLC cell lines were characterized for ER and CXCR4 by western blot. Activity of the CXCR4 and ER pathways in each cell line after stimulation with SDF-1 and estradiol (E2), respectively, were assessed by western blot of downstream signaling targets ERK, AKT, phospho-ER and PR. Cross activity of the CXCR4 and ER pathways was examined by stimulating cells with E2 and quantifying SDF-1 and PR mRNA by rtPCR. Tumor specimens from stage IV NSCLC patients (Glans-Look Lung Cancer Database) previously assessed for CXCR4 were analyzed for ERα and PR expression by quantitative immunohistochemistry (IHC) using the HistoRx AQUA® platform. Correlation between CXCR4 and ER/PR expression was assessed using Pearson’s rank correlation, and associations between marker expression and clinical factors/overall survival were assessed using a Cox proportional hazards model.

Results
All cell lines expressed varying levels of CXCR4, ERα and ERβ, and were responsive to both SDF-1 and E2 stimulation. Preliminary data suggests that activation of AKT and ERK after stimulation with SDF-1 occurs more rapidly in the male cell lines than in the female cell lines, and that there were differences in SDF-1 gene expression after E2 stimulation between the male and female lines. Other experiments are ongoing and full data will be presented. ER and PR AQUA scores were obtained for 131 patients (63 females and 68 males). There were weak positive correlations between both ER/CXCR4 (r = 0.153) and PR/CXCR4 (r = 0.278), however, only the correlation between CXCR4 and PR was significant (p = 0.002). Similarly, only PR expression was significantly associated with overall survival in the model (p = 0.03)(HR = 1.46). More detailed sub-group analyses further exploring the association with gender is ongoing, and will be presented.

Conclusion
The CXCR4 and ER pathways are active in NSCLC cell lines. There appears to be differences in the responsiveness of male and female NSCLC cell lines to CXCR4 and ER pathway activation. ERs and PRs are present in stage IV NSCLC tissue samples, and are associated with both CXCR4 expression and overall survival in our patient cohort. The full implication of these observations is still being investigated and further analyses will be presented.

Background
Tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (4D) that forms perfusable tumor nodules on tissue that mimics human lung cancer histopathology and protease secretion patterns better than tumor cells grown on a petri dish (2D). In this study, we aim to determine if the gene expression profile of cells grown in the model (4D) is a better predictor of survival in lung cancer patients compared to the gene expression profile of cells grown on a matrigel (3D).

Methods
We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, human lung cancer cell line, grown on petri dish (2D) against the same cells grown in the tissue of our ex vivo model (4D) and performed gene ontology (GO) analysis. We obtained gene expression data of A549 cells grown on petri dish (2D) and matrigel (3D) from GEO Accession No. GSE17347 and compared the gene expression profiles. We analyzed the differential gene signature for 4D and 3D in human lung cancer database for survival.

Results
Expression array analysis showed that there were 2954 gene probes differentially expressed between 2D and 4D. The analysis showed up-regulation of genes associated with mesenchymal cells (CDH2 and VIM). GO analysis showed up-regulation of several genes associated with extracellular matrix (MMP1, MMP9, MMP10, COL4A1, COL5A1), polarity (DLX2, GLI2, HOXD10, HOXD11), and cell fate and development (PPM1A, SALL1, SOX4, ZEB2, JAG1, SOX2, TP63). Moreover, expression array analysis of the 2D and 3D showed 1006 genes that were differentially expressed, with only 36 genes (4%) having the same expression pattern as differential expression between 2D and 4D. There was no difference in expression of genes associated with mesenchymal features (CDH2 and VIM) between 2D and 3D. Finally, the differential gene expression signature between 2D and 4D correlated with poor survival in patients with lung cancer (n = 1492, Log rank p = 1.5 x 10[-7]) while the differential gene expression signature between 2D and 3D correlated with good survival in patients with lung cancer (n = 1492, Log rank p = 1.7 x 10[-9]).

Conclusion
The genes necessary to form a perfusable nodule in the 4D model are the genes that are important in cell-matrix interaction, polarity and cell fate, which are lacking in a 2D model. The gene expression signature in the 4D model correlates with poor survival in lung cancer patients, which may be due to presence of more cells with mesenchymal features in the 4D model compared to 2D culture. On the other hand, the tumor cells grown on 3D model show the genes important in tumor cell interaction with matrix without difference in genes identify cells with mesenchymal features. Thus, there may be fewer cells with invasive properties, which may explain the good survival in lung cancer patients. The 4D ex vivo lung cancer model may be a better mimic of the natural progression of tumor growth in lung cancer patients compared to 3D model.

Background
Circulating tumor cells are tumor cells found in the vasculature or lymphatics of cancer patients that are thought to be responsible for metastasis. Recently, we developed an ex vivo 4D lung cancer model that forms perfusable tumor nodules. We have found that there are live tumor cells in the circulation in the model (CTCs). In this study, we aim to determine (i) the characteristics of these cells in vivo and (ii) whether the gene expression profile signature of these cells predicts survival in patients with lung cancer.

Methods
We used 393P and 344SQ mouse lung cancer cells for the in vivo experiment. The 393P cells that were grown on petri dish (2D) did not form metastatic lesions when injected into the flank of 129sv mice while 344SQ 2D cells did form metastatic lesions. Both cells were grown in the 4D model. We measured the size of the tumors and the number of CTCs for 14 days. We analyzed the mesenchymal characterisitics of 2D vs CTCs. We injected the CTCs in the tail vein of the 129sv mice and determined if they formed metastasis. We used A549 cells for the gene expression experiment. We placed the A549 2D cells in the 4D model and measured the size of the tumors and the number of CTCs. We compared the gene expression profile (Human OneArray v5 chip) of A549 2D against the A549 CTCs. We analyzed the differential gene signature in human lung cancer database for survival.

Results
All of the cell lines formed perfusable lung nodules in the 4D model by day 2 and formed circulating tumor cells starting day 5. The 344SQ cells grew faster (p = 0.01) and formed more circulating tumor cells (p = 0.8) compared to the 393P cells initially but by day 14 there was no significant difference in tumor size (p = 0.8) and number of circulating tumor cells (p = 0.7). The 393P CTCs were less mesenchymal (lower CDH2 (p < 0.0001), ZEB1 (p = 0.001) and VIM (p < 0.0001)) compared to 393P 2D while 344SQ CTCs were more mesenchymal (higher CDH2 (p < 0.0001), ZEB1 (p < 0.0001) and VIM (p < 0.0001)) compared to 344SQ 2D. When 393P CTCs were injected into the tail vein of 129sv mice, they did not form metastatic lesions while 344SQ CTCs formed metastatic lesions in the lung. Gene expression analysis of A549 2D compared to A549 CTCs showed that there were 2504 gene probes that were differentially expressed. This signature correlated with poor survival in patients with lung cancer (n = 1492, Log rank p = 2.6 x 10[-5]).

Conclusion
The circulating tumor cells that were isolated from the ex vivo 4D lung cancer model mimic the pattern of metastasis in vivo. Moreover, the circulating tumor cell signature correlates with poor survival in patients with lung cancer. The circulating tumor cells that are isolated in the ex vivo 4D lung cancer model may be the cells responsible for metastasis.

Background
We previously reported that lung adenocarcinoma cell lines could be classified into two groups according to gene expression patterns (Matsubara et al. Am J Pathol 2010). Group 1 cell lines expressed bronchial epithelial markers (CK7, MUC1, TTF-1) at high levels, while Group 2 cell lines showed epithelial-mesenchymal transition (EMT) phenotype (low-E-cadherin and high vimentin) and reduced expression of the bronchial epithelial markers. All cell lines mutated for EGFR, MET, HER2, and a cell line, LC-2/ad, recently found to harbor CCDC6-RET fusion (Matsubata, et al. J Thorac Oncol 2012), belonged to Group 1, and expressed EGFR, MET, HER3 at high levels, while KRAS-mutated cells lines were equally distributed in the two groups. Also, these two groups showed distinct sensitivity for gefitinib and cisplatin, respectively (Matsubara et al. J Thorac Oncol 2010, 2012). Here we tested the relevance of this classification for morphology and cancer-stromal interaction in 3 dimensional culture and mouse xenograft.

Methods
The 40 lung carcinoma cell lines consisted of 35 adenocarcinomas, 4 large cell carcinomas, and 1 adenosquamous carcinoma. These cells were plated onto Matrigel with or without lung-derived fibroblasts. Cell lines were also allowed to form spheroid in suspension culture, and then plated into collagen gel with or without lung-derived fibroblasts. To form xenograft tumors, cell lines were injected subcutaneously into NOD/SCID mice and allowed to form tumors, and resulting tumors were subjected to histologic analysis at 4-8 weeks.

Results
We demonstrated that on Matrigel essentially all Group 1 cell lines formed round spheroid, while Group 2 cell lines formed either round, stellate, or grape-like spheroid. Round spheroid forming cells remained non-invasive in monoculture, but upon co-culture with fibroblast, they acquired the ability to invade into Matrigel or collagen gels. In contrast, Groups 2 cell lines that formed stellate or grape-like spheroid showed invasive growth in monoculture, and co-culture with fibroblast seemed to enhance the invasive growth in some, but not all Groups 2 cell lines. Thus, Group 1 cell line required stromal fibroblast for invasion, while most Group 2 cell lines are endowed the ability to invade the stroma on their own. Consistent with this notion, when subcutaneously injected into immunocompromized mice, essentially all tumors derived from Group 1 cell lines were enriched with stromal fibroblast, while most tumors derived from Group 2 cell lines exhibited medullary histology with scanty stromal fibroblast.

Conclusion
Collectively, the data suggest that our two-way classification based on gene expression pattern has relevance for genetic, morphologic, and biologic properties of lung adenocarcinomas.

Background
The molecular screening is a key step to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. We investigated the clinical relevance of targeted next generation sequencing (NGS) as a molecular screening for EGFR-TKI therapy in never-smoking lung adenocarcinoma (NSLA).

Methods
We obtained DNA from 48 NSLA received gefitinib or erlotinib for their recurrent disease after surgery. The Sanger sequencing and peptide nucleic acid clamp polymerase chain reaction (PCR) were used to analyze EGFR, KRAS, BRAF and PIK3CA mutations. We analyzed ALK, RET and ROS1 rearrangements by fluorescent in situ hybridization or reverse transcriptase-PCR and quantitative real-time PCR. Finally, Ion Torrent NGS was performed in 31 cases harboring only EGFR exon 19 deletions (19DEL) or L858R mutation or none of above mutations.

Results
After excluding mutations other than EGFR 19DEL or L858R, samples were divided into 4 groups; 1) responders to EGFR-TKIs with only 19DEL or L858R (n=15); 2) primary resistance to EGFR-TKI with only 19DEL or L858R (n=4); 3) primary resistance to EGFR-TKI without any mutations (n=8); 4) responders to EGFR-TKI without any mutations (n=4). All conventionally detected mutations were confirmed with NGS. Additionally uncovered predictive mutations include; one PIK3CA E542K and one BRAF in group 2; two KRAS (G12V and G12D), one PIK3CA E542K and one concomitant PIK3CA and EGFR L858R in group 3; one EGFR 19DEL in group 4. Newly detected mutations were validated by Sanger sequencing.

Conclusion
Targeted NGS provided more accurate and clinically useful molecular classification of NSLA. It may improve personalized therapy for individual patients.

Background
Figure 1During thoracoscopic surgery, rounded cotton-tip dissectors (Blunt Cherry Dissectors[®]) have been used to maintain the position of the lungs. However, moistening of cotton tips due to blood or pleural effusion often makes it difficult for surgeons to maintain the lung position when using this equipment. Therefore, we developed a polygonal-shaped tip dissector using porous polypropylene, called the Rotary Dissector, in order to achieve a greater amount of frictional force against the lung. In the present study, we assessed the difference in the rotational frictional force between the Blunt Cherry Dissector and Rotary Dissector, as well as the usefulness of the Rotary Dissector in thoracic surgery.

Methods
The rotational frictional force of the Rotary Dissector and the Blunt Cherry Dissector was estimated using a gel. We measured the weight and volume of gel that was scooped and pushed out in one direction by each dissector. Furthermore, we used the newly developed Rotary Dissectors for video-assisted thoracic surgery (VATS), and assessed the usefulness of this equipment.

Results
The weight and volume of gel pushed out was 1.14 g and 948.4 mm[3] with the Rotary Dissector and 0.34 g and 270.6 mm[3] with the Cherry Dissector, respectively. Moreover, the Rotary Dissector had 3 times the frictional force compared to that of the Cherry Dissector. During VATS, we used the Rotary Dissector and successfully detached the pleural adhesion without causing any lung injuries and could maintain the lung position to obtain a clear surgical field.

Conclusion
Thus, we noted that Rotary Dissectors can yield a greater amount of frictional force as compared to conventional dissectors, and can be safely used in VATS.

Background
Next-generation sequencing (NGS) studies in cancer are often limited by the amount, quality and purity of tissue samples obtained from patients. In this situation, primary xenografts have proven useful in providing preclinical models. Although xenograft lines are maintained in immunodeficient mice, we and others have shown that they retain important characteristics that are irreversibly lost in cell culture. Since the stromal component of xenograft tumors is derived from the host, the presence of mouse DNA and RNA has the potential to limit the use of these models for next-generation sequencing (NGS) analysis.

Methods
We prospectively addressed this question in an established primary xenograft model of small cell lung cancer (SCLC), a malignancy that is almost always diagnosed using small biopsies or needle aspiration cytology. We first developed an in-silico strategy that separates human and mouse reads with at least 97% accuracy. We then compared NGS data from a series of primary xenograft models with clonally derived, stroma-free cell lines, and with published datasets derived from the same models.

Results
Starting with the NCI-H209 cell line as a reference sample, we show that low coverage whole genome analysis demonstrated remarkable concordance between published genome data and internal controls, despite the presence of mouse genomic DNA. NGS analysis of exon-capture DNA revealed that this enrichment procedure was highly species-specific, with less than 4% of reads aligning to the mouse genome. Human-specific expression profiling with RNA-Seq replicated array-based gene signatures, whereas mouse- transcript profiles correlated with published datasets from human cancer stroma.

Conclusion
Primary xenograft models may therefore be a useful NGS platform for cancers where tissue samples are limiting.

Background
Smoking-mediated lung cancer will cause at least 134,000 deaths in the USA this year. Even when detected at the earliest stages (stage IA and IB), five year survival is just slightly more than 50%. Chronic pulmonary inflammation is an established risk factor for lung cancer. Increased lung tumor macrophage infiltration is associated with poor prognosis, and murine lung tumor models exhibit increased macrophage infiltration. We hypothesize that chronic cigarette smoke exposure causes changes in inflammatory cell numbers and phenotypes creating a permissive environment for tumor formation. Chemopreventive agents such as the prostacyclin analog iloprost, may mitigate these changes.

Methods
FVB mice were given control AIN-76A chow or AIN-76A with 0.015% pioglitazone two weeks prior to smoke exposure. Mice were exposed to 70-90 mg/m[3] particulate level cigarette smoke for 6 hours/day, 5 days/week. Lungs were harvested 1 and 22 weeks after smoke exposure and after 22 weeks smoke/20 weeks ambient air (standard protocol for tumor induction). Bronchoalveolar cells were collected for qRT-PCR analysis of macrophage markers. Tumors were harvested and dissected from uninvolved tissue. Uninvolved lung tissue was digested and immune cell content analyzed by flow cytometry.

Results
Cigarette smoke exposure induced changes in macrophage phenotype after 1 week as indicated by CD11b exression (flow cytometry) and phenotypic markers (qRT-PCR). Macrophage infiltration increased in 22 week smoke/20 week ambient air exposed mice. Neutrophil numbers were increased at one week of smoke exposure. CD4 and CD8 positive T cell numbers decreased during smoke exposure but returned to control levels after smoking cessation. Smoke exposure differentially affected macrophage programming at each time point.

Conclusion
Cigarette smoke exposure affects pulmonary inflammatory cell numbers and function as early as 1 week after smoking initiation. Some of these changes are transient (increases in neutrophil numbers), while others are consistent but return to normal after smoking cessation (decreases in T cell populations). Smoke exposure resulted in early functional effects on macrophages and alveolar macrophage infiltration was still increased 20 weeks after smoking cessation, indicating that the effects of cigarette smoking on innate immunity are long lasting.