Virtual Library

Background
The median survival of patients with advanced stage malignant pleural mesothelioma (MPM) ranges between 9 and 12 months after diagnosis, regardless of the recent achievements with systemic therapies combining cisplatin and antifolates such as pemetrexed or raltitrexed. Since MPM is a relatively rare malignancy and early pre-neoplastic lesions are clinically difficult to be identified, the understanding of molecular pathogenesis including sequential accumulation of genetic/epigenetic alterations for MPM development has lagged behind other common malignancies. According to the COSMIC database the most frequently mutated genes in MPM include CDKN2A, NF2 and BAP1, followed by other 12 genes having been found mutated in a fraction of MPM cases (c-MET, VHL,WT1 among others). Clearly, a better and more systematic understanding of the role of genomic alterations in MPM is needed. In this retrospective study, a consecutive series of 123 formalin-fixed, paraffin embedded (FFPE) MPM tissue samples with clinical annotates, collected at two institutions, was retrospectively analyzed through Next-Generation Sequencing (NGS) technology to enhance knowledge about tumor-specific genomic profiling.

Methods
Genomic DNA was extracted by tumour microdissected FFPE samples for all 123 patients. Amplicons NGS libraries for 50 Oncogene included in Ion AmpliSeq™ Cancer Hotspot Panel (CHP) v.2 were generated as indicated by manufacturer, and sequenced in Personal Genome Machine IonTorrent. Variant Caller included in Torrent Suite Software was utilised to identify mutations in the samples, annotation was performed with Annovar software. Genomic analysis for BAP1 and NF2 (not included in the CHP) is separately ongoing.

Results
Of 123 advanced stage MPM patients, all treated with pemetrexed-based chemotherapy, 70% were males, current smokers 50%, median age 66.5 (range 36-82) years and histological subtypes were 96/22/5 epithelioid/biphasic/sarcomatous. With a cut off for allele frequency(AF)>=10% a total of 966 non-synonymous, 8 del-ins, 62 nonsense, 637 intronic, 204 regulatory and 1140 synonymous somatic sequence variations were detected in 107 patients already screened. Excluding synonymous mutations and irrespective of AF, the five most frequently altered genes were CSF1R (mut:154, pts:80), KDR (mut:148, pts:73), FLT3 (mut:132, pts:99), PIK3CA (mut:126, pts:60), TP53 (mut:111, pts:66). Evaluating mutations identified at least once, a correlation between HRAS and PIK3CA mutations and patient status (dead or alive) was observed (p=0.017 and p=0.039, respectively). Specifically, HRAS silent mutation p.H27H (rs12628) was responsible for the association (p=0.021) and occurred in 54% of 107 MPM compared to 30% of reported AF in available databases. PIK3CA p.I391M missense mutation (rs2230461; AF 24% in this series) was significantly associated to progression-disease (p=0.003). Among the other SNPs reported in at least 15 pts there are rs3729674(PIK3CA), rs1800863(RET), rs3822214(KIT), rs10006115(KDR), rs75580865(FLT3) and rs5030613(SMARCB1).

Conclusion
These extremely preliminary data indicate that NGS technology is feasible in FFPE MPM tissues and some of the detected genetic mutations are novel observations of potential prognostic and therapeutic interest.

Background
Following our publication (Cancer Immunol Immunother 2011) demonstrating the prognostic importance of chronic inflammatory cell infiltration in epithelioid malignant pleural mesothelioma (MPM), we investigated the prognostic significance of the immune microenvironment in the tumor nest and the tumor-associated stroma in epithelioid MPM.

Methods
A tissue microarray (TMA) was constructed from 170 epithelioid MPM cases, with 6 representative tumor cores and 3 representative stromal areas. Immunohistochemical analyses for immune cell infiltration (CD3, CD4, CD8, CD20, FoxP3) and interleukin receptors (IL-7R and IL-12Rβ2) were performed. TMA slides were analyzed for immune cell infiltration of tumor and stroma (low vs high, divided by use of the median), as well as for immune marker expression (sum of intensity and distribution). Overall survival (OS) was estimated using Kaplan-Meier analysis, and log-rank tests and Cox proportional hazards models were used to analyze the association between each marker and OS.

Results
Analysis of single immune cell infiltration for all patients revealed that high tumor CD8+ T-cell infiltration, high CD20+ B-cell infiltration, and low tumor IL-7R expression correlated with higher OS (Figure). Combined tumor CD8+ and CD4+ cell infiltration significantly correlated with better OS (5-year OS, 36% [n=61] vs. 20% [n=96]; p=0.008). In a multivariate analysis including age, stage, lymph node metastases, lymphatic invasion, and vascular invasion, high CD8+ T-cell infiltration and low tumor IL-7R expression were independent predictors of OS (Table). Figure 1Figure 2

Conclusion
Tumor CD8+ T-cell infiltration and tumor IL-7R expression are independently associated with survival, which highlights the biologic and prognostic significance of the immune microenvironment for patients with epithelioid MPM.

Background
SS1P is a recombinant immunotoxin targeting the tumor differentiation antigen mesothelin, which is highly expressed in mesothelioma. Anti-tumor activity of SS1P was limited in phase I clinical trials due to development of neutralizing antibodies (NAbs) that limited treatment to one cycle. In immunocompetent mice P and C (P-C) can abrogate development of anti-SS1P NAbs. This pilot study was performed to determine the impact of P-C-based immune depletion on anti-SS1P NAb formation and to assess safety of P-C-SS1P.

Methods
Patients with progressive pleural or peritoneal mesothelioma who previously received platinum-based therapy were eligible. Up to 6 cycles of P 4 mg/m2 IV (cycle 1: days 1, 5, 9; cycle 2-6: day 1); C 200 mg PO (cycle 1: days 1-12; cycle 2-6: days 1-4) and SS1P IV (35 µg/kg, cycle 1: days 10, 12, 14; cycle 2-6: days 2, 4, 6) were administered (cycle 1 was 30 days and cycles 2-6 were 21 days) with restaging every 2 cycles in the absence of progressive disease and anti-SS1P NAbs.

Results
Eleven patients were enrolled. The median age was 52 years (range 43-68); male 7, female 4; pleural 9, peritoneal 2; median number of prior treatments was 3 (range 2-6). Three out of 10 evaluable patients had partial response with tumor regressions of 74%, 70% and 44% with complete resolution of metabolic activity in two patients and >70% reduction in the third (Table). The overall survival of these patients is 17+, 15+ and 18+ months. In addition, one patient with stable disease and one patient with progressive disease had dramatic response to post-SS1P chemotherapy using drugs to which they had not responded previously. All five patients who responded are alive with overall survival ranging from 11 to 18 months. The regimen of P-C delayed development of NAbs to SS1P, thereby allowing multiple cycles of therapy with SS1P. Only 2 of 10 (20%) patients developed anti-SS1P NAbs after one cycle compared to 88% of patients who received single agent SS1P in a previous study (p=0.0001), thus meeting the primary endpoint. The regimen of P-C-SS1P was safe and well tolerated and no patient developed opportunistic infections. Grade ≥ 3 adverse events were P-C related lymphopenia (100%), transaminitis (18%) and SS1P related back pain (9%), non-cardiac chest pain (18%) and fever (9%).

Conclusion
SS1P and immune depletion with P-C results in significant and durable anti-tumor activity in heavily pre-treated chemotherapy refractory patients with mesothelioma.

Abstract not provided

Background
AMA is chimeric monoclonal antibody that binds to mesothelin, which is highly expressed in malignant mesothelioma and largely absent from normal tissue. In vitro studies indicate that AMA potentially has anti-tumor activity via antibody-dependent cellular cytotoxicity. AMA was studied in a Phase 2 mesothelioma trial.

Methods
This was a global, single arm, open label Phase 2 trial in 89 patients with previously untreated epithelial or mixed histology unresectable malignant pleural mesothelioma. Subjects received P/C every three weeks for 4 to 6 cycles combined with AMA 5mg/kg on days 1 and 8 of each 21 day cycle. All patients were fully supplemented with folate and B12 as per pemetrexed label requirements. Single agent AMA was then continued in the same schedule until disease progression. The primary endpoint was progression-free survival (PFS) at 6 months with a secondary end point of overall survival (OS).

Results
Median PFS was 6.1 months while median OS was 14.8 months. An evaluation of serum drug concentration relationship with clinical response noted that those subjects who achieved a median trough serum concentration of 32.9 µg/mL had an improved median PFS over those whose trough serum concentration was below the median (238 days vs 115 days, p<0.001). Similarly those subjects with a serum trough concentration of AMA above a median of 38.2 µg /mL had a median OS of 583 days while those with a median serum concentration of AMA below 38.2 µg /mL had a median OS of 375 days, p=0.0202. The most commonly reported adverse event was that of hypersensitivity to the chimeric antibody at first dose second cycle.

Conclusion
The safety profile of AMA in combination with P/C was consistent with that seen previously for the PC regimen. Although PFS is not significantly different from historical results of P/C alone, the median OS was 14.8 months (as compared to 13.3 months for P/C[1]). PK/PD analysis demonstrated that AMA trough concentrations were a significant predictor of both PFS and OS where higher concentrations were associated with longer OS and PFS. [1]Reference: Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. J Clin Oncol, 2003; 21:2636-2644.

Background
The role of maximal cyto-reductive surgery in malignant pleural mesothelioma (MPM) remains controversial. Although selected patients achieve long-term disease control following extended pleurectomy and decortication (PD), not all patients benefit. In addition surgical complications and side effects may adversely affect quality of life (QoL). We previously observed significant improvement in the quality of life following PD in patients who were symptomatic at baseline (Mollberg et al, Ann Thorac Surg 2012). In this study, we further examined the effects of PD on pulmonary function and correlated changes in pulmonary function with QOL.

Methods
Consecutive patients with MPM undergoing PD were prospectively enrolled at a single center. The primary endpoint was to determine the effects of PD on QoL. Health related QoL was assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionaire-C30 (EORTC QLQ-C30) before operation and at one,4-5, 7-8 , 10-11 and 12-13monthsmonths postoperatively. Pulmonary function testing was performed (PFTs) were measured immediately before the operation and at 6-7 months postoperatively. Patients were grouped according to the World Health Organization baseline performance status (PS) and compared.

Results
Twenty-seven patients with a median age of 71 years old (range 59 to 91 years), 19 males and 8 females, were enrolled in the study from March 2010 to October 2012. At the time of the operation, 17 patients were WHO PS 0, 10 were PS 1. At baseline, the PS 1 patients had a significantly worse global QoL (p<.0001), functional (p<0.0001) and symptoms scores (p<0.0001). PS 0 patients had not significant change in global QoL or functional) and symptoms scores (except for emotional function and insomnia p<0.01) following the operation. In addition they demonstrated a significant decrease in FVC (p<0.003), FEV1 (p<0.005), TLC (<0.001) and DLCO (<0.009) following PD. PS 1 patients showed significant improvements in Global Health (p=0.05) functional measures (p< 0.01) and symptoms scores (p <0.03) at 4-5 months and this was maintained at 6-7 months following PD. Improvement also was noted in the FVC (p=0.09), FEV1(p=0.04) and DLCO (p=0.09) in these patients.

Conclusion
At intermediate follow-up, extended PD for MPM had a negative impact on pulmonary function in minimally symptomatic patients without any significant improvement in QoL. In contrast, patients who were symptomatic at baseline significantly improved in QoL and showed a modest improvement in pulmonary function after PD. The change in pulmonary function may be partially responsible for the observed QoL in symptomatic patients undergoing PD.

Background
Medical management of malignant pleural mesothelioma (MPM) has obtained a moderate survival improvement over the years, while surgery with pleurectomy / decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option for selected patients with resectable disease. The aim of this study was to investigate the impact of surgical treatment on the outcome of patients with MPM.

Methods
We retrospectively reviewed data from 1365 consecutive patients with histologically proven MPM, treated from 1982 to 2012 in six Institutions.Patients received either chemotherapy alone (n=172) or best supportive care (n=690) or surgical treatment (n=503), by either P/D (n=202) or EPP (n=301) with or without chemotherapy. All patients were followed up until death or for a minimum period of one year. The cox proportional hazards regression model was used to estimate relative improvements and to test the statistical hypothesis; a p-value less than 0.05 was considerd statistical significant.

Results
Figure 1 Figure1. Kaplan-Meier survival curves according to the treatment (non surgical treatment vs EPP vs P/D) considering only patients with independent good prognostic factors After a median follow-up of 6.7 years (range 1.1-14.8), 230 (16.8%) patients were alive; median survival for patients who received palliative treatment or chemotherapy alone, P/D and EPP groups were 11.7 (95%CI: 10.5-12.5) months, 20.5 (95%CI: 18.2-23.1) months, and 18.8 (95%CI: 17.2-20.9) months, respectively. Testing the hypothesis of equal survival distributions the statistical significance was reached for the P/D and EPP groups versus non surgical treatment group (p <0.001) but not for the EPP versus P/D groups (p=0.885). The 30 day mortality was 2.6% after P/D and 4.1% after EPP (p=0.401). According to multivariate analysis (n=1227) age < 70, epithelial histology and chemotherapy were independent favourable prognostic factors. In the subset of 312 (25.4%) patients with all favourable prognostic factors median survival was 15.5 months after medical therapy alone, 19.4 months after P/D, and 18.7 months after EPP (Figure 1). A risk reduction of 31% (95%CI: 14-45%) for the P/D group and of 23% (95%CI: 7-36%) for the EPP group was observed compared to the medical treatment group.

Conclusion
Our data suggest that patients with good prognostic factors had a similar survival whether they received medical therapy only, P/D or EPP. The modest benefit observed after surgery over medical treatment requires further investigation, and a large multicenter randomized trial, testing P/D after induction chemotherapy versus chemotherapy alone in MPM patients with good prognostic factors, is needed.

Abstract not provided

Background
Measurement of volume doubling time (VDT) of small pulmonary nodules is clinically useful for discrimination between benign and malignant etiology, because this discrimination capability based only on the initial CT is limited. Recent advancement of CT technology enabled direct 3D measurement of volume of pulmonary nodules using commercially available software and enabled VDT measurement with these data. However, there are only a few reports in which accuracy of the 3D method was assessed with comparing the 3D method with the traditional 2D method. Here, we compared intra- and inter-observer variability (OV) to assess the accuracy of these two methods and compared VDT of pulmonary nodules in 2D-method with those in 3D-method. We also discussed the clinical relevance of our results.

Methods
Forty-two pulmonary nodules of 3 cm or smaller (CT type, 11 of ground-glass opacity, 15 of mixed type, and 16 of solid type) of peripheral lung cancer (37 of adenocarcinoma, 4 squamous cell carcinoma, and one small cell carcinoma) in 41 patients (mean age±SD, 67±10 years; 25 men and 16 women) who underwent 16-slice MDCT with 1-mm collimation twice (mean interval, 369 days, range 60-1119 days) before surgical resection during June 2006 and December 2008 were included in this study. Five examiners independently calculated VDT by 2D (nodule diameter measurement) and 3D methods (nodule volume measurement using in-house programmed software) with the use of Schwaltz equation and repeated the measurements one month after. Thus, intra- and inter-OV in VDT for the two methods was compared using 95% confidence intervals (CI) in Blant-Altman plots, and VDT calculated with the two methods was compared in each examiner. In evaluating inter-OV, averaged values of the two measurements in each examiner were used for analysis. A p of less than .05 was considered to be significant.

Results
As for inter-OV (n=10), 95% CI (mean±SD in days, 398±123) for 3D method was significantly greater than that (231±87) for 2D method (p=0.005). Regarding intra-OV (n=5), 95% CI (291±199) for 3D method tended to be greater than that (195±36) for 2D method (p=0.388). VDT calculated with 3D method was significantly greater than that calculated with 2D method in all of the 5 examiners (all p of <0.05).

Conclusion
Inter-OV in VDT measurement was significantly greater in 3D method than in 2D method and VDT calculated with 3D method was greater than that calculated with 2D method. Therefore, in calculating VDT of pulmonary nodules, the same examiner should evaluate with the same method.

Background
PET is a useful tool in the diagnostic workup of lung cancer. However, its role in lung cancer screening with low dose Computed Tomography (CT), in which small sized nodules are detected, is still to be determined. We present final PET results from the 5 year (2005-2010) randomized Danish Lung Cancer Screening Trial (DLCST).

Methods
DLCST participants with indeterminate nodules mostly between 5 and 15 mm were referred for a 3-month rescan. Between the initial scan and the 3-month rescan, participants were also referred for a PET scan. Uptake on PET was categorized as most likely benign or malignant on a scale from I to IV). Receiver operating characteristic (ROC) analyses were used to determine the sensitivity and specificity of PET. Resected nodules and indolent nodules (i.e. stable for at least 2 years) were included, and the latter was categorized as benign. Nodules were only included once in the study, thus repeat PET scans were excluded.

Results
A total of 90 nodules were included, 50% men, mean age 67 years (58-79), prevalence of lung cancer was 38% (35/90). Mean follow-up time for benign non-resected nodules was approx. 2.8 years in screening. Clinical follow-up in central digital medical logs was done for all participants in 2013. The sensitivity and specificity of PET was 66% and 91%, respectively, with cut-off points for malignancy at PET>II (i.e. categorized as possibly or probably malignant at PET). The positive predictive value was 82% (23/28) and negative predictive value was 81% (50/62). 12 PET results were false negative, and of these 75% (9/12) were either ground glass nodules or partly solid nodules. Figure 1

Conclusion
PET is a valuable tool in lung cancer screening; our results show fair sensitivity and high specificity in a trial with long time follow-up of benign nodules. False negative PET results were found in non-solid nodules. We recommend PET as an integrated part of future lung cancer screening programs.

Background
The objective of this study was to develop a pretreatment prognostic model based on metabolic imaging biomarkers that could be used to predict overall survival (OS) in patients with stage I non–small cell lung cancer (NSCLC).

Methods
We evaluated 198 patients with pathologic stage I NSCLC who underwent pretreatment FDG PET/CT. Metabolic imaging biomarkers included maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and coefficient of variation (COV) for primary tumors. SUV is a semiquantitative index of metabolic activity. TLG is a volumetric measurement of tumor glycolytic activity. COV is an index of tumor uptake heterogeneity. The prognostic significance of clinical variables and imaging biomarkers (age, sex, histologic cell type, tumor size, SUVmax, TLG, COV) was assessed by Cox proportional hazards regression model. Statistically significant clinical variables and imaging biomarkers in the multivariable analysis were used to construct a prognostic model for predicting survival. The predictive accuracy of the prognostic model was evaluated by Harrell's concordance index (C-index).

Results
Median follow-up for surviving patients was 7.5 years with a range of 5.2 to 9.9. At the time of analysis, 52 (26.3%) patients had died. Age (HR = 1.05 for 1-year increase, P = 0.007), histologic cell type (HR = 0.54 for adenocarcinoma, P = 0.027), SUVmax (HR = 1.08 for 1-unit increase, P = 0.002), and TLG (HR = 1.23 for a doubling of TLG, P = 0.021) were significantly associated with OS by univariable analysis, whereas only age (HR = 1.07 for 1-year increase, P = 0.005) and SUVmax (HR = 1.04 for 1-unit increase, P = 0.012) were significantly associated with OS by multivariable analysis. The final prognostic model included age as a clinical variable and SUVmax as a metabolic imaging biomarker to predict OS. The predictive performance of the prognostic model for OS was not improved by addition of TLG or COV. The C-index was 0.694 for the final model with age and SUVmax. Kaplan-Meier survival curves stratified by risk score showed high-risk group of patients (n = 58, SUVmax > 12 and age > 60) and low-risk group of patients (n = 48, SUVmax ≤ 12 and age ≤ 60). Figure 1

Conclusion
A new prognostic model based on pretreatment metabolic imaging may have potential clinical utility for risk stratification of stage I NSCLC patients.

Background
During the past decade many studies have used FDG-PET/CT for response evaluation to therapy, both in NSCLC and several other cancer forms. A preferential method for evaluation has not been established as of yet. Two main approaches tend to single out: A visually based model as described by Mc Manus et al in 2003 and semi-quantitative approaches, like the recently proposed PERCIST 1.0 2009, by R. Wahl et al. Few studies have evaluated the interobserver variability when using sequential PET/CT scans for response evaluation, and comparison of qualitative- and semi quantitative approaches are also scarce. The aim of this study is to determine which method will provide the more robust evaluation of response when using FDG-PET/CT, the qualitative approach or the SUV based semi quantitative approach prior to the introduction of routine early response evaluation in NSCLC.

Methods
FDG-PET/CT scans at baseline and after 2 cycles of chemotherapy from 35 patients with locally advanced NSCLC were analysed by 8 different readers using two different methods: PERCIST 1.0 and the qualitative McManus approach. Both methods result in allocating patients into one of four response categories. Observers were given short written presentations outlying the criteria for evaluation by the two methods. The observers represent a wide range in experience with PET evaluation, only half had experience in response evaluation in NSCLC, but most were experienced in similar evaluation in lymphoma patients.

Results
When using PERCIST 1.0, the agreement between observers in determining the percentage change in SULpeak was “almost perfect” with ICC=0.959 similar ICC values were found looking at SUL peak at baseline and follow up scans. There was strong agreement amongst readers allocating patients to the different response categories with Fleiss kappa of 0.761 (0.714-0.808). In 22 of the 35 patients there was complete agreement. When using the qualitative method (A.M. McManus), agreement was lower, down to moderate agreement, with Fleiss kappa of 0.596 (0.554-0.639). And complete agreement was observed in only 10 of the 25 patients. Using chi squared the difference is statistically significant (p < 0.005). No difference was found between experienced and non-experienced observers.

Conclusion
In spite of a wide range of experience among 8 readers receiving minimal introduction to the two methods they were to use, we found rather high kappa values, for both methods compared to its nearest competitor: Size change in CT images, known to be very observer dependent. The more objective, semi-quantitative method showed substantially higher agreement than the more subjective method. We suspect that a more detailed introduction into the methods would have improved the kappa values even further, but believe that our method is more likely to provide an introduction similar to the one you receive when introduced as a new physician at the department. Perhaps then the agreement reflects the long-term agreement.

Abstract not provided

Background
Emerging evidences suggests that diffusion-weighted magnetic resonance imaging (DW MRI) at 1.5-T could be useful for tumor detection, together with N and M staging in patients with lung cancer, especially non-small cell lung cancer (NSCLC), with accuracy as good as, or even better than, that of FDG PET/CT most recently. This investigation prospectively examined whether DW MRI at 3.0-T might be as useful as FDG PET/CT for detection of pulmonary malignant tumors.

Methods
This study was approved by the institutional review board, and written informed consent was obtained from all patients. DW MRI and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules, including lung cancer, lung metastases, and benign lesions, diagnosed by pathological examination. Apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV~max~), and five-point visual scoring were assessed. Immunohistochemical staining for Ki-67 was performed in 36 patients with lung cancer, and Ki-67 score was evaluated. Receiver operating characteristic (ROC) curve analysis was used to determine feasible threshold values. Diagnostic capabilities for detection of pulmonary malignant tumors were compared with the McNemar test on a per-patient basis, and correlation between malignant degree of lung cancer and ADC or SUV~max~ was analyzed by Spearman rank test.

Results
As for diagnostic capability, area under ROC curve (A~z~) for ADC (0.91) were significantly higher than that for SUV~max~ (0.78, P < 0.05), and A~z~ value for DW MRI (0.94) were not significantly different from that for FDG PET/CT (0.92, P > 0.05). For quantitative assessment, specificity and accuracy of ADC (91.7%, 92.9%) proved to be significantly higher than those of SUV~max~ (66.7%, 77.9%, P < 0.05), although sensitivity of ADC (93.5%) was not significantly different from that of SUV~max~ (83.1%, P > 0.05). When feasible threshold values were used to assess qualitatively, sensitivity, specificity, and accuracy of DW MRI (96.1%, 83.3%, 92.0%) were also not significantly different from that of FDG PET/CT (88.3%, 83.3%, 86.7%, P > 0.05). Significant correlation was found between Ki-67 score and ADC (Spearman coefficient r = -0.66, P < 0.05), as well as ADC and SUV~max~ (r = -0.37, P < 0.05). On the contrary, Spearman coefficient was -0.11 between Ki-67 score and SUV~max~ (P > 0.05).

Conclusion
In conclusion, quantitative and qualitative assessments for detection of pulmonary malignant tumors obtained with DW MRI at 3.0-T are as useful as, even superior to, those obtained with FDG PET/CT. Furthermore, another significant outcome of this study was that ADC in DW MRI at 3.0-T can also play a role in prediction for malignant degree of lung cancer in particular, but SUV~max~ did not in FDG PET/CT.

Background
To compare the diagnostic efficacies of diffusion-weighted magnetic resonance imaging (DWI) and F-18 fluorodeoxyglucose positron emission tomography (PET) findings for the preoperative prediction of mediastinal nodal metastasis in stage N2 disease of non–small cell lung cancer (NSCLC).

Methods
The study included 68 patients (42 men and 26 women; mean age, 62 years) with a supicious stage N2 due to NSCLC. In all patients, DWI (using a sigle-shot echo-planar sequence with diffusion factor of 0-600 s/mm² at 1.5 Tesla) and PET were performed before surgery. In DWI, a patient was regarded to have stage N2 disease when an ipsilateral mediastinal lymph node showed apparent diffusion coefficent (ADC) value of ≤0.98 s/mm², regardless of nodal size. A node was considered as positive for malignancy, if it showed standardized uptake value (SUV) of 3 or higher by PET. Both DWI and PET images were prospectively evaluated for malignancy on a per-node basis by two observers. Histopathologic results served as the reference standard. N2 disease was decided by using the American Joint Committee on Cancer staging system. The results were compared between the two modalities and statistically significant differences in nodal metastasis between DWI and PET were determined with p<.05 obtained by using the McNemar test or with a generalized estimating equation.

Results
Nodes were positive for malignancy in 36 (32%) of 114 nodal stations and 22 (32%) of 68 patients. The N2 staging was correctly diagnosed in 56 (82%) and 52 (76%) patients by DWI and PET (p=.09), respectively. For the depiction of malignant nodes, DWI and PET showed sensitivities of 78% (31 of 40 nodal groups) and 78% (28 of 36), specificities of 93% (69 of 74) and 90% (70 of 78), positive predictive values of 86% (31 of 36) and 78% (28 of 36), negative predictive values of 88% (69 of 78) and 90% (70 of 78) and accuracies of 88% (100 of 104) and 86% (91 of 104), respectively (p=.23, p<.05, p<.01, p=.08, and p=.12). There were nine false-positive interpretations by DWI, compared with eight by PET. Eight false-negative assessments were present on PET images, but only five false-negative results were found in DWI. .Figure 1

Conclusion
DWI has a higher specificity for N2 staging of NSCLC compared with PET and has the potential to be a reliable alternative imaging method with an advantage of radiation-free imaging for the preoperative staging of mediastinal lymph nodes in patients with NSCLC.

Abstract not provided

Background
Worldwide, lung cancer is the leading cause of death by cancer and most common cancer among occupational related cancers. Approximately 90% of men and 60% of women. developing lung cancer are smokers. Cancer Morbidity and the increase in cancer mortality in South Africa is well documented and has been attributed to different factors, including tobacco consumption, occupational exposures, infections, changing lifestyles, ageing population and environmental pollution The International Agency for Research on Cancer (IARC) has estimated that almost 40 000 deaths from cancer (58 000 cases) occur annually in South Africa. In men the leading causes of deaths were lung cancer (comprising 16% of all cancer deaths). Environmental and occupational risk factors contribute to the burden of lung cancer, but the extent of this contribution is still unclear in most settings especially in Africa, confirmed in a review by McCormack and Schuz Estimating the attributable fraction for specific risk factors helps to assess the potential impact the preventive interventions could have on the population. The proposed study will estimate lung cancer risk attributable to the different occupations and types of workplaces in black South African population represented in the data base while controlling for smoking and domestic fuel use. Identification of the role of occupation on the risk of lung cancer may enhance the ability to prevent the disease by permitting better focused occupational health and other preventive strategies in the fight against non-communicable diseases in black South Africans. There is very limited research on cancers and occupations in Africa; hence findings will contribute to the knowledge of lung cancer in relation to occupations in South Africa.

Methods
Data from the on-going Johannesburg Cancer Case-Control Study (JCCCS) of black African adult cancer patients (2001-2008) was used. Information from 579 lung cancer cases and 1120 frequency matched controls was analysed. Controls were randomly selected from cancers not known to be associated with the effects of tobacco, matched by sex and age (±5years). Usual occupation and/or workplace stated at interview were used as an indicator of occupational exposure. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression and attributable fraction (AF) by Miettinen’s formula, adjusted for smoking pack years, HIV status and domestic fuel type use.

Results
The mean age of cases and controls was 56.0 and 57.1 respectively. Among men the adjusted OR for lung cancer was 3.0 (95% CI 1.4-6.4) in miners and 1.7 (95% CI 1.3-3.2) in those working in transport occupations. In women working as domestic worker (maids, child minders etc) the adjusted OR was 7.3 (95% CI 1.7-11.3) whereas working in the food & beverage industry, the adjusted OR was 4.9 (95% CI 1.4-26.8). Occupation / workplace resulted in an AF of 14% in men and 26% in women.

Conclusion
Occupational risk factors for lung cancer in South Africa are gender-specific, having more impact in women than in men. Further studies are needed to assess possible specific exposures in the mining and transport industries for men, and food industry and private homes for women.

Background
South-East Scotland Cancer Network (SCAN) serves 1.4 million people using unified protocols collecting prospective data. We published population-based data from 1995 and 2002 (J Thorac Oncol. 2008;3(5):491-8) demonstrating increased cancer treatment and improved overall survival. This review investigates whether this has been sustained.

Methods
Patients were identified from Scottish Cancer Registry (SCR), SCAN audit and Edinburgh Cancer Centre databases to extract tumour characteristics, initial management (usually ≤6 months of diagnosis) and overall survival (OS). Missing data was sought from patients’ health records. Multivariate analysis (MVA) examined sex, age(<60,60-69,70-79,80+), deprivation, Healthboard of residence, performance status (PS), pathology and stage (localised, regional, metastatic) affecting use of any treatment, potentially curative treatment (PCT) defined as surgery (S) or potentially curative radiotherapy (PC-RT - ≥50Gy for NSCLC or ≥40Gy+chemo for SCLC) using Cox’s proportional hazards model to obtain factors affecting survival.

Results
1117 patients were identified in the audit. 51.5% were men, median age 72 (range 31-98) years. 47.3% were from the two most deprived quintiles. 49.5% had WHO PS 0-1, 23.5% WHO2, 24.2% WHO3-4. 58.5% NSCLC (23.5% Stage I-II, 25.7% III, 48.8% IV), 13% SCLC (37.9% stage I-III, 61.4 stage IV) and 28.5% radiology-only diagnosis (24.5% Stage I-II, 19.5% III, 52.8% IV). 59.9% received some form of treatment; 28.4% with PCT ((126 S+/-chemo(C) = 19% of NSCLC), 190 PC-RT +/- C), and 31.5% palliatively. 467 (41.8%) received any RT, 268 (24%) any C. MVA showed age >70, PS≥2, metastatic disease, ‘not-SCLC’, but not sex, deprivation or Healthboard, were associated (all p<0.01) with lower treatment delivery, and only age > 80, PS≥2, radiology-only diagnosis and non-localised disease (all p<0.01) with reduced PCT. Median survival was 5.03 months (95%CI 4.3-5.8) with 46.8% alive at 6 months, 32.0% 12 and 17.7% 24 months following diagnosis. Male sex, PS≥2 and non-localised disease were associated with increased HR for death (all p<0.01). Comparison with the 2002 cohort (n= 971, Dumfries excluded from both cohorts) showed similar age and pathology profile, but increased women, residents from most deprived quintile and metastatic disease. Uni-variate analysis showed a similar proportion received treatment (62.3% 2002 v. 59.9% 2010 p=0.14) but more received PCT (23.6% v. 28.2% p=0.02) principally through increased use of PC-RT (13.1% v. 17.1% p=0.01). On MVA (without PS) the use of any treatment reduced (OR 0.73 (0.59-0.92) however, use of PCT increased (OR 1.84 (1.37-2.47) due to more PC-RT (1.57 (1.18-2.08)), but not surgery. Median (5.16 v. 4.90 months p=0.65), 1 year (29.0% (31.9-26.1) v. 31.4% (34.3-28.5) and 2 year (14.9% (17.3-12.5) v. 17.4% (19.8-15.0) survival were unchanged.

Conclusion
In the last 8 years in SCAN, there has been an increase in the number of women with lung cancer along with a worsening deprivation profile and increased identification of stage IV disease, possibly through improved staging. There has been an increase in potentially curative, but reduction in all therapy delivered without any apparent impact on survival. This analysis demonstrates the challenges of improving population-based outcomes in a disease where most present with advanced disease and are often unfit for treatment .

Background
In the United States (US), anti-smoking policies have resulted in a population-wide decline in lung cancer rates over the past decade. However, little is known about how lung cancer incidence trends vary among Asian-American ethnic populations, the largest growing population in the US.

Methods
For the first time, annual population estimates for Asian-American ethnic populations were developed for the regions in the Surveillance, Epidemiology, and End Results program, comprising half of the total U.S. Asian-American population. From 1990-2010, incidence rates and average annual percentage change (APC) were computed for each racial/ethnic group for lung cancer overall and by gender and histology.

Results
Among Asian-American males, trends were either stable or declining in all groups (Figure 1). The declines were statistically significant among Koreans (APC = -3.0), Hawaiians (APC = -2.3), Vietnamese (APC = -1.4), Filipino (APC = -1.9 from 1996-2010), and Chinese (APC = -1.5). Among Asian-American females, declining trends were seen among Hawaiians (APC = -5.9 from 2002-2010) and Vietnamese (APC = -1.5). In contrast, increasing trends were seen among Japanese (APC = 1.7) and Filipinas (APC = 1.5). Among Asian-American males, all histologies exhibited stable or declining trends with the exception adenocarcinoma, which increased among Chinese males from 1997-2010, appearing independent of the decrease in NOS, which occurred much later in this group. Among Asian-American females, declining or stable trends were seen for most histologies, with the exception of adenocarcinoma among Filipina and Korean females (APC = 2.5 and 3.0, respectively), and squamous cell carcinoma among Japanese females (APC = 2.4). Figure 1

Conclusion
To the extent that Asian-Americans have distinct primary and second-hand smoking profiles, unique environmental exposures , and population-specific genetic predisposition, analysis of incidence trends by histology suggests that, among Asian-American females, additional risk factors beyond primary and perhaps secondary smoking may be important for lung cancer etiology. The continued increase of lung cancer incidence among Filipina, Korean, and Japanese American females, especially in adenocarcinomas and squamous cell carcinomas, warrants further attention.

Background
BACKGROUND: Second primary lung cancer (SPLC) in patients who have been treated for a prior lung cancer is a recognized phenomenon. There has been an improvement in the staging and treatment of lung cancer in the last several decades resulting in longer survival for pts and affording an opportunity for the development of SPLCs. The objective of this study was to establish the frequency of SPLCs and to characterize the demographics, histology and stage at presentation, time interval between diagnoses, and cumulative risks of developing a SPLC in this pt population.

Methods
METHODS: The pts were identified from population-based SEER-9 Registries Data Base. All pts with a primary lung cancer between 1973 and 2004 were included with follow-up to 2009. The histology and stage of the SPLCs were evaluated in comparison to the initial primary lung cancer (IPLC). The incidence of SPLCs was compared to the expected incidence by calculating multiple primary-standardized incidence ratios (MP-SIRs) using the SEER Stat program. Selected cohorts were stratified by sex, race, age at diagnosis, and date of diagnosis. Sex-specific cumulative risks of developing SPLCs were calculated using the Kaplan-Meier method.

Results
RESULTS: 208,486 pts had an IPLC diagnosed from 1973-2004. No smoking history was available. Patient Characteristics at time of IPLC: 60.4% male; 84.3% white; 8.5% (20-49 yr), 55.9% (50-69 yr), 35.6% (≥ 70 yr); 84% non-small cell lung cancer (NSCLC); 33.8% distant disease, 23.5% regional, 29.9% local. 5,302 pts developed SPLC. The majority were male (56.6%), white (84.9%), and in the 50-69 yr age group (68%). Females had the highest SIR values across all ethnicities and age groups particularly in the youngest cohort (20-49 yr) where the SIR was 8.58. The SIR values were ≥ 2 for all cohorts expect for males ≥ 70 yr (SIR=1.65). The predominant histologic types for IPLCs were adenocarcinoma (ADC) and squamous cell cancer and the associated SPLCs were usually of the same histology. IPLC ADC and BAC pts were most likely to develop a SPLC. Most SPLCs (50%) presented with regional or distant disease, while only 37% were localized at diagnosis. The median time to development of SPLCs was 68 mo for males and 74 mo for females. The risk of developing a SPLC continually increased as a function of time for both sexes.

Conclusion
CONCLUSION: Patients with a history of IPLC are at high risk for developing SPLC and this risk increases over time. This is especially true of females who are diagnosed at an early age with their initial lung cancer. The majority of SPLCs present late and at a more advanced stage. These findings could have major implications with regard to the length and type of surveillance in pts who survive their initial lung cancer diagnosis.

Background
Obesity has been shown to be an adverse prognostic factor in several cancers, including breast, colorectal, endometrial, ovarian, pancreatic and prostate. However, studies of body mass index (BMI) and outcomes in lung cancer are lacking. Understanding the clinical impact of body weight on cancer outcomes is important given the high prevalence of obesity globally. We retrospectively evaluated the distribution of BMI at diagnosis and its effects on survival in stage 3 and 4 lung cancer patients.

Methods
1,121 patients with stage 3 or 4 lung cancer from a single institution were analyzed. Clinicopathologic data were collected retrospectively. Adjusted hazard ratios (aHR) for overall survival (OS) and progression-free survival (PFS) were generated by Cox regression for each BMI (kg/m[2]) category (underweight: <18.5, normal: 18.5-24.9, overweight: 25.0-29.9, obese: ≥30), after adjusting for age, gender, Charlson Comorbidity Index, performance status (PS), clinical stage and treatment regimen.

Results
In this cohort (n=1,121), the frequencies of stage 3A, 3B and 4 lung cancers were 35%, 32% and 33%, respectively. There were 633 (57%) adenocarcinomas, 238 (21%) squamous cell carcinomas, 38 (3%) small cell lung cancers, and 210 (19%) other histologies. Patients had variable BMI: 82 (7%) underweight, 550 (49%) normal weight, 333 (30%) overweight, 156 (14%) obese. Being overweight/obese was associated with older age (p=0.002) and stage 3A disease (p=0.001); underweight patients were more likely current smokers (p<0.001). OS was significantly decreased with age ≥65, males, PS 2-3, stage 4, and lack of systemic treatment (p<0.001). Median OS in underweight, normal weight, overweight and obese patients were 14, 23, 24 and 26 months, respectively. Compared with BMI ≥18.5, being underweight was associated with significantly poorer OS (aHR 1.33, 95% CI 1.01-1.77, p=0.045), but not PFS (aHR 1.12, 95% CI 0.86-1.46, p=0.414). The magnitude of this association was greatest among those aged less than 65 years (aHR 1.57, 95% CI 1.11-2.22, p=0.011).

Conclusion
In stage 3 and 4 lung cancer, being underweight at diagnosis is associated with significantly poorer OS, especially in patients younger than 65 years of age. Lower BMI is mostly observed in current smokers, while above normal BMI is seen in older patients and stage 3A disease. Unlike other malignancies, obesity does not increase mortality in this population. The BMI-survival relationship in lung cancer requires further study.

Abstract not provided

Background
In HIV, cancer, and other diseases, stigma is known to have a negative impact on patient outcomes. Regardless of smoking status, lung cancer patients feel stigmatized because their disease is strongly associated with smoking. In addition, higher levels of lung cancer stigma (LCS) are associated with higher levels of depression and poorer quality of life (QOL). Previous studies have measured LCS in heterogeneous samples of patients at various stages of their disease and treatment. The purpose of this study was to evaluate LCS levels in a homogenous sample of patients 5 months after lung cancer surgery and to identify correlates of LCS.

Methods
Patients were recruited from three university hospitals in Norway. They completed a number of self-report questionnaires and the Cataldo Lung Cancer Stigma Scale (CLCSS). The CLCSS is a 31-item scale with each item rated on a 4-point Likert scale (i.e., strongly disagree to strongly agree). Descriptive statistics were used to present demographic and clinical characteristics. Reliability of the CLCSS was assessed using Cronbach’s alpha. Multiple regression analysis was done to identify characteristics associated with higher levels of LCS.

Results
Findings from this study provide data on the first time use of the CLCSS in a Norwegian sample of patients with lung cancer. Cronbach's alpha for the total CLCSS score was 0.95. The sample consisted of 121 (57.1%) men and 91 (42.9%) women who had a mean age of 66.1 years (SD=8.3, range 30 to 87). The mean stigma score was 44.0 (SD=13.8) with a range of 31 to 109 (a higher score, indicates higher level of stigma). Bivariate analysis of demographic and clinical characteristics revealed that patients with a higher level of stigma were younger (r = -.18, p =.01), more likely to live in a small town compared to rural areas (p=.04), had smoked until the time of surgery (p=.008), and had higher levels of depression (r = .24, p˂.001). Marital status was included in the multivariate analysis, because it approached significance in the bivariate analysis (p=.07). In the multivariate analysis, marital status (p=.002) and depression (p=.006) remained significant. The final multivariate model explained 13.5% of the variance in stigma scores. Marital status and depression symptom scores uniquely explained 3.6% and 4.6% of the variance of stigma, respectively. Patients who were married and patients who reported higher depression scores reported higher stigma scores.

Conclusion
The CLCSS is a valid measure of stigma in Norwegian patients with lung cancer. The majority of the patients (97%) reported stigma scores below 75.7, the mean score obtained in a United States sample. However, 3% of the sample had a stigma score of >75.7. In a Norwegian sample of lung cancer patients, being married and having a higher mean score on the Center for Epidemiological Studies-Depression Scale (i.e., 27.3 (SD=13.4)) were associated with higher LCS.

Background
Lung cancer patients in Australia report a profound experience of stigma. Therapeutic nihilism, differences in chemotherapy treatment options compared to other cancers, and the onset controllability of the disease are some of the contributing factors to the stigma and its effects on the patient, such as poor psychosocial and quality of life outcomes. This is the first known study to investigate the constructs underlying the community’s views on lung cancer through the lens of a prominent social stigma model. This model explores three domains of stigma; enforcement of social norms, avoidance of disease and exploitation of the stigmatised group. Health Locus of Control Theory and Terror Management Theory explore the role of health beliefs and death anxiety as antecedent variables to the social stigma of lung cancer.

Methods
A total of 211 university students (males = 56, females = 155) (64% undertaking a health degree) completed an online survey containing the Cataldo Lung Cancer Stigma Scale (CLCSS), the Death Anxiety Inventory (DAI) and the Internal and Chance subscales of the Multidimensional Health Locus of Control scale (MHLC). Approximately 65% of participants were 18-25 years of age and “never smokers”. Approximately 40% had current or previous contact with a person suffering lung cancer.

Results
The underlying structure of the CLCSS was investigated using principal axis factoring with varimax rotation. Four factors accounted for 61% of variance in lung cancer stigma. To test the hypothesis that the fear of death and health beliefs respectively account for a portion of variance in lung cancer stigma, a hierarchical multiple regression analysis (MRA) was employed. On step 1, demographic variables, smoking status, family smoking history and contact with lung cancer accounted for a significant 10% of the variance in lung cancer stigma, R[2 ]=.10, F(7, 201) = 3.03, p =.005. Entering death anxiety and health beliefs respectively at step two explained an additional 4% variance in lung cancer stigma, ∆R[2 ]=.14, ∆F(3, 198) = 3.16, p =.001. A combined effect of this magnitude can be considered “medium” (f [2] = .16). Smoking status (sr[2] = .03) and fear of death (sr[2] = .03) were significant predictors of lung cancer stigma. Health beliefs were non-significant predictors.

Conclusion
A lung cancer patient is likely to evoke emotions associated with a fear of death for community members who are high on death anxiety. This result aligns with the social stigma model; empathy for the patient is replaced with avoidance of the diseased person. This has implications for media and research representations which focus on the high mortality rate and the “ugly” nature of the disease. The 60% variance in social stigma explained by the CLCSS conceptually aligns with domains of lung cancer stigma identified in the theoretical model. However, for the remaining variance, health beliefs were non-significant predictors of stigmatising norms against lung cancer patients. This suggests the moral dimensions underpinning the social stigma of lung cancer may warrant further investigation, particularly in relation to smoking behaviours.

Background
Lung cancer is associated with greater levels of psychological distress than any other cancer. Anxiety and depression are associated with diminished QOL for lung cancer patients, but do not explain the total variance in QOL. Lung cancer stigma (LCS) may explain some of the additional variance in QOL. LCS is a perceived stigma resulting from negative perceptions about the relationship between smoking and lung cancer. This study’s theoretical framework is the Lung Cancer Stigma Model (LCSM), a patient-centered model that includes precursors, perception and responses to LCS. LCS, according to LCSM, is characterized by diagnosis and connections to tobacco exposure and smoking stigma; experiences of discrimination, isolation or shame; and responses ranging from increased symptom burden to Stigma Resistance (SR), defined as “opposition to the imposition of … stereotypes by others” (Thoits, 2011)and shown to positively correlate with self-esteem, empowerment and QOL. Study aims and hypotheses were to: 1) Investigate the relationship of LCS with anxiety, depression and QOL; 2) Explore whether LCS has a unique contribution to the explanation of QOL after controlling for significant covariates (i.e., sex, age); and 3) Compare whether study variables vary by smoking status.

Methods
This was a descriptive, cross-sectional study (N=149). An online survey of lung cancer patients recruited from cancer information and support websites included demographic questions, the Cataldo Lung Cancer Stigma Scale, the Spielberger State Anxiety Questionnaire, the CES-D, and the Quality of Life Inventory.

Results
Data from primarily Caucasian female participants with a history of smoking demonstrated strong negative associations among anxiety, depression, LCS and QOL, regardless of smoking status; this confirmed previous findings that LCS is positively correlated with anxiety and depression and negatively correlated with QOL. A final hierarchical multiple regression with revealed an overall model explaining 71.5% of the total variance of QOL (F~5,143~=71.61, p<.001). After controlling for significant covariates, anxiety, and depression, LCS provided a small but significant unique contribution to the explanation of variance in QOL (1.2%; p=.015). Furthermore, results substantiate previous findings of no difference in these relationships by smoking status. Both ever and never smokers’ experiences are similar with respect to anxiety, depression, LCS and QOL.

Conclusion
Because lung cancer is widely viewed as a smoker’s disease, patients who have never smoked often experience the same stigmatization as smokers, characterized by a feeling imparted from others that one’s disease was self-inflicted. This investigation explored this experience of LCS and validated previous findings linking QOL and LCS. LCS provides unique explanatory contribution to the understanding of QOL for lung cancer patients. Therefore, providers should consider not only typical psychosocial aspects of the diagnosis, but also patient experience of LCS. Related, LCS literature suggests a gap in the psychosocial care of lung cancer patients; no stigma reduction intervention is currently available. Providers might encourage their patients to engage in potential stigma reduction behaviors that may positively impact QOL: 1) self-educate about their diagnosis, 2) critically evaluate their treatment plans, 3) attend support groups, and 4) advocate against stigma.

Background
Lung cancer survivors experience more physical and psychosocial problems for a longer period of time than survivors of other cancers. Whether they have ever smoked or not, lung cancer patients feel stigmatized because their disease is strongly associated with smoking. In our previous work, lung cancer stigma (LCS) was a significant predictor of increased depression and decreased quality of life (QOL). With an increased number of lung cancer survivors and a dearth of information on all perspectives of their health and QOL, additional research is needed to understand not only the associations among LCS and psychosocial factors, but also associations among LCS and physical symptom burden. This study was designed to investigate the relationship between LCS, anxiety, depression and physical symptom severity.

Methods
This study employed a cross-sectional, correlational design with recruitment of patients from online lung cancer websites. LCS, anxiety, depression and physical symptoms were measured by patient self-report using validated scales via the Internet. Hierarchical multiple regression was performed to investigate the individual contributions of LCS, anxiety, and depression to symptom severity.

Results
One hundred and forty-four participants ranged in age from 23 to 79 years (mean age=56.7 years); 93% were Caucasian, 79% were current or former smokers, and 74% were female. There were strong positive relationships between LCS and anxiety (r=0.413, p<.001); depression (r=0.559, p<.001); and total lung cancer symptom severity (r= 0.483, p<.001). Although small, LCS provided a unique and significant explanation of the variance in symptom severity beyond that of age, anxiety, and depression, by 1.3% (p<.05).

Conclusion
Because LCS is associated with both psychosocial and physical patient outcomes, research is needed to develop interventions to assist patients to manage LCS Some evidence suggests that LCS is a hindrance to help-seeking behavior and prevents early detection and treatment and may keep patients from reporting distressing symptoms. A significant number of smokers report feeling unworthy of treatment. Patients are frequently reluctant to report respiratory symptoms when they are smokers, a behavior clearly related to the feelings of shame and guilt. This reluctance is a consequence of general supposition that lung cancer is a self-inflicted disease. Because lung cancer is widely viewed as a smoker’s disease, those who have never smoked often experience the same stigmatization: a feeling that their disease was self-inflicted. Although the prognostic outlook for lung cancer patients is changing, clinicians know that lung cancer has one of the poorer prognoses of all human malignancies and that might unintentionally limit communication, treatment options, and symptom management. Future research is needed to elucidate the mechanisms that underlie lung cancer stigma; longitudinal investigations of LCS and patient outcomes are needed to understand causal relationships; and development of effective interventions to decrease both perceived and projected stigma are essential.

Background
It has been proposed that stigma and nihilism surrounding lung cancer may influence lung cancer outcomes. A clear understanding of the impact of lung cancer related stigma and nihilism from the perspectives of health professionals and consumers will assist in informing best practice lung cancer care and health promotion messages in Australia. As part of a national lung cancer program, Cancer Australia commissioned Cancer Council Queensland, in partnership with Griffith University, to undertake a three-phase research project on stigma and nihilism about lung cancer in the Australian context.

Methods
Phase 1: A systematic literature review examined the evidence on the influence of stigma and nihilism on lung cancer patterns of care; patients' psychosocial and quality of life (QOL) outcomes; and how this may link to public health programs. Phase 2: The perspectives of health professionals on the impact of stigma and nihilism on diagnosis and disease management were investigated. Semi-structured interviews and a Delphi process with 31 key informants developed a consensus view, which was then tested with 323 health professionals in a national online survey. Phase 3: The perspectives of lung cancer patients and carers on the effects of stigma and nihilism on their cancer experience were investigated. Qualitative interviews were undertaken with 17 patients and 11 carers followed by a cross-sectional survey with 147 lung cancer patients in QLD and NSW.

Results
Systematic review: Stigma relating to lung cancer was reported by both patients and health professionals and was related to poorer QOL and higher psychological distress in patients. Empirical explorations of nihilism were not evident. Qualitative evidence from patients’ perspectives suggested that public health programs contribute to stigma about lung cancer. Health professionals’ perspectives: Health-related stigma and the need for positive messaging about lung cancer and smoking cessation were priorities. Geographical barriers to access and a lack of rural/regional services were described. Barriers for Aboriginal and Torres Strait Islander people included fear of dying away from community and poor cancer knowledge. Patient and carer perspectives: Qualitative data were consistently indicative of stigma amongst patients due to perceived personal responsibility in the smoking-lung cancer relationship and perceived links between lung cancer and negative outcomes. Quantitative data revealed high levels of psychological distress but low help seeking; health-related stigma was significantly related to poorer psychological and QOL outcomes.

Conclusion
Health-related stigma has negative impacts on people affected by lung cancer in Australia and may contribute to poorer psychological health and QOL outcomes. The research helps to build the evidence about factors influencing lung outcomes in Australia. It provides an important foundation for further research and the development of strategies to ameliorate the effects of stigma on patients and carers.

Background
Limited (wedge) resection of pulmonary lesions is frequently performed as a diagnostic/therapeutic procedure. Some lesions may be difficult to locate thoracoscopically and conversion to open thoracotomy or incomplete resection are potential limitations to this approach. Multiple methods have been described to aid Video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules including hookwire localization, percutaneous tattoo or intra-operative ultrasound. We report on our experience using Electromagnetic Navigational (EMN) bronchoscopic dye marking of small subpleural lesions to assist wedge resection.

Methods
Six patients planned for VATS resection of a peripheral pulmonary lesion underwent pre-operative bronchoscopy. Electromagnetic navigation was utilized to accurately guide a 25-gauge needle to within/adjacent to the lesion for resection and 1mL of methylene blue or indigo carmine was injected under fluoroscopic vision.

Results
Six patients underwent bronchoscopic marking of peripheral pulmonary lesions. Navigation to lesions was successful in all six patients. Surgery was performed within 24 hours of bronchoscopic marking. Pleural staining by dye was visible thoracoscopically in all six lesions either adjacent to or overlying the lesion. All lesions were fully excised with wedge resection. Pathologic examination confirmed accuracy of dye staining and established the diagnosis of malignancy.

Conclusion
EMN bronchoscopic dye marking of peripheral lesions is feasible, and is not compromised by complications associated with percutaneous marking procedures. Further experience is required but early findings suggest this method may have utility in aiding minimally invasive resection of small subpleural lesions.

Background
The National Lung Cancer Audit (NLCA) (NHS Information Centre, 2011) reports annually on services provided to 38,000 lung cancer patients in the nited Kingdom (UK). The 2010 NLCA reported that only 58% of lung cancer patients in England and Wales received active treatment (chemotherapy, surgery and radiotherapy), with only 14% of patients receiving surgery. Lung Cancer Nurse Specialists (LCNS) make an important contribution to patient care and patient experience and their input is captured in the audit. The 2010 NLCA revealed a possible association between access to a LCNS and access to treatment: 64% of patients seen by a LCNS received anti-cancer treatment compared to 30% of those who did not (Ford, 2011, The Lancet 2011). The reason for this observation cannot be ascertained from the NCLA data. Thus investigation outside of the audit is required. This study begins that process using case study methodology. The study is funded by a grant from the General Nursing Council Trust. The aims of this study are to explore the role of the LCNS within the lung cancer multi-disciplinary team (MDT), identify ways the LCNS can increase treatment access for people with lung cancer and generaterecommendations for MDTs and for future research.

Methods
A collective case study, comprising four individual LCNS in four different lung cancer MDTs (McDonnell, 2012, Stake 1995). LCNS cases were selected on the basis of variation in access to treatment rates and access to a LCNS according to the NLCA data. The four LCNSs also had different models of working within the MDT and patient pathway. Methods included in-depth individual interviews with the LCNS and clinical lead plus four other MDT members, giving a total interview sample of 24. Observation of practice and documentary analysis were also used. Findings will be tested further in group interviews over the summer.

Results
These findings provide insight into how the LCNS works across the patient pathway to influence access to treatment, while maintaining patient preference as central to practice. The findings are presented here in four themes: practice approaches, people, places and facilitators, with illustrations of how factors combined to increase or decrease access to treatment. Approaches to LCNS practice identified in the study included negotiating, brokering and co-ordinating in order to maximise treatment access and maintain patient focus. The range of people and places the LCNS works with across different disciplines, services and health sectors means they become the lynchpin to clinical treatment decisions. The study indicates how workload, relationships, job security and organisational structures operate as key facilitators to effective treatment decision making

Conclusion
This in-depth qualitative study provides valuable insights into the complex landscape that MDTs operate within and helps to explain why the observed association between seeing a LCNS and access to treatment may occur. The study illustrates the value of qualitative research in understanding quantitative data such as that generated by national registries and audits. Recommendations for MDTs and data capture in the NLCA audit are considered.

Background
The UK National Lung Cancer Forum for Nurses together with the Roy Castle Lung Cancer Foundation have produced a report which aims to showcase the difference Lung Cancer Nurse Specialists (LCNS) make to the lives of patients with lung cancer and their families. Eleven recommendations were made after an examination of peoples experiences of care delivered by LCNSs in addition to LCNSs own accounts of how they help to improve patient outcomes. The recommendations, combined with existing evidence of the positive impact of LCNSs on patient experience from the Cancer Patient Experience Survey and outcomes shown in the National Lung Cancer Audit, builds a compelling picture of the positive value of LCNSs. The report is called Understanding the Value of Lung Cancer Nurse Specialists.

Methods
The National Lung Cancer Audit data was used to gather information about whether patients had been seen by a LCNS and at what point in their pathway. A survey was conducted of patients with lung cancer and their carers with the aim of uncovering people`s experiences of the care delivered by LCNS. A survey of LCNS own accounts of how they help to improve patient outcomes was also undertaken. Information was taken from the Cancer Patient Experience Survey in England to assess the influence that Clinical Nurse Specialists had on the patient`s experience of care. Evidence was analysed from a number of different sources to highlight the potential efficiency savings that LCNS could make due to their role.

Results
Results from the Cancer Patient Experience Survey showed that one of the most important findings being that those patients with access to a CNS gave more positive scores of experience than those without. When considering efficiency savings, one study found that service improvments along the lung cancer pathway led by LCNS could release about 10% of cancer expenditure in the area. The National Lung Cancer Audit revealed that around two thirds of patients seen by a LCNS went on to receive active treatment compared to less than a third who did not see a LCNS who were given active treatment.

Conclusion
The report examines the information made available and the role of the LCNS with the aim of helping to understand that vital contribution they make to the delivery of high quality care and to improved outcomes for patients with lung cancer. The report can be found at http://www.roycastle.org/Resources/Roy%20Castle/Documents/PDF/UnderstandTheValueOfLungCancerNurseSpecialists_V03.pdf

Background
In a recent landmark US study, metastatic NSCLC patients who received palliative care from the time of diagnosis concurrently with standard oncology management reported improvements in quality-of-life, symptom control, reduction in “aggressive therapies” at end-of-life, and a survival advantage compared to those receiving standard oncology management alone. The aim of this qualitative sub-study was to explore Australian health care professionals’ perceptions of early integration of palliative care for patients with incurable lung cancer.

Methods
Members of the lung cancer multi-disciplinary teams of three large metropolitan teaching hospitals in Melbourne were invited to attend a focus group discussion. Data from focus groups were supplemented with interviews from a purposive sample of individual health care providers who were unable to attend the groups. Participants were asked to describe barriers and facilitators to implementation of a model of early integration of palliative care.

Results
Three focus groups and six individual interviews were conducted with 28 health care professionals. Key facilitators and barriers to referral (see table) were grouped into 4 themes: 1. Trust; 2. Care Coordination; 3. Ease of Referral; and 4. Perceived patient/family reaction.

Conclusion
Early involvement of palliative care in patients with incurable lung cancer is acceptable to the majority of treating clinicians. Palliative care services must be embedded into the system, sufficiently resourced and of high quality. For early referral to occur the model ideally involves a physical presence of a palliative care clinician in clinic who is easily accessible for referrals and considered a core team member.

Abstract not provided

Background
Radiotherapy (RT) is a clinically and cost effective modality of treatment for symptom palliation. It plays a significant role in advanced lung cancer, by providing relief from symptoms such as haemoptysis and bone pain, as well as preserving neurological function in patients with brain metastases or spinal cord compression. The standard clinical approach for RT may require multiple attendances for consultation and planning, followed by a waiting period for treatment. However, patients with advanced lung cancer presenting for palliative radiotherapy are often of poor performance status with limited life expectancy. Prompt and streamlined RT is required to improve the experience of care for these patients. The Palliative Radiotherapy Rapid Assessment Clinic (PRRAC) was developed as an innovative and sustainable clinic to align consultation, planning and treatment within a single visit to facilitate efficient access to palliative radiotherapy for patients with advanced lung cancer. The PRRAC aims to i) increase accessibility of palliative RT for symptomatic patients with lung cancer, ii) reduce waiting times and iii) improve patient and referrer satisfaction.

Methods
A retrospective audit of symptomatic patients with lung cancer who received low dose palliative RT from June – November 2012 at Peter Mac, East Melbourne was performed. Patient demographics, dates of initial clinic, planning and RT commencement, and RT dose fractionation schedules were collected. A service model (PRRAC) was developed based on the adaptation of similar clinics in operation in Canada and Brisbane, Australia. The proposed PRRAC will be piloted for 6 months. Eligibility criteria include those patients with symptomatic locally advanced or metastatic lung cancer who require low dose simple RT techniques. Service utilisation and average waiting times will be compared to previous patterns of care. Patient outcomes and surveys of referring physicians will be evaluated prospectively. Overall utilisation of the service will help assess clinical need & sustainability.

Results
The retrospective audit has demonstrated 79 patients with lung cancer who were prescribed low dose palliative RT. The mean age was 70 years and 17% of patients were ECOG status >3. The mean waiting time from initial clinic assessment to planning was 3.6 days (SD 3.7), and from planning to RT commencement was 5.4 days (SD 5.1). 48% of patients were prescribed a single dose of RT. The early results and challenges in developing the prospective PRRAC as a new model of care for patients with lung cancer will be presented.

Conclusion
The PRRAC is expected to improve access of patients to palliative radiotherapy, and shorten waiting time from clinic to RT commencement date with less visits and potentially shorter dose fractionation schedules. It is anticipated that PRRAC will also improve patient and referrer satisfaction. Following successful completion of the project, the PRRAC will be embedded into clinical practice, and extended to other tumour streams.

Background
This study aims to investigate the influence of a geriatric assessment (GA) on cancer treatment decisions in older lung cancer patients (pts). We also studied the changes in functionality during treatment and the occurrence of severe chemotherapy-related toxicity.

Methods
For this analysis, we selected the lung cancer cohort that was part of a larger study on GA in older cancer pts in 6 tumor types in two Belgian university hospitals[1]. Between July 2009 and September 2011, pts aged 70 years or older with a newly diagnosed or progressive lung cancer were evaluated at baseline using a uniform GA including geriatric screening with G8 and the Flemish Triage Risk Screening Tool (fTRST), pain, social data, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), fall history, Mobility-Tiredness Test (MOB-T), Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Mini Nutritional Assessment (MNA), ECOG-Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and poly-pharmacy assessment. GA results were communicated to the treating physician and, after the treatment decision, the physician was interviewed using a predefined questionnaire focusing on unknown geriatric problems revealed by GA and impact on cancer treatment decisions. Between two and three months of follow-up, functionality was reassessed and severe toxicity in pts receiving chemotherapy was recorded.

Results
Seventy three lung cancer pts were included with a median age of 76 years; 82.2% were non-small cell lung cancer (NSCLC) and 74% were stage IV. Treatment was modified from standard according to standard clinical assessment (including age) in 56.1%. GA revealed unknown geriatric problems in 25.8% of cases, leading to a geriatric intervention in 10.6%. 30% of physicians consulted the GA before final treatment decision and in three pts (4%) only this led to a modification of the proposed treatment: dose reduction, no chemotherapy or no radiotherapy. At follow up (n=50), functional decline was observed in 24% and 54% of pts for ADL and IADL, respectively. Grade III-IV toxicity occurred in 14/42 pts treated with chemotherapy (33%), mainly non-haematological (64%).

Conclusion
This analysis indicates that the treatment of older lung cancer pts is often influenced (deviated from standard) by standard clinical assessment and age. Although GA revealed previously unknown information in 25.8% of pts, only a minority of physicians consulted these results before the final cancer treatment decision. There was little impact on geriatric intervention and even less on cancer treatment decision. This discrepancy reveals the need to get physicians treating lung cancer acquainted with GA and geriatric interventions in an attempt to decrease chemotherapy related toxicity and improve quality of care. Further evaluation of GA and geriatric interventions in larger pt groups as well as their implementation in clinical practice is warranted.

Background
Although lung resection still provides the best long-term outcome for lung cancer, it is also associated with a considerable decay in physical and psychosocial health status[1,2]. If not controlled, these symptoms can hamper postsurgical recovery, and lead to unscheduled healthcare use[3]. This study aimed to determine the clinical relevance of and functional requirements for a telerehabilitation (TR) service to support recovery following lung resection.

Methods
A sociotechnical scenario-based design approach was used, characterized by early and systematically involvement of patients and healthcare providers during an iterative design process (figure 1). First, end users’ requirements for the TR service were explored by means of semi-structured interviews. Subsequently a small focus group with healthcare providers from the Netherlands Cancer Institute – Antoni van Leeuwenhoek hospital (NKI-AVL) in Amsterdam was organised to establish requirements for the TR service in more detail. The findings from the interviews and focus group were summarized in a scenario and validated by healthcare professionals from the NKI-AVL. Figure 1

Results
Survivors and professionals expected a TR service to be beneficial for improving quality of current care, and identified three modules that should be included in the TR service: ambulant monitoring of recovery and symptoms, home exercise programs and patient-provider contact. The functional requirements for these three modules and general requirements as reported by the patients and professionals are presented in table 1. The results also indicated that successful implementation of the service will be promoted by structurally embedding the service in existing healthcare processes, and record clearly the specific roles and responsibilities of all involved healthcare professionals. Figure 1

Conclusion
End-users showed positive intention to use a TR service for home-based symptom monitoring and rehabilitation. At this moment, a prototype of the TR service is designed, which will be evaluated this summer in patients and healthcare providers to improve end-users’ acceptance.

Abstract not provided

Background
Current management of lung cancer (LC) (chemotherapy - CHT, radiotherapy – RT, and biological therapies) occurs predominantly in the ambulatory care (AC) setting. Post-surgery hospital admission is becoming progressively shorter due to advances in technique and greater reliance on home recovery.[1,2]As such, LC management occurs outside the scope of current thromboprophylaxis (TP) guidelines.[2-8] Recommendations for TP strategies in these high thromboembolism (TE) risk patients are lacking.[9] The aim of this study was to profile TE incidence in LC patients receiving anti-cancer therapy, exploring patient-, disease- and treatment-related risk factors associated with higher thrombotic rates. This could identify high-risk populations, disease features and/or treatment periods that warrant strong recommendations for targeted preventative strategies to reduce LC-associated TE, and in particular consideration of pharmacological-TP (P-TP).

Methods
Retrospective review of LC patients referred to Peter MacCallum Cancer Centre, a tertiary dedicated cancer centre, between 01/07/11 - 30/06/12 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records. Follow up was defined as time from study entry (referral date) to first occurring event; TE, death, loss to follow-up or study end. Hazard ratios were calculated using Cox proportional hazards model.

Results
222 patients were followed for a median 10 months from time of first hospital registration. The cohort was predominantly newly diagnosed (77%), with advanced disease (71%), NSCLC (92%). Among NSCLC adenocarcinoma was the predominant histological subtype (77%). 30% of patients received multiple lines of therapy within the study period; 49% received CHT (alone or combination chemoradiotherapy, CRT), 73% RT (alone or CRT), 19% biologic therapy and 19% surgical intervention. 10.8% of patients had radiologically confirmed TE, giving an incidence rate of 131 events per 1000 person-years (95%CI 87-195). 83% (20/24) of events occurred in the AC setting; 71% symptomatic, 29% asymptomatic. 16 events were pulmonary embolism (PE) (5 fatal), 4 deep vein thrombosis (DVT), 1 combination DVT/PE, 1 atrial and 2 arterial thrombosis. TE occurred frequently in both NSCLC and SCLC (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell histology (14.7% and 5.3% respectively). Presence of more advanced or metastatic disease, prior history of TE and comorbidity score>2 were associated with higher rates of TE. More than a third (38%) of TE events occurred during the CHT period, 13% post-surgery, 8% during RT and biologic therapy respectively. CHT demonstrated more than five-fold increased TE risk compared to no CHT (HR 5.7 95% CI 2.2-14.8) with a similar finding for RT (HR 5.2 95%CI 2.0-13.2). Importantly, P-TP was not routinely or systematically prescribed for ambulant LC patients during any treatment phase, at this institution.

Conclusion
LC patients are at high risk of preventable and potentially life-threatening thrombotic events. TE events occur frequently in the AC setting and consideration of P-TP is warranted, but not used routinely due to a lack of high quality data. There is a demand for appropriate risk-stratification and directed preventative strategies. Prospective data and the development of dynamic risk profiles which can direct clinical practice are needed.

Background
Venous thromboembolism (VTE) is common in lung cancer patients and the incidence is increased by treatments including radiotherapy, surgery and chemotherapy. Research suggests a survival benefit in cancer patients receiving long term low moecular weight heparin (LMWH). LMWH may also have antimetastatic effects through the inhibition of P-selectin. This trial was developed to investigate whether or not adding LMWH to standard treatment increases overall survival. The study is funded by a research grant from Cancer Research UK (C13275/A5323) and free drug and an educational grant from Pfizer. The trial is sponsored by Velindre NHS Trust, and coordinated by the Wales Cancer Trials Unit, Cardiff, UK.

Methods
An open label, multi-centre, Phase III randomised controlled trial in patients with lung cancer comparing anticancer treatment according to local practice plus dalteparin (Fragmin®), with anticancer treatment alone. Eligible patients had a histopathological or cytological diagnosis of primary bronchial carcinoma (SCLC or NSCLC) within the previous 7 weeks, performance status 0, 1, 2 or 3 and were willing and able to inject daily subcutaneous injection. The dalteparin was given as a daily 5,000 IU subcutaneous injection for 24 weeks. The primary outcome measure is overall survival and the secondary outcome measures include toxicity, VTE-free survival, metastasis-free survival, quality of life, and cost utility. To detect an advantage of 5% in overall survival at 1 year (to 30%) a total of 2200 patients were required (1100 in each arm).

Results
2202 patients were enrolled and randomised in 4 years. The two groups were well balanced for key variables. 60% were men; the median age was 65 years; 82% had NSCLC (5% Stages I and II, 38% Stage III, 57% Stage IV) and 18% SCLC (63% Extensive Disease); 85% had WHO PS 0 or 1; 95% received chemotherapy as first treatment. 56% of those in the dalteparin arm received at least 90 of the 168 planned injections. By 1/8/2013 there had been 1891 deaths recorded and, on advice from the Independent Data Monitoring Committee, the primary results have been released. There was no significant difference in overall survival (HR 0.97; 95% CI 0.89-1.06) nor in metastasis-free survival. Exploratory subgroup analyses do not suggest a significant survival advantage in any subgroup. Dalteparin use was not associated with a significant increase in major bleeding complications. There were 78 (7.1%) confirmed VTEs in the control group and 47 (4.1%) in the treatment group.

Conclusion
This large RCT which recruited mainly good PS lung cancer patients having chemotherapy, has confirmed that prophylactic dalteparin reduces the risk of VTE events without a significant increase in major bleeding. The baseline VTE risk of 7% and relative risk reduction of 40% are consistent with previous studies. There was no significant difference in overall survival. These results do not support a policy of routine prophylactic anticoagulation of all lung cancer patients undergoing chemotherapy.

Background
Improving overall survival (OS) in locally advanced or metastatic non-small-cell lung cancer (NSCLC) remains a goal for clinicians. OS is often the primary endpoint in Phase III clinical trials, however with the increased use of multiple lines of treatment and crossover/rescue therapy in NSCLC trials, overall survival differences are frequently confounded. Other clinically meaningful endpoints such as progression-free survival (PFS) are becoming increasingly important. A systematic review and meta-analysis was undertaken to investigate whether the treatment effect on PFS, or objective response rate (ORR), was predictive of the treatment effect on OS in locally advanced or metastatic NSCLC.

Methods
Embase, MEDLINE and the Cochrane Library databases were searched to identify relevant published randomised controlled trials (RCTs). Included RCTs compared pharmacological treatments in two or more groups in patients with locally advanced or metastatic (Stage IIIb or IV) NSCLC. The reported outcomes had to include median PFS and median OS. Data were analyzed with locally weighted least squares regression (LOWESS) to validate the linear relationship. Unweighted linear regression and weighted linear regression were used to estimate the relationship between OS treatment difference and PFS treatment difference. A similar analysis was also done to compare ORR difference and OS difference. The analysis also considered whether potential baseline prognostic factors could also change OS difference. Univariate weighted linear regression was used to assess the relationship of each prognostic factor with OS difference, followed by multivariate weighted linear regression.

Results
A total of 124 RCTs (N=40,568 patients) were included in the analysis. Of the 124 trials, 98 (79%) were published since 2005. The age of patients ranged from middle aged cohorts to the elderly. There were 87 studies (70%) with first-line therapy and therapy type was predominantly chemotherapy (71 studies, 57%). The LOWESS of OS difference versus PFS difference was a relatively straight line, therefore a linear relationship appeared to be justified. Weighted linear regression showed a highly significant relationship between OS treatment difference and PFS treatment difference [slope 1.317 months (95%CI 1.000, 1.634) p<0.001 R[2] = 36.6%]. Diagnostic plots revealed several statistical outliers. A weighted linear regression of OS difference versus PFS difference with six outlier studies removed also showed a highly significant linear relationship [slope 0.994 months (95%CI 0.749, 1.240) p<0.001 R[2] = 36.7%]. The relationship between ORR difference and OS difference was also significant [slope 12.503 (95%CI 7.042, 17.963) p<0.001 R[2] = 16.0%]. Univariate weighted linear regressions showed that the only baseline prognostic factor with a significant linear relationship with OS difference was the proportion of patients with non-squamous histology. Multivariate weighted linear regression showed none of the baseline prognostic factors was significant when PFS difference or ORR difference was included in the model.

Conclusion
The treatment effect on PFS was predictive of the treatment effect on OS. For a 1 month increase in PFS treatment difference, OS treatment difference increases by approximately 1.3 months. A 10% increase in ORR treatment difference was also associated with an increase in OS of 1.25 months. PFS is an important outcome for healthcare decision-making.

Abstract not provided

Background
[18]F-fluoro-2-deoxy-D-glucose positron emission tomography complements conventional imaging for staging lung cancer although its ability to predict outcome is less well established. Two literature-based meta-analyses suggest a prognostic value in univariate analysis. To assess FDG-PET value in predicting survival adjusted for some known prognostic factors, we carried out a meta-analysis based on individual patients data from multiple independent studies.

Methods
Following literature search, and after writing of a protocol for the meta-analysis, we contacted the authors of identified studies and requested individual patients data; we also tried to collect some unpublished data. Data analysis used Cox regression models stratified for the study with overall survival as primary outcome. SUV max was used as a binary covariate (median value for each study).

Results
Data were collected for 1526 patients (57% of the identified patients) from 11 publications and 1 unpublished series (median age : 64 years, 60% male patients, squamous cell in 34%, adenocarcinoma in 47%, stages I-II in 58%). Combined univariate hazard ratio (HR) was 1.43 (95% CI : 1.22-1.66); no statistically significant interaction between SUV and one of six additional freatures (age, gender, histology,stage, tumors size –in stages I-III patients- and surgical treatment), was found except for stage (p=0.05) with a decreased prognostic value of SUV for stage IV patients. Without considering SUV, multivariate analysis identified, in stage I-III patients, age, stage, tumor size and surgical treatment as independent prognostic factors. The addition of SUV improved that model : HR estimate for SUV effect was 1.58, statistically significant (95% CI : 1.27-1.96), p<0.0001. No interaction was found with SUV. When tumor size was not included in the tested covariates, we found SUV of additional value (adjustment for age, stage, surgical treatment) with a HR of 1.35 (95% CI : 1.15-158). Interaction between SUV and stage was detected, restricting the significant impact of SUV on survival to stage I-III patients.

Conclusion
Conclusions : Although suffering from selection bias and lack of homogeneous SUV assessment, these data suggest that SUV at the time of diagnosis is an independent prognostic marker for patients with stage I-III NSCLC. The utility of SUV in predicting survival in stage IV patients requires further studies.

Background
There is a lack of data on the effect of conventional resistance training (CRT) on exercise capacity, muscle strenght and quality of life (QoL) in patients with lung cancer. Whole body vibration (WBV) is proposed as an alternative to CRT. We investigated the effect of a radical treatment and of two post-treatment resistance training programmes on the 6-minutes walking distance (6MWD).

Methods
Selected patients with clinical stage I-IIIB (non-) small cell lung cancer or I-II mesothelioma were evaluated before (M1) and at completion (M2) of their radical treatment, and thereafter randomised to either control (CON), CRT or WBV. 6MWD was measured at M1, M2 and at least 12 weeks (w) after randomisation (M3) considering a minimal clinically important difference (MCID) of 54 m. Assuming that this MCID would occur in 10% of the CON-group and aiming for an increase to at least 50% in the combined intervention groups (CRT and WBV), a sample size of 25 participants in each arm was required for a power of 90%. Secondary endpoints were estimated by appropriate MCID's for maximal exercise capacity (Wmax), muscle strenght (Quadriceps Force (QF)) and QoL (physical functioning (PF), fatigue (F), pain (P) and dyspnea D)). Multiple imputation was used to correct for patients not finishing the intervention.

Results
Of the 86 patients completing radical treatment, 70 were randomised: 24 to CON, 24 to CRT and 22 to WBV. Characteristics at M1 were well balanced. Radical treatment significantly decreased 6MWD, Wmax, QF, PF and increased P, F and D at M2. At M3, 20 of 37 (54%) patients in the combined CRT-WBV-group reached the MCID for 6MWD vs. 5 of 21 CON (24%) patients (p=0·031). 6MWD increased with 95 m (58–132) in CRT (p<0·0001), 37 m (-1–76) in WBV (p=0·06) and 1 m (-33–36) in CON (CRT vs. CON p=0·0006 and WBV vs. CON p=0·16). CRT and WBV patients recovered and exceeded their M16MWD, albeit not significantly. A significant mean increase in Wmax occurred in both CRT and WBV but not in CON, while QF increased only significantly in CRT. The mean score for PF at M3 improved in CON and WBV but only significantly with WBV. The mean score for P and F at M3 did not change significantly, however the MCID for F was reached in 37% of CRT, 44% of WBV and 30% of CON-patients. The mean score for D at M3 decreased significantly after WBV only. Multivariate analysis showed that there was no significant interaction between rehabilitation and surgery with regard to the MCID in 6MWD (p=0.96).

Conclusion
Radical treatment significantly impairs exercise capacity, muscle strength and QoL. CRT significantly improves and restores functional exercise capacity, whilst WBV does not fully substitute for CRT. Resistance training by CRT should be offered to radically treated lung cancer and mesothelioma patients. Supported by research grant 070708 of the Belgian Government Agency of Innovation by Science and Technology for applied Biomedical Research (NCT: 00752700)

Background
Molecular analysis (MoA) of non-small cell lung cancer has led to definition of many subgroups that require dedicated treatments, strategy and trials. We created a monthly MMTB dedicated to lung cancer patients (pts) with potential driving molecular abnormalitie(s). MMTB includes physicians from the lung tumor board and the phase I unit, pathologists and biologists. A medical report summarizes the findings and treatment recommendations. We report 2 years of activity of MMTB.

Methods
All consecutive files discussed in MMTB in Gustave Roussy were reviewed. Tumor and pts characteristics were collected as well as treatment. Pts outcome was calculated from the MMTB.

Results
245 pt files were discussed between February 2010 and March 2012. 53% were male, 27% never-smokers, 89% had PS 0 or 1, median age was 59. Clinical initial stage was III-IV in 17 pts (7%) and 78%/11%/11% were adenocarcinoma/squamous cell carcinomas/others NSCLC. Time from diagnosis to MMTB was 7 months (m) (1-222), 102 (42%) of pts received more than 1 line of treatment before MMTB. Biopsy for MoA mostly came from CT guided biopsies (61%), surgery (22%) or endoscopy (15%). Biopsy was repeated in 20% of pts to get enough material for MoA. The MoA results were ALK rearrangement in 10%, exon 18/19/21 EGFR mutation (mut) in 2/14/8%, KRAS mut in 30%, PI3KCA mut in 0.4%, BRAF mut in 3%, HER2 mut in 1%, FGFR1 amplification in 3%, other rare mutations in 14%. MMTB recommendations were: a clinical trial in 75 pts (31%), receive an EMA-approved drug in 49 pts (20%), an off-label commercial drug in 18 pts (7%), an expanded access program in 18 pts (7%), none in 85 pts (35%). Out of the 160 MMTB pts with treatment recommendations, 63 (42%) received the proposed targeted therapy and 16 (11%) might receive it at the time of disease progression. After MMTB, 84 pts (34%) received 1 line, 66 pts (27%) 2 lines or more, 56 pts (23%) no treatment (unknown in 39 pts). Median follow-up is 20.6 m. Progression-free (in 224 pts) and overall survivals (OS, in 221 pts) from MMTB are 3.5 and 13.4 m. In univariate analysis for OS, the pts who received the recommended treatment from the MMTB had a better prognosis (hazard ratio [HR]: 0.56, p=0.002), confirmed in multivariate analysis (HR=0.61 [95% confidence interval: 0.42-0.88], p=0.009) after taking into account histology, previous platinum-based treatment and the number of previous treatment lines.

Conclusion
MMTB leads to treatment recommendations in a majority of the pts, fosters inclusion in clinical trials or expanded access programs, and limits the use of off labelled drugs. Updated data will be presented

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Abstract
Staging: Positron emission tomography (PET) using the radiopharmaceutical, 18F-2-deoxy-D-glucose (FDG), a D-glucose analog, is useful in the detection of nodal (N) and extrathoracic metastases (M1b) in patients with non-small cell lung (NSCLC). FDG-PET has a higher sensitivity (83%) and specificity (92%) than CT in the detection of nodal metastases. However, a commonly encountered dilemma occurs when nodal imaging is discordant i.e. in patients with NSCLC and small nodes on CT and a positive PET, the predicted post-test probability of N2 malignancy is 62% and when the nodes are >16-mm and the PET is negative, the post-test probability of N2 malignancy is 21%. When the findings are concordant (enlarged nodes on CT and positive PET) the post-test probability of N2 malignancy is 90%. Accordingly, FDG-PET is usually used to direct invasive nodal staging. Metastatic disease (additional nodule/s in the contralateral lung, pleural nodules, malignant pleural or pericardial effusion (M1a) and extrathoracic metastasis (M1b)) are common in patients with NSCLC at presentation. Whole-body FDG-PET imaging improves the accuracy of staging and has a higher sensitivity and specificity than CT in detecting extrathoracic metastases although many solitary FDG-avid extrathoracic lesions are unrelated to the NSCLC. The American College of Surgeons Oncology Trial reports PET sensitivity, specificity, positive predictive value and negative predictive values of 83%, 90%, 36% and 99%, respectively for M1 disease. Importantly, whole-body PET imaging is useful in the detection of occult extrathoracic metastases in patients considered resectable by standard imaging and clinical evaluation and prevents inappropriate resection in up to 20% of these patients. Response: PET is being evaluated in the assessment of therapeutic response and may allow an early and sensitive assessment of the effectiveness of anticancer chemotherapy as FDG uptake is not only a function of proliferative activity but is also related to viable tumor cell number. FDG-PET/CT can predict early response to therapy in patients with stage IIIB-IV NSCLC who receive standard chemotherapy or molecular-targeted therapy. Early metabolic response (after one cycle of systemic therapy) has a significant correlation with best overall response. FDG-PET has also been reported to be useful in the assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Additionally, in patients with advanced NSCLC, FDG-PET can potentially be useful in identifying a subgroup of patients that would benefit from maintenance treatment after completion of first-line chemotherapy. Furthermore, FDG-PET can be useful in the assessment of early response during radiotherapy with respect to overall survival in patients with NSCLC. While FDG-PET/CT assessment may be useful in the prediction of early treatment response, progression-free survival and overall survival in NSCLC, the response to therapy and survival is multifactorial with stage at presentation, performance status and genomic patterns influencing outcome. It is not certain whether FDG-PET in patients with NSCLC will provide reliable and routinely applicable clinical information in terms of therapeutic response. Restaging: In patients with recurrent malignancy after attempted curative treatment of NSCLC, repeat resection, salvage chemotherapy, or radiotherapy are therapeutic options. FDG-PET can detect local recurrence of tumor after definitive treatment with surgery, chemotherapy, or radiotherapy before conventional imaging and has been reported to have a sensitivity of 98-100% and specificity of 62-92%. In one recent prospective study of patients with NSCLC who had undergone surgical resection, PET was able to detect tumor recurrence (sensitivity 93%, specificity 89%, and accuracy 92%) and predict which patients would benefit most from surgical retreatment. Additionally, in patients with NSCLC treated with radical radiotherapy, FDG-PET performed a median of 70 after completion of radical radiotherapy was useful in the assessment of therapeutic response.