Virtual Library

Background
The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non small cell lung cancer (NSCLC). ALK rearragement is detected in 2-7% of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method of detection. The clinical features of lung cancer that harbors ALK include light- or never-smokers, younger age, adenocarcinomas with acinar pattern or signet ring adenocarcinoma, and a lack of EGFR or KRAS mutations. Crizotinib has shown an important benefit in terms of overall response rate (ORR) and progression free survival (PFS) in the 2nd/3rd line setting. Treatment related adverse events were gastrointestinal and visual disorders.

Methods
Retrospective analysis of the clinico-pathological profile of ALK NSCLC patients between May 2011 and December 2012 in our Institution.

Results
10 cases (6,7%) were identified from 150 screened patients with adenocarcinoma histology and EGFR wild-type status. 7 (70%) patients were women. Median age at diagnosis was 62 years old (range=36-77). 90% patients were light-or-never smokers. All tumours were adenocarcinomas with EGFR wild type status: acinar growth pattern was detected in 4 cases (40%); 4 (40%) patients showed mucous cells and previous described signet-ring cells were detected in the last 2 (20%) cases. Only 5 (50%) patients received crizotinib therapy: 2 patients were treated during first line with partial response, 1 patient was treated in second line with stable disease and 2 patients received therapy in third line with partial response and no response, respectively. Only one patient required a dose reduction (200 mg bd) due to gastrointestinal toxicity.

Conclusion
Most of the patients with ALK rearregements in our serie have clinical and pathological characteristics to previously described. More women and older population were showed. In stead of the small sample size, pathological pattern based on acinar growth and mucous or signet-ring cells in adenocarcinomas with no EGFR mutation should guide the ALK screening process. ORR and toxicity profile confirmed Crizotinib benefit as soon as ALK status was detected.

Background
Molecular classification of lung cancer correlates well with histomorphologic features. However, detailed histomorphologic features which differentiate ALK rearranged tumors from ALK wild type has not been fully evaluated. To investigate histomorphologic features of tumors harboring ALK rearrangement to evaluate the predictive significance of morphologic characterization, we compared the histomorphological analysis between ALK-rearranged and ALK negative lung adenocarcinomas based on driver oncogene mutations.

Methods
Eighty resected ALK rearranged lung adenocarcinomas and two hundred thirteen resected ALK negative adenocarcinomas (91 EGFR mutated, 29 K-ras mutated and 93 triple-negative) were analyzed for several histomorphological parameters and histologic subtype based on newly proposed IASLC/ATS/ERS classification.

Results
ALK rearranged tumors were associated with a younger age at presentation, frequent nodal metastasis and higher stage at diagnosis, compared with patients with other genotypes. ALK rearranged tumors were more likely to show solid predominant pattern (43.8%, 35/80) than other genotypes (p<0.001) and a lepidic predominant histology was not observed in ALK rearranged tumors (p<0.001). In ALK rearranged tumors, considerable number of the tumors (67.5% , 54/80) contained at least 5% solid pattern but only small number of the tumors (12.5%, 12/80) contained at least 5% lepidic pattern, compared with other genotypes (p<0.001). The most significant morphological features distinguishing ALK rearranged tumors from ALK negative tumors were cribriform formation (OR: 3.253, p=0.028), presence of mucin-containing cells (OR: 4.899, p=0.008), close relation to adjacent bronchioles (OR: 5.361, p=0.001), presence of psammoma body (OR: 4.026, p=0.002) and solid predominant histological subtype (OR: 13.685, p=0.023). ALK-rearranged tumors exhibited invasive histomorphological features, aggressive behavior and frequent expression of epithelial-mesenchymal transition markers (loss of E-cadherin and expression of vimentin) compared with other genotype (p =0.015). Spatial proximity between bronchus and ALK-rearranged tumors and frequent solid histologic subtype with p63 expression may cause diagnostic difficulties to differentiate squamous cell carcinoma in the small biopsy, whereas p40 was rarely expressed in ALK-rearranged adenocarcinoma.

Conclusion
Knowledge of these features may improve the diagnostic accuracy and lead to a better understanding of the characteristic behavior of ALK-rearranged tumors.

Background
We have recently demonstrated that presence of the micropapillary pattern increases the risk of local recurrence after limited resection for ≤2 cm lung adenocarcinoma (ADC). In cases of tumors with the micropapillary pattern, a detached collection of tumor cells is frequently identified within an alveolar space separate from the main tumor, which we have named “Spread Through Alveolar Spaces” (STAS). However, the prognostic significance of this finding is not known. The purpose of this study is to investigate whether the presence of STAS correlates with an increased risk of recurrence after limited resection versus lobectomy.

Methods
All available tumor slides from patients with therapy-naive, surgically resected solitary lung ADC ≤2 cm in size (1995-2009) were reviewed (n=697; stage IA/IB, 600/97; limited resection/lobectomy, 226/471). Comprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification. STAS was defined as isolated tumor islands (morphologically solid or micropapillary pattern) or single cells within alveolar spaces separate from the main tumor. The distance between the tumor surface and the STAS was measured by a ruler (mm) and by the number of alveolar spaces. Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method.

Results
STAS was identified in 224 cases (32%). The morphologic types of STAS were as follows: 119 micropapillary, 91 solid, and 14 single cell. Presence of the micropapillary or solid pattern (>5%) in the main tumor and presence of lymphatic invasion were significantly associated with presence of STAS (p<0.001 for each). Presence of STAS correlated with an increased risk of recurrence (5-year RFP, 75.6%), compared with absence of STAS (5-year RFP, 83.5%; p=0.022). In the limited resection group, tumors with STAS were associated with an increased risk of recurrence, compared with those without STAS (5-year RFP, 58.3% vs 81.9%; p=0.004); this did not follow in the lobectomy group (5-year RFP, 84.1% vs 84.2%; p=0.658) (Figure). The distance between the tumor surface and the STAS did not correlate with risk of recurrence (p=0.992). Figure 1

Conclusion
Presence of STAS correlated with an increased risk of recurrence in patients treated with limited resection for ≤2 cm lung ADC. This finding may guide surgeons to choose lobectomy over limited resection for the treatment of these patients.

Background
Immunohistochemical screening of anaplastic lymphoma kinase (ALK) rearrangement has been regarded essential and routinely carried out to select the treatment for lung adenocarcinoma. However, due to difficulty to approach a tumor by transbronchial lung biopsy (TBLB), it often fails to obtain tumor tissues whereas tumor cells are contained in cytology specimens simultaneously obtained when the bronchoscopy is done. Therefore we evaluated the expression of ALK protein by using immunohistochemistry (IHC) on TBLB specimens and immunocytochemistry (ICC) on brushing smear cytology slides in the same cases, and compared the concordance rate of IHC and ICC results. ICC was carried out on routine Papanicolaou-stained slides after cytology diagnosis and decolorization.Background: Immunohistochemical screening of anaplastic lymphoma kinase (ALK) rearrangement has been regarded essential and routinely carried out to select the treatment for lung adenocarcinoma. However, due to difficulty to approach a tumor by transbronchial lung biopsy (TBLB), it often fails to obtain tumor tissues whereas tumor cells are contained in cytology specimens simultaneously obtained when the bronchoscopy is done. Therefore we evaluated the expression of ALK protein by using immunohistochemistry (IHC) on TBLB specimens and immunocytochemistry (ICC) on brushing smear cytology slides in the same cases, and compared the concordance rate of IHC and ICC results. ICC was carried out on routine Papanicolaou-stained slides after cytology diagnosis and decolorization.

Methods
IHC was done using the commercially available antibody against ALK (dilution 1:100, clone 5A4; Novocastra, Newcastle, UK), and signals were detected using the EnVision FLEX Mini-kit (Dako, Tokyo, Japan). Papanicolaou-stained bronchoscopic brushing smear cytology slides containing cells cytologically diagnosed as adenocarcinoma were used. ICC was carried out by using the same antibody and the detection kit as used in IHC. IHC and ICC expressions were quantified by three cytopathologists. Cytoplasmic ALK expressions were quantified using a three-value intensity score (0, 1+, 2+) and the intensity scores 1+ and 2+ are defined positive.

Results
Eighteen patients with adenocarcinoma were extracted in the Hirosaki University Hospital and the Hirosaki National Hospital. IHC and ICC results showed a very high concordance rate: sensitivity of ICC in comparison with IHC was 85.7% (6/7), specificity was 100% (11/11), positive predictive value was 100% (6/6), and negative predictive value was 91.6% (11/12).

Conclusion
Detection of ALK rearrangement using ICC on routine Papanicolaou cytology slides is considered to be advantageous for lung cancer treatments.

Background
The rational use of tailored therapy for lung cancer depends crucially on high quality pathology. Not only must subtyping of the tumour be achieved consistently and with accuracy, but as much material as possible from increasingly small specimens must be preserved for the genetic analysis upon which such treatment is increasingly predicated. Although there is a general presumption that pathologists have risen to this challenge, reliable data is sparse and the nature and degree of variation in practice and quality is unknown.

Methods
We collected and scrutinised anonymised information, including pathology reports, on all consecutive, newly-diagnosed patients with lung cancer referred to 19 lung cancer units across the UK for a period of 6 months commencing late 2011, a total of 1507 cases. Centres surveyed ranged from district general hospitals to specialist regional cardiothoracic units.

Results
Achievement of a positive tissue diagnosis of malignancy ranged from 53 to 88%, figures accompanied by ‘suspicious but non-diagnostic’ rates of 10 and 2% respectively. Despite apparent adherence to the diagnostic criteria and terminology of the WHO classification of tumours of the lung, variation in proportions of tumour subtypes was wide, the prevalence of squamous carcinoma, for example, varying from less than 10 to greater than 50%. The proportion of tumours unclassified beyond ‘non-small cell lung cancer not otherwise specified’ varied from 3 to 20% despite the almost universal use of immunochemistry (most often TTF-1, class 7 cytokeratins and p63) to aid in this differential diagnosis. Testing for EGFR gene mutations was directly instigated by the pathologist at diagnosis in only 4 of the 19 centres and the proportion of tumours tested ranged from 12 to 92%.

Conclusion
Variations in practice amongst pathologists and arguably in the quality of pathology ranged widely across the centres surveyed, raising important questions about variable expertise of pathologists, adherence to guidelines, applicability and rigour of external quality assessment and, ultimately, the reliability of the pathology that crucially underpins the management of lung cancer.

Background
Treatment of non-small-cell lung cancer (NSCLC) has changed drastically in recent years with an increase in rates of detection of driver mutations in a subgroup of NSCLC patients (p); the most recent mutations described in NSCLC are HER2 and BRAF. Overexpression of HER-2 (insertion in exon 20) occurs in 2-6% of NSCLC patients and is more common in women, never-smokers, Asian and adenocarcinoma hystology (adc). BRAF is found in 1.6-4.9% of p, with a higher rate of V600E mutations in smokers, and non-V600E mutations in non-smokers.

Methods
We systematically analyzed HER2 and BRAF mutations in EGFR wild type and non-translocated ALK p and retrospectively reviewed the results. Forty six NSCLC p were included between December 2011 to June 2013. Clinical characteristics such as histological subtype, sex, age, smoking status, and mutational status were analyzed. BRAF mutation was assessed by Taqman based assay (5’ nuclease activity) in an AB 7900HT system, with specific primers and probes for V600E positions. HER2 insertion was assessed using Sanger sequencing. All samples were PCR amplified and sequenced in AB 3130, using specific primers for exon 20.

Results
All patients were Caucasian; 25 p (54.3%) were women and 21 p (45.7%) men. Fourteen p (30.4%) were never-smokers, 11 (23.9%) former smokers and 19 (41.3%) smokers. Median age was 58.74 years. Forty one p (89.1%) had adc, 2 had squamous cell histology and 3 had another histology (1carcinod tumour, 1 large cell lung cancer and 1 poorly differentiated NSCLC) . Two p (4.3%) had BRAF V600E mutation: 1 female and 1 male, with median age of 56.5, both smokers. One 65 year old, female, never-smoker p (2.2%) had HER-2 insertion. All mutations were found in adc.

Conclusion
Analysis of less common driver mutations such as BRAF and Her2 mutations is feasible for daily clinical practice and could be useful to decide treatment. In our European population, incidence of BRAF and HER-2 mutation is similar to that previously reported (4.3% and 2.2%). Both p with BRAF V600E mutation were smokers, and the p with mutation in HER-2 was a 65 year-old female never-smoker.

Background
Our understanding of the molecular landscape of lung adenocarcinoma (ADC) is evolving rapidly. Furthermore, the IASLC/ATS/ERS lung ADC classification was recently published. The histologic and molecular correlations have not yet been thoroughly explored in this rapidly changing field. We sought to investigate the molecular findings according to the IASLC/ATS/ERS classification. .

Methods
Aperio© scanned H&E stained slides were reviewed from 230 tumors according to the 2011 IASLC/ATS/ERS lung adenocarcinoma classification criteria. Molecular profiling was performed on 230 resected, untreated lung adenocarcinomas, using mRNA, miRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. Histologic molecular correlations focused on mRNA and DNA sequencing and TTF-1 proteomic findings.

Results
We found 12 lepidic predominant ADC (5%), 21 papillary predominant (9%), 77 acinar predominant (33%), 33 micropapillary predominant (14%), and 58 solid predominant (25%) as well as, 9 invasive mucinous (4%), and 20 unclassifiable ADCs (9%). EGFR mutation and KRAS mutations were found in 8% and 17% of lepidic ADC, respectively. Nine of 12 lepidic ADC (75%) were of the terminal respiratory unit (TRU) gene expression subtype (GES) and 3 (25%)were in the 19p-depleted transcriptional GES, but none were found in the solid-enriched GES (Figure; p=0.007). Most of the papillary ADC were of the TRU (10/21, 47.6%) and 19p-depleted transcriptional (9/21, 42.9%) GES (p=0.026). 46% (41/89) of acinar ADC tumors were in the TRU-GES compared to the solid enriched (18/78, 23.1%) and 19p-depleted transcriptional (18/63, 28.6%) GES (p=0.005). When the oncogene positive group was defined including KRAS, EGFR, ALK, RET, ROS1, BRAF, ERBB2, HRAS and NRAS, there was a higher percentage of solid ADC in the oncogene negative (30/93, 32.3%) compared to the oncogene positive group (28/137, 20.4%, p=0.046). The highest percentage of solid ADC was found in the solid-enriched GES (47/78, 47.4%) compared to the 19p-depleted transcriptional (17/63, 27%) and TRU GES (4/89, 4.5%) (p<0.001). Invasive mucinous ADC correlated with KRAS (but no EGFR) mutations (67%) compared to other ADC (28%, p=0.02) and also lacked elevation of TTF-1 (p=0.007). GES was associated with histologic grade: high grade with solid-enriched GES and intermediate/low grade with TRU GES (p<0.001). Figure 1

Conclusion
Our data reveal multiple correlations between molecular (mutation and GES) and histologic (subtyping and grade) features. This reveals insights into the biology of these tumors in particular genetic characteristics of the high grade tumors which may lead to better understanding of why these are more aggressive tumors.

Background
Non-small-cell lung cancers (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement are highly sensitive to the ALK kinase inhibitor crizotinib, but drug resistance invariably emerges. Morphological transformation from adenocarcinoma to SCLC represents one acquired resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors. We present the case of transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma which developed acquired resistance to crizotinib.

Methods
not applicable

Results
A 32-year-old man presented with cough and bloody sputum. Computed tomography (CT) showed a mass in the S6 segment and diffuse consolidation throughout the lower lobe of the left lung. Transbronchial lung biopsy revealed adenocarcinoma with lymphangiosis. Immunohistochemistry (IHC) showed ALK protein expression and break-apart fluorescent in-situ hybridization (FISH) showed ALK gene rearrangement. First-line chemotherapy with cisplatin and docetaxel was started. After tumor progression, the patient was enrolled in the clinical trial and was allocated to the pemetrexed arm. Subsequently, he was enrolled in other trial to receive crizotinib in July 2011. After partial response was observed, a nodule in the S9 segment developed to 2cm in February 2012, and crizotinib was discontinued. CT scans performed after 4 cycles of carboplatin and gemcitabine showed a mixed response, with improvements in lymphadenopathy and lymphangiosis but progression of the mass in S9. CT-guided core-needle biopsy revealed ALK-positive atypical cells but it was impossible to distinguish histological types because of degeneration and necrosis. Thereafter, carboplatin, paclitaxel, and bevacizumab were administered, but the same mixed response was observed. The mass in S9 increased rapidly and reached 7 cm. 　Left lower lobectomy was performed. The primary tumor in S6 was diagnosed as adenocarcinoma positive for thyroid transcription factor (TTF)-1 immunostaining, whereas the tumor in S9 was TTF-1-negative sarcomatoid carcinoma. ALK was positive with IHC in both tumors, and FISH revealed high-level gene amplification of the ALK fusion gene only in the sarcomatoid carcinoma. Reverse transcriptase polymerase chain reaction revealed the same variant of echinoderm microtubule-associated protein like 4-ALK (E13; A20) and it indicated that these tumors have the same origin. Moreover, in the sarcomatoid carcinoma, DNA sequencing revealed no additional resistance point mutations from ALK exon 20 to exon 23. Brain metastases occurred 2 months after pulmonary resection and he underwent brain surgery. The tumor was diagnosed as sarcomatoid carcinoma. Ten days later, he died due to exacerbation of lymphangiosis To discuss potential epithelial-to-mesenchymal transition (EMT), we performed E-cadherin and keratin staining as epithelial markers, and vimentin staining as a mesenchymal marker in 4 specimens. The specimens were pre-crizotinib specimen in S6, surgical specimen in S6, rebiopsied specimen in S9 after carboplatin and gemcitabine, and surgical specimen in S9. Rebiopsied specimen in S9 was unevaluable for IHC staining because of degeneration and necrosis. All of the 3 evaluable specimens showed positive expression of vimentin and only surgical specimen in S9 showed negative of epithelial markers.

Conclusion
The transformation from adenocarcinoma to sarcomatoid carcinoma could be interpreted as kind of EMT. This transformation might represent a novel acquired resistance mechanism to crizotinib, although there is another possibility that subsequent chemotherapies induced this transformation.

Background
Patients with non-small cell lung cancer (NSCLC) harboring sensitizing mutations in epidermal growth factor receptor (EGFR) benefit from treatment with EGFR tyrosine kinase inhibitors. As most patients with NSCLC present with advanced-stage disease and are not candidates for surgical resection, somatic mutation testing is often performed on small biopsy and cytology specimens. Compared to resection specimens, the suitability of these specimens is not well established. We aimed to explore the suitability of small biopsy and cytology specimens for mutation testing in NSCLC.

Methods
We undertook a retrospective review of NSCLC mutation testing cases performed at Royal Prince Alfred Hospital, Sydney, from March 2012 to May 2013. Mutation testing was requested by the treating physician. DNA was extracted from formalin-fixed, paraffin embedded tissue and a multiplex PCR assay (OncoCarta Panel v1.0) used to identify mutations in 19 oncogenes including EGFR, KRAS, and BRAF. The results were analyzed on the Sequenom MassArray platform. Fragment analysis was also undertaken to assess for exon 19 deletions.

Results
Mutation testing was undertaken on 151 NSCLC specimens, including 44 (29.1%) resection specimens (27 lung resection specimens and 17 metastatic site resections), 67 (44.4%) small biopsy specimens, and 40 (26.5%) cytology specimens. Overall, EGFR mutations were detected in 32/151 (21.2%) cases, KRAS mutations in 29/151 (19.2%) cases, and BRAF mutations in 3/151 (2%) cases. Mutations were detected in 25/44 (56.8%) resection specimens, principally lung resection specimens (19/27, 70.4%), 26/67 (38.8%) small biopsies and 13/40 (32.5%) cytology specimens. The mutation rate was significantly lower in small biopsies (p=0.006) and cytology specimens (p=0.002), compared to lung resection specimens. Specifically, EGFR mutations were identified in 13/44 (29.5%) resection specimens, again mainly in lung resection specimens (10/27, 37%), 9/67 (13.4%) small biopsies and 10/40 (25%) cytology specimens. Compared to lung resection specimens, the proportion of EGFR mutation positive cases was significantly lower in small biopsy (p=0.01), but not in cytology specimens (p=0.29). One paired cytology and lung resection specimen from a single patient was available and both specimens confirmed the presence of an L858R EGFR mutation.

Conclusion
Mutations, including EGFR mutations, were most frequently detected in lung resection specimens. Compared to lung resection specimens, the EGFR mutation rate was significantly lower in small biopsy, but not in cytology specimens. This suggests that cytology specimens are more likely to be adequate for mutation testing than small biopsies such as core and bronchial biopsies. However, we cannot exclude bias in this study from differing referral patterns which may affect these results. Careful assessment of DNA quality and quantity is important for all specimens, particularly small biopsy specimens, to reduce the risk of false positive or negative results.

Background
ALK fusion is a unique gene transversion detected among lung adenocarcinomas. It emerged as a target for cancer therapy, but little is known how this genomic abnormality is created. To unveil the underlying mechanisms leading to gene fusion, we compared the genomic structures of the two groups using SNP-array allelokaryotyping analysis.

Methods
35 ALK fusion positive and 95 ALK fusion negative cases were involved in this study. Immunohistochemical staining and multiplex RT-PCR was employed for screening and confirmation. Chromosome 2p were closely examined using SNP-array based allelokaryotyping.

Results
Copy number changes of the regions including ALK and EML4 were detected among ALK fusion positive tumors (10/35, 29%) in contrast with ALK fusion negative tumors (0/95, 0%). In other words, the genomic regions unnecessary to constitute each fusion gene variants were deleted in ALK fusion positive tumors. And some of them showed copy number gain of fusion gene. In addition, clustered genomic number changes within 2p were more frequently encountered in ALK fusion positive tumors compared with fusion negative ones.

Conclusion
Copy number changes within the genomic region including EML4 and ALK are particular findings in ALK fusion positive tumors. In addition, genomic structure of the short arm of chromosome 2 was more unstable than ALK fusion negative tumors. We speculate that clustered chromosomal rearrangements of the short arm of chromosome 2 contribute to EML4-ALK gene fusion.

Background
The distinction between typical (TC) and atypical carcinoids (AC) is currently based on histologic criteria reported by Travis and al., then accepted by WHO classification and widely used today. The crucial microscopic features that distinguish TC from AC are mitotic activity and necrosis. TC has fewer than 2 mitotic figures/2mm[2 ], whereas AC has 2 to 10 mitoses/2mm[2] and/or small foci of necrosis. The aim was to analyze the microscopic features and immunohistochemical (IHC) profile of TCs and ACs, and to identify the other pathological criteria that could be simple, and reproducible, as well as helpful in daily practice of surgical pathology and usefulness in differentiation between both of them.

Methods
We retrospectively collected 236 cases of resected BPC from 1998 to 2011 at National Tuberculosis and Lung Diseases Research Institute. All tumors were reclassified according to the 2004 WHO classification. The clinicopathological features were correlated and survival analysis were performed. We evaluated size and location of tumors (central or peripheral), depth of bronchial invasion, destruction of bronchial cartilage, tumor invasiveness, the infiltrative growth of the adjacent normal architecture, presence of pleural, perineural and vascular invasion. We also assessed cellular atypia, growth pattern, cellular morphology, especially oncocytic and clear cell, as well as spindle-cell components. The expression of a range of antigens including markers of epithelial differentiation (cytokeratins: AE1/AE3 and 19, TTF-1, napsin A), neuroendocrine markers (chromogranin A, synaptophysin, NCAM/CD56), peptide products (calcitonin, serotonin) and antigens involved in cell proliferation and death (Ki-67, p53, Bcl-2, CD117) were studied.

Results
After reclassification, 8 cases were diagnosed as LCNEC, 102 tumors (44,7%) were classified as TC and 126 (55,3%) as AC. Most tumors are localized centrally (73,7%) and occurred in females (69%). AC were larger than TC (2,54 vs 1,9 cm). Solid and insular pattern, medium and high cellular atypia, oncocytic component, centrally located tumors with cartilage destruction, invasion of peribronchial tissue and/or adjacent lung parenchyma correlated with AC. Mitotic activity was one of most accurate method of diagnosis TC and AC but more advantageous would be increasing a number of mitoses figures to 2 for TC and to ≥3/2mm[2] for AC. AC more often revealed positive reaction with CK19 and higher cellular index for p53. Routinely staining for proliferative index (PI) with Ki-67 is recommended, for TC ≤4% and for AC >4%. Immunoreactivity of broad-spectrum cytokeratin was observed in 95% cases, more then 50% showed „dot-like“ reactivity. Peripherally located tumors were distinctly different morphologically and IHC than centrally carcinoids. Peripherally tumors were smaller (1,9 vs 2,4cm), usually not-well demarcated, with solid or insular pattern and spindle-cell component as well as fibrosis. In contrast to centrally tumors, they showed expression of TTF-1, serotonin and Bcl-2 but sparsely CK19.

Conclusion
The following pathological features should be evaluated in diagnosis of AC: localization, the infiltrative growth, solid and insular pattern, high grade atypia, oncocytic and spindle-cell components, mitotic figures and IP (Ki-67). We proposed for TC 0-2 mitosis/2mm[2] and PI ≤4%, for AC ≥3 mitosis/2mm[2] and PI >4% and/or foci of necrosis.

Background
Bronchial washings/brushings (BW/B) are often used for early screening and cytological diagnosis of lung cancer. We examined the possibility of EGFR testing on cytology samples, as compared to bronchial biopsy sample.

Methods
116 BW/B samples with non-squamous histology were submitted to our department for EGFR mutation testing at Chonnam National University Hospital within 8-month period. Biopsy samples was concurrently submitted for histologic diagnosis. We used the PNA clamping method for EFGR mutation test.

Results
Histologic diagnosis were 103 cases of adenocarcinomas and 13 cases of NSCLC, not otherwise specified (NOS). Each sample was assessed by a pathologist for adequacy and DNA content. At BW/B samples, 22 cases showed exon 19 deletion, 13 exon 21 mutation, 79 were wild type and 2 failed. The EGFR mutation rate using BW/B sample was 30.2%. At bronchial biopsy samples, 23 cases showed exon 19 deletion, 13 exon 21 mutation, 72 were wild type and 12 failed. The EGFR mutation rate using bronchial biopsy sample was 31.0%. Mutation detection cases were nearly identical in both samples. But, in only one case, exon 21 mutation was detected in biopsy sample, not in BW/B sample. The median DNA content for BW/B samples compared to biopsy samples were 3.7ug and 3.2ug. The failure rate for cytology samples was lower than biopsy samples.

Conclusion
BW/B samples are superior to bronchial biopsy samples in terms of DNA quantity and rate of failure. Moreover, in case of inadequate biopsy sample, BW/B samples were a substitute material for EGFR mutation test.

Background
The incidence of EGFR mutations has been systematically analyzed in a large cohort in Germany within the REASON trial. However, systematic data on KRAS, BRAF, ALK, and p53 within the same cohort have not been published in German cohorts of patients with lung cancer. Therefore we studied the incidence of these alterations in 159 patients from a single center and correlated these with clinical characteristics and survival.

Methods
159 patients from a single center diagnosed with lung cancer were studied for the presence of EGFR mutations, ALK rearrangements, KRAS codon 12/13/61 and BRAF V600E and G469A, as well as inactivating p53 mutations. Methods for the detection of EGFR mutations included Sanger Sequencing and hybridization based COBAS testing. ALK rearrangements were either tested by RT-PCR or ALK-FISH (break apart probe, Vysis). BRAF mutations were detected by allele specific PCR, KRAS and p53 by Sanger Sequencing

Results
159 consecutive patients at the lung cancer center of the Pius-Hospital Oldenburg were studied. In all cases EGFR mutations status was successfully determined. 33/159 (21%) had EGFR mutations, of which 3 had primary resistance mutations. 5/132 successfully studied pts had ALK rearrangements (3,7%). 29/142 (20%) successfully studied for KRAS mutations had codon 12 or 13 mutations. 2/136 (1,4%) successfully studied for BRAF mutations had G469A (2) mutations, V600E mutations were not observed. p53 mutations were observed in 47% of successfully studied pts (21/45 pts). Just analyzing the 60 never or light smokers (< 100 cigarettes lifelong or < 10 packyears and ex-smoker), revealed 23/60 (38%) EGFR mutations, 4/44 (9%) ALK rearrangements, 4/49 (8%) KRAS mutations, 1/49 (2%) BRAF mutations and 7/19 (37%) p53 mutations, demonstrating that EGFR and ALK were overrepresented in never-light smokers, whereas BRAF, KRAS and p53 mutations were overrepresented in smokers. ALK, EGFR, KRAS and BRAF mutations were mutually exclusive in this patient population. However p53 mutations were observed in pts with activating EGFR mutations in 7/15 successfully studied cases. Outcome in the different subgroups will be presented at the meeting.

Conclusion
EGFR and ALK mutations were overrepresented in never-light smokers, BRAF and KRAS mutations were underrepresented. P53 mutations occurred independently of smoking status in combination with EGFR mutations, but not ALK- translocations. OS data will be presented at the meeting.

Background
The vast majority of non small cell lung cancers (NSCLC) presents as advanced disease and histological diagnosis is widely based on small biopsy or cytological samples. Recently, the adoption of new pharmaceutical agents targeting individual histotypes requires a precise subtyping of NSCLC. This task is often difficult according to morphological criteria only and the use of immunohistochemistry (IHC) is recommended for small samples or undifferentiated tumors to define the most probable histotype. However, the real impact of IHC characterization of NSCLC-Not otherwise Specified (NOS) in terms of response to therapy and outcome (compared to cases classified by morphology, only) is not well established.

Methods
A large series of 224 advanced "non-squamous" NSCLC diagnosed from year 2005 to 2010 on small biopsy or cytological samples and homogeneously treated, was retrospectively selected, all with adequate follow-up data available. All diagnoses were reviewed resulting in two groups of adenocarcinoma (ADC) and NSCLC-NOS. The latter were further characterized by IHC to identify the most probable differentiation lineage. Disease Control Rate (DCR) and Response Rate (RR) were calculated and Overall Survival (OS) curves were analyzed by Kaplan Meier.

Results
After review 120/224 (53.6%) cases were ADC based on morphological examination, only (“ADC morphology”) and 104/224 (46.4%) remained NSCLC-NOS. In terms of response to therapy no significant difference was found between the two groups (“ADC morphology” had DCR= 0.66 and RR=0.31; NSCLC-NOS had DCR=0.64 and RR=0.35; Chi-Square p=0.83). The NSCLC-NOS cases that underwent IHC profiling resulted in 66/104 (63.5%) cases that had an ADC phenotype (“NSCLC favor ADC”) and 38/104 (36.5%) cases that lack ADC features (including 5 “NSCLC favor squamous carcinoma” and 33 “NSCLC null phenotype”). The “NSCLC favor-ADC” had DCR and RR similar to “ADC morphology” group (Chi-Square p=0.23), while the “non-ADC” NSCLC group had significantly different both DCR=0.47 and RR=0.29 (Chi-Square p=0.006). Survival curves confirmed no difference in terms of survival between the “ADC morphology” and the “NSCLC favor-ADC” groups, while showed a significantly poorer survival for the “non-ADC” NSCLC group with respect the other two groups (median survival: 8.5 vs 12.3 months, respectively; HR=0.5999; p=0.018).

Conclusion
These preliminary findings indicate that the practice of minimizing the NSCLC-NOS diagnoses by means of IHC has an impact on chemotherapy response. Stratifying such tumors by IHC, cases having an ADC immunoprofile had response rates comparable to those of morphologically diagnosed ADC, thus supporting the value of IHC to maximize lung cancer histological typing in the perspective of obtaining the best response to therapy.

Background
EGFR and KRAS mutations guide treatment selection in NSCLC patients. With 75% of newly diagnosed cases at advanced stages, mutational analysis is performed in small samples: core needle biopsies (CNB) and fine needle aspiration (FNA). Both the cobas EGFR and KRAS test are CE-IVD. No validation studies of the cobas tests have been performed using cytological smears but it is important to extend the benefits of molecular targeted therapy while preserving tissue for additional marker testing.

Methods
EGFR and KRAS mutation status were studied in 140 non-selected samples from NSCLC patients: 49 CNB, 91 FNA. DNA was extracted directly from one stained smear in FNA samples and one 5-micron section in CNB using the cobas DNA Sample Preparation Kit. All samples contained ≥ 50% tumor cells. DNA concentration and ratio (A260/280) were recorded. All cases were studied using the cobas EGFR and KRAS mutation tests. Moreover, 123 and 125 cases were analyzed respectively for EGFR and KRAS mutational status using Sanger sequencing.

Results
CNB diagnosis was: 29 SqCC, 17 AC, 1 BAC, 1 adenosquamous, 1 NSCLC-NOS. FNA diagnosis was: 64 AC, 13 SqCC, 3BAC, 2 LCC, 2 adenosquamous, 7 NSCLC-NOS. DNA concentrations from CNB were higher and significantly different than DNA from FNA (p<0.001,U Mann Whitney). DNA quality was similar between sample types. Mutational analysis is shown in Table 1. Mutation rate for EGFR was 15.9% and 8.2 % and for KRAS 37% and 16.7% in FNA and CNB, respectively, but should be considered within the context of tumor type. 8.6% and 36.4% of the cases were below the manufacturer’s recommendations of 2ng/µl and 4ng/µl for EGFR and KRAS testing, respectively. Invalid rates were 2.1% (3) for EGFR and 5.5% (9) for KRAS. These results may be due to low DNA concentration (EGFR) or technical performance (KRAS) that was resolved with later samples. Sequencing invalid results were 42.3% for EGFR and 0.8% for KRAS. Table 1.

		FNA	CNB
EGFR	WT	74	45
	Exon 19 Del	8	2
	Exon 20 Ins	0	1
	L858R	5	1
	Exon 18 G719X	1	0
	Invalid	3	0
KRAS	WT	51	40
	12/13 Mutation	29	8
	61 Mutation	1	0
	Invalid*	8	1

* By sequencing 6 WT and 3 mutated

Conclusion
In addition to FFPE samples, identification of EGFR and KRAS mutations in FNA and CNB samples using cobas EGFR and KRAS Mutation Tests is faster, easier to use, and reproducible. Although DNA concentrations were lower from FNA, DNA quality was similar to CNB and provided valid results. Sequencing had lower sensitivity and was more time-consuming. Careful sample management, especially for FNA, by the pathologist is critical to ensure quality and to optimize DNA yields.

Background
The identification of EGFR mutations as a driver for oncogenic proliferation in Non-Small Cell Lung Adenocarcinoma (NSCLC), in parallel with the development of the tyrosine kinase inhibitors has opened the way to “theranostics”. However, as more targets are identified and more targeted inhibitors are marketed, the medical community now needs to interrogate multiple genes to generate an accurate molecular profile for each individual tumor and determine matching targeted therapeutics. The development of the Next Generation Sequencing (NGS) has opened a new area offering for more comprehensive screening of somatic mutations across 10s to 100s of genes. However, its application in routine clinical practice within the individual therapeutic setting remains impractical due to the large data sets produced, as well as the high potential for generating false positive mutations Therefore atargeted approach seems more appropriate when screening for actionable somatic mutations. MALDI-TOF mass spectrometry (MassARRAY® System) is a flexible high-throughput solution that can easily adapt to newly discovered mutations as well as detect minority alleles of mutated DNAof large sample sets.

Methods
We have evaluated the LungCarta™ Panel, a panel targeting 213 somatic mutations in 26 genes. The method relies on multiplex PCR followed by single base extension and analysis using MALDI-TOF Mass Spectrometry.Genes such as EGFR, KRAS, BRAF, ERBB2 or PI3KCA,MAP2K1, EPHA3, NTRKs, STK11, TP53 and DDR2are well-represented.

Results
For verification of this panel we have screened a set of 37 lung metastatic adenocarcinoma DNA isolated from formalin fixed paraffin embedded (FFPE) biopsies.These samples were previously characterized for EGFR, KRAS, ERBB2, PIK3CA and BRAF. We identified a total of 26 mutations in 23 of the 37 samples (62%) localized in 10 genes. 100% of the previously known mutations were verified and an additional 12 mutations were identified, 10 of these mutations were located in genes not previously screened. We were able to significantly reduce the DNA amount to as little as 24ng. To further validate the LungCarta panelresults we selected 15 of the samples to be analyzed using NGSand theTruSeqAmplicon - Cancer Paneland11 of the samples generated high quality libraries that could be sequenced. Using this NGS approach we validated the hits obtained by LungCarta. When comparing the two methods, NGS has a quite complicated workflow and we identified more than 50 positive hits for each sample requiring a large bioinformatics effort in order to separate true positives hits from false positive hits. This problem was not seen using the LungCarta where the standard turnaround time for each sample batch was less than 24 hours and the panel showed excellent robustness using DNA obtained from FFPE.

Conclusion
We have now applied the LungCarta™ panel to more than 400 patients with NSCLC and were able to not only treat patients promptly, but also enter some others in clinical trials We have identified targets that could be very interesting in the future. Compared to the NGS approach,LungCarta offers a relatively simple workflow with quick turnaround time and minimal sample input requirements.

Background
The advent of specific therapies for non small cell lung cancer (NSCLC) based on individual tumour genotype has impacted the development of high throughput genomic profiling strategies. A single platform designed for the synchronous screening of multiple mutations across different genes can potentially enable molecular profiling in samples of limited tumour tissue such as small biopsy samples.

Methods
Haematoxylin and eosin-stained sections and accompanying reports were reviewed from patients diagnosed with NSCLC (2008 to 2012) in Greater Manchester, U.K. Samples with less than 20% tumour cell content (TCC) were macrodissected to increase the final TCC. In each case DNA was extracted manually from 1 5µM curl/section using the cobas® DNA Sample Preparation Kit. Mutation analysis was performed with the Sequenom LungCarta™ Panel which enables screening of 214 mutations in 26 genes, and utilises multiplexed polymerase chain reactions, single base extension reactions and mass spectrometry (Sequenom MassARRAY® platform).

Results
Results Sixty cases comprising 47 lung biopsies, 1 wedge resection, 6 lymph node biopsies, 4 pleural biopsies, 1 brain biopsy and 1 pericardial effusion were classified as 21 adenocarcinomas (ACA), 17 squamous cell carcinomas (SCC), 8 NSCLC favour ACA, 10 NSCLC favour SCC, 1 adenosquamous carcinoma and 3 NSCLC not otherwise specified (NOS). Mutations were successfully detected at a mutant allele frequency of 10% and definite mutations were reported in 28 cases (47%). Possible mutations of low allele frequency or uncertain significance were detected in an additional 15 cases (25%) and also in 10 cases with a definite mutation. In total 32 definite and 39 equivocal mutations have been detected and are currently being validated by a combination of pyrosequencing, next-generation sequencing and immunohistochemistry (IHC).

Table 1. Unequivocal mutations detected according to histological subtype. ([a]Includes double mutant; TP53 and MAP2K1, [b]includes triple mutant; 2 TP53 and 1 KRAS, [c]includes double mutant; KRAS and MET)

No. of definite mutations detected	No. of mutated samples	ACA	NSCLC favour ACA	SCC	NSCLC favour SCC	NSCLC NOS	% of mutations detected in all ACA or SCC	Comment
13 TP53	12	3[a]	2[b]	5	1	1	17 % ACA 22% SCC	1 confirmed by next generation sequencing. 7 of 8 tested cases were strongly positive for P53 IHC
12 KRAS	12	8[c]	1[b]		3		31% ACA 11% SCC	7 confirmed by pyrosequencing
3 MET	3	2[c]	1				10% ACA 0% SCC	1 confirmed by next generation sequencing
2 EGFR	2	2					7% ACA 0% SCC	2 previously detected by Sanger sequencing
1 EPHA5	1			1			0% ACA 4% SCC	Moderately differentiated SCC
1 MAP2K1	1	1					3% ACA 0% SCC	Poorly differentiated ACA TTF1+

Conclusion
The MassARRAY® system of testing for multiple mutations is a sensitive method that facilitates the optimal use of tumour DNA present in small specimens, and can detect concurrent mutations with the potential to influence responses to targeted therapies. Unequivocal mutations were reported in 59% and 37% of cases diagnosed/favoured as ACA and SCC respectively. This may reflect the LungCarta™ panel design, which was based on mutations detected in ACA.

Background
Pathologically, signet ring cells (SRC) describe singly dispersed tumor cells with intracytoplasmic mucin vacuoles, which eccentrically displace and compress the nucleus. SRCs are traditionally associated with adenocarcinoma of the gastrointestinal tract and are rare in lung adenocarcinoma (LACA). Patients with primary LACA with SRC features (SRC+) have been associated with poor clinical outcome and ALK gene rearrangement (ALK+). However, the impact of SRC+ on clinical outcome is not well delineated. We systematically studied LACA survival outcomes for the impact of SRC status.

Methods
Three distinct groups of surgically treated patients with LACA (n=763) that were followed for ≥5 years were reviewed: never smokers (n=266), 2006-2007 cohort (n=222), and smokers enriched for various degrees of lepidic growth pattern (LGP, n=275). Two pulmonary pathologists reviewed all cases; SRC+ tumors were defined as having >10% SRCs, agreed by both pathologists. SRC+ tumors were TTF1+, and generally cytoplasmic mucin+ and CDX2-. ALK immunostain was performed on all SRC+ cases, and ALK status was confirmed by FISH for cases with any degree of immunoreactivity. Impact of SRC+ on patients’ survival outcomes (overall and disease-free, OS and DFS) were analyzed using Cox models (by hazard ratio, HR) separately for the three groups, with careful evaluation of known prognostic factors: age at diagnosis; gender; smoking status; lung cancer history; tumor subtype; grade and stage; and treatment (surgery, chemotherapy and/or radiation).

Results
In the total of 763 patients (61% women, mean age at diagnosis 68 years), 53 (7%) were SRC+. In never smokers (73% women), 9% were SRC+; 33% of the SRC+ were ALK+ vs. 5% among the SRC- cases (p<0.0001). In the 2006-2007 cohort (55% women), 9% were SRC+; in LGP-smokers (54% women), 3% were SRC+. Across all three groups, SRC+ tumors were more likely to occur in men and have higher stage. Univariate analysis showed SRC+ never smokers had shorter survival: median DFS was 2.4 years (vs. 5.2 in SRC- never smokers, p=0.0004), and median OS was 3.7 years (vs. 7.6, p=0.0064). However, multivariate analysis did not confirm a significant impact of SRC+ on survival. In contrast, for the other two groups, crude 5-year survival was 6%-27% decreased in SRC+ cases compared to SRC- cases (none reached statistical significance); however, multivariate analysis revealed a 2-fold higher mortality (HR=2.30, 95% CI=1.01-5.27, p=0.048) for smokers with SRC+ tumors.

Conclusion
Based on results from three patient groups, we confirmed that SRC+ is significantly associated with ALK+. Worse survival in patients with SRC+ tumors was observed in never smokers by univariate analysis. A potential negative impact of SRC+ tumors on OS in LGP-smokers was only uncovered after adjusting for known prognostic factors. These results need to be furthered confirmed.

Background
Some of molecular pathways have been shown to have prognostic impact in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations predict the effect of EGFR tyrosine kinase inhibitors. KRAS is also critical oncogene, and it has been reported that KRAS pathway might interact with EGFR. But, the role of KRAS in NSCLC is unclear. We investigated the relationship between EGFR and KRAS mutation status and clinicopathological features in NSCLC.

Methods
A total of 383 consecutive patients with NSCLC underwent complete resection from 2006 to 2008 were examined retrospectively. The expression of EGFR and KRAS were evaluated by tissue microarray.

Results
The mutations of EGFR and KRAS were detected in 181/383 (47.3%) and 32/383 (8.4%) patients, respectively. On analysis of EGFR mutations, female were 107/181 (59.1%) and 51/202 (25.2%), adenocarcinoma were 177/181 (97.8%) and 123/202 (60.9%), no vascular invasion were 147/181 (81.2%) and 110/202 (54.5%), and non-smoker were 99/181 (54.7%) and 41/202 (20.3%) patients in EGFR mutation and wild type patients, respectively. As a result, EGFR mutation was found more frequently in female, adenocarcinoma, no vascular invasion, and non-smoker. The number of patients with pathological T1a were 49/181 (27.0%) and 42/202 (20.8%), T1b were 63/181 (34.8%) and 41/202 (20.3%) in EGFR mutation and wild type patients, respectively. Moreover, average tumor diameter was smaller in patients with EGFR mutation (2.68 cm±0.92) than wild type (3.34cm±1.70) (P<0.001). There were no differences in clinicopathological characteristics between exon19 and 21 EGFR mutations. In contrast, there were no significant differences between KRAS mutation and gender, histopathological type, vascular invasion and.smoking. Although KRAS status was not correlated with pathological T factors, average tumor diameter was larger in patients with KRAS mutation (3.49 cm±2.00) than wild type (2.98 cm±1.35) (P<0.001).

Conclusion
Our results suggest that EGFR mutation may suppress vascular invasion, and tumor growth, on the other hand, KRAS mutation may correlate with activation of tumor growth.

Background
The frozen section diagnosis is often performed in the sublobar resection of lung tumor. As no standard of preparation method for the frozen section is proposed, its methodology differs depending on institutions. In this study, we examine appropriateness of our preparation method for a resected specimen with a small adenocarcinoma by comparing between radiological and pathological tumor size.

Methods
We retrospectively reviewed the records of 59 resected lung specimens for the frozen section diagnoses (54 wedges and 5 segmentectomies) of lung adenocarcninomas from January to December 2008. After the specimen was well inflated with saline using injector, the pathologist cut it into segments with a width of 3-5mm and immersed them in saline. Taking the segment with maximum diameter of tumor as a sample, the pathological tumor sizes were measured (I) macroscopically by using metal straight ruler, (II) microscopically on the frozen section, and (III) microscopically on the permanent paraffin section. For obtaining the stereoscopic tumor size (Ⅱ and Ⅲ), we used a stereoscopic image analysis software, Leica Application Suite (Leica Microsystems; Tokyo, Japan). CT tumor size was measured by using 1-2mm thin-section CT (X-Vigor/Real or Aquillion, Toshiba Medical Systems, Tokyo, Japan). We obtained the tumor shadow disappearance rate (TDR) by comparing tumor size on the lung and mediastinal window image, to classify 59 cases into two groups according to TDR; TDR≧50% defined as the air-containing type (Group A, n=44) and TDR＜50% as the solid-containing type (Group S, n=15). We also calculated the diremption rate (DR%) between the pathological and the CT tumor size (DR% = |CT tumor size － each pathological tumor size|/CT tumor size×100(%)) and compared Group A and Group S.

Results
Mean CT tumor size and its standard deviation(SD) were 18.36±5.23mm, and mean pathological tumor sizes and SD of Ⅰ, Ⅱ, and Ⅲ were 17.17±6.12, 14.29±3.66, and 14.23±4.38mm, respectively. Mean CT tumor size was statistically larger than that of Ⅱ and Ⅲ (p<0.001 using Paired t-test). All the three pathological tumor sizes were correlated to the CT tumor size by Pearson’s correlation analysis (correlation coefficient were 0.766, 0.700, and 0.682, respectively). DR% of Ⅱ and Ⅲ were significantly higher in Group A than Group S by Mann-Whitney U-test (Mean DR% of group A / S (p-values) of Ⅰ, Ⅱ, and Ⅲ were 17.0/13.8% (p=0.196), 25.8/19.3% (p=0.093), and 27.3/15.5% (p=0.032) , respectively).

Conclusion
There was a strong correlation between CT tumor size and each pathological tumor size, which shows that our preparation method of the specimen for the frozen section is appropriate to obtain sufficient information about the lung tumor. Furthermore, we found that the pathological tumor size is considerably underestimated by measuring tumor size on the frozen or permanent paraffin section, especially the tumor classified as “air-containing type” including adenocarcinoma with good prognosis. It is therefore important to inflate the lung specimen sufficiently and to transfer it to microscopical examination without tissue shrinking.

Background
Distinction between different subtypes of non–small cell lung carcinoma (NSCLC) particularly separating squamous cell carcinoma (SCC) from non-SCC is important due to the availability of specific targeted therapy based on histologic subtypes. Recent molecular testing guideline for selection of lung cancer patients for epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor therapy from the College of American Pathologists (CAP), International Association for the Study of Lung Cancer (IASLC) and Association for Molecular Pathology (AMP), recommend that in the setting of fully excised lung cancer specimens, EGFR and ALK testing is not recommended in lung cancers that lack any adenocarcinoma component, such as pure SCC (Lindeman et al, J Mol Diagn 2013, 15:1-39). However, more than two-thirds of lung cancer presents as advanced stage disease and cytology specimens may only be available in most of these cases. Accurate distinction between SCC and non-SCC can be challenging in these cytology specimens due to limited cellularity. We report our institutional experience regarding the diagnostic accuracy of classifying SCC in cytology preparations compared with histopathological follow-up.

Methods
A retrospective review of the cytology specimens diagnosed as squamous cell carcinomas was carried out from January 2011 – June 2012 from our cytopathology and surgical pathology databases. All cases were correlated with subsequent histopathological diagnoses, immunohistochemical (IHC) and molecular analyses.

Results
A total of 200 histopathological specimens diagnosed as squamous cell carcinoma (SCC) were retrieved from our electronic medical records. 30 were excluded due to multiple specimens from the same patient. Corresponding cytology specimens including fine needle aspiration (FNA) specimens, bronchial brushings and bronchial washings were available in 88/170 (52%) cases. Out of these 88 cytology specimens, a diagnosis of malignancy was made in 58 (66%) specimens; these were subcategorized into (1) definite diagnosis of malignancy (32/58=55.2%), (2) favor tumor subtype (14/58=24.1%), (3) unclassified (9/58=15.5%) and (4) suspicious for malignancy (3/58=5.2%). Overall, the diagnoses of malignancy was made in 57/58 (98.3%) while the accurate diagnoses of squamous cell carcinoma was made in 52/55 (95%) cytology specimens. IHC was employed in cases 21/88 (23.9%). Molecular testing was performed on 12/170 (7%) specimens. Molecular testing was successful in these cases with mutations identified in two cases.

Conclusion
Our study demonstrates that cytology specimens are an excellent source of making a reliable, quick and accurate diagnosis of lung squamous cell carcinomas in 95% of cases and can serve as an excellent source for IHC and molecular analyses, if necessary.

Background
Adenocarcinoma (ADC) of the lungs may harbor EGFR- and KRAS-mutations, which are relevant for treatment decisions. Approximately 35% of non-small cell lung cancer (NSCLC) biopsies are diagnosed as not-otherwise-specified (NOS).To improve segregation between ADC and squamous cell carcinoma (SqCC), the classification of lung cancer was updated in 2011, adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm. The aim of our study was to investigate the hypothesis, that additional IHC reliably delineates lung cancer harboring EGFR- and KRAS-mutations.

Methods
From an institutional lung cancer database of specimens routinely analyzed for the presence of EGFR- or KRAS-mutations (n=816), cases harboring a mutation were selected (n=343) and corresponding original histological diagnoses and IHC for TTF-1, p63 and PAS-D were collected. Cases with a pattern compatible with SqCC were histologically reassessed.

Results
From the 343 cases 25% were resection specimen, 70% biopsy and 5% cytology specimens. 69% of cases had a KRAS-mutation and 31% an EGFR-mutation. IHC-data were conclusive in 89%. The combination of positive TTF-1 and/or mucin stain and a negative p63 stain, favoring ADC, was found in 264 cases (77%). Six (1.7%) specimens were positive for p63 only, favoring SqCC.

Conclusion
The current 2011 classification of lung tumors, based on histology and immunohistochemistry for TTF-1, p63 and mucin, segregates specimens of ADC and SqCC sufficiently well. Our study results support the use of IHC in the diagnosis of lung cancer.

Background
Since IASLC/ATS/ERS reported their new classification for lung adenocarcinoma (ADC), several groups have validated its association with prognosis in early stage. We know do not any study in advanced disease.

Methods
We included 313 patients with stage IIIB and IV histologically confirmed lung ADC from the Instituto Nacional de Cancerología (INCan). All patients received platinum-based chemotherapy (CT) and only 30% received EGFR-TKIs. ADCs were re-classified using the new IASLC/ATS/ERS criteria. Clinical characteristics, mutational profile, response and progression-free survival (PFS) to CT and overall survival (OS) were analyzed.

Results
ADCs were classified as lepidic 6.1%, acinar 36.7%, papillary 8.3%, micropapillary 2.9%, solid 28.1% and 17.9% were unclassifiable. We divided them into two groups: intermediate-grade (lepidic and acinar-predominant) and high-grade (micropapillary, papillar and solid-predominant). The response rate and PFS to CT were better in the high grade group (36.9% vs 25.4% p= 0.034; 6.4 vs 5.5 months p= 0.009, respectively). The OS was better in the high grade group (25 vs 16.8 p= 0.023). In multivariate analysis, factors associated with better OS were ECOG of 0-1, EGFR mutations and high grade group histology. We did not find association between EGFR mutations and this classification.

Conclusion
Unlike early stages, patients with advance disease and with high-grade ADC according to the new classification have longer OS compared with intermediate grade ADC, probably due to a better response to CT.

Background
Aim: We aimed to compare F-18 FDG PET-CT imaging characterictics in non-small cell lung cancer (NSCLC) with and without epidermal growth factor (EGFR) reseptor mutation.

Methods
Methods: A total of 47 NSCLC patients (38 male, 9 female, mean age : 47±10.45 )were included in this retrospective study. All patients underwent EGFR mutation resting and pretreatment F-18 FDG PET-CT scan. The maksimum standardized uptake (SUVmax) of the primary tumor and metastases was calculated for all lesions in all patients. We compared the SUVmax values for primary tumor and metastatic lesions in patients with and without EGFR receptor mutation.

Results
Results: In our study group, there were 17 adeno, 10 squamous, 2 large cell, 1 mixt-type and 17 non-small cell cancer patients. Seven patients had EGFR-mutant and 40 patients had EGFR wild-type tumors. There was a trend for higher SUVmax in primary tumors among patients with EGFR-mutant (mean SUVmax: 14.20±10.40) versus patients with wild-type EGFR (mean SUVmax:11.53±6.46). In patients with wild-type EGFR, the mean SUVmax was 7.05±3.39, 7.83±4.66, 6.10±4.44, 12.83±4.89 for hilar(17 pts), unilateral mediastinal (23 pts), contralateral mediastinal (13pts) and supraclavicular (3 pts) lymph node metastates (LNM), respectively. In 5 patients with EGFR-mutant , SUVmax was 6.48±3.39 for unilateral mediastinal LNM. There was no hilar, contralateral and supraclavicular LNM which can be demonstrated by F-18 FDG PET-CT in EGFR-mutant patients. The mean SUVmax was 7.97±6.67, 8.98±4.31 and 5.85±3.39 for lung (6 pts), bone (9 pts) and adrenal (6 pts) metastases in wild- type EGFR patient group. In EGFR-mutant group , one patient had lung, bone and adrenal metastases in which SUVmax was 4.20, 11.20 and 22.20, respectively.

Conclusion
Conclusion: Higher FDG uptake was found in primary tumors among EGFR-mutant patients than wild-type EGFR patients. In this study group, the incidence of hilar, contralateral mediastinal and supraclavicular LNM were higher in wild-type EGFR group than that in EGFR-mutant group. Bone and adrenal metastases in a patient with EGFR-mutant showed markedly increased FDG uptake. Further analyses with large number of patients are needed to describe a predictive role of FDG uptake on EGFR mutations in NSCLC patients.

Background
Acute infections can sometimes radiologically be suspected to be lung cancer. Only rarely are, however, the mediastinal lymph nodes enlarged. Tularemia is a disease in rodents caused by the bacterium Fransiscella tularensis but it can also infect humans if infective material is inhaled, and typically lung infiltrates and PET-positive nodes persist for a few months. We have not found any good description of this entity in the literature and therefore we describe three such cases.

Methods
During two years, three patients were referred for suspected lung cancer. One was a farmer and two who had cleaned out their summer house after the winter invasion of mice. PET investigation with [18]F-fluorodeoxyglycose (FDG) was strongly positive both in the "tumor" and in the enlarged mediastinal lymph nodes. Bronchoscopy showed inflammatory cells only.

Results
There was a spontaneous regression of the lesions during the investigations and serology proved the etiology.

Conclusion
Like the classical plague, there are two variants of tularemia: peripheral wounds or insect bites can cause the ulceroglandular form, with an ulceration and enlarged local lymph nodes nodes which can suppurate, and inhalation of infectious material (for example, mouse excrements) can cause a localized pulmonary infiltrate and enlarged mediastinal lymph nodes which will readily be mistaken for lung cancer. Diagnosis is by serology; treatment is mainly by tetracyclines, but by the time investigation is started the disease is usually already healing spontaneously. History is very important: has the patient has any contact with mice or other rodents or their droppings?

Background
Quantitative analysis of thoracic computed tomography (CT) scans may be used to assess response to radiation therapy (RT). The purpose was to (1) identify a set of mathematical descriptors of image texture that correlate with the severity of radiologic normal lung tissue changes following RT and (2) quantitatively measure the extent of severity-dependent change in the values of these texture features.

Methods
Twenty-four patients who underwent definitive RT (median dose: 66 Gy, 2 Gy/fraction) for lung cancer were retrospectively identified. For each patient, three CT scans were collected: pre-treatment scan, post-treatment (median: 34 days, range: 8-82 days) scan, and RT planning scan with an associated dose map. Four dose regions (0-10 Gy, 10-30 Gy, 30-50 Gy, and >50 Gy) in the RT dose map were identified and mapped to the post-treatment scan through demons deformable registration. Sixty regions of interest (ROIs) distributed evenly among the four dose regions were automatically identified in the normal lung tissue of each post-treatment scan. An experienced radiologist compared the severity of change in each ROI from pre-treatment to post-treatment and categorized each as containing: 1) no abnormality, 2) mild abnormality, 3) moderate abnormality, or 4) severe abnormality. Twenty texture features that characterized gray-level intensity, region morphology, and gray-level distribution were calculated in all post-treatment ROIs and compared with anatomically matched ROIs mapped to the pre-treatment scan using demons registration. Fitted coefficients for the percent feature value change (ΔFV) between pre-treatment and post-treatment ROIs at each category of visible radiation damage were calculated using linear regression.

Results
Most ROIs contained no abnormality (66%) or mild abnormality (30%). ROIs with moderate (3%) or severe (1%) abnormalities were observed in 9 patients. For 19 of 20 features, significant differences (p<0.05) in ΔFV existed among ROIs assigned to various severity levels. For 12 features, significant differences in ΔFV existed among all four categories of radiation damage (see figure). Compared with regions with no abnormality, ΔFV for these 12 features increased, on average, by 1.6% (95% CI: 1.3-2%), 12% (95% CI: 9-15%), and 30% (95% CI: 19-41%), respectively, for the mild, moderate, and severe abnormality ROI categories.Figure 1

Conclusion
For 12 of the 20 features, ΔFV was significantly different among all categories of visible radiation damage. As severity increased, the mean feature value change from the pre-treatment scan also increased. In future studies, this approach may be used as a quantitative indicator of the severity of acute normal lung tissue damage following RT.

Background
To evaluate the diagnostic accuracy of dynamic contrast enhanced (DCE)magnetic resonance (MR) and diffusion weighted imaging (DWI) sequences for defining benign or malignant character of solitary pulmonary lesion (SPL) in a preoperative setting.

Methods
This study was approved by the local ethics committee; all patients provided written informed consent. First, 54 consecutive patients with SPL, clinically staged (CT and PET or integrated PET-CT) as N0M0, were included in this prospective study. An additional MR examination including DCE and DWI was performed one day before the surgical procedure. Histopathology of the surgical specimen served as standard of reference. Subsequently, this functional method for SPL characterization was validated with a second cohort of 54 patients.

Results
In the feasibility group, 11 benign and 43 malignant SPL were included with a maximal diameter that varied from 3 to 71 mm (mean 23.2 mm). Using the conventional MR sequences with visual interpretation of DCE-MR curves sensitivity, specificity, accuracy were respectively 100%, 55% and 91%. By additional interpretation of quantitative apparent diffusion coefficient (ADC) values (with a cutoff value of 1.52x10-3 mm2/sec for ADC calculated from high b-values (ADChigh) these results improved to 98%, 82% and 94% respectively. In the validation group, with 14 benign and 40 malignant SPL (diameter ranged between 7 mm and 10 cm - mean 26.5 mm), these results were confirmed with a sensitivity, specificity and accuracy of 95%, 79%, and 91%, respectively.

Conclusion
Visual DCE-MR-based curve interpretation can be used for initial differentiation of benign from malignant SPL, while additional quantitative DWI-based interpretation can further improve the specificity.

Background
Pulmonary ground-glass nodules (GGNs) often grow over a long period of time. Elucidating the growth rate of GGNs is of great importance in deciding on follow-up intervals in clinical practice. The objective of this study was to clarify the natural history and tumor growth rate of GGNs after a long-term follow-up.

Methods
We retrospectively studied 121 cases of patients with GGNs, who had more than 50% of ground-glass opacity component and were monitored using high-resolution computed tomography (CT) for >2 years. Factors affecting the time to tumor progression were evaluated using the Kaplan–Meier method and Cox proportional hazard model analysis. Tumor growth rate was evaluated using specific growth rate (SGR), which was calculated using volume-doubling time (VDT) data (SGR = ln 2/VDT).

Results
During a median follow-up period of 59.7 months, GGNs showed enlargement or increase in attenuation in 66 patients and no change in 55 patients. In multivariate analysis using Cox proportional hazard model, the initial mean CT attenuation value > –670 Hounsfield unit (HU) and initial tumor size > 8 mm were independent predictive factors for time to tumor growth (p < 0.0001 and p = 0.0006, respectively). The Kaplan-Meier curves evaluating time to tumor progression, which was divided into 4 parts according to the initial mean CT attenuation value and initial tumor size, showed that the final estimated probability for patients with GGNs with a mean CT attenuation value < –670 HU and tumor size < 8 mm was 14.5%, whereas that for the other 3 groups was more than 50%, and with a significant difference (p < 0.0001). Comparing the tumor growth rates in these 4 groups, the SGR in GGNs with a mean CT attenuation value < –670 HU and tumor size < 8 mm was significantly lower than that in GGNs with a mean CT attenuation value > –670 HU and tumor size > 8 mm (p < 0.0001) and with a mean CT attenuation value > –670 HU and tumor size < 8 mm (p = 0.0005).

Conclusion
A combination of the measurement of the mean CT attenuation and the tumor size in the initial CT examination may be useful for predicting GGN growth. Lower-attenuation and smaller-size GGNs grow, but with slow growth rate, and, for patients with such GGNs, longer follow-up intervals may be useful in clinical practice.

Background
Preoperatively distinguishing non-invasive or minimally invasive lung adenocarcinomas from invasive lung adenocarcinomas on the basis of the classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS) is essential. However, in some cases, this distinction is potentially difficult to make by using the conventional computed tomography (CT) settings, i.e., lung and mediastinal windows. The objective of this study is to evaluate novel CT window settings for preoperative detection of pathologically invasive adenocarcinomas.

Methods
We retrospectively investigated 112 pathological T1a adenocarcinomas with a ground-glass opacity pattern ratio on preoperative CT of more than 50%. In the CT performed before an operation, the window level/window width was set as follows: -300/600, -250/500, -200/400, -150/300, and 30/400 (conventional mediastinal window). Under these viewing conditions, a maximum diameter of residual tumor was defined as the predictive invasion diameter. Receiver operating characteristic curve analyses were used to verify whether each viewing condition could be used to predict pathologically invasive adenocarcinomas that have a maximum invasion diameter of more than 5 mm.

Results
The area under the curve values for the -300/600, -250/500, -200/400, -150/300, and 30/400 settings were 0.87, 0.91, 0.86, 0.84, and 0.78, respectively. The sensitivity and specificity in the window setting of -250/500 was 98.1% and 67.8%, when the cut-off value for the predictive invasion diameter was set at 6 mm.

Conclusion
We determined novel CT window settings. The window level/window width setting of -250/500 might be useful for predicting pathological invasion of more than 5 mm in T1a lung adenocarcinomas.

Background
Junior doctors may fail to detect subtle pulmonary pathology on plain chest X-ray (CXR). Digital tomosynthesis (DT) is an emerging radiographic technique that provides multiple coronal chest images at only 2% of the radiation of a standard chest CT. Previous studies have demonstrated that pulmonary nodule detection sensitivity is three times greater with DT compared to CXR. We investigated whether DT can increase nodule detection rates by junior doctors compared to CXR.

Methods
Ten volunteer junior doctors (post-graduate years 1-3) at The Prince Charles Hospital in Brisbane, Australia, a secondary and tertiary referral hospital, were recruited to view CXR and DT images of 11 patients. All patients had CXR, DT and CT images acquired within a 30 day period for the evaluation of lung nodules. CT images (Philips Brilliance, Philips Medical Systems, Best, Netherlands), with collimation 0.625 mm and reconstructed slice width 0.9 mm, reported by experienced radiologists, served as the gold standard. DT images, consisting of 60 exposures through a 30° arc, were acquired using the GE Definium 8000 Xray Unit (GE Healthcare, Little Chalfont, United Kingdom), with simultaneous CXR as a scout image. Nine of these patients had at least one nodule >10 mm on CT, with two control patients without nodules. All participants undertook brief training to familiarise them with DT images one week prior to the study. In the study session, participants were showed anonymised CXR and DT images in random order and asked to mark “definite” or “possible” pulmonary nodules electronically. The markings were compared to CT detected “true” nodules. Markings made where there were no true nodules on CT were recorded as false positives. The time taken to view each image was measured. Participants completed a brief survey after viewing the images.

Results
Nodule detection sensitivity, represented by the proportion of true nodules marked “definitely” present, was significantly higher using DT than CXR (28/65 [43%] versus 3/70 [4%], χ[2], p<0.001), as was the proportion of nodules marked either “definitely” or “possibly” present (32/65 [49%] versus 13/70 [19%], χ[2], p<0.001). When considering instances where a nodule was marked either “definitely” or “possibly” present, where there was no true nodule on CT, significantly fewer false positives were made, on average, when viewing DT compared to CXR (0.36 versus 1.18 false positives per image, t-test, p<0.001). Although the time taken to view each DT image was statistically significantly longer than for each CXR image (86.9 seconds versus 67.9 seconds, t-test, p<0.01), the absolute difference was small. Ninety percent of participants agreed that they could identify nodules more confidently with DT than CXR.

Conclusion
In this study, junior doctors correctly identified more pulmonary nodules using DT compared to CXR and reported fewer false positive results. The time taken to view DT images was slightly longer than for CXR images, but this difference was small. Despite the small sample size, this pilot experiment has shown that DT may potentially improve identification of pulmonary nodules by junior doctors and a larger study is underway.

Background
Over the recent years, PET-CT studies have become the golden standard for the planning of high-dose definite radiotherapy of non-small-cell lung cancer (NSCLC). This is justified by their proven superiority over computer tomography in both sensitivity and specifity to determine the location of all tumor sites, helping avoid underirradiation of active malignancy as well as using unnecessarily large field sizes. Numerous reviews have pointed out that the quantifiers of tumor metabolism, primarily the maximal Standard Uptake Value (SUVmax) of [18]F-deoxyglucose as measured in PET-CT studies can as well serve as a prognostic factor in NSCLC. As we were expecting this to be particularily significant for patients with unresectable tumors yet irradiated with intention to cure, we decided to retrospectively investigate the prognostic value of tumor metabolism quantification for this group.

Methods
The material of our study consists of 53 patients, treated with definite radiotherapy (with sequential chemotherapy in 50 cases) for locally advanced, unresectable NSCLC. The doses prescribed for radiotherapy ranged from 60 to 71,2 Gy; all patients completed the intended radiation treatment. We assessed the tumor metabolism on PET-CT studies used for radiotherapy planning; in addition to measuring the SUVmax value, we quantified the tumor metabolic volume (TMV) using three different algorithms varying by the threshold above which voxels within the tumor were considered its volume. Results were co-related to various clinical parameters and the therapeutic outcome, measured as progression-free and overall survival at 36 months of follow-up.

Results
Figure 1 Of all clinical variables as well as the tumor metabolism quantifiers, the TMV was found to be the only standalone statistically significant prognostic factor for both overall (log-rank test p=0,048) and progression-free survival (p=0,014). Its value was confirmed in both Kaplan-Meier (shown) and Cox models. No co-relation was found between TMV and SUVmax, tumor type, sex or the pattern of failure. Tumor stage in PET-CT studies (after or during chemotherapy) was co-related to TMV, yet its prognostic value was not significant.

Conclusion
TMV is a simple parameter to calculate during routine analysis of PET-CT study, which provides - independently on the clinical variables and more accurately than radiological re-staging - relatively reliable prognostic information for patients who are to be treated with definite radiotherapy for NSCLC. Prospective studies on larger number of patients need to be undertaken to answer whether and how to alter the treatment regime (dose escalation, hypofractionation) in order to improve the outcome for patients with unfavorably high TMV.

Background
Most solitary pulmonary nodules(SPN) discovered by CT scan are benign. 18F-FDG PET has been reported better differentiated benign from malignant pulmonary nodules. Three previous developed clinical prediction models (Mayo model,VA model and Peking University model) are based on CT scan. We intergrating PET-CT and Clinical Data to increase accuracy in estimate the probability of malignancy of SPN.

Methods
From January 2009 to December 2012, 365 consecutive patients diagnosed SPN by PET-CT have been identified and reviewed. Clinical data were collected retrospectively. The data set was split into two groups: training set (305 patients) and testing set (60 patients). Independent factors associated with benign and malignancies were identified using training set by logistic regression analysis, and a prediction model has been established. Patients from the testing set were then used to validate the predictive value of this model, and compared accuracy with Mayo model and Peking University model.

Results
Logistic analysis showed three clinical characteristics(gender,age, smoking data) and six radiological characteristics(diameter, upper lobe,speculation, lobulation, pleural tail, FDG uptake) were independent predictors for malignancy. The area under the evaluated receiver operating characteristics curve was 0.854±0.043. Compared to Mayo model,VA model and Peking University model, this PET-CT based model showed better predictive value. Figure 1

Conclusion
Our PET-CT based clinical prediction model has better accuracy in estimate the pretest probability of malignancy in patients with SPNs.

Background
Pulmonary nodules with ground-glass opacity (GGO) are frequently encountered. We previously reported that, based on natural history of 108 pulmonary nodules that were 3 cm or less and had 50 % or more GGO component, these nodules should be followed for at least 3 years to accurately evaluate lesion growth. However, it remains unclear whether all GGOs should be followed for as long as 3 years. To establish reasonable follow-up plan, it would be useful to if we could predict which of GGO lesions tend to grow by any of clinical-radiographic characteristics. The purpose of this study was to clarify which baseline clinical and radiological characteristics were associated with growth of these nodules.

Methods
We retrospectively studied patients between 1999 and 2013 with pulmonary nodules that met the following criteria: (1) lesion diameter of ≤ 3 cm, (2) GGO proportion of ≥ 50%, and (3) observation without treatment in the prior 6 months. We evaluated the changes in lesion size on serial computed tomography. Two endpoints, “Time to 2-mm growth” and “2-mm growth incidence”, were analyzed using Cox proportional hazards and logistic regression models, respectively.Variables for univariate analysis were as follows: age; gender; smoking history; past history of lung cancer; lesion multiplicity; lesion diameter; and solid proportion. Factors for which p-value was < 0.05 in univariate analysis, as well as past history of lung cancer which was reported as a predictor in previous reports, were included in multivariate analysis. To strictly define “no growth”, we excluded lesions which had been observed for less than 3 years in logistic regression analyses.

Results
120 pulmonary lesions in 67 patients fulfilled inclusion criteria. At the median observation period of 4.2 years, 34 lesions had become larger by 2mm or more, whereas the remaining 86 had persisted without changing in size. Smoking history and initial lesion diameter were statistically significant in both regression and time-to-event analyses. In terms of time to 2mm growth, hazard ratio (HR) for smoking history was 3.67 (P < 0.01). Compared to those ≤ 1 cm, HRs for 1.1–2 cm and 21-3 cm lesions were 2.23 (P = 0.08) and 5.08 (P = 0.04), respectively. In contrast, odds ratio (OR) for the likelihood of 2mm growth for smoking history was 6.51 (P < 0.01), and OR for lesion diameter of 1.1–3 cm in comparison to ≤ 1 cm was 4.06 (P = 0.02).

Conclusion
Smoking history and initial lesion diameter are significantly associated with the growth of these nodules. These results suggested that closer follow up of larger size GGO in smoking patients be recommended.

Background
Major lung resection may induce expansion of the remaining lung, accompanied by some gain in the function of this lung. Pulmonary function studies have been performed in thoracotomy patients mainly for the purpose of predicting postoperative morbidity and mortality. Lobectomy is the standard operative procedure for lung cancer. However, the impact of this compensatory response of the residual lobes remains unclear, because spirometry cannot evaluate pulmonary function of individual lobe as single units.

Methods
Thirty-one patients who underwent lobectomy were included in this study. They were consisted of 15 males and 16 females, and 67 years old in average. Surgical procedures were 30 lobectomies and 1 bilobectomy. Chest CT scans at inspiratory and expiratory levels were performed at the same time using 40-slice MDCT (Brilliance 40, Philips, Netherlands). Scan conditions were 120 kV, ≤ 250 mAs, 0.5 sec./rotation, 32x1.25 configuration, pitch 0.906, and 5 sec. scan time. We then calculated the volume of individual lobes using graphic workstation (Virtual Place Lexus 1.0, AZE, Japan). Voxels with -215 HU or less were regarded as the air in the lung. VC of each lobe (VCL) was calculated as lobar volume at the inspiratory level subtracted by lobar volume at the expiratory level. This CT volumetry was performed before and 1 year after surgery.

Results
VCLs of the residual lobes in the operated side were 1.01±0.47L before surgery, and significantly (p=0.0094) increased to 1.22±0.74L after surgery. There was 22.3±43.6% gain in VCL of the lobes in the operated side after surgery compared with that before surgery. However, there was no significant difference (p=0.7040) in VCLs of the lobes in the unoperated side between before (1.71±0.71L) and after (1.69±0.63L) surgery. The rate of compensatory response of VCL of the residual lobes in the operated side was significantly (p=0.0002) correlated with the percentage of the VCL of the resected lobes. Statistical analysis revealed that the rate of compensatory response (%) could be calculated as the ratio of VCL in resected lung (%) before surgery multiplied by the constant of 1.556.

Conclusion
The compensatory response in pulmonary function after lobectomy appeared to occur only in the lobes in the operated side. The rate of this functional gain was significantly correlated with the ratio of the VCL in the resected lobes. These data may provide more precise prediction of postoperative lung function in patients who underwent lung resection.

Background
This study aimed to: 1) compare qualitative and semi-quantitative assessment of [18]F-fluorodeoxyglucose PET based categorical metabolic response in patients with NSCLC and determine their value for prognosis prediction; 2) investigate the relationship between semi-quantitative assessments of post-treatment change of metabolic activity and survival and explore an optimal cutoff to distinguish a subset of responders with more favorable outcome.

Methods
This is a secondary analysis of prospective studies with IRB approval. Enrolled patients with NSCLC underwent PET/CT imaging within 2 weeks prior to (pre-RT PET/CT), at 4 weeks during and after radiation treatment (post-RT PET/CT). Post-RT metabolic therapeutic response was assessed using 1) visual assessment and 2) semi-quantitative measurement based on reduction in tumor FDG uptake; SUVmax normalized to mediastinal blood pool (NSUV-A). Interpretation of PET/CT scans was performed by three nuclear medicine physicians, blinded to clinical information. The three physicians did independent reads of the patients, performing a single read for each patient’s set of PET studies. Kappa coefficient was used to evaluate the agreement between categorical variables. Survival analysis and Cox proportional hazard regression model were adopted to analyze the effect of various response criteria on overall survival (OS) and progression free survival (PFS).

Results
Forty-four patients (36 male: 8 female) were eligible for analysis. The median interval between end of RT and post-RT PET/CT scan was 93 days. A poor agreement was observed between visual and semi-quantitative responses (Kappa coefficient = 0.393). Categorical responses were significantly correlated with both OS and PFS independent of employed response assessment criteria (either visual or semi-quantitative, p < 0.001) and patients with complete metabolic response (CMR) obtained the longest survival. As a continuous variable, reduction percentage of NSUV-A showed significant correlations with OS (hazard ratio, HR = 0.980, p < 0.001) and PFS (HR=0.984, p < 0.001). Analysis of OS and PFS consistently recommended NSUV-A reduction of sixty percent (60%) as another discriminative cutoff to distinguish patients with different outcome (p < 0.01).

Conclusion
There is a great discrepancy in metabolic response rates between qualitative and semi-quantitative methods. Categorical metabolic response criteria, either from qualitative visual assessment or a semi-quantitative method, demonstrate significant association with overall survival and progression free survival. Visual method offers a simpler approach that provides good information with regard to predicting OS and PFS, while the semi-quantitative method provides ordinal value that correlates with prolonged OS. As a continuum, the numerical percentage reduction in the normalized SUV is positively correlated with longer overall survival, reinforcing the prognostic value of metabolic change on FDG PET/CT. A sixty percent reduction of SUV may be the optimal cutoff for metabolic response to identify subsets of the PMR population with distinct outcomes, pending validation by an independent population.

Background
Screening lung cancer with low dose computed tomography (CT) improved the likelihood of detection of small non-calcified nodules, and thus lung cancer might be detected earlier with more potential for a cure. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. However, the cost-effectiveness of using low dose CT screening was still debatable in the normal population even in the smoking population. The Northern Thailand Thoracic Oncology Group (NT-TOG) would like to study focusing on the first relative of lung cancer patients which may benefit from low dose CT screening.

Methods
From January 2013 to May 2013, a prospective cohort study was performed at Chiang Mai University Hospital. We enrolled asymptomatic participants, 20 to 65 years of age who were the first relative of lung cancer patients and received a structural interview and informed consent. Low-dose CT scan and chest radiography were performed on the same day for each participant. Nodules or other suspicious findings were classified as positive results. Nodules or suspicious findings from either low-dose CT or chest radiography which have a high risk of malignancy will be worked up rapidly for tissue pathology whereas low risk nodules will be followed up with low-dose CT and chest radiography every six months, for two years. This study reports findings from the initial screening examination.

Results
There were 14 (45.2%) cases of positive nodule from low- dose CT screening out of a total of 31 cases, whereas, there were no positive nodules from the chest radiography. The average number of nodules was 2.1 nodules and the average size of nodule was 0.4 cm in diameter. There was ground-glass opacity (GGO) in seven cases (22.6 %), subsegmental atelectasis in 14 cases (45.2 %), traction bronchiectasis in four cases (12.9 %), and a lung cyst in one case with subcentimeter lymphadenopathy in 26 cases (83.9 %). The average size of the mediastinal lymph node was 0.7 cm in diameter (range 0.2-0.9 cm).

Conclusion
This study reported initial findings from low-dose CT and chest radiography. These results demonstrated that low-dose CT screen may be a valuable method for screening in the first relative of lung cancer patients compared with chest radiography. However, all of the positive cases need to be worked up for a definite tissue diagnosis in order to have an earlier diagnosis of lung cancer and potentially more curative treatment or at least to be closely monitored. This study will be continued and more participants will be recruited and evaluated.

Background
Therapeutic decision and prognosis in non-small cell lung cancer (NSCLC) relies on accurate staging. Currently, Positron Emission Tomography/Computed Tomography (PET/CT) appears to have better efficacy, and is considered the gold standard method for staging lung cancer. Diffusion-weighted Magnetic Resonance Imaging (DWI) for the whole body has become feasible and provides images with good resolution. Some investigators have suggested that DWI could be used for assessment of primary tumor, lymph nodes and distant metastases in lung cancer. To date there are few data assessing DWI for staging of NSCLC. The purpose of this study is to compare the role of DWI and PET/CT for staging NSCLC patients.

Methods
This is a prospective study. Institutional review board approval and written informed consent was provided by all patients. From May 2011 to April 2012, thirty-two patients were included. Twenty (62.5%) were men, and the mean age was 62.4 years old. Non-small cell lung cancer (NSCLC) was proved at pathological examination. PET/CT and brain MRI was performed as a routine staging work up. DWI was studied as an alternative method for staging. Final stage in each patient was defined by pathological examination when available or through radiologic and clinical examinations/follow-up. Sensitivity, specificity, and accuracy were evaluated and were compared between both groups.

Results
Preliminary results demonstrate that WB MRI and PET/CT have satisfactory levels of sensitivity, specificity and accuracy, with no significant difference (p>0.05), as disclose in Table 1. Table 1 – Sensibility, specificity and accuracy of WB MRI and PET/CT.

	WB MRI	PET/CT
Sensibility	72.3%	73.5%
Specificity	91.6%	94.5%
Accuracy	86.8%	88.2%

Conclusion
PET/CT has shown to be an excellent tool for the clinical staging of lung cancer. DWI has been considered an alternative method for staging these patients. Advantages of whole-body DWI include absence of ionizing radiation exposure, excellent contrast resolution and information from different sequences allowing a better characterization of lesions, mainly brain and liver metastasis. Our preliminary results demonstrate no significant difference in accuracy between both methods for staging patients with NSCLC.

Background
Sputum cytology is a widely accepted non-invasive diagnostic method for lung cancer. However, the efficacy to reduce lung cancer mortality has not been clearly proven in mass screening setting. To understand the potential value of sputum cytology to detect squamous cell carcinoma (SCC) of the lung, we evaluated its sensitivity and specificity. We simultaneously attempted to clarify the effect of repeated screening on the incidence of SCC.

Methods
In total, 104,872 sputum cytology tests combined with miniature chest X-ray were performed on 44,809 people belonging to the high-risk population of Miyagi Prefecture in Japan from 1990 to 1996. The sensitivity and specificity were calculated based on the information from the Cancer Registry. The incidence of SCC in the year after sequential annual repeat or sequential annual absences was analyzed.

Results
In total, 183 SCC-positive cases were diagnosed. The sensitivity and specificity of sputum cytology for SCC were 66.7% and 99.9%, respectively. Among cases with known localization, sensitivity for the central type was 90.7%, while that for peripheral type was 64.2%. Similarly, significantly decreased screen-detected SCC was observed in the third repeated test . A significant increase in screen-detected SCC cases was observed in the third year of sequential absence from screening.

Conclusion
Annual screening by sputum cytology for the high-risk group showed high sensitivity for SCC of the lung, particularly for central type SCC. Significantly reduced incidence of central type SCC was observed by repeating annual sputum cytology screening.

Background
Doctors´ delays can sometimes be very large in investigations of suspected lung cancer. The main problem seems to be the many steps involved, with delays at all levels. In order to speed up the process within the available limited resources we have in Stockholm constructed a “fast track”.

Methods
The majority of suspected lung cancers in the Northern Stockholm area are referred to the Lung Clinic in Solna from GP:s and other clinics. Patients who from this information were judged to suffer from potentially curable lung cancer were admitted to the fast track, where the first visit should occur within a week and the investigations (broncoscopy, PET-CT, spirometry etc) was planned by a special nurse within the next week.

Results
From December, 2009, to march, 2013, 219 patients, 109 women and 110 men, have been investigated. The mean age was 67 years (55-82). The mean time from referral to first visit was 6,1 days and 77% were seen within one week. From referral to treatment decision, the mean was 17.8 days. There were 149 primary lung cancers, thereof 105 adenocarcinomas, 18 squamous, and 13 small cell cancers. Stage I-II were 74, III 35, and IV 41. Surgery was performed on 65 patients, 17 of whom the diagnosis was made at surgery. Potentially curative radiotherapy or chemoradiotherapy was given in 44 patients. Three lymphomas, one sarcoma, and 6 metastases from earlier unknown cancers were also seen. Thus, 109 (73%) received a potentially curative therapy. Benign lesions were seen in 56 persons (26%), mostly hamartomas or infections but only one active TB. Two granulomas were operated. PET-CT also disclosed 6 concurrent and earlier unknown cancers in other organs among the cancer patients and in two with a benign diagnosis. During the period, approximately 900 primary lung cancers were diagnosed at the clinic, so about 17% went in the fast track, which was limited by available resources.

Conclusion
A fast track is feasible and possible even without added resources. PET-CT gives very valuable information on spread of disease but also other cancers.

Background
Low-dose computed tomography (LDCT) screening improves lung cancer prognosis, but also results in diagnostic work-up and surgical treatment in many individuals without cancer. We therefore analyzed procedures that screening participants underwent to better understand the extent of overdiagnosis.

Methods
Between 2009 and 2011, 8649 healthy volunteers in the age 50-75 with 20 pack-years smoking history underwent LDCT screening with two years control in individuals with lung nodules. Participants with nodules diameter >10 mm or with suspected tumor morphology underwent diagnostic work-up. It was performed in 283(6%) of 4694(54%) screening participants with detected lung nodules. One hundred four individuals were operated, 27 were underwent oncological treatment and in 154 patients without cancer diagnosis further follow up with LDCT was applied.

Results
Our results showed that in 75% of the participants accepted for diagnostic work-up those procedures were futile. The same holds for 25% receiving surgery. Only in 70(24,7%) participants a specific diagnosis was obtained. That was mainly due to low efficacy of Fine Needle Aspiration Biopsy (Sensitivity 65,2%, NPV 95,9%) and bronchofiberoscopy (sensitivity 71,4%, NPV 50%) caused by overinterpretation of LDCT (PPV 2%). Of 104(36.7%) participants that were accepted for surgery, forty-three patients (41,4%) had preoperative cancer diagnosis and 61(58,6%) underwent operations without obtained pathology. In the latter group intervention was justified in 35(57,3%) patients. Complications occurred in 49 (17.3%) participants subjected to diagnostic work-up. In patients accepted for surgery 67 (64.4%) malignant and 37 (35.6%) benign lesions were resected. In the latter group intervention was justified in only 11 (29,7%) patients. No patient died as a result of diagnostic or treatment procedures during the study. The complication rate was 14,5% in the malignant and 10,8% in the benign groups. Finally in 94 screening participants a neoplasm was found. Of those, 67(71.3%) patients underwent operation; the remaining 27(28.7%) patients were not candidates for surgery. Adenocarcinoma accounted for 49/67(73%) operated NSCLC patients; 56/67(84%) patients had stage I non-small cell lung cancer, and 26/67(38%) underwent video-assisted thoracoscopic surgery lobectomy.

Conclusion
Futile diagnostic work-ups and operations must be reduced before LDCT screening can be broadly used. Stage I adenocarcinoma dominated in the operated NSCLC patients.

Background
Individuals who present with squamous metaplastic and dysplastic lesions are considered at high risk of lung cancer. However, these lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer. We recently identified a DNA copy number aberration (CNA)-classifier, including changes at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, as a risk predictor for cancer in individuals presenting with endobronchial squamous metaplasia (van Boerdonk et al, AJRCCM, 2011). The current study was set out to validate this classifier in an independent series of endobronchial squamous metaplastic and dysplastic lesions.

Methods
DNA copy number profiles (i.e., chromosomal gains and losses) were determined in a set of endobronchial lesions (8 squamous metaplasia (SqM), and 28 dysplasias (Dys) of various grades), identified and biopsied during autofluorescence bronchoscopy, of 36 high-risk subjects using a nested case-control design. Of the 36 patients, 12 cases had a carcinoma in situ or invasive carcinoma at the same site at follow-up (median 11 months, range 4-24), while 24 controls remained cancer-free (median 78 months, range 21-142). DNA copy number profiles were related to lesion outcome. The prediction accuracy of the predefined CNA-based classifier to predict endobronchial carcinoma (in situ) in this series was determined.

Results
All SqM and Dys lesions of controls showed no or a relatively low number of CNAs (i.e., quiescent profile with on average 0.2% altered probe features, range 0.0 – 2.4%), while the majority of lesions of cases showed multiple CNAs (i.e. highly aberrant profile with on average 38.8% altered probe features, range 0.0 – 76.7%). The previously defined CNA-classifier demonstrated 92% accuracy for cancer (in situ) prediction in the current series. All nine subjects with CNA-classifier-positive endobronchial lesions at baseline had cancer as final outcome (i.e., a positive predictive value of 100%). The negative predictive value of the classifier was 89%, i.e., all 24 controls and 3 cases were classified as being low-risk.

Conclusion
CNAs are a highly accurate biomarker for assessing the progression risk of endobronchial squamous metaplastic and dysplastic lesions. This classifier could assist in selecting subjects with endobronchial lesions who might benefit from more aggressive therapeutic interventions.

Background
To evaluate the volume doubling times (VDTs) of subsolid nodules (SNs) detected using low-dose CT lung cancer screening.

Methods
Patients with SNs detected between February 2004 and January 2005 were enrolled. Among the SNs that were detected after February 2005, increasing SNs and resected SNs after follow-up were also included in this study. After confirming the persistency of the SNs at 3 months after screening, a follow-up thin-section CT examination was performed every year, in principle. Dedicated software was developed to analyze the SNs. The volumes of the subsolid nodules were calculated based on the summation of the area of each CT slice multiplied by the CT slice thickness (i.e., 1 mm). The area of a SN on each CT slice was determined semiautomatically. The measurement of each area was performed twice, and the average of the first and second measurements was used for the volume calculation. VDTs were calculated using the following formula; (T1-T0)*log2/log(V1/V0).

Results
As of June 14, 2013, the measurements of 81 SNs in 72 cases had been completed. The interim results were as follows. VDTs were classified into positive values (n = 56) and negative values (n = 25). VDTs with positive values ranged from 333 to 83384 days (median, 1981 days; VDT >4500 days, n = 13), while the VDTs with negative values ranged from -110007 to -1014 days (median, -13317 days; VDT <-4500 days, n = 20). The initial volumes for the positive VDTs ranged from 45 to 3486 mm[3 ](median, 199 mm[3]), while the initial volumes for the negative VDTs ranged from 45 to 1037 mm[3 ](median, 189 mm[3]); the difference in initial volume between the positive VDTs and the negative VDTs was not statistically significant (P = 0.468)[. ]Among the 72 cases, 9 SNs in 9 cases (12.5%) were resected and diagnosed as adenocarcinomas (adenocarcinoma in situ [AIS], n = 4; minimally invasive adenocarcinoma [MIA], n = 3; and invasive adenocarcinoma [IA], n = 2). The VDTs for AIS ranged between 726 and 1723 days (median, 1154 days), the VDTs for MIA ranged between 333 and 806 days (median, 536 days), and the VDTs for IA ranged between 348 and 448 days (median, 398 days). The measurements of other SNs are ongoing.

Conclusion
The interim results showed that adenocarcinomas with a higher degree of invasiveness had a shorter VDT. Tentatively assuming that absolute values of VDTs >4500 days indicate clinical stability in volume despite the inherent variability of semiautomatic volumetry, 40% of the SNs were stable after an eight-year observation period.

Background
EarlyCDT®-Lung, a clinical blood test that detects autoantibodies to lung cancer-associated antigens, has shown high specificity in case-control validation studies[(1)].The performance of this test in routine clinical use was audited in an initial series of 1612 patients tested by EarlyCDT-Lung who signed HIPAA authorization permitting disclosure of their health information to Oncimmune®; the reported specificity and sensitivity (91%/41%) of the test was as predicted by case-control studies[(2)].

Methods
A prospective audit was conducted of 423 individuals known to have a lung nodule for whom lung cancer-associated autoantibodies were measured by EarlyCDT-Lung. Physicians were contacted following patient testing by EarlyCDT-Lung to determine whether a cancer diagnosis had been made or a pulmonary nodule identified by imaging. Imaging and pathology reports were reviewed. This report focuses on patient outcomes at 6 months following EarlyCDT-Lung, and specifically on the 318/423 individuals for whom a lung nodule was detected prior to EarlyCDT-Lung testing. The EarlyCDT-Lung panel was modified in November 2010 from a 6 autoantibody (AAB) panel to 7AAB to improve specificity of the test[(3)] ; there were 152/318 individuals with nodules who had the 6AAB test and 166/318 who had the 7AAB test. Analyses comparing EarlyCDT-Lung results by malignant and non-malignant nodules were made using chi-squared tests.

Results
Of the 423 individuals with nodules, there were 77 patients diagnosed with a lung cancer, and 346 were deemed to have a non-malignant nodule; 32/77 and 76/346 were positive for EarlyCDT-Lung, respectively (p=0.0004). Overall, this represented a 2-fold increased incidence of lung cancer with a positive result. Of the 318 individuals with lung nodules known prior to testing by EarlyCDT-Lung, the number of positive tests were 27/62 lung cancers and 43/256 non-malignant nodules (p= 0.000005); therefore, a positive result reflected a 2.7-fold increased incidence in this group. Considering nodule size, there was no difference for nodules <8mm, but the number of lung cancers in this group was small at only n=3. For nodules between 8-20mm and ≥20mm, a positive EarlyCDT-Lung test was statistically more likely to signify a lung cancer (p=0.06 & p=0.002, respectively; p=0.00008 combined). When only the 7AAB test was assessed, which has greater specificity, for 8-20mm and ≥20mm nodules a positive EarlyCDT-Lung test remained significantly more likely to indicate a lung cancer even though the numbers in each group were relatively small, n=58 & n=52, respectively (p=0.01 & p=0.004, respectively; p=0.0001 combined). For the 7AAB test overall and also for indeterminate nodules (8-20mm), a positive result represented a 3.5-fold increased incidence of lung cancer.

Conclusion
EarlyCDT-Lung positivity reflects a statistically significant increased risk of malignancy for lung nodules ≥8mm. This varies from 2-fold to 3.5-fold depending on nodule size. These data confirm that EarlyCDT-Lung adds to the armamentarium of the pulmonologist in assessing the risk of malignancy in nodules ≥8mm. More data are required for lung nodules <8mm size. References: (1) Boyle P, et al. Ann Oncol. 2011;22:383-389. (2) Jett JR, et al. J Thoracic Oncology 2012;7:S222. (3) Chapman CJ, et al. Tumor Biol. 201;33(5):1319-1326.

Background
NLST generated excitement reporting that CT-screening reduces lung cancer mortality in comparison to CXR-screening. In randomized population trials (RPTs) on cancer screening, disease-specific mortality is assumed to provide an unbiased measure of screening effectiveness. This is based upon the assumption that randomization produces comparison groups with equal probability of death from the target cancer, unless the intervention reduces risk. However, these assumptions have often been violated in the RPT setting, leading to uncertainty about the effectiveness of several screening interventions. Objectives of this analysis are to assess whether the mortality endpoint provides an unbiased measure of screening efficacy in NLST.

Methods
In NLST, 53,454 current/former smokers, age 55-74 years, were randomized to CT or CXR-screening. Participants were offered a prevalence screen followed by two annual incidence screens.

Results
There was a highly significant 20% lung cancer mortality reduction in the CT-group (TABLE). There was also a significant 12% increase in lung cancer incidence in CT-group. Because CT is more sensitive than CXR, higher lung cancer incidence is predictable based upon lead-time and length-biases, and possibly overdiagnosis. The significant three-fold excess of BAC in the CT-group may reflect some overdiagnosis. Moreover, the highly significant two-fold excess of stage I cancers may reflect conventional biases. However, incidence of the most virulent lung cancers, including small-cell lung cancer and NSCLC-not-otherwise-specified was 16% lower in experimental-group. There exists no plausible hypothesis to explain lower incidence of highly biologically aggressive lung cancers in the CT-group. These differences strongly suggest imbalances in randomization. This is not to suggest that CT is not superior to CXR. While survival has not been reported, there is a significant 29% reduction in case-fatality in CT-group. Moreover, despite higher incidence, there was a highly significant one-third reduction in the absolute number of stage IV cancers in CT-group.

	CT Group	CXR Group	p value	Relative Risk (95% Confidence Interval)
Population	26,722	26,732
LUNG CANCER DEATHS
mortality	356 (1.33%)	443 (1.66%)	0.0022	0.80 (0.70-0.92)
fatality	356/1060 (33.6%)	443/941 (47.1%)	<0.0001	0.71 (0.64-0.80)
LUNG CANCER INCIDENCE AND STAGE
incidence	1,060 (3.97%)	941 (3.52%)	0.0067	1.12 (1.03-1.23)
stage I lung cancer	416 (1.56%)	196 (0.73%)	<0.0001	2.12 (1.79-2.51)
stage IV lung cancer	226 (0.85%)	335 (1.25%)	<0.0001	0.67 (0.57-0.80)
LUNG CANCER HISTOLOGIC SUBTYPES
bronchioalveolar carcinoma (BAC) incidence	110 (0.41%)	35 (0.13%)	<0.0001	3.14 (2.15-4.60)
adenocarcinoma, squamous cell carcinoma, or large cell carcinoma incidence	664 (2.48%)	527 (1.97%)	<0.0001	1.26 (1.12-1.41)
small cell carcinoma or nonsmall cell carcinoma-not otherwise specified (NSCLC-NOS) incidence	268 (1.00%)	317 (1.18%)	0.046	0.84 (0.72-0.99)
carcinoid incidence	6 (0.022%)	2 (0.007%)	0.18	3.00 (0.61-14.87)

Conclusion
In NLST, lower incidence of lethal lung cancer subtypes in CT-group predicts for lower lung cancer mortality, independent of CT-screening efficacy. Accordingly, lower lung cancer mortality does not provide an unbiased measure of CT-screening efficacy in NLST. While stage distribution and case-fatality advantages strongly support that CT is superior to CXR, further analysis, which must include survival, is required to judge the true effect of CT-screening. While a simple survival comparison of CT versus CXR would also be biased, an analysis comparing survival stratified by histologic subtype or other outcome predictors, would be useful in judging the effectiveness of CT-screening in NLST.

Background
Early diagnosis and referral to specialist treatment are critical factors in the management of lung cancer. Survival is improved when lung cancer is diagnosed at an early stage and the patient is referred to a multidisciplinary specialist lung cancer team for diagnosis, staging and treatment planning. However, as symptoms can be non-specific and often present similarly to other chronic health issues, an early diagnosis of lung cancer may be missed. Patients with symptoms of lung cancer are likely to present to their general practitioner (GP). Therefore, it is important to enhance awareness of the risk factors, signs and symptoms of lung cancer, and provide GPs with the most recent evidence to facilitate timely and effective assessment and appropriate referrals. Cancer Australia commissioned Monash University (MU) to develop an evidence-based guide for GPs (the Guide), and to develop strategies for promoting uptake of the Guide.

Methods
An Expert Advisory Panel (EAP) was established to oversee development of the Guide, using the ADAPTE framework for guideline adaptation. Following a search of the literature to identify potentially relevant guidelines and shortlisting using the Appraisal of Guidelines for Research and Evaluation instrument (AGREE), three international guidelines (UK, NZGG, USA) were selected to inform development of the GP Guide. MU conducted interviews with GPs to assess the feasibility of incorporating the Guide into a computerised decision support tool for the GP setting. An evidence-based, multifaceted approach to promoting the Guide and supporting uptake of best practice cancer care within the general practice setting is ongoing, in consultation with a Project Working Group. The approach includes development and implementation of an Active Learning Module (ALM) and workshops for primary care providers and organisations.

Results
The Guide includes 24 recommendations focusing on key topics including: risk factors and symptoms of lung cancer; appropriate investigations in primary care; and effective referral to a specialist linked to a lung cancer multidisciplinary team and services. The Guide was published on the Cancer Australia website and disseminated to GPs throughout Australia. The feasibility assessment found that GPs’ consultation styles did not support additional online ‘pop-up’ reminders, preferring to access the Guide external to patient consultations. Incorporation of the Guide into an appropriate format is ongoing. The ALM provides a structured learning activity in an online, interactive format, providing further detail and context to using the Guide in the primary care setting. The ALM includes case-based learning, literature for further reading, and reflection and reinforcing activities. Workshops for GPs have been held to promote and support implementation of the Guide, including strategies to adopt the Guide’s recommendations in practice. Train-the-Trainer workshops have commenced with primary care providers. Evaluation of the uptake of the Guide into clinical practice is currently unavailable.

Conclusion
A new evidence-based guide is available to support GPs to assess symptoms that may be lung cancer, to undertake appropriate investigations, and to support rapid referral into the cancer care pathway. The evidence-based, multifaceted implementation strategy supports the translation of the evidence into best practice cancer care.

Background
BACKGROUND: Chest radiographic screening is a commonly used conventional method for the detection of lung and mediastinal tumors. However, more than half of the tumors detected by chest radiography are those that have already progressed to the advanced stage. Recent studies have shown that low-dose spiral computed tomography (CT) is effective for the early stage detection of lung cancer, and this facilitates better resectability and long-term survival. The present study was performed to evaluate the usefulness of chest radiography and spiral CT in the diagnosis of mediastinal tumors.

Methods
METHOD: More than 50000 consecutive asymptomatic individuals had undergone a health check-up at our institution during a 1-year period (from December 2011 to November 2012). Of these individuals, approximately 45000 had undergone chest radiography or low-dose spiral CT. The presence of mediastinal tumors was investigated in these individuals.

Results
RESULTS: Five mediastinal tumors were detected (2 thymoma, 1 teratoma, 1 liposarcoma, and 1 neurofibroma with Recklinghausen’s disease). Two cases were detected using both chest radiography and CT, whereas the other 3 were detected using chest CT only. In these 3 cases, no abnormal opacity was observed on chest radiographs. The tumors in all 5 cases were successfully resected, and to date, no tumor recurrence has been observed.

Conclusion
CONCLUSION: These results suggest that screening using low-dose spiral CT is more useful than chest radiography and might contribute to the early detection and treatment of mediastinal tumors, although further studies to confirm of these findings will be needed.

Background
Lung cancer is the top cancer killer in North America and worldwide. Current lung cancer detection tools involving X-ray, CT and bronchoscopy are relatively time-consuming and costly. Breath analyses done by mass spectrometry have shown that certain endogenous volatile organic compounds (VOCs) are related to lung cancer and revealed the potential of breath analysis for lung cancer detection. But mass spectrometry is costly and has slow turnaround times. In another interesting development, electronic noses were made for breath analysis, however the signals generated from semiconductor array cannot accurately quantify nor correlate with VOCs. Raman spectroscopy is a promising candidate for breath analysis because it can offer unique fingerprint-type signals for molecular identification. Our objective is to develop a simple, cost-effective and non-invasive tool based on Raman spectroscopy for breath analysis and potentially for lung cancer screening.

Methods
A Raman-gas analyzer was designed and built, based on photonic technologies. We employed a hollow core-photonic crystal fibre (HC-PCF), a novel light guide that allows light to be guided in a small hollow core and it can be filled with a gaseous sample (i.e., human breath) for spectral analysis. A gas supply system was built to provide a sealed environment for the loading and unloading of gaseous samples. A 785 nm diode laser was used for Raman excitation. Stokes Raman signals generated in the hollow core of the HC-PCF were guided to the collection optics and were analyzed by a Raman spectrometer for molecular identification.

Results
Raman spectra have been obtained successfully from air, reference gases (hydrogen gas, oxygen gas, carbon dioxide gas), and human breath. The limit of detection of the system was found to be approximately 15 parts per million by CO~2~ concentration in the ambient air, characterized by the Raman peaks at 1286 cm[-1] and 1388 cm[-1]. This is a more than 100-fold improvement over the recently reported detection limit with a reflective capillary fibre-based Raman cell. The detection limit can be further improved by changes to the optical configurations, optimizing the interaction length of the HC-PCF and the use of sample pre-concentration method to enhance signal-to-noise ratio.

Conclusion
This work demonstrated a working prototype of a simple, compact, and cost-effective breath analyzer based on hollow core photonic crystal fibre and Raman spectroscopy. With further improvement in the detection sensitivity, this method can potentially be used for lung cancer screening.

Background
Lung Cancer accounts for the greatest cancer related mortality worldwide. To date, no effective screening tool for Non-Small Cell Lung Cancer (NSCLC) exists. For patients with operable stage IA NSCLC, the 5-year survival can be as high as 80%. Early detection is crucial in improving long-term survival. MicroRNAs (miRNAs), a class of short noncoding RNA molecules. miRNA expression in biological fluid samples such as sputum has shown promise as a potential means of detecting NSCLC. Our objective was to utilize an efficient, cost-effective panel consisting of 3 miRNAs (miR-21, miR-210 and miR-372) for prospective validation as a potential means of accurately detecting NSCLC. This panel was selected based on retrospective analysis of 11 miRNAs our group had previously undertaken using separate NSCLC and control cohorts.

Methods
21 early NSCLC (≤ Stage II) patients, 22 advanced NSCLC (≥ Stage III) patients and 10 control subjects were prospectively accrued. A single sputum sample was obtained through spontaneous expectoration from each study participant. Detailed study participant and tumor characteristics were obtained. miR-21, miR-210 and miR-372 expression was conducted on each sputum sample and normalized to an endongenous control (U6) relative to a MRC-5 reference sample, using RNA reverse transcription and Quantitative real-time Polymerase Chain Reaction (RT-qPCR). Statistical evaluation consisted of unsupervised hierarchical cluster analysis of the experimental-normalized miRNA expression profiles using within-group linkage.

Results
The median ages of the early NSCLC cases, advanced NSCLC cases and controls were 68, 68 and 58.5 respectively. The majority of the early and advanced NSCLC patients had smoking histories (>90%). 60% of the controls had smoking histories. Mean tumor size (± standard deviation) for early and advanced NSCLC cases were 3.4 cm (± 2.1 cm) and 4.8 cm (± 1.7 cm) respectively. Adenocarcinoma and squamous cell carcinoma comprised 62% and 23.8% of early NSCLC cases. Adenocarcinoma and squamous cell carcinoma comprised 45.5% and 22.7% of advanced NSCLC cases. Comparing early NSCLC to controls, the use of miR-21, miR-210 and miR372 expression yielded a diagnostic sensitivity of 66.7% and a specificity of 90.0%. Advanced NSCLC patients had an improved sensitivity of 81.8% with the same specificity of 90.0%.

Conclusion
The utilization of miR-21, miR-210 and miR372 sputum expression might provide a sensitive and specific means of detecting NSCLC. The potential linkage between their expression and NSCLC stage may account for the higher sensitivity observed in the advanced NSCLC group. Future use of this promising panel on a larger population will be required to establish its potential application as a screening tool.

Background
Primary and metastatic squamous cell carcinomas (SCC) in the lung are often histologically indistinguishable, and the differential diagnosis between them is primarily dependent on clinical information such as the location of the lung lesion, the tumour stage, and the disease-free interval, particularly when the pulmonary nodule is solitary. The management of solitary pulmonary SCC in patients with a history of SCC may pose diagnostic and therapeutic challenges.

Methods
A retrospective chart review analysis was conducted. The study included 244 consecutive patients with antecedent cancer histories who subsequently underwent pulmonary resections for newly discovered solitary pulmonary nodules (new SPNs) from January 1998 to December 2007 at our institute.

Results
Of the 244 patients, 36 had a history of SCC (neck: 14, oesophagus: 9, neck and oesophagus: 3, lung: 5, anal canal: 1, unknown: 1, uterine cervix: 3), and 208 had no history of SCC. A history of SCC was significantly associated with the squamous pathology of new SPNs (22 of 36, p < 0.0001). Of the 22 new SPNs with a squamous pathology, 14 of them were diagnosed as metastatic (mSCC), and 8 were diagnosed as primary carcinomas (pSCC). The mSCC showed a more advanced initial disease (p = 0.0109) and a marginally shorter disease-free interval (p= 0.0818) than the pSCC. The overall survival (OS) and recurrence-free survival (RFS) of patients with pSCC were superior to those of patients with mSCC (OS: p = 0.0413, RFS: p = 0.0282) (Figure 1). Notably, 6 intra-thoracic recurrences were observed in the mSCC group.Figure 1

Conclusion
The current policy for differentiation between mSCC and pSCC, which is based on clinical information, appears to be acceptable. In cases in which the origin of the pulmonary lesion is unclear, it might be better to treat solitary lung SCC as a primary lung cancer because it might offer the best chance for a cure.

Background
Malignant pleural effusions (MPEs) are a common and important cause of cancer-related mortality and morbidity. Prompt diagnosis using minimally invasive procedures is a key point in the evolution of disease since the overall median survival after diagnosis is only 4-9 months. Tumour markers analysis has been proposed as a less invasive alternative for categorizing malignant and non-malignant pleural effusions. This multi-centre study aimed at establishing diagnostic cut-offs for a panel of markers in pleural fluid and plasma to identify patients with lung cancer.

Methods
Pleural fluid specimens and plasma samples from 112 patients (46 malignant, 66 non-malignant) consecutively admitted over one year in three Italian university hospitals were analyzed for Ca 125, Cyfra 21.1, NSE, CEA, M2PK. The diagnosis of malignant or non-malignant effusion was based on cytology, pleural biopsy, thoracoscopy, video-assisted thoracic surgery (VATS). Statistical evaluation included Kolmogorov-Smirnov, Mann-Whitney, Chi-square and Fisher’s exact tests. Non parametric (Spearman) correlations were determined. ROC curve analysis was performed to determine analyte cut-offs, sensitivity, specificity and AUC values of each marker. A p-value <0,05 was considered statistically significant.

Results
Cytological negative samples were analyzed to ensure that they truly represented non-malignant effusions related to other diseases such as congestive heart failure (CHF), renal imbalance, pneumonia, tuberculosis or post-traumatic. Patients with a history of malignancy or subsequent diagnosis of malignancy with a cytological negative pleural sample were excluded from the study. All examined concentrations were significantly higher in malignant effusions compared to non-malignant effusions. The value of AUC of pleural samples was always higher than in plasma for all malignant cases. The best AUC value in both pleural samples and plasma was detected for Cyfra 21.1 (0,91 vs 0,695) and CEA (0,836 vs 0,681).

Conclusion
Tumour markers assay in pleural fluid complements cytology and other classifying tests. A few tumour markers over-expressed in pleural fluid of patients with known malignancy have been identified. Therefore the use of a panel including the best performing markers may prevent patients with suspected malignancy from undergoing invasive procedures such as thoracoscopy or VATS. Our study shows a significant performance of pleural fluid vs plasma samples when comparing AUC values. Tailoring a specific marker assay in pleural fluid for a specific malignancy is highly advisable especially in patients with relevant comorbidity. Moreover, the evaluation of tumor markers in pleural fluid may well be considered as a prognostic factor in those patients with known malignancy undergone surgery and/or chemoradiotherapy during follow up.

Background
The bone is the most common distant site of metastasis in non-small cell lung cancer (NSCLC), and patients with bone metastasis have a markedly poor prognosis. There are three types of bone metastasis; such as osteolytic type, osteoblastic type, and mixed type. Assessment of bone metastatic type may be important as a part of therapeutic strategy because it has been noted that osteoblastic tumors would have lead to both a better prognosis and activating epidermal growth factor receptor (EGFR) mutation presence. The aim of this study was to examine the relationship between the type of bone metastasis and clinical characteristics including EGFR gene mutation status in NSCLC patients.

Methods
We reviewed the records of 85 unresectable or postoperative recurrent NSCLC patients with at least one site of bone metastasis. The type of bone metastasis was classified by two radiologists reviewing the radiological examination as osteolytic type (OL), osteoblastic type (OB), and mixed-type from the CT findings.

Results
Median follow-up time for survivors was 25.4 months. There were 53 (62%) patients with unresectable NSCLC and 32 (38%) patients with postoperative recurrent disease. The number of patients with adenocarcinoma is 75 (87%). The bone metastasis type was OL group in 39 (46%) patients, OB group in 37 (43%) patients, and mixed type in 9 (11%) patients. Survival analysis incorporating mixed type bone metastasis into OB group revealed median survival time of 20.3 months and 30.9 months for OL and OB group, respectively. The difference was not significant (p=0.314), but OB group seems to have better prognosis than OL group. The prevalence of activating EGFR gene mutation was marginally significance in OB group (58%) than in OL group (36%) (p = 0.052). There are no significant relationship between the type of bone metastasis, and sex and smoking history.

Conclusion
This study shows that evaluating the type of bone metastasis by CT image enable prediction of EGFR gene mutation status and prognosis in NSCLC patients with bone metastases separately from sex, smoking habit, and race. The presence of osteoblastic metastases or the evolution to metastases should always be noted since it might represent an important predictive factor of response to EGFR-TKI treatment.

Background
Background: Vibrational infrared (IR) spectroscopy is a powerful chemical analytical tool that can be used to detect and analyse many types of chemicals and materials including complex mixtures. Absorptions in this region arise from molecular vibrational properties and most molecules have characteristic IR spectra. There is a growing literature on its possible medical diagnostic use to distinguish cell types and states by characterising their IR ‘molecular fingerprints’ in the 1800 -900 cm[-1 ]range. Such spectra are complex since they represent an overlapping mixture of proteins, lipids, carbohydrates, DNA and cellular metabolites. Hypothesis: IR spectroscopy will differentiate histological grade of bronchial biopsies by identifying spectral changes corresponding to the stepwise progression from dysplasia to invasive cancer.

Methods
Methods: 52 biopsy specimens were obtained bronchoscopically from 38 patients representing 21 normal, 9 low grade dysplasia, 18 high grade dysplasia and 7 invasive squamous cell carcinomas. Matched histopathological samples were examined by H&E staining and microscopy for pathological classification. In all cases, IR data were collected in the 4000 – 900cm[-1] region using a Bruker IFS66s FTIR spectrometer, both absolute absorbance spectra and their second derivatives were calculated. Biopsies are analysed fresh; time taken to capture each reading is approximately 1 minute.

Results
Results: There were minimal changes to differentiate low grade changes from normal epithelial cells however there were significant and reproducible changes corresponding to high grade dysplasia and cancer (Fig 1). We have developed an algorithm analysing the relative size of IR peaks in the 1290-1270cm[-1 ]range that differentiates with 100% accuracy between normal/ low grade and high grade/ cancer in this small pilot study. We have observed differences in regions suggesting changes in intracellular glycoproteins and lipids and work continues to define the exact cause of the observed differences. More subtle spectral changes also discriminate between high grade dysplasia and cancer and are the subject of further algorithm development and validation.Figure 1

Conclusion
Conclusions: High quality mid-IR spectra of ex-vivo biopsies do reveal differences between normal and dysplastic/ cancerous cells in bronchial tissues. This technology has the potential to provide real-time near patient cytopathological diagnosis for the bronchoscopist or thoracic surgeon for instance to confirm clear resection margins at surgery. Identification of the chemical changes occurring at a cellular level may lead to reverse translation and better understanding of the processes driving progression to malignant transformation. Future work will refine and validate the observed changes.

Background
Lung cancer is the leading cause of cancer-related death in the United States, with non-small cell lung cancer (NSCLC) accounting for 87% of cases. Roughly half of all patients present with advanced disease and the majority with earlier stage disease eventually develop disease recurrence. The objectives of this study were to characterize patients diagnosed with NSCLC and assess overall survival in the United States Military who receive equal and open access to healthcare in the Department of Defense (DoD) medical system.

Methods
We identified patients (military service members and their dependents) ≥18 years old, with an initial diagnosis of NSCLC from January 2003- March 2013 in the DoD Cancer Registry (N=4,751). Descriptive statistics were generated for demographic and clinical characteristics. Kaplan Meier (KM) curves and Cox proportional hazards regression assessed overall survival (OS).

Results
Military service members comprised 63% of the cohort. The mean age at diagnosis was 66, 64% were male and 72% were Caucasian. Adenocarcinoma (AC) histology was the majority (45%), followed by 31% NSCLC not otherwise specified (NOS), 21% squamous cell (SC), and 2% Large Cell (LC). A majority (57%) were diagnosed at advanced stage and tended to be younger (mean age 65 vs. 67; p<.0001) and more likely male (66% vs. 61%; p<.0001) compared to patients diagnosed with earlier stage disease. In the early stage cohort 78% had stage I disease. Patients with advanced stage disease presented predominately with either AC (41%) or NOS (38%) compared to SC (20%) or LC (2%). Most of the cohort were either currently using or had a history of tobacco use (82%). The unadjusted OS for the cohort was 14.97 months (95% confidence interval (CI): 13.9-15.7) with significantly decreasing survival as stage increased (Table). In the multivariate survival analysis, older age, male gender, increasing stage (Table), squamous cell histology, higher number of comorbidities, and tobacco history were associated with a higher risk of death.

Conclusion
In this DoD cohort, NSCLC patients were diagnosed at a younger age and had a higher proportion of Stage I disease than often seen in the general US civilian population, perhaps due to more open access to health care. Stage at diagnosis was a significant predictor of mortality and further research comparing factors influencing survival relative to the general population is warranted including the role of open access to care.

Table: Unadjusted and Adjusted Survival by Stage

		Unadjusted		Adjusted
Stage	N	Median Survival (Months)	95% CI	HR	95% CI
I	1141	64.2	58.4-70.1	ref
II	324	29.5	26.2-34.1	1.78	1.49-2.12
III	1049	13.5	12.5-15.2	3.31	2.94-3.73
IV	1678	6.5	6.0-7.0	7.15	6.38-8.02

Background
In advanced lung cancer, for the treatment based on one specific driver mutation, it is important to make diagnosis by the use of small biopsy or cytological samples obtained from bronchoscopy examination. With the development of multiple molecular target agents, we need to simultaneously examine several kinds of genetic alterations in small samples.

Methods
Patients who were considered necessary to examine bronchoscopy for diagnosis of lung cancer were prospectively enrolled. Between November 2012 to March 2013, 123 patients were enrolled, and molecular analysis were performed in 115 patients. Liquid based cytological samples (LBC) by bronchoscopy were divided equally into routine pathological examination and molecular examination. After extraction of DNA and RNA from LBC, we evaluated EGFR, KRAS and BRAF mutations and ALK fusions.

Results
Patients characteristics were as follows: the median age 69 (range: 42-83); female 43 (37%); never smoker 40 (22%). Finally, 80 patients were pathologically diagnosed as lung cancer (Ad/Sq/NSCLC/Sm/Unclassified; 50/14/8/6/2). Fifty-nine patients showed class V of LBC, and 16 patients had molecular change (11 EGFR mutation and 5 KRAS mutation). Moreover, 1 patient of class III had an EGFR mutation. In a procedure of bronchoscopy (EBUS-TBNA, bronchoscopy for peripheral lesions and bronchoscopy for central lesions), median quantities of DNA in class V patients of LBC were 1.19, 0.67 and 0.16μg, respectively (Fig1 shown). Median quantities of RNA were 1.24, 0.37 and 0.49μg respectively (Fig2 shown). The quantity of DNA and RNA extracted from EBUS-TBNA were more than that of other bronchoscopy procedures. Figure 1Figure 2

Conclusion
Small samples such as LBC by bronchoscopy may be used to molecular analysis. Especially, our results suggest that LBC from EBUS-TBNA is very usefulness.

Background
Computed tomography (CT)-guided fine needle aspiration (FNA) and biopsy is a well-established diagnostic method for pulmonary lesion.The aim of our study was to update the diagnostic outcomes and the safety profile of CT-guided lung biopsies.

Methods
We retrospectively analyzed the results of the CT -guided FNA and biopsies for 750 pulmonary lesions in 696 patients, and investigated the diagnostic yield, and complication rates.The independent risk factors for the diagnostic failure (ie, nondiagnostic, false-positive, and false-negative results) and the complications (severe pneumothorax) were determined using multivariate logistic regression analysis.

Results
The study included 417 male patients and 279 female patients, with a mean age of 71 years.The mean lesion size was 2.0 cm in maximal diameter.The biopsy results were nondiagnostic in 1.4% of the lesions (11 of 750 cases).The diagnostic accuracy was 92.6% (685/739cases).The sensitivity and specificity for the diagnosis of malignancy was 91.7% (534 of 582 cases) and 99.3% (156 of 157 cases), respectively.The significant independent risk factor for diagnostic failure was Lesions measuring < 2.0 cm (OR, 3.94; p <0.0001).Pneumothorax was the most common complication, and occurred in 36% (272 cases), pneumothorax requiring temporal drainage or chest tube insertion in 7.3% (55 cases), and tension pneumothorax, in 0.2% (2 cases).There were 27 cases (3.6%) with pulmonary hemorrhage, 63 cases (8.4%) with hemoptysis, 2 cases (0.2%) with air embolism , 5 cases (0.6%) with hypertension requiring antihypertensive treatment , 1 case (0.1%) with posterior reversible encephalopathy syndrome（PRES）, and 8 cases (1.0%) with others, including pain, shock, subcutaneous emphysema, subcutaneous hematoma, epilepsy, and bradycardia or tachycardia spell.From a total of 13 patients with severe complications, 12 patients recovered without sequela, however 1 patient recovered but developed paraplegia due to spinal cord infarction; there were no fatalities.The significant independent risk factors for pneumothorax requiring drainage were the depth from pleura < 3.0 cm (OR, 3.60; p <0.001), lesions in the middle lobe (OR, 2.25; p 0.0284),　and COPD patients(OR, 4.38; p <0.001).

Conclusion
CT-guided lung FNA and biopsy have a high diagnostic yield, but factors such as the acquisition of lesions measuring <2.0 cm significantly increased the rate of diagnostic failure.The complication rates were acceptable and comparable to previously published figures.The rate of pneumothorax requiring drainage was correlated with the depth from pleura < 3.0 cm, lesions in the middle lobe, and COPD patients.

Background
Anaplastic Lymphoma kinase (ALK) alterations play a significant role in the pathogenesis of non-small-cell lung cancer (NSCLC), and the ALK pathway has become an important target for novel NSCLC treatment. Despite strong participation in industry-sponsored and recently investigator-initiated multicenter clinical trials, little is known about the prevalence, clinic-pathological parameters and clinical outcomes related to ALK fusion in Latin American (LATAM) NSCLC patients. Preliminary data from previous small studies suggest that the prevalence of other NSCLC driver genes such as EGFR and BRAF may be more frequent in LATAM than in other non-Asian populations. This highlights a clear need for a comprehensive molecular epidemiology investigation in this genetically heterogeneous region.

Methods
Collaboration with the Brazilian National Cancer Institute (INCA) and Latin America Oncology Group (LACOG), through a research agreement with Pfizer Inc., was established and 11 sites from 5 different LATAM countries were contacted for participation (Brazil, Mexico, Argentina, Peru and Bolivia). Countries and site selection was based on ethnic, social and cultural characteristics in order to (appropriately) represent the continent’s population. A total of 1,154 patients will be retrospectively enrolled for molecular analysis. Considering that the expected prevalence is no greater than 10%, this sample permits this estimation with a half-width of the 95% confidence interval < 1.7%. Tissue samples will be shipped to INCA (the coordinator center) for central analysis. Clinical data will be collected by local investigators and retrieved by the coordinator center. The primary goal of the study is to estimate the prevalence of ALK fusion gene in LATAM nonsquamous NSCLC patients and build a stable LATAM network for future molecular epidemiology studies. The secondary objective is to perform a comparison of FISH, PCR and IHC methods for ALK fusion gene detection. FISH will be considered the standard method for comparison and performed using the ALK Dual Color Break-Apart probe (Abbott Molecular Inc.). Real time PCR will be performed in collaboration with Fundación Santa Fé, Colombia (probes and primers synthesized at TIB MOLBIO, LLC and designed with Primer 3 software) and IHC performed with Ventana[TM] reagents.

Results
The protocol was planned in 2011. Since then, the first LATAM molecular epidemiology network was established with LACOG collaboration, and molecular analysis methodology standardization completed.

Conclusion
This trial represents the first cooperative effort for genotype patients in LATAM using sample shipment for central analysis. Enrollment of patients is still pending, waiting for final approval from country regulatory agencies which have different requirements and timeframes for review. Moreover, additional data on tumor specific biomarkers and diagnostic testing across the region may provide a basis to guide future decisions by regulators and treating physicians.

Background
Patients with advanced lung cancer and EGFR mutations can derive significantly benefit by receiving first line EGFR tyrosine kinase inhibitor (TKI) therapy. Multiple trials have showed that clinical selection is not sufficient and that EGFR mutations test should be requested for all non-squamous patients. Moreover there is a suggestion that a lag time between diagnosis and molecular test could harm patients. In this retrospective trial we describe EGFR mutation analysis after the implementation of reflex testing in a cohort of Brazilian patients.

Methods
After May 2011 EGFR reflex testing was recommended for all stage IVA and IVB non-squamous lung cancer patients treated at INCA. EGFR exons 18, 19, 20 and 21 were examined using a commercially available Polymerase chain reaction and Sanger sequencing assay. We retrospectively reviewed clinical and EGFR tests characteristics from medical charts of all patients with available results.

Results
From May 2011 to May 2013 samples from 189 patients (56.2%) out of 336 were screened for EGFR mutations. Main reason for non-testing was insufficient material. Turn around time for EGFR mutation processing substantially improved over this period, from over three weeks to less than 5 working days. Of those patients tested 58.8% were women and 22% were non-smokers or light smokers. Results were obtained from cytological specimen in 33 cases (17.4%). Most patients had adenocarcinoma (95.2%) with only 6 cases (3.2%) of unspecified carcinoma. EGFR mutations were detected in 52 patients (27.5%). The incidence of mutations was higher in females (58.8%) and non-or light smokers (56%). Of the mutations identified 18 (34.6%) were in frame deletions in exon 19, and 8 (15.3%) were exon 21 L858R. Exon 18 G719A and exon 20 insertions were detected in only 1 (1.9%) and 2 (3.9%) cases respectively. We found a high incidence of atypical mutations (44.3%). All of them were single aminoacidic substitutions in exon 18 (7 cases; 30.5%), exon 19 (5 cases; 21.7%), exon 20 (5 cases; 21.7%), exon 21 (5 cases; 21.7%), and a single case of double mutation (exons 19 and 20). We did not detect any de novo T790M exon 20 mutation.

Conclusion
The results of the first 2 years of reflex molecular testing at a single Brazilian institution reported demonstrate the feasibility and potential for a non-clinical selective approach. This high frequency of atypical mutations must be further investigated since to date there are no published data regarding EGFR mutations in the Brazilian population.

Background
Histological differentiation in NSCLC has been addressed recently due to the importance regarding prognosis and treatment options. Adenocarcinoma is considered the most frequent histology and recent guidelines recommend the EGFR mutation testing. Epidemiological characteristics of EGFR mutation positive patients have been widely described in Caucasian and Asian population. Given the differences between these populations, it is important to evaluate the epidemiology in other populations. More than 90% of Costa Rica’s population is treated in a government-based hospital. Hospital San Juan de Dios (HSJD) attends approximately a 40% of Costa Rica’s population. Starting at the end of 2011, all patients with lung adenocarcinoma are evaluated for EGFR mutations.

Methods
We conducted a retrospective analysis of all patients diagnosed with NSCLC in HSJD between January and December 2012. A total of 42 patients were diagnosed with a NSCLC but 2 patients were excluded from the study due to insufficient clinical information. Epidemiologic data was obtained and EGFR mutation status was analyzed.

Results
The NSCLC population analyzed had a median age of 68 y (41-87 y). The most frequent histology reported was adenocarcinoma. All adenocarcinomas were analyzed for EGFR mutations (exon 18, 19, 20, and 21). 33.3% of adenocarcinoma patients had an EGFR mutation. Smoking history was statistically associated with the occurrence of an EGFR mutation. Patient characteristics are summarized in Table 1.

Table 1: Characteristics of patients diagnosed with NSCLC in HSJD-Costa Rica during 2012 Total NSCLC population n=40 Adenocarcinoma population n=27 EGFR mut positive population n=9 Median age 68 y (41-87 y) Sex p=0.504 M (%) 24 (60) 15 (55.6) 4 (44.4) F (%) 16 (40) 12 (44.4) 5 (55.6) Smoking history (PY) p=0.022 Non smoker (%) 14 (35) 12 (44.4) 7 (77.8) 5-20 (%) 3 (7.5) 3 (11.1) 0 21-40 (%) 4 (10) 1 (3.7) 0 41-60 (%) 9 (22.5) 4 (14.8) 1 (11.1) >60 (%) 10 (25) 7 (26) 1 (11.1) Adenocarcinoma histology (%) 27 (67.5) Stage of diagnosis I-II 3 (7.5) 2 (7.4) 0 IIIA 9 (22.5) 4 (14.8) 0 IIIB 5 (12.5) 2 (7.4) 0 IV 23 (57.5) 19 (70.4) 9 (100) % EGFR mutation positive 22.5 33.3 % of type of EGFR mutation Exon 18 0 0 0 Exon 19 17.5 25.9 77.8 Exon 20 2.5 3.7 11.1 Exon 21 2.5 3.7 11.1

Conclusion
In Costa Rica, the incidence of EGFR mutations in adenocarcinoma patients tends to be higher to that of the Caucasian population and lower than the Asian population. This incidence might be similar in other Latin American countries. Epidemiological characteristics of EGFR mutation positive patients are similar to that reported in the literature.

Background
Differentiation of atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma(IA) on computed tomography (CT) is useful for determining ‘‘follow-up or resection’’ strategies for lesions displaying ground-glass opacity nodules(GGN). The purpose of this study is to compare the morphologic features of persistent GGNs of <20 mm in diameter at thin-section CT (TSCT) with histopathology.

Methods
Jan 2010 and Dec 2012, a total of 200 nodules in 191 resected GGNs that were evaluated with TSCT were included in this study. Correlations between histopathology and CT characteristics were examined.

Results
The nodules included 45 AAH (22.5%), 99AISs (49.5%), 11 MIAs (5.5%), and 45 invasive adenocarcinomas (22.5%). The mean CT value (P < .0001), size of nodule (P < .0001) were significant factors that differentiated AAH lesions from invasive adenocarcinoma or AIS or MIA. While the size of nodule (P < .0001) and mass of nodule (P < .0.001) were significant factors that differentiated invasive adenocarcinoma from AIS or MIA.

Conclusion
Size of nodule less than 10 mm and mean CT value less than -510Hu are determinants of AAH, while size and mass of the nodule are determinants of invasive adenocarcinoma in Chinese population.

Background
The Japanese Joint Committee of Lung Cancer Registry (JJCLCR) is jointly established by the Japan Lung Cancer Society, the Japanese Respiratory Society, the Japanese Association for Chest Surgery and the Japan Society for Respiratory Endoscopy, conducting Japanese nation-wide registries of lung cancer patients

Methods
In 1999, 2004 and 2009, registries were conducted for surgical patients in 1994, 1999 and 2004, respectively. In 2002, both surgical and non-surgical (non-biased) patients in 2002 were registered with a follow up period of 3 years or more. In 2012, a registry has been conducted for non-surgical patients in 2012 with a follow up period of 3 years. In 2016, surgical patients in 2010 will be registered. These registries were observationally assessed.

Results
Registries for surgical cases in 1994, 1999 and 2004 which were conducted in 1999, 2004 and 2009 revealed the trend of increase in mean age, rates of female, the aged, small sized lesion, adenocarcinoma and stage I, and that of decrease in the rate of perioperative death. Furthermore proposals for TNM classification were stated as peer reviewed papers- invasion to visceral pleura, chest wall and fat tissue in the mediastinum for T factor. In addition, status of N2 disease were assessed resulting in that highly selected cases (3.8%) were subjected to surgery or surgery-included multimodal therapy with a 5-year survival rate of 30.1% in cN2/pN2-Stage IIIA and it was better than previous registries. Registry for surgical and non-surgical patients in 2002 revealed that stage-specific prognosis was within a range similar to other reports and stage, gender, surgery and performance status were independent prognostic indicator of both non-small and small cell lung cancer. Registry of non-surgical cases in 2012 was conducted and greater than 8,000 cases were registered. In this study, status of usage of FDG-PET scan for staging, EGFR gene mutation and individual therapy were, and prognosis of patients will be registered. In up-coming registry for surgical cases in 2010 which will be performed in 2016, new parameters- the size of tumor regarding non-invasive regions in adenocarcinoma (ground grass opacity in computed tomography), quantitative assessment of lymph node metastasis (the number of metastasized lymph node) as a prognostic indicator, which may be assessed as factors of TNM classification in the future. Besides, the TNM classification will be revised in 2016 according to the proposal from IASLC staging project, to which the JJCLCR offered data of 47,306 cases (approximately 25% of whole world wide cases) from the recent 4 registries.

Conclusion
The JJCLCR conducted nation-wide lung cancer registry in Japan, revealing the condition of the treatment of lung cancer and contributing to the TNM staging program.

Background
Malignant Pleural Mesothelioma (MPM) is a rare disease and often associated with a history of long-term exposure to asbestos. Recently, It’s related to Simian virus 40 (SV-40). The determination is related to exposure to asbestos based on clinical history and possible asbestos in tissue pathology specimens. Diagnosis related to SV-40 based on immunohistochemical staining The Simian Virus 40 Large T Antigen.

Methods
: Retrospective descriptive statistics. Survey by interviewing patients and pathological examine specimens can find asbestos and immunohistochemistry with The Simian Virus 40 Large T Antigen.

Results
From Jan, 2008 to Dec, 2012 at the Pham Ngoc Thach Hospital, we have take diagnosis of 60 cases of malignant pleural mesothelioma, including 29 men and 31 women, with histopathological classification: 28 cases of epitheliod MPM (46.7%), 11 cases with biphasic MPM (18.3%), 09 cases with sarcomatoid MPM (15%), 06 cases with Desmoplastic MPM (10%), 04 cases with Well-Differentiated Papillary Mesothelioma (6.7%) and 02 cases with Anaplastic MPM (3.3%).  Elements related to contact asbestos: 22cases (44.4%).  Confirm the diagnosis of asbestos in tissue specimens:12cases(20%).  Presence of The Simian Virus 40 Large T Antigen: 11 cases (18,3%).  Only one case (1,7%) with both two factors positive asbestos and SV-40.  And having 16 cases (26,7%) did not identify epidemiological factors.

Conclusion
Through the the study series cases of Malignant Pleural Mesothelioma, initially issued a warning about the causative factors in those tumors, including long-term exposure to asbestos and can be caused by infections with Simian virus 40.

Background
BIM (BCL2L11), which encodes a BH3-only protein, is one of major pro-apoptotic factors that facilitate cell death. A 2,903-bp genomic deletion polymorphism in intron 2 of BIM showed 12.3% carrier frequency in East Asian population. This polymorphism results in expression of BIM isoforms lacking the pro-apoptotic BH3. We evaluated whether the presence of the BIM deletion polymorphism is a major risk factors of lung cancer in Korean population.

Methods
We designed 1:1 matched case-control study between lung cancer and control subjects. Lung cancer patients and age, gender and smoking status matched control subjects without other types of malignancies were prospectively enrolled from Feb. 2013 to now. Subjects under 18 years old and who denied to present informed consent were excluded. The presence of 2,903-bp genomic DNA deletion polymorphism in intron 2 of BIM were analyzed by PCR and validated by sequencing. BIM deletion polymorphism status and relationship with clinical and pathological parameters were analyzed using chi-square test, t-test, Kaplan-Meyer estimator, and Log-Rank test.

Results
There were no statistically significant differences in age, gender and smoking status between lung cancer and control subjects. Twenty-three out of 102 (22.5%) lung cancer patients revealed a BIM deletion polymorphism whereas 9 out of 75 (12%) control subjects showed polymorphism. The odd ratio for the association of BIM deletion polymorphism and lung cancer was 2.139 (p=0.076). Sixty-nine out of 102 (67.6%) lung cancer patients were male and 52 (51%) were smoker. Among them 97 (95%) were non-small cell lung cancer (NSCLC) and 5 (5%) were small cell lung cancer. Adenocarcinoma was the most common histological subtype accounting for 69 out of 97 (71%) in NSCLC. When lung cancer patients were categorized according to the presence of polymorphism status, there was no difference in the age between subjects with and without polymorphism (mean age; 63.3 vs. 63.4 year). Among the lung cancer patients harboring BIM deletion polymorphism, there were more female (9 out of 23, 39%) and non-smokers (15 out of 23, 65%) when compared to those without polymorphism showing 24 out of 79 (30%) female and 35 out of 79 (44%) non-smokers. The histological subtypes between the two groups were not significantly different. A total of 64 out of 102 lung cancer patients had been tested EGFR mutation status. The odd ratio for the association of BIM deletion polymorphism and EGFR activating mutation was 0.87. In lung cancer patients, the BIM deletion polymorphism did not have a statistically significant impact on the clinical outcome of the patients.

Conclusion
Our results indicate that BIM deletion polymorphism may be one of major lung cancer risk factors in Korean population. To strengthen our results, we are extending the sample size and are going to perform hierarchical analysis prospectively. To validate our results, we are performing a validation analysis with an external validation dataset from the national cohort.

Background
Due to its high incidence and bad prognosis, lung cancer is a major health problem. In the 2000s, several social and scientific changes (such as decreased smoking, improved diagnosis methods, or the development of new drugs and therapeutic strategies) may have changed the epidemiology and prognosis of this cancer. The objective of the present study was to compare 1-year mortality in adult patients with primary lung cancer at a 10-year interval.

Methods
In 2000 and 2010, the French College of General Hospital Respiratory Physicians (CPHG) performed 2 prospective multicenter cohort studies collecting information on all new cases of lung cancer diagnosed histologically or cytologically from 01 January 2000 to 31 December 2000, and from 01 January 2010 to 31 December 2010, and managed in the respiratory department of one of the participating general hospitals. A standardized form was completed for each patient. A steering committee checked recruitment exhaustiveness.

Results
137 hospitals in 2000 and 104 hospitals in 2010 included respectively 5667 and 7051 patients. The 2 cohorts represented about 1 in 5 lung cancers diagnosed in France in 2000 and 2010. The characteristics of patients and lung cancer changed during the 10-year period in France. In 2010, compared to 2000, patients were older (mean (SD): 65.5 (11.3) years vs. 64.3 (11.5) years; p<0.0001), more frequently women (24.3% vs. 16.0%; p<0.0001) and more frequently never-smokers (10.9% vs. 7.2%; p<0.0001); they had a lower performance status score (PS) at diagnosis (PS 3 or 4: 12.7% vs. 17.7%; p<0.0001); their tumor was more frequently an adenocarcinoma (45.4% vs. 29.0%; p<0.0001). One-year mortality also changed, decreasing from 61.8% in 2000 to 56.4% in 2010. Multivariate analysis showed that the year of diagnosis was an independent risk-factor for death. Other independent risk-factors were older age, male sex, higher PS, active smoking, and small cell lung cancer (please see the table hereafter).

	Odds ratio	95% CI	p-value
Year of diagnosis
2000	1 (Ref)
2010	0.84	0.77-0.91	<0.0001
Age (years)
<60	1 (Ref)
60-75	1.03	0.94-1.13	0.55
>75	1.53	1.35-1.42	<0.0001
Sex
Female	1 (Ref)
Male	1.28	1.15-1.42	<0.0001
Smoking status
Never-smoker	1 (Ref)
Former-smoker	1.02	0.87-1.19	0.84
Active-smoker	1.23	1.05-1.44	0.01
Performance status
0- Asymptomatic	1 (Ref)
1- Symptomatic but completely ambulatory	2.45	2.23-2.69	<0.0001
2- Symptomatic, < 50% in bed	6.49	5.73-7.36	<0.0001
3- Symptomatic, > 50% in bed	15.2	12.6-18.3	<0.0001
4- Bedbound	39.0	23.5-64.8	<0.0001
Small cell lung cancer
Yes	1 (Ref)
No	0.83	0.74-0.93	0.002

Conclusion
In 10 years, 1-year mortality decreased in patients with primary lung cancer. The improvement in survival was not solely due to epidemiological changes in patient characteristics (age, sex, smoking habits, or PS) and tumor characteristics (histological type) over the 10-year period. This supports the hypothesis of improved management of lung cancer in patients followed up in French general hospitals.

Background
In Japan, crocidolite had been used for asbestos cement pipe and spraying and amosite had been used for building board and spraying. These two types of asbestos had stopped to use in Japan in the late 1970s. Asbestos exposure will increase the risk of lung cancer, mesothelioma and nonmalignant lung parenchymal and pleural disorders, including asbestosis, pleural plaques, pleural thickening, and pleural effusions. Asbestosis is a form of diffuse interstitial pulmonary fibrosis and pneumoconiosis caused by the inhalation of excessive amounts of asbestos fibers. By contrast, pleural plaques are the most frequent response to asbestos exposure, appearing even with low-dose, often intermittent, exposures. Plaques occupy irregular, discrete areas on the parietal pleura and are often found as incidental chest radiographic findings. Therefore, radiographic evidence of pleural plaques in lung cancer patients indicates the history of asbestos exposure.

Methods
Between 2003 and 2011 in our hospital, there were 979 patients in whom pleural plaque was confirmed by computed tomography (CT) scanning of the chest. Among those patients, 62 were histologically diagnosed as primary lung cancer.

Results
Grouped according to sex, there were 61 men and an woman. The frequent histologic types of the cancers were adenocarcinoma ( 21 patients ) and squamous cell carcinoma ( 22 patients ), followed by small cell carcinoma (8 paients). 16 patients had Stage1A disease, 8 patients had stage 1B disease, 3 patients had stage 2B disease, 8 patients had stage 3A disease, 6 patients had stage 3B disease and 21 patients had stage 4 disease. The median overall survival was 23.0 months and 1 year, 2 year and 5 year survival rate of all the patients were 56.0 %, 49.0 % and 23.7 %, respectively. Based on the primary treatment, 28 patients received surgery, 4 patients received radiation therapy, 5 patients received chemoradiotherapy, 19 patients received chemotherapy and 6 patients received best supportive care. The median overall survival of the patients treated by surgery, radiation therapy, chemoradiotherapy, chemotherapy, and best supportive care, were 96.0 months, 40.9 months, 6.3 months, 8.4 months and 3.0 months, respectively. Six patients showed radiographic findings of asbestosis accompanied with pleural plaques. Five patients received surgery and a patients received chemotherapy as a primary treatment, but the median overall survival of these 6 patients was as short as 6.5 months.

Conclusion
Among the lung cancer patients associated with pleural plaques alone, early stage patients showed favorable prognosis. But the lung cancer patients in whom pleural plaque and asbestosis were detectable in chest CT showed poor prognosis even after diagnosis at early stage. Therefore, the early detection of lung cancer may contribute to a better outcome in the population which has pleural plaque alone, not accompanied with asbestosis.

Background
Lung cancer is the leading cause of death from cancer in the world and 70 to 85% of these tumors are non-small cell (NSCLC) type. Up to 50% of patients have metastatic disease at the diagnosis, and the brain is one of the most common sites of metastasis. Prognosis of patients with central nervous system (CNS) involvement is usually dismal and is determined by performance status (PS), systemic disease status and age. Recently there is a growing amount of evidence suggesting that aggressive treatment for patients with brain oligometastasis may improve prognosis.

Methods
In this retrospective cohort, forty-nine charts of patients with non-small cell lung cancer (NSCLC) metastatic to the brain and treated with neurosurgery (NS) or radiosurgery, between 1996 and 2008, were reviewed at the Brazilian National Cancer Institute. The primary outcome was overall survival (OS), defined as the interval from the diagnosis to death or last follow-up.

Results
Median age was 54 years (range 32-82), 61% were male and more than 95% had PS 0-1. Most patients were smokers (95.7%) and had adenocarcinoma (77.6%). Twenty-three patients (47.9%) presented with metastatic disease at diagnosis, and 13 (38.8%) with BM upfront. Imaging for the diagnosis of BM varied between computed tomography (CT) (n=19;38.8%), magnetic resonance (MRI) (n=12;24.5%), both CT and MRI (N=15;30.6%) and positron emission tomography (n=1;2%). Forty-three patients (87.8%) were submitted to NS and only one was treated with radiosurgery. Patients had more often single metastasis (84.8%), and none had more than three lesions. Most patients (80%) still received adjuvant whole brain radiotherapy (WBT) after NS. The median OS was 15.8 months (95% CI 9.4-22.2).

Conclusion
Our data confirmed that compared to historical control patients with good PS and brain oligometastasis could derive a better survival when submitted to aggressive local therapy. In our center, until 2008 NS was the most common procedure used and adjuvant WBT was still frequently indicated.

Background
New drug developments in the past decades have improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC). This study aimed to quantify the change in 5-year overall survival of patients ≥65years diagnosed with advanced NSCLC from 1991 to 2009 in United States (US).

Methods
Patients aged ≥65years that were first diagnosed with NSCLC stage IIIB/ IV between 1991 and 2009 (n= 83,930) were identified in the Surveillance, Epidemiology and End Results database that collects data from several US cancer registries. Four cohorts were defined based on patients’ diagnosis year: 1991-1995, 1996-2000, 2001-2005 and 2006-2009. For each cohort, median survival time from diagnosis and 6-month, 1-year, and 5-year survival rates were reported. The 5-year hazard of death was compared between cohorts using Cox multivariable regression adjusted for age, sex, tumor ‘s differentiation level, cancer stage and patient’s socio-economic status.

Results
The main study results are summarized in the table and figure. Patient characteristics changed over time, with patients in the 2006-2009 vs. 1991-1995 cohorts being older (26.1 vs. 17.5% aged ≥80 years), more patients being females (47.6 vs. 42%) and having stage IV cancer (74.1 vs. 64.7 %) at their first diagnosis. Median survival was 4.03 months for the 1991-1995 cohort and increased to 4.30, 4.62 and 4.98 months for the 1996-2000, 2001-2005 and 2006-2009 cohorts. From the earliest (1991-1995) to the latest (2006-2009) cohort the 6-month and 1-year survival rates have increased by 23% (from 37.4 to 46.0%) and 63% (from 16.6 to 27.0%) respectively. After adjustment for potential confounding factors, the 5-year hazard of death decreased by 11%, 21% and 30% respectively for the patients diagnosed in 1996-2000, 2001-2005 and 2006-2009 vs. those diagnosed in 1991-1995.Figure 1Figure 2

Conclusion
The last 20 years witnessed a steady improvement in extending the survival of the patients ≥65years diagnosed with advanced NSCLC.

Background
Gender differences in lung cancer (LC) have been reported, but with many unresolved issues . Family history of cancer might play an important role in lung cancer, especially in never-smoker patients. The aim of this study was to analyze potential clinical, molecular and epidemiological differences between WLC with or without family history of cancer.

Methods
WORLD07 is a Spanish prospective, multicenter, epidemiologic female-specific LC database sponsored by ICAPEM, a professional association committed with WLC research. Clinicopathologic data, tumor genotype, family and personal history of cancer were collected and analyzed in order to detect differences between both groups.

Results
From October/2007 to November/2012, 2081 WLC were included in an e-database from 32 centers. Family history of cancer was common (49.4%, in first-degree was 77%), family history of lung cancer was present in 33%, of breast cancer in 25% and of colorectal cancer in 17%. No differences in median age of diagnosis of LC, previous hormonal therapy, number of children, menstrual status, tumor histology or stage at diagnosis were observed between WLC with or without family history of cancer. WLC with family history of cancer were ever smokers in a higher percentage (63% vs 56%, p=0.006), with no differences in passive smokers. The presence of EGFR mutations was similar in WLC with family history of cancer versus WLC without family history (38% vs 37%), although WLC patients with family history of cancer had a higher rate of exon 21 mutation (36% vs 28%), both in smokers WLC (32% vs 16%, p=0.220) and in never smokers WLC (43% vs 32%, p=0.094). The median overall survival was 25 months (CI95% 21.0-29.0) for WLC with family history of cancer and 22.0 months (CI95% 19.4-24.5) for patients without family history of cancer (p=0.027). Of note, the median overall survival was 34.8 months (CI95% 22.9-46.6) for WLC with family history of LC and 22.5 months (CI95% 20.5-24.5) for patients without family history of LC (p< 0.001).

Conclusion
The presence of familiar history of cancer in WLC patients included in the WORLD07 database was high (49.4%), being lung cancer the most common, followed by breast cancer. No clinical or pathologic characteristic differences were observed between patients with or without family history of cancer. The presence of EGFR mutations was similar, although WLC patients with family history of cancer had a higher rate of exon 21 mutation. The median overall survival was significantly higher in WLC patients with family history of cancer and LC. Family history of cancer, especially of LC, might have a role in LC development and deserves further studies focused in inherited genetic alterations related with an increased susceptibility to LC.

Background
Lung cancer is the fourth most common cancer in Victoria and the leading cause of cancer mortality. Little local knowledge exists of the factors which influence outcome in lung cancer. A pressing need exists to describe regional structure, process and outcome in lung cancer care to improve quality of care and to inform translational research and health care planning. We aim to develop and pilot a population-based lung cancer clinical quality registry to describe clinical assessment, diagnosis, staging, management and outcomes in lung cancer in Victoria.

Methods
The establishment of the Victorian Lung Cancer Registry Pilot Project commenced with the appointment of a Steering Committee to provide project governance. Review of current literature and evidence-based national and international clinical practice guidelines was undertaken by an expert working group. Included data items were epidemiologically sound, reproducible and valid. The data set enables the capture of identified quality indicators designed to describe the structural quality, process quality and indicators of outcome in lung cancer management. Case ascertainment is derived from institutional ICD-10 coding of small and non-small cell lung cancer. Consent to recruitment to the registry occurs via an “opt-off” system. Follow up and outcome measures are collected 6 and 12 months after initial diagnosis capturing survival, treatment and quality of life assessments. Survival will be reconfirmed at 2 and 5 years post diagnosis. Institutional recruitment was designed to sample from metropolitan public, metropolitan private and regional hospitals. A quantitative, case finding audit was employed to evaluate the case ascertainment methodology at a major metropolitan hospital.

Results
Ethics approval was received for 8 pilot sites and a mechanism for rapid case ascertainment and secure data transfer has been established. A web enabled data collection tool has been developed and data has been collected on 576 eligible and consenting patients. Evidence of distress screening was available for 13.02% of subjects. Diagnosis was confirmed < 28 days from referral in 56-86% of cases across institutions. A statement of ECOG status was available in 52.51% of cases and clinical T staging in 48.43% prior to treatment. A record of multidisciplinary team meeting presentation was available in 48.43% of cases. Curative surgery was provided for 27.78% of subjects, curative chemotherapy <5% and curative radiotherapy < 5%. Curative surgery was provided < 14 days from diagnosis in 82-100% of cases. 30 day post curative surgery mortality was 3.12% following 160 curative surgical procedures.

Conclusion
Cancer registries have proven capacity for improving process in the delivery of cancer care and the ensuing outcomes. The development of rapid case ascertainment and “opt off” recruitment strategies appear viable and should ensure broad recruitment from eligible patients diagnosed with lung cancer in Victoria. For registries to inform quality of care and benchmark performance, high quality data is needed on all eligible cases. Our study has identified significant gaps in the documentation of this information in the patient’s medical record. Efforts to improve documentation are required to ensure that registries can perform their important function.

Background
According to a Lung cancer report by The Australian Institute of Health and Welfare, between 2003 and 2007 the highest number of lung cancer diagnosed in New South Wales. The incidence of in lung Cancer in NSW was 59 per 100 000 population, the second highest in Australia. This report also found that the incidence of lung cancer was higher in those living in outer regional, remote and very remote area compared to males living in major cities and inner regional areasAccording to a Lung cancer report by The Australian Institute of Health and Welfare, between 2003 and 2007 the highest number of lung cancer diagnosed in New South Wales. The incidence of in lung Cancer in NSW was 59 per 100 000 population, the second highest in Australia. This report also found that the incidence of lung cancer was higher in those living in outer regional, remote and very remote area compared to males living in major cities and inner regional areas

Methods
Retrospective and descriptive study.

Results
In this study a total of 1245 new cases were included. Mean age at diagnosis was 70 years and 67% were men. 63 % of the cases were from the Illawarra region. The age adjusted incidence of lung cancer in Illawarra region was 70.7/100,000 and 42.5/100,000 for males and females respectively, which was not statistically different compared to the rest of Australia and the world. However, the age adjusted incidence for Shoalhaven region was 103/100,000 and 76.5/100, 000 for male and female respectively which was higher and statistically significant compared to Australian data (P = 0.0239 for NSW and 0.0369 for Australia). Non-Small Cell Lung Carcinoma comprise 73% and 70 % of cases in the Illawarra and Shoalhaven region respectively. The incidence of pleural Mesothelioma was similar to rest of the Australia. The proportion of sub types of lung cancers was not statistically different compared to national and world data. Only 11.2% of cases were diagnosed at early stage of the disease but surgical resection rate for early stage lung cancer was similar to international data. More than 50% of the patients with NSCLC and more than 80% of patients with SCLC received some form of Chemotherapy. More than 80% of patients received radiotherapy at some point of their treatment cycle. 10% with stage IV disease did not receive treatment and 85% of patients of patients with late stage disease were referred to palliative care. Average mortality from lung cancer in Illawarra and Shoalhaven region was not statistically different to national data and international data. Only 42 % of cases were discussed in the Multi Disciplinary Team (MDT) Meeting.

Conclusion
This study confirms a higher incidence of thoracic malignancy in regional and rural Australia compared to metropolitan areas. A significantly higher percentage of lung cancer was diagnosed in late stage of disease compared to national and international data but outcomes were not statistically different. We also found that a significant proportion of the cases were not discussed in MDT meeting

Background
Non-small cell lung cancer (NSCLC) comprises 87% of all lung cancer in the United States with the vast majority diagnosed in advanced stage. Military personnel have higher smoking rates compared to the general population and consequently an increased incidence of lung cancer. We set out to examine whether there were variations in smoking rates and outcomes among patients diagnosed with NSCLC, based on self described ethnicity, in the United States Military and their dependents who receive equal and open access to healthcare in the Department of Defense (DOD) medical system.

Methods
We identified 4,547 patients ≥18 years, with an initial diagnosis of NSCLC from January 2003- March 2013 in the DOD Cancer Registry and categorized into the following self described ethnic groups: Caucasian, African American, Hispanic and Asian/Pacific Islander (PI). Differences in patient characteristics by race were compared using Chi-square and t-test. Kaplan Meier curves and Cox proportional hazards regression assessed overall survival.

Results
There were 3434 (76%) Caucasian, 533 (12%) African Americans, 468 (10%) Asian/PI, and 112 (2%) Hispanics who met the study inclusion criteria. Mean age at diagnosis was highest among Caucasians (67 yrs) followed by Asian/PI (64 yrs), Hispanics (63 yrs) and African Americans (62 yrs). A large majority of Caucasians (87%) and African Americans (86%) had a history of tobacco use, followed by Hispanics (74%) and Asian/PI (65%). Asian/PIs were also more likely to be female, married, have adenocarcinoma histology and were more likely to be sporadic cases (no family history) compared to the other self described ethnic groups. Asian/PIs had significantly higher unadjusted overall survival (Log rank p = 0.0012) and in the multivariate survival analysis, adjusting for age, sex, race, stage, histology, comorbidity, tobacco history, alcohol history, family history, and marital status, Asian/PI patients demonstrated a 20% lower risk of death (Table 1) compared to Caucasian patients. There was no difference in mortality risk between Caucasian and African Americans, and Caucasian and Hispanics.

Conclusion
In this military cohort, equal open access to care in NSCLC patients resulted in similar overall survival among Caucasian, African Americans and Hispanics with significantly higher OS among Asian/PIs. Racial disparities in survival often seen in US civilian populations were not seen in this study of patients treated in the military health system, perhaps due to more equal access to health care. Continued research evaluating treatment patterns and outcomes in the military relative to the general population is warranted.

Table: Cox Proportional Hazards Regression of Overall Survival

RACE	N	HR	95% CI
Caucasian	3434	ref
African American	533	1.001	0.89-1.12
Asian/Pacific Islander	468	0.803	0.71-0.91
Hispanic	112	0.984	0.77-1.26

Background
Lung cancer survival remains poor with only modest progress in absolute terms in recent years. Survival has been lower in the UK than many comparable European countries. There is some evidence that this survival deficit is particularly apparent early during follow-up. Within the UK, survival has been lower among deprived patients. Recent evidence suggests that this 'derivation gap' in survival also predominates early during follow-up. Although early deaths could reflect advanced disease, previous research in both Scotland and England does not support the hypothesis that deprived patients with lung cancer present with more advanced disease.

Methods
Using Scottish lung cancer audit records linked to cancer registrations, hospital discharge records and mortality records, the aims of this project were 1) to describe patterns of survival from lung cancer by socio-economic position 2) to explore the influence of the 'deprivation gap' in survival factors such as age, sex, tumour stage, tumour morphology, emergency presentation, performance staus and co-morbidity by modelling deprivation category-specific relative survival.

Results
Preliminary results confirm that survival remains lower in patients with lung cancer from deprived areas of residence. In multivariate modelling, this finding does not seem to be explained by competing causes of death or stage of disease at diagnosis. The main explanatory variables seem to be performance status and treatment.

Conclusion
Preliminary analysis suggests that performance status and treatment are the most important explanations for the 'deprivation gap' in survival from lung cancer in Scotland.

Background
At diagnosis approximately 25-40% of patients with non-small-cell lung cancer (NSCLC) are older 70 years. There is a scarcity of data on this elderly subpopulation. The aim of this study was to report clinical characteristics of this subpopulation, highlighting some challenges in their clinical management.

Methods
In this retrospective cohort, data from 631 patients with lung cancer diagnosed from 1995 to 2011 at a private Cancer Center in Brazil were analyzed.

Results
At diagnosis, 33% patients (n=214) were older than 70 years. Within this elderly group most patients (n=193; 90%) were classified as NSCLC and became the focus of our analysis. As expected, performance status (PS), staging and smoking were associated with survival (table1). Metastatic disease was present in 60% of this subpopulation, and most patients had good PS (PS0-1: 83%) and 84% were smokers. Additionally, 70% of this group with NSCLC had at least one comorbidity. The median overall survival time was 15 compared to 22 months for patients aged <70 years (p<0.001). In the metastatic group the majority of patients (62%) received only one cycle of chemotherapy (CT) and only 10% received more than 3 cycles. Of note, in patients with stage II and III adjuvant CT was correlated with survival (14 months vs 69 months in no adjuvant CT and adjuvant CT group respectively; p=0,02), although this therapy was administered in only 30% of patients with stage II and 20% of those with stage III. Figure 1

Conclusion
These data show that in this cohort elderly patients with NSCLC do constitute a special subpopulation with associated comorbidities. However, despite most of them had good PS at diagnosis, limited oncology treatment options were offered leading to suboptimal treatment. The fact that oncologists do not feel confortable to offer standard oncology treatment for this population may be due to the fact most of clinical trials exclude elderly patients. Although these data were generated in a private Cancer Center in Brazil we believe it mirrors the stiatuation across the country. These results highlight the urgent need for clinical trials focused on elderly patients, in order to provide a better care for those patients.

Background
Smoking appears to start at ever earlier ages, occurring in the great majority of adolescents between 13 and 15 years old. It is often associated with body image dissatisfaction and eating behaviors disorders. Objective: Assess tobacco consumption and its influence on body image dissatisfaction among high school Portuguese students, aged 15 and 19 years old.

Methods
Based on all students attending 3 high schools from the northern Portugal, the sample was randomly selected and 100 students were recruited from each high school. The adolescents smoking behavior was evaluated according to a protocol adapted from the Global Youth Tobacco Survey (Centers for Disease Control and Prevention, 2001) and body image dissatisfaction was also assessed.

Results
The mean age of the total sample (n=285) was 16.6 ± 1.2 years (min = 15, max = 19) and 46% were male. More than half (55.8%) were dissatisfied with their body image and had already started smoking (59.6%), with greater incidence among girls (54%). More than a half of these students who have tried smoking referred that it had happened between 12 and 15 years old. In all the three schools, 41.1% of adolescents think that smoking leads to weight loss (EA = 40.4%; EB = 41.7%, EC = 41.2%). There was not found any association between body image dissatisfaction and onset of tobacco use (p=0.388), although a stronger association was seen between the wish to be thinner and the fact that they had tried smoking.

Conclusion
Tobacco consumption is increasingly associated with diet behaviors and body image dissatisfaction among adolescents, particularly in girls. Such behavior points to the need for an early, clarifying and effective educational intervention.

Background
Lung cancer caused 1.37 million deaths in 2008 worldwide, 71% of which are caused due to tobacco smoking. Secondhand smoke (SHS) exposure can lead to lung cancer. 60% of the global lung cancer deaths occur in low and middle income countries (WHO). Despite the existing prohibition on smoking in public places in India (Section 4, COTPA), the prevalence of SHS exposure is 40% in homes, 30% in workplaces and 17-48% in other public places. The objective of this study was to describe air quality through PM~2.5~ and air nicotine levels, as well as smoking behavior, in public places and hospitality venues in two Indian states, Gujarat and Andhra Pradesh (AP).

Methods
A random sample of 400 public places was recruited; stratified into hospitality venues (N=200) and other public places (N=200). The air nicotine study was conducted in a subsample of 38 venues out of those recruited. Air nicotine monitors were put in place for 1 week according to standard protocol. PM 2.5 side packs, indicative of ambient SHS, were used with 30 minutes spent each in several rooms including restrooms and offices at each venue. Median and range were reported as the data was skewed.

Results
Air Nicotine monitoring - Detectable levels of air nicotine were found in all building types. In Gujarat, the highest recorded air nicotine concentrations were found in Hospitals (3.319 ug/m[3]), however the highest median air nicotine concentration was recorded in Tea Shops (0.214 ug/m[3]), followed by Railway Station, Waiting Rooms and Restaurants. In AP, air nicotine was highest in Bars/Pubs (median value: 4.445 ug/m[3]), followed by the Tea Shop and Hospitals. 90% of the hospitals monitored in Gujarat and 80% in AP registered smoking on the premises. PM~2.5~ monitoring – Overall, across the states, the highest median PM~2.5~ concentrations were found in recreational venues (44 μg/m[3]), followed by auditoriums (25 μg/m[3]) and offices (20 μg/m[3]). Transportation (19 μg/m[3]), hospitals (15 μg/m[3]) and educational venues (14 μg/m[3]) also recorded PM~2.5~ concentrations. PM~2.5~ levels were significantly higher in places where smoking was observed. PM2.5 levels were significantly higher in hospitality venues as against other public places.

Conclusion
Concentration of tobacco smoke and nicotine was found in most public places including hospitals and government offices. Apart from violation of Section 4 of COTPA these results also suggest that the smoke-free policy as currently implemented is not effectively protecting the masses from SHS and the resulting adverse effects including lung cancer. There is an urgent need to strengthen compliance with smokefree laws at all levels, while provision of designated smoking areas should be removed from the law to ensure 100% protection from SHS.

Background
The status of lung cancer in rural and remote Aboriginal and Torres Strait Islander ( from this point referred to as Indigenous) communities in Queensland is unclear. It is not known how much of a problem lung cancer is in these communities nor how much awareness exists regarding lung cancer risk factors and early symptoms. Several factors contribute to the uncertainty of lung cancer status in rural and remote communities. Factors include the quality of reporting Indigenous status and cancer registration, cultural influences affecting treatment decisions, access to health services and availability of culturally appropriate lung cancer information resources . Research on lung cancer in rural and remote Indigenous communities in Queensland is needed to improve lung cancer diagnostic and referral pathways and develop culturally appropriate and effective lung cancer information resources. Study Aims: 1. Describe the local and regional health care facilities for Indigenous people who may be referred for suspected lung cancer across the state of Queensland. 2. Interview Indigenous people and health workers in 3 population sample groups from six rural and remote Indigenous communities in Queensland to identify if there are variations in patient flow relative to predicted utilisation of local and regional health care facilities.

Methods
1. Using publically available information, identify relevant health care facilities including those with diagnostic bronchoscopy (with or without endobronchial ultrasound (EBUS) services across Queensland to predict expected referral pathways for suspected lung cancer. 2. Using quantitative and qualitative approaches to learn preferred referral pathways from 3 target population groups including patients referred for medical treatment with symptoms suspicious of lung cancer or confirmed lung cancer, Indigenous health workers, Indigenous community members aged 18 years and older. Frequency distributions in terms of the following will be analysed: demographics, current health status, social situation, access to health services, social and financial impact of treatment and information resources. Frequency distributions will be cross tabulated with age, education attainment, socio-economic characteristics, cultural influences, lung cancer awareness and knowledge. The responses to narrative questions will be analysed to identify main themes. These themes will be categorised by issues relating to lung cancer knowledge, cultural influences and beliefs, the patient experience and access to lung cancer medical and support services.

Results
We identified a spectrum of health care services across Queensland where patients may be referred for lung cancer management, ranging from public to private facilities. There are seventeen discrete Indigenous communities in Queensland. Compared to the nearest health care facility which offer diagnostic bronchosopy, 5 discrete Indigenous communities are situated > 200km away, 9 > 500km away and 2> 1000km away. Only one is situated 50km away.

Conclusion
The research findings will provide a clear understanding of the affect of lung cancer in rural and remote Indigenous communities in Queensland. Knowledge gained from research will enable better health service planning and help reduce any health disparities experienced by Indigenous people; particularly those who live in less advantaged areas compared to other Australians when facing a diagnosis of possible or confirmed lung cancer.

Background
Adjuvant Cisplatin and Vinorelbine chemotherapy has been shown to improve overall survival for patients with resected non-small cell lung cancer. In the Auckland region, we administer 400mg/m2 of Cisplatin over 5 cycles in an attempt to reduce toxicity. The aim of this audit is to review the number of patients treated with this chemotherapy at our centre, assess the rates of toxicity, examine patient outcomes, and identify barriers to adjuvant chemotherapy administration.

Methods
Patients starting Cisplatin and Vinorelbine between 1 January 2008 and 31 December 2010 were identified by the Auckland Hospital oncology pharmacy department. Their clinical records were reviewed with respect to demographics, details of chemotherapy received, and toxicities encountered. Cancer outcomes were also analysed, including recurrence and mortality rates. Subsequently a review of our local thoracic multidisciplinary team meetings held over the same time period was undertaken to identify barriers to adjuvant chemotherapy access.

Results
A total of 29 patients received Cisplatin and Vinorelbine over the 3 years as adjuvant treatment for non-small cell lung cancer. 24 patients had stage 2 or early stage 3 cancer, four patients had stage 1B, and one patient had stage 4 cancer with an isolated brain metastasis which had been resected. 23 (79%) patients received all planned cycles of chemotherapy. Five patients did stop early due to toxicity and one because of travel plans. The average number of cycles given was 4.58 and the average dose of Cisplatin received was 349mg/m2. The average time from surgery to chemotherapy initiation was 87 days. There were no treatment related fatalities in our group. 25 (86.2%) patients had at least grade 3 toxicity requiring either dose reduction or deferral. The majority of side effects were haematological in origin. As of the 31/05/2013, 14 of 29 patients have had cancer recurrences (48.3%) and 14 patients have died (48.3%), the lung cancer specific mortality was 37.9%. One patient has been lost to follow-up. One, two, and three year survivals were 89.7%, 79.3%, and 56% respectively. Over the three years examined, 48 patients discussed at our thoracic multidisciplinary meeting had resection of a primary lung cancer between stages 1b (size >40mm) and 3a. 20 of these patients received adjuvant chemotherapy. Of the remaining 28 patients, four declined treatment, five were not medically fit enough for chemotherapy, and four developed cancer recurrence shortly after their operation. 15 (54%) patients were mistakenly not offered chemotherapy when it may have been of potential benefit.

Conclusion
This audit would suggest lower utilisation of adjuvant chemotherapy than predicted, and no improvement in toxicity rates by reducing the dose of Cisplatin used per cycle. A higher likelihood of completing all planned chemotherapy was found. It highlights the prolonged waiting times to access chemotherapy and identifies barriers that inhibit suitable patients from accessing this important treatment. Several areas for improvement are identified. Our main recommendation would be to present all patients and review their pathology at multidisciplinary meeting following surgery. Our data is limited by its retrospective nature and small study population.

Background
Lung cancer is the leading cause of cancer-related deaths globally, with a 15% 5-year survival rate. Platinum-based chemotherapy constitutes the main treatment modality, with a median overall survival (OS) of approximately 10-12 months. The current National Comprehensive Cancer Network (NCCN) guidelines recommend several options for first-line and second-line therapies but endorse only erlotinib/gefitinib as third-line therapy in unselected patients, as well as crizotinib in ALK-positive selected patients.The paucity of approved agents for third-line therapy and beyond for patients with non-small cell lung cancer (NSCLC) constitutes an important unmet medical need.

Methods
Retrospective analysis of 22 patients with advanced/metastatic NSCLC in progression after a minimum of 3 lines of therapy.

Results
Between January 2009 and October 2012, 22 patients were analysed. Median age at diagnosis was 62 years old. 15% of patients were never smokers and 72.7% had non squamous NSCLC histology. Stage at diagnosis resulted: 6 (27.3%) stage IIIA, 3 (13.6%) stage IIIB and 13 (59.1%) stage IV. 3 (13.6%) patients were EGFR mutation carriers and 1(1%) patient had ALK translocation. Third line therapy options resulted a clinical trial (27.3%), erlotinib (22.7%), paclitaxel/gemcitabine (13.6%), docetaxel (9.1%) and crizotinib (4.5%). Estimated median progression-free survival (PFS) between first and second line therapy was 5.3 months; PFS between second and third line resulted 4.4 months. Median PFS and overall survival (OS) beyond third line treatment has not been reached yet.

Conclusion
Currently, erlotinib/gefitinib and crizotinib, which target EGFR and ALK, are the only recommended agents for third-line therapy in patients with advanced/metastatic NSCLC. Real-world clinical practice reveals a variety of chemotherapeutic agents used in this setting. Additional systemic and/or targeted therapeutic under development, with complementary biomarker analysis, should be the key in identifying those patients most likely to benefit from newer agents.

Background
SABR is well established in medically inoperable patients with early lung cancer. These patients are usually elderly with multiple comorbidities. Chest wall toxicity is seen in 15% of cases, however in radiotherapy planning no chest wall constraints are used to minimise this risk. Some centres actively exclude the chestwall from PTV margin and some feel that the risk of sustaining a fracture is as high with 3 as with 5 fractions as rib is likely to behave similar to a serial structure.

Methods
Of the 85 patients treated with SABR from 2009 to 2013, cases with at least one year follow up were audited. Patients were treated with 18 Gy x 3# and 11 Gy x 5# on alternate days. Chest wall was defined as 3cm from the ipsilateral lung border excluding the skin. For the chest wall, the maximum dose and volume getting 30, 40 and 50 Gy was recorded. Patients were followed up three monthly for the first year with CT imaging and toxicity was scored using CTCAE v3.0. Dosimetric parameters were correlated against chest pain and rib fracture.

Results
50 patients with a median age of 70 (range 56-89) and follow up of 16.8 (range 1.2-44.9) months were audited. The majority (62%) of the patients had a PS of 2 and 66% had a T1 tumour. 6 patients developed a rib fracture and patients complained of dysaesthesia/chest pain. One patient sustained fractures in three adjacent ribs at two different time points. The rate of any grade rib fracture and chest pain was 12% and 16% respectively with median time to development of respective toxicities of 15.6 and 4.6 months. Grade 3 rib fracture was seen in one patient. All of the patients that sustained rib fracture/chest pain had SABR delivered over 5 fractions as the PTV overlapped the chest wall. Median survival is 34 months with a 1 year survival of 88%. No correlation was seen between rib fracture and chest wall dosimetric parameter. However chest pain correlated well to all dosimetric parameters.

Conclusion
Our series shows a similar rate of chest wall toxicity to that reported in the literature, which is largely less than grade 3 in severity. However it is important to minimize this side effect as much as possible as the patient population currently being treated with SABR is elderly with multiple comorbidities. As the incidence of this toxicity is low, large patient data is needed to identify useful dosimetric parameters to predict chest wall toxicity. Developing SABR in the UK within the consortium structure with national guidelines opens up the potential to obtain and analyse such data. However there are logistical challenges of pooling data across various hospitals.

Background
Therapeutic armamentarium for advanced NSCLC includes oral EGFR-TKIs. There is paucity of data from India on experience with oral EGFR-TKIs in newly diagnosed NSCLC. The current study sought to assess demographic profile and treatment outcomes for NSCLC patients receiving first line treatment with oral EGFR-TKIs at a tertiary care institute in North India.

Methods
Retrospective analysis of data on newly diagnosed NSCLC patients initiated on treatment with oral EGFR-TKIs over a 4 year period (January 2008 to December 2011). Demographic characteristics, histology, disease stage and smoking status were noted. Radiological response to treatment was assessed using RECIST. Toxicity was graded as per Common Toxicity Criteria (CTC v3.0). Numerical and categorical data were compared between groups using Mann Whitney U test and chi-square test respectively. Survival probabilities and median survivals were calculated by Kaplan-Meier method and group differences analyzed using the log-rank test.

Results
Of the 76 patients who comprised the study population, the percentage of males and current/ex-smokers was 67.1% (n=51) and 51.3% (n=39) respectively. Histological distribution was as follows: Adenocarcinoma 59.2% (n=45), Squamous cell 23.7% (n=18), NSCLC-NOS 11.8% (n=9) and Large cell carcinoma 5.3% (n=4). Majority of patients were in stages IV 64.5% (n=49) and IIIB 26.3% (n=20) while only 9.2% (n=7) were in stages I-IIIA. Malignant pleural effusion was present in 20 (26.3%) patients. Baseline Karnofsky performance status (KPS) was 80-100 in 25.5%, 60-70 in 42.6% and ≤50 in 31.9%. Gefitinib (n=70, 92.1%) was the most frequently used EGFR-TKI. Most common indications for use of oral EGFR-TKI were poor PS/physiological status in 65.8% (n=50) and unwillingness for chemotherapy in 27.6% (n=21). Overall, 47 patients had atleast one follow up visit after one month and were eligible for assessment for response and toxicity. There were no complete responses while partial response (PR), stable disease (SD) and progressive disease (PD) were documented in 36.2%, 29.8% and 34.0% respectively of assessable patients. The most common side effects were skin rash and diarrhoea that developed in 17.0% and 10.6% of patients respectively. These were mild (grade 1/2) in all except one patient each with grade 3. Objective PR was observed in all (100%) patients with skin rash as compared to 23.1% among those without skin rash (p<0.001). Among patients without skin rash, the median OS was 178 days (IQR 53-320 days) while among those with skin rash the median OS had not been reached (figure 1).Figure 1 Gender, histology and smoking status did not differ amongst patients with and without skin rash. However, skin rash occurred in 25.0% and 5.4% of patients with and without malignant pleural effusion (MPE) respectively (p=0.26). On multivariate logistic regression analysis, only MPE was associated with occurrence of rash [odds ratio=0.19 (95% CI=0.04-0.95); p=0.04].

Conclusion
Oral EGFR-TKIs are a useful treatment option for clinically selected patients with advanced NSCLC who have either poor PS or are unwilling for chemotherapy. Occurrence of skin rash has an independent association with objective treatment response and with better OS. Presence of MPE is associated with occurrence of skin rash.

Background
BALT Lymphoma accounts for only 1% of Non Hodgkin’s Lymphoma leading to the paucity of randomized clinical trials to outline the treatment options (1). There are a few recently published case reports in the literature claiming success with single agent rituximab therapy but none in the relapsed setting with repeat rituximab treatment.

Methods
A 67-year-old woman was initially diagnosed with BALT lymphoma involving the left lower lobe 10 years prior, for which she underwent wedge resection alone. Five years later, she developed recurrence with multiple bilateral lung nodules noted on her annual CT scan. She was then treated with chemotherapy using Rituximab, cyclophosphamide, vincristine and prednisone given for 12 cycles. She achieved completed remission. Her annual surveillance CT scan four years later showed a left lower lobe lesion. Staging PET/CT scan showed isolated uptake in the left lower lobe lesion with SUV of 4.7 with no evidence of disease elsewhere. The biopsy showed recurrent BALT lymphoma. Immunostains were positive for CD20 and CD79a. Bone marrow biopsy showed no evidence of lymphoma. She was then treated with four weekly doses of Rituximab at 375mg/m2. Follow up CT scan after completion of the treatment showed complete resolution of the left lower lobe lesion. She was started on maintenance treatment with Rituximab to be given every 3 months.

Results
There are no set guidelines for treatment of BALT lymphoma but general consensus has been local therapy with either surgery or radiation for early stage disease, and chemotherapy for late stages. Also resection might not possible for patients with poor lung function (1). A phase II study of monoclonal antibody rituximab showed overall response rate of 73% (2). Several case reports also suggested completed remission (CR) with 4 to 8 weekly doses of rituximab (3). However, high relapse rate of 36% , observed in a phase II study (2) suggests that perhaps the 4-weekly-doses regimen may not represent the best schedule. Recent meta-analysis showed improvement in the overall survival with maintenance rituximab treatment in the relapsed setting in patients with follicular lymphoma (4). Given that BALT lymphoma is a subtype of Non-Hodkins Lymphoma, we extrapolated the data to our patient and started her on maintenance treatment.

Conclusion
Although longer follow-up is needed in our case, the demonstration of minimal toxicity and considerable activity of this biologic agent in the relapsed setting is promising. 1. Ferraro P et al. Primary non-Hodgkin’s lymphoma of the lung. Ann Thorac Surg 2000;69: 993-7. 2. Conconi A et al. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood 2003;102: 2741-5 3. Ahmet Bilici et al. Pulmonary BALT lymphoma successfully treated with eight cycles of weekly Rituximab: Report of first case and F-18 FDG PET/CT Images. J Korean Med Sci. 2011 April; 26(4): 574–576. 4. Vidal L et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2011 Dec 7;103(23):1799-806.

Background
Chemotherapy (CT) for advanced non-squamous non-small cell lung cancer (NS-NSCLC) without oncogenic drivers remains palliative with suggested similar efficacy and survival among different regimens. Histotype, maintenance therapy (m) and quality of life (QoL) have been explored to improve patients (pts) outcome. The ERACLE trial (NCT01303926), a QoL-oriented phase III trial, was designed to compare the QoL for two CT regimens.

Methods
Pts with stage IIIB/IV NS-NSCLC (ECOG 0/1) were randomized (1:1) to receive first-line CT. Arm A received 6 cycles of Cisplatin (C) (75 mg/m[2])/Pemetrexed (P) (500 mg/m[2]) q3w, followed by mP (500 mg/m[2]), while Arm B received Carboplatin (Cb) AUC 6/Paclitaxel (T) 200 mg/m[2] plus Bevacizumab (Be) 15 mg/kg q3w for 6 cycles, followed by mBe 15 mg/kg. Both treatments were administered until progression, unacceptable toxicity or death. Stratification was based on Study Centre and disease stage. Co-Primary endpoints were EQ5D Index (EQ5D-I) and EQ5D-VAS (Euro-QoL questionnaire). Quality of life data were collected at three time points during the induction phase and at 12 and 18 weeks during the maintenance phase. Secondary endpoints were QoL over time, safety and activity of CT arms. A sample size of 49 pts per arm (that have not progressed during initial CT and during maintenance therapy for at least 12 weeks) would have 91% chance to have 12-point Minimal Interesting Difference (MID) between arms for EQ5D-VAS, and 87% chance to find 0.137 MID between arms for EQ5D-I. It is assumed that about 20% of pts in both arms experience progressive disease before the evaluation of the primary endpoint. The study sample was then increased to 118.

Results
From 1/2011 to 3/2012, 118 pts were randomized to Arm A (n=60) or Arm B (n=58). Baseline demographics were well balanced across arms; Arm A/Arm B male: 70%/77.6%, PS 0: 78.3%/79.3%, stage IV 95%/93%, smokers: 63%/52% . Seventy four pts (62,7%) received maintenance chemotherapy. Treatment differences (mean change from baseline), EQ5D-VAS = 1.82 (95%CI -8.60 to 12.24; P=0.73), EQ5D-I = 0.15 (95%CI 0.01 to 0.29), favoured arm A. Safety was as expected without relevant haematological toxicity and with a significant impact of G3/4 alopecia (p=0.002) and G 1-3 neurotoxicity in ARM B (p=0.008) during induction. Response rates were (Arm A/Arm B) partial responses 40%/51%; stable disease 48.3%/27.6%. The Hazard Ratio (HR) for Progression Free Survival Arm A/Arm B [Cox's analysis] was 0.62 (95%CI 0.41 to 0.95) p=0.03 and HR for Overall Survival Arm A/Arm B [Cox's analysis] was 0.69 (95%CI 0.61 to 1.04) p=0.08.

Conclusion
Arm A showed better (over the MID) health profile (EQ5D-I) as compared to Arm B. EQ5D-VAS didn’t find any significant difference between treatment arms. By assuming equal activity, the choice of a treatment for advanced NSCLC should be mainly based on QoL.

Background
eviQ Cancer Treatments Online, launched in October 2009, is a Cancer Institute NSW flagship program. Its primary remit is to improve service delivery, standardise cancer treatment and improve patient outcomes. The primary audience is health professionals involved in delivering cancer care. Tailored information is also available for people with cancer and their carers, and other non-cancer health professionals. This open-access, web-based repository provides approximately 600 peer-reviewed cancer treatment protocols designed to support the way in which cancer care is implemented. eviQ treatment protocols and nursing resources provide detailed and extensive instructions on how to deliver evidence-based cancer treatments safely and appropriately. Provision of eviQ information promotes equity of access to the same information across rural, remote and metropolitan settings. eviQ provides reference standards that support the measurement and reporting of cancer treatment delivery to further determine strategies to reduce variation and improve patient outcomes.

Methods
Treatment protocols are developed according to the eviQ Governance Framework. Content specific reference committees, made up of clinical experts, discuss and review protocols at face to face meetings, and endorse them for publication on the site. Content is reviewed and updated in accordance with strict risk stratification criteria. This work is underpinned by the use of a tailor-made bibliometrics system, ensuring that the latest published evidence drives protocol development.

Results
eviQ includes a mechanism to record de-identified usage of the website. Usage has increased significantly; from 1932 in December 2009 to 27,853 (2,386 international) registered users in May 2013. Registered users by primary role: Australia (+ international) Medical 4,192 (+ 536) Nursing 11,377 (+653) Radiation therapy 1,031(+185) Allied Health 840 (+38) Other 4,889 (+486) There are currently 31 chemotherapy and 7 radiation respiratory cancer treatment protocols available on the site which were last reviewed and updated in 2012. The most frequently accessed respiratory treatment protocols (NSCLC carboplatin & gemcitabine and SCLC cisplatin & etoposide) are visited on average over 1000 times per month (based on figures from 2012-2013), this being comparable to similar breast treatment protocols (adjuvant adriamycin & paclitaxel and docetaxel & cyclophosphamide). Statistics confirm eviQ is accessed by a wide range of users in both public and private health care settings. eviQ is utilised in the tertiary setting as a teaching tool, further embedding the use of evidence based practice in the clinical setting. Independent evaluation undertaken in 2012 concluded eviQ is an easily usable, quality resource that supports evidence based practice in cancer care.

Conclusion
Every health professional engaged in cancer care has a responsibility to ensure work practice systems are optimised to ensure best patient outcomes. As a unique evidence- based online resource, eviQ contributes to reducing this variability. By harnessing the collective expertise of health care professionals in Australia, eviQ has developed an efficient, safe, quality national resource of evidence-based cancer treatment information for use at the point of care.

Background
PLCH is an orphan disease of unknown etiology, occurring almost exclusively in smokers, histopathologically characterized by focal Langerhans cell granulomas infiltrating and destroying distal bronchioles and lung parenchyma. Unlike other types of histiocytosis, PLCH was considered to be a polyclonal disease, but recently the monoclonal presence of the BRAF V600E mutation was demonstrated in some patients.

Methods
A 51-year old caucasian male smoker was referred due to lymphadenopathy and disseminated, progressive, apical accentuated pulmonary nodules (up to 12 mm) with beginning cavitation on CT-scans and elevated 18F-FDG uptake on PET/CT. The patient negated any B symptoms, while complaining of frequent coughs. Lung function tests showed a worsening restrictive pattern Hematological work up proved the diagnosis of a stage IV A SCL-NHL with marrow infiltration by a CLL-like lymphocyte population (Matutes score 4/5).No extrapulmonary involvement of PLCH was observed. Due to the CT findings suspicious of infectious disease, lymphoma infiltration or metastasis a CT-guided lung biopsy was performed. For BRAF analysis DNA was extracted from formalin-fixed paraffin-embedded lung biopsies and subsequent pyrosequencing.

Results
The biopsy revealed a granulomatous infiltration with CD1a positive Langerhans cells, molecular analysis confirmed a BRAF V600E mutation. Treatment with steroids and nicotine abstinence was initiated with impressive regression of pulmonary nodules after 1 month of therapy, as well as a decrease of F-18 FDG uptake on PET-CT. Lung function returned to normal.

Conclusion
PLCH should be considered in smokers with upper lobe predominant small nodules associated with cysts on high-resolution CT scans. These characteristic radiologic features are sufficient to establish a presumptive diagnosis. In case of doubt a lung biopsy should be performed. Our patient did not show typical PLCH HRCT aspects, presenting with large randomly distributed pulmonary nodules (up to 12 mm). The histological diagnosis of PLCH was clinically unexpected. The FDG uptake is compatible with this diagnosis, but unspecific. Predominant nodular patterns of PLCH have been described and may determine the early phase of the disease, whereas cystic patterns prevail later on. To the best of our knowledge, it has still to be determined how cystic lesions are formed, and how rapidly the dynamics of lung parenchymal abnormalities evolve. We demonstrate within a surprising short clinical course progressive nodular lesions, beginning with cavitation and partial regression after one month of therapy. Low incidence and spontaneous recovery of PLCH hamper the performance of clinical trials. Glucocorticoid therapy is successful only in a subgroup of patients and is advocated on empirical grounds in the treatment of nodular PLCH to accelerate the resolution of inflammation. Because of the predominantly macronodular pattern our patient received steroids in addition to nicotine abstinence and showed impressing regression within one month. The long-term impact of this strategy in BRAF V600E positive PLCH patients and the possible superiority of a targeted therapy with vemurafenib remain to be elucidated. But early therapeutic intervention, before conversion into cystic stages of PLCH may have the largest benefit.

Background
Patients with advanced non-small cell lung cancer are qualified to chemotherapy treatment with palliative intentions. Median survival time of those patients is 10 months and 24% live longer than 12 months. Current treatment modalities with targeted drugs and maintenance treatment extend survival time in limited group of patients beyond 24 months.The aim of the paper is to analyze selected patient-related factors, tumor factors and treatment regimens among patients who survived more than 24 months.

Methods
47 patients selected among 390 patients with advanced non-small cell lung cancer whose data were previously presented on WCLC 2011, not qualified to radical chemoradiotherapy treatment, who survived more than 24 months. Patients were treated with various platinum-based chemotherapy regimens – CDDP+Navelibine, CDDP+Gemcitabine, CDDP+Pemetrexed, Paclitaxel+Carboplatin and targeted drugs like erlotinib, gefitinib and bevacizumab. Usage of specific treatment regimen depended on clinical situation. Retrospective analysis of selected host factors, tumor factors and treatment regimen.

Results
Host-dependent factors: sex – 30 women, 17 men, age – range 39-67, median age 58 yrs, stage – IIIB – 15 patients, IV – 21 pts, reccurence after radical treatment – 9 pts; active smokers – 11 pts, former smokers – 32, non-smokers – 4; ECOG performance status – 0 – 32 pts, 1 – 15pts. Tumor-related factors: NSLC subtypes – not-otherwise specified – 28 pts, adenocarcinoma – 14, squamous cell carcinoma – 5 pts. Number of metastatic sites – 1- 30 pts, 2 – 17 pts; Metastatic locations – bone – 17 pts, lymph nodes – 20 pts, liver – 21 pts, brain – 0 pts. Treatment related factors – antyEGFR treatment – 6 patients, monoclonal anti body maintenance- 2 pts, premetreksed maintence-7 pts, taxenes maintenance- 8 pts. Patients recieved from 1 up to 4 lines of treatment. Median survival time was 34 months.

Conclusion
Survival time depends on various factors including usage of targeted drug therapies and maintenance treatment. Good performance status during treatment initialization still is one of the most important prognostic factors.

Background
Thoromboembolism has been reported as one of side effects of bevacizumab (BEV). An occurrence frequency of venous thoromboembolism caused by BEV is 0.2%. Specifically, it increases to approximately 4% within 1 to 3 months soon after chemotherapy. However, a ventricular thormbosis caused by BEV has almost never reported as far. We report a case of a ventricular thormbosis that occurred during chemotherapy using BEV for the lung cancer.

Methods
(case) 55 year-old, Japanese woman, who suffered myocardial infarction at 27 year-old and had a history of smoking (B.I.:350), complained of left.hemiplegia for brain tumor at first. After surgical treatment for brain tumor, she was diagnosed as lung adenocarcinaoma, cT1aN3M1b stage IV and was referred to our hospital. The first line pemetrexed(500 mg/m2) / carboplatin (AUC 6) /BEV (15 mg/kg) chemotherapy for two cycles every 3 weeks was performed. A partial response was found in the initial computed tomography (CT) evaluation, whereas the examination showed a thrombus of 26 × 25 mm in diameter in the left ventricle. D-dimer is 2.0 μg / mL at this point (D-dimer before treatment is 1.5 μg / mL). The anticoagulation therapy by using heparin continuous infusion and sequential oral agent therapy of warfarin and aspirin reduced the thrombus to 11 × 22 mm in diameter.

Results
(Discussion) Thromboembolism is clinically diagnosed by clinical findings, ultrasonography, contrast CT, and D-dimer. D-dimer is a simple indicator even for asymptomatic thrombus formation and has been reported to be valid for the evaluation of thrombus formation. In this case, D-dimer value was almost conserved through this event. We cannot be undeniable the relation the chemotherapy including BEV and left ventricular thrombosis. Also, since there is no evaluation of left ventricular function before chemotherapy treatment, it can not be denied the possibility of thrombus formation by reduced left ventricular function.

Conclusion
(conclusion) We have experienced a case that developed ventricular thrombosis during chemotherapy for lung cancer. It is believed to be evaluated, such as ultrasonography before using BEV in the case passing a long period of time after myocardial infarction.

Background
Lung cancer is the leading cause of cancer death yet public engagement with efforts against lung cancer is low. Public engagement with a cancer is critical to efforts to combat it yet the reasons for low support for efforts against lung cancer have not been systematically characterized.

Methods
We conducted a telephone survey of 1,071 people to determine levels of engagement and attitudes that might potentially drive engagement. These were then analyzed by univariate and multivariate analysis.

Results
8% of participants were involved with a lung cancer organization and 12% chose it among cancers to receive more support. Most participants felt that lung cancer was principally caused by external factors, that it could be cured if caught early, and that lung cancer patients were at least partly to blame for their illness. In multivariate analysis, participants who were supportive in some way of efforts against lung cancer were more likely to be employed, live in suburbia, and to be unsure of the cause of lung cancer. Potential supporters were more likely to be employed, female, younger, have higher income, to believe that genetics is the primary cause of lung cancer and to believe that lung cancer can be cured when caught early. Participants frequently noted that they supported a particular cancer because of knowing someone affected. Full demographic, univariate, and multivariate data will be presented.

Conclusion
As the lung cancer movement attempts to grow and increase its impact, the most successful recruitment efforts will be targeted to these groups.

Background
Background: Erlotinib is inhibitor of epidermal growth factor receptor tyrosine-kinase activity that has been shown to significantly increase survival, delayed symptom progression and improve quality of life in previously treated advanced non-small cell lung cancer (NSCLC). Here we report safety and efficacy data from open label, phase IV trial of erlotinib in Croatian population.

Methods
Methods: patients with advanced NSCLC who had failed prior chemotherapy were treated with oral erlotinib 150 mg daily until disease progression or unacceptable toxicity.

Results
Results: a total of 384 patients (276 men and 108 women, mean age 62) with advanced NSCLC were enrolled in the study from 2006 to 2012 in 10 centers in throughout Croatia. Patient characteristics: Non-squamous NSCLC had 57% of patients, squamous NSCLC 32% and NOS 11%; active smokers 41%, former and/or never smokers 57%; ECOG 0 36%, ECOG 1 54%, ECOG 2 7%, ECOG 3 1%. Most of the patients (83%) received erlotinib in third line of treatment. Progression-free survival (PFS) was 2,3 months showed trend to improved PFS in patients with squamous compared to non-squamous NSCLC (3,7 vs. 2,1 months). PFS in non-smokers was longer than in smokers (2,6 vs. 2,1 months). Disease control rate after two cycles of treatment was 40%; most patients had stable disease. Most common adverse event (AE) was rash which developed in 58% of patients and diarrhea in 28%. Most of AEs were grade I and II. Grade III rash developed only in 10% of patients.

Conclusion
Conclusion: These data confirmed favorable efficacy and safety profile even in non-selected NSCLC Croatian patients, including patients with squamous cell lung cancer.

Background
Various tumors metastasize to the lung and they are often detected as multiple nodules. Regardless of recent advances in computed tomography for detecting small pulmonary nodules and ground-glass opacity components which indicate possible primary lung cancer, preoperative differential diagnosis of either metastatic or primary lung cancer is usually difficult.

Methods
Four cases of such multiple lung metastases that coexisted with primary lung cancer were retrospectively examined: in three of the cases (case 1 is a myxoid liposarcoma in the right thigh, case 2 is a colon cancer, and case 3 is a renal cell carcinoma), a pulmonary metastasectomy revealed that one of the tumors was primary lung cancer. In case 4, the patient had a proven lung cancer that was combined with small nodules in the ipsilateral lung, one of which was pathologically diagnosed as a metastasis from rectal cancer.

Results
In case 1, the patient was diagnosed with clinical stage IA primary lung cancer (a well differentiated adenocarcinoma in the left lower lobe), and a left lower lobectomy was performed 17 days after the initial surgery. In case 2, a postoperative pathological examination revealed that one of the resected pulmonary tumors in the left upper lobe, measuring 5 mm in diameter, was Noguchi type B bronchioloalveolar carcinoma. In case 3, two nodules in the right lower lobe increased in size. An intra-operative pathological examination revealed that one of the pulmonary tumors in segment S9 measuring 7 mm in diameter was adenocarcinoma, and the other tumor in segment S8 located deeply near the pulmonary artery. Subsequently, a right lower lobectomy was performed. A postoperative pathological examination revealed that the tumor in segment S9 was Noguchi type A bronchioloalveolar carcinoma, and the other tumor measuring 8 mm in segment S8 of the resected lobe was metastatic clear cell carcinoma from renal cell carcinoma. In cases 2 and 3, the patients were diagnosed with clinical stage IA primary lung cancer and no additional treatment for lung cancer was required. In case 4, the patient, who had a history of rectal cancer, underwent left upper lobectomy with mediastinal lymph node dissection, combined with partial resection of the left lower lobe. A postoperative pathological examination using immunohistological staining revealed that the nodule in the left lower lobe and a hilar lymph node were metastasis from lung cancer (pT4N1M0, stage IIIA). The remaining nodule besides the tumor in the left upper lobe was diagnosed as metastasis from rectal cancer. The patient recovered uneventfully and was discharged with a treatment plan involving postoperative chemotherapy for lung cancer.

Conclusion
Possible coexistence of primary lung cancer should be considered in multiple metastases from other organs. On the other hand, the stage of the lung cancer depends on a definitive tissue diagnosis of the coexisting small nodules, and the importance of active tissue diagnosis including surgery should therefore be emphasized, especially in patients with previous malignancies.

Background
The diagnosis and treatment of cancer are traumatic events for patients with cancer and their families. It can be a time of a emotional distress for both and can evoke a wide range of emotions related to poor quality of life. The expression of these feelings is crucial in order to cope with a diagnosis of cancer and with treatment side effects and any action where people perceive that they’re moving those feelings outside may be beneficial to them emotionally and physically. Even patients who receive the best support from family and friends may need to connect with other patients, who are facing the same challenges. Patients may seek emotional and/or practical support from cancer patient organizations and find programs designed with the aim to help them and their families to alleviate the emotional concerns.

Methods
During the last five years, WALCE addressed their emotional care needs designing programs to ameliorate the cancer patient quality of life during the treatments. These projects are addressed to caregivers too and are observational studies. - The Look Good ... Feel Better® is active in 25 countries worldwide. WALCE started its collaboration with “La forza e il sorriso – L.G.F.B. Italia” in 2009. From March 2009 to June 2013, 68 make-up workshops were organised at the San Luigi Hospital (Orbassano, Italy) in collaboration with five local cancer centres. 487 ladies attended, guided by 7 voluntary beauticians, with the support of a psycho-oncologist. - Relaxation technique sessions may be helpful to face with stress. They are intended to promote physical, emotional and mental relaxation to get a better recovery of energies. From March 2012 to May 2013, 12 sessions were organised and 28 people attended. - Natural cooking classes are a good opportunity for patients and caregivers to learn that the health is closely related with nutrition and actively get involved during the preparation of food. The natural cuisine plays a key role in healthcare and these lessons provide useful tips for a balanced diet. Participating in these classes can empower people affected by cancer to learn vital skills that enable them to regain control, reduce isolation and restore hope. - Mindfulness Based Intervention (MBI) based on the assumption that a non-judgmental awareness and acceptance of one’s moment-to-moment experience have an effect on the distressing tendencies to escape from or to over-engage with one’s disturbing feelings, emotions and thoughts. MBI can positively impact on coping strategies and on the adaptation to the disease, by encouraging patients to relate differently to their physical and psychological symptoms.

Results
NOT APPLICABLE

Conclusion
Cancer patients tend to cope better with the illness and daily-life when self-confidence is regained. The sense of well-being shared in a relaxed atmosphere a acknowledging social, emotional and psychological needs, whilst being amongst other people with the same fears or anxieties, is an incentive to fight against cancer. It is important to know that there are ways to relieve the discomfort of most treatment-related side effects and to prevent them from becoming severe.

Background
We have previously characterized chemotherapy (CT) administration in the end of life (EOL) of solid tumor patients (pts) and found that close to 40% of them are treated with CT in the last month of life (LMOL). With this work we want to understand the reasons for CT administration in the EOL and chose lung cancer as a model.

Methods
We used a population of dead lung cancer pts that were treated by one oncologist in one hospital from 2004 to 2012. The oncologist was blinded to study design, data collection and analysis. We collected data retrospectively in the pt clinical charts and hospital electronic medical records. For group comparisons we used Chi square and Mann-Whitney tests and logistic regression for multivariate analysis.

Results
We identified 223 pts. The median age of the cohort was 65 years and 83% were males. The histology was NSCLC in 88% of the pts and the stage distribution was stage I or II in 6%, stage IIIA in 9%, stage IIIB in 23% and stage IV in 62%. The median survival of the cohort was 12 months. Of these, 190 pts were treated with CT, 74 (40%) in the LMOL and 50 (26%) in the last two weeks. Univariate analysis shows 11 variables significantly associated with CT administration in the LMOL: (1) dying in the hospital, (2) no asymptomatic interval after first therapeutic modality, (3) no opioid use, (4) less than 7 month survival, (5-6) progression to first and to last CT line, (7-8) worse performance status (PS) at first and at last CT line, (9) PS of 3 at last CT line, (10) having had less total time on CT and (11) having a low median duration of response to CT. In the logistic regression model, living less than 7 months, undergoing more than 3 lines of CT, dying in the hospital, no opioid use, progression to last CT line and PS of 3 at last CT line were considered predictors of CT administration in LMOL.

Conclusion
We show that CT administration in the EOL occurs in symptomatic pts that have short survival and chemoresistant disease. It is known that pts, families and society have unreasonable expectations on the efficacy of EOL CT and oncologists feel obliged to try to obtain disease control in poor PS pts with aggressive disease. Additionally, the subjective nature of the bond between oncologists, pts and families in the EOL is impossible to capture in this report.

Background
Recently, with the progress of treatment, the patients showing prolonged survival has increased in advanced lung cancer. Even though local treatments for the patients with vertebral metastasis, such as radiation therapy and/or surgery, are considered with effective, the indication of the treatment has not been determined. We report 5 cases who underwent posterior spinal fixation, they could maintain ADL(Activities of Daily Livings) well and could keep a long-term prognosis.

Methods
Between December 2012 and June 2004, we objectively evaluate postoperative state and prognosis of the 5 cases that underwent the posterior spinal fixation surgery for vertebral metastasis in advanced lung cancer.

Results
5 patients were underwent this surgery, 3 were male and 2 were female and the average age was 58.9 years. We added the surgery to remove the pressure of the spine in 3 cases, fortunately there was no spinal invasion in these 5 cases. We preformed chemoradiotherapy in 4 cases and chemotherapy alone in 1 case. EGFR mutation was positive in 2 cases. All patients were possible to ambulate in early postoperative day, and they showed improvement of neurological symptoms of paralysis. It was possible to maintain a relatively well ADL.

Conclusion
There may be an excessive burden to perform the surgery for the patients with vertebral metastasis in advanced lung cancer, the surgery for selecting patients may have been able to improve neurological symptoms such as paralysis. Therefore, we thought that the surgical procedure for the patients who are possible to survive long term period might have been one of the important treatment methods because of maintaining possibly their ADL well.

Background
Castleman’s disease, an uncommon disease that causes benign lymph node hyperplasia, must be distinguished from reactive lymph node hyperplasia and malignancies. Unicentric Castleman’s disease in patients with anemia is rarely described.

Methods
We describe the case of a 25-year-old woman with plasma cell type of unicentric Castleman’s disease presenting as iron deficiency anemia. We report the clinical course from the initial presentation to diagnosis and surgical cure and review the literature.

Results
Figure 1 A 25-year-old woman was referred with abnormal chest X-ray which was found during pre-employment screening. She had no other complaints, and her previous medical history was unremarkable, as was her family medical history. No fever, acute infectious symptoms and signs, or any other abnormalities were found in the physical examination. Normocytic anemia was found based on initial blood tests (hemoglobin 7.7 g/dl, mean corpuscular volume 88.9 fl, with normal white blood cells, red blood cell distribution width, liver renal functions, and electrolytes). Further laboratory examinations (ferritin 89.0 ng/ml; serum iron 23 mg/dl; and total iron binding capacity 206 mg/dl) demonstrated that she was iron deficient. Chest X-ray and chest CT scan confirmed a mass (6x4x4 cm) at right superior and mid-mediastinum (Fig. 1). PET/CT showed paratracheal mass shows inhomogeneously high FDG uptake. In suspicion of lymphoma, diagnostic thoracoscopic surgery was planned. However, intraoperative frozen section diagnosis of a specimen was benign. Thus, the mass was completely removed and diagnosis was consistent with unicentric plasma cell type Castleman’s disease. Three months after surgery, without any medical intervention, the laboratory data had recovered to normal range (hemoglobin 14.5 g/dl). She receives regular follow ups and no recurrence has been found for 4 years since surgery.

Conclusion
The surgical resection would appear to be the optimal treatment modality, and constitutional symptoms may be resolved. The prognosis following complete surgical resection appears to be good.

Background
Pleurodesis is an accepted therapy for patients with recurrent and massive pleural effusion in patients with advanced non small cell lung cancer.Bleomycin is safe and effective for chemical pleurodesis in several studies.The aim of this study was to study the effectiveness of bleomycin pleurodesis in advanced non small cell lung cancer.

Methods
Seventy five cases of proven non small cell lung cancer ; with recurrent and symptomatic pleural effusion admitted to our hospital between 2006 - 2012 were included in the study. All patients received chemical pleurodesis with 60 units of bleomycin after pleurocentesis using intercostals drainage.All patients received systemic chemotherapy following pleurodesis.

Results
The clinical control of pleural effusion by 4 weeks of procedure and the need for a repeat pleurodesis was analysed.The success rate was 76.7 per cent (95% CI,68.6 – 88.7 %). The only significant complication reported was chest pain of varying degrees. There were no deaths associated with bleomycin pleurodesis.

Conclusion
Bleomycin pleurodesis may be considered as safe and cost effective treatment in patients with advanced non small cell lung cancer with symptomatic pleural effusion in developing countries.

Background
A number of recent studies have reported poor cancer survival in England when compared to other developed countries worldwide. In particular, lung cancer has been highlighted as amongst the worst, with only Scotland and Malta showing poorer survival rates in Europe. The aim of this study was look for an explanation for these findings by assessing our post-operative survival in patients undergoing surgery for lung cancer. Through this we hope to establish whether the management of patients with curative disease is inferior or whether other key factors, such as stage and timing of diagnosis, are to blame.

Methods
501 patients were identified who had undergone lobectomy, bilobectomy or pneumonectomy for non-small cell lung cancer between January 2003 and January 2011. Information regarding patient demographics and histological stage of disease was collected. NHS number tracing was used to obtain patient status at follow-up. Survival data was plotted using the Kaplan-Meier method with comparison of stage 1 and 2 disease. In addition, information was collected from the NHS lung cancer database to identify the percentage of patients diagnosed with non-small cell lung cancer who underwent surgical management during the research period.

Results
Of the 501 patients within this cohort, 263 had stage 1 disease, 147 stage 2 disease and 91 stage 3 or 4 disease. Average age at the time of surgery was comparable between the groups (mean 67 years) and there were considerably more men within the study than women (M:F = 303:198). 5 year survival in patients with stage 1 or 2 disease was 75% or 40% respectively (Figure 1). On average, 12.9% of patients diagnosed with NSCLC underwent surgical resection. Figure 1: Comparison of survival following lung resection in patients with stage 1 and 2 NSCLC Figure 1

Conclusion
Cancer survival is an important measure of the effectiveness of both management strategies and healthcare systems. These findings demonstrate that in patients with early, operable lung cancers we are achieving survival rates comparable, and in some cases superior, to other developed countries. Only a very small number, 12.9% of patients, are diagnosed early enough to undergo surgery. This would suggest that it is not the treatment provided in England that is inferior, but our ability to diagnose lung cancer at an early stage.

Background
it is well known that combining chemotherapy and radiation therapy is beneficial to patients with locally advanced non small cell lung cancer compared to radiation alone or compared to a sequential approach using chemotherapy and radiation therapy. However, it is not obvious what is the best schedule. A few randomized trials assessed chemotherapy as induction before chemoradiotherapy (CT -> CTRT) versus chemotherapy as consolidation, after chemoradiotherapy (CTRT -> CT). Most of those trials are phase II trials with moderate sample sizes and were not designed to demonstrate treatment effect in terms of overall survival.

Methods
the study coordinators of those trials (T. Berghmans, H. Choy, P. Fournel, P. Garrido, J. Van Meerbeeck) agreed on a protocol for carrying out a meta-analysis of individual patients data and for sharing the individual patients data that were sent to the coordinating institution. Overall survival was the primary outcome, progression-free survival and toxic death occurrence were among the secondary outcomes. The treatment effect was assessed through the estimation of the hazard ratio of the survival distributions using CTRT -> CT as reference. Combined hazard ratio was obtained through Cox regression models (fixed effects) with a stratification by trial. Preplanned interactions between baseline covariates (age, sex, performance status, stage, histology) and treatment effect were assessed. Toxic death rates were analyzed per trial and odds ratios have been estimated to assess the treatment effect. Combined odds ratio was obtained by the Peto method.

Results
the data bases of the 5 eligible identified trials (3 with cisplatin based chemotherapy regimens, 2 with carboplatin based regimens) were shared for a total of 534 patients (CT -> CTRT 271, CTRT -> CT 263). Median ages were 60 and 61 years, stage IIIB represented 69%/70% of the patients and EOCG PS > 1 was rare (3%/2%). Median follow-up ranged from 12 months up to 66 months and rates of events from 44% to 88%. No significant difference was detected either for overall survival with an estimated HR of 0.96 (95% CI : 0.79-1.17) without heterogeneity between the 5 trials (I[2]=0) or for progression-free survival (analysis restricted to 4 out of the 5 trials), HR=0.91 (95% CI : 0.75-1.11) and absence of heterogeneity (I[2]=2%). For both outcomes, no interaction between the above specified covariates and treatment effect was found. Toxic deaths occurred overall in 3% of the patients, no detectable impact of treatment arm was found with a combined odds ratio of 0.40 and a 95 % CI overlapping 1 (0.15-1.06).

Conclusion
our results suggest that there is no argument in favour of one of the two therapeutic schedules when looking at overall survival or at progression free survival; however, in the absence of benefit in terms of prognosis, a more detailed evaluation of toxicity is warranted and is ongoing.

Background
Dyspnea is a distressing symptom that occurs in up to 75% of patients with lung cancer as measured by the Edmonton Symptom Assessment System (ESAS). Appropriate dyspnea management (DM) can improve the patient’s quality of life, performance status and emotional well-being. However DM is not uniform or standard across Regional Cancer Centers (RCC). A quality improvement intiative on DM was implemented through the Disease Pathway Management (DPM) of Cancer Care Ontario (CCO). DPM is a unifying approach to quality improvement that integrates program activity across the cancer continuum in order to advance system-wide improvements. This initiative provided advice on various delivery models and strategies for DM.

Methods
Seven RCCs received funding from CCO to undertake one year pilot projects in DM. These projects had to have potential for significant impact, be innovative and be cost effective. Each RCC project was required to address the physical and psychological aspects of dyspnea that affect the patient, their families and/or caregivers. The precise methodology was left to each RCC to develop and initiate within the specified criteria. Approaches included educational sessions for patients and family members, individual counseling and treatment plans, and symptom management clinics. Four measures were tracked: ESAS for patient-reported symptom severity, Palliative Performance Status (PPS) for evaluation of functional status, European Organization for Research and Treatment Quality of Life Questionnaire (EORTC-QOL) to measure quality of life and a Patient Survey to evaluate the patient’s knowledge of dyspnea, preparedness for self-management and overall satisfaction with the DM initiative.

Results
188 patients were evaluable. 45% of patients with an initial severe dyspnea score on ESAS reported a shift to either a moderate or mild score by the last visit. 32% of patients with an initial moderate dyspnea score on ESAS reported a shift to a mild score. Patient satisfaction was high, with feelings of empowerment to carry on daily activities as a result of the interventions offered; caregivers reported a better understanding of dyspnea and better ability to support their loved ones; clinicians noted a difference in patients attending the dyspnea care initiative and valued the helpful resource for their patients. Challenges encountered during the project were lower than expected recruitment due to lack of clinical engagement from busy clinicians, multiple additional visits that sometimes conflicted with other scheduled patient visits to the RCC, and declining performance status of the patients precluding in-person attendance for training in DM techniques.

Conclusion
DM can be effectively implemented and tailored to local needs of a RCC or program. Key factors for success included a clinical champion and a multidisciplinary team approach in order to build the necessary knowledge and expertise for DM. The lessons learned as a result of these pilot projects have led to a new initiative to improve the quality and consistency of DM across the province of Ontario. This new initiative will incorporate novel approaches for knowledge transference with the possibility of engaging healthcare providers beyond the RCC.

Background
At Cancer Care Manitoba (CCMB), Canada, lung cancer patients when considered incurable, are often enrolled into the palliative care program. One of the most important pre-requisites for patients to enroll into this program is to have a Do Not Resuscitate (DNR) status determined and signed by an authorized cancer care provider.Currently there are no guidelines on how and when to address advanced care planning and more specifically when to discuss DNR status. At this time the issue appears to be addressed on an individual basis depending on the patient’s unique circumstances and the personal practice of the physician involved. DNR discussions in the context of incurable lung cancer can be difficult for a number of reasons that include but are not limited to: social or family complexities such as dysfunctional dynamics or conflicted goals for medical attention, cultural differences, limited patient and/or family understanding of the patient’s prognosis, a recent diagnosis, limited time for discussion, physician preferences, and questionable patient cognitive competence secondary to pain, medications, brain metastases, whole brain radiotherapy, and emotional stress caused by the disclosure of incurable nature of the disease . Lung cancer team at CCMB has identified a need to explore the current practice and opinions around DNR discussion and future development of advance care planning guidelines. The findings from the current pilot study may serve the basis for a prospective randomized trial that tests an intervention that incorporates the timing of DNR discussions.

Methods
From January 2012 to November 2012 a total of 10 lung cancer patients who had previously discussed and determined their DNR status, 9 family members, and 10 health care providers were identified and agreed to participate. A mixed quantitative and qualitative methodology including a written questionnaire followed by a nurse directed audio recorded interview was employed to determine participant’s views. Interviews were transcribed and then content analysis and constant comparison techniques were used to identify, code, and categorize primary patterns in the collected data.

Results
Major themes identified from the patient and caregiver’s perspective include their trust in the health care system, the need for clear communication, the desire to be respected, and the benefit of having family present during discussion. Health care provider’s commonly expressed the importance of having adequate clinic time for discussions and the need for the process to be adaptable. Admission into a palliative care program is the most common trigger for initiating discussions but other points earlier in the disease course may also be appropriate. The presumed level of stress that patients are thought to undergo with DNR discussions is less than they actually report. Fnal data analysis is pending and subject to refinement before final presentation.

Conclusion
DNR status decision-making is a complex process, influenced by patient, family, and health care provider factors. The implementation of a standard approach to DNR discussions could potentially be restrictive. Potential areas of improvement include additional resources, and the specific guidelines. A need for a prospective trial addressing the timing of DNR discussion was identified but may not be feasible.

Background
Limited disease of small cell lung cancer (LD-SCLC) respond well to concurrent chemo-radiation (CCRT), but have high relapse rates and short relapse-free survival (RFS). We aimed to evaluate tumor metabolic activities measured by [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET) as a prognostic factor and analyze its relationships with markers of tumor biologic behavior.

Methods
Forty-one LD-SCLC patients receiving 4 cycles of EP (etoposide 120 mg/m[2], days 1–3; cisplatin 60 mg/m[2], day 1), 2 cycles of EP (etoposide 130 mg/m[2], days 1–3; cisplatin 30 mg/m[2], day 1) with concurrent mediastinal irradiation were enrolled. SUVmax of primary tumor was revised with the SUV of liver (SUVlivermax). Differences between pre- and post-treatment average SUV uptake of the primary tumor and intrathoracic lymph nodes were presented as ∆SUVliveravg. Thirty-one tumor biopsy specimens were immunostained for glucose transporter-1 (GLUT-1), Bcl-2, and hypoxia inducible factor-1α (HIF-1α).

Results
Objective response rates (ORRs) after CCRT were 92.7% and 87.8% on chest CT and FDG-PET, respectively. Median overall survival (OS) and RFS were 13.7 (range 4.4–54.1) months and 10.4 (range 0.97–54.1) months, respectively. In multivariate analysis, pretreatment lactate dehydrogenase (LDH) and ∆SUVliveravg correlated significantly with RFS (hazard ratio [HR] 2.8, P = 0.043 and HR 0.3, P = 0.004, respectively). Gender, pretreatment LDH, objective tumor metabolic response, and SUVlivermax correlated significantly with OS (HR 12.1, P = 0.006; HR 3.7, P = 0.037; HR 10.1, P = 0.008 and HR 0.2, P = 0.014, respectively). High GLUT-1-positivity (>75%) and pretreatment LDH levels (>400 U/L) correlated significantly with better ORR (P = 0.012) and HIF-1α immunoreactivity score (IRS, P = 0.029), respectively.

Conclusion
∆SUVliveravg and GLUT-1, with respect to tumor glucose metabolism, might predict RFS and ORR, respectively, in definitive CCRT-treated LD-SCLC patients.

Background
Clinical data suggests low molecular weight heparin (LMWH) may produce a survival benefit when given to cancer patients. Several studies are being conducted in different cancer primaries to explore this hypothesis including FRAGMATIC, which will be presented at the World Lung Conference. The FRAGMATIC trial is 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 according to local practice alone. The primary outcome measure is overall survival and the secondary outcome measures include; toxicity, VTE-free survival, metastasis-free survival, quality of life, patient experience and cost utility. 2202 patients have been recruited in order to detect an advantage of 5% in overall survival at 1 year (to 30%). Fragmin is given as a daily subcutaneous injection for six months by the patients themselves or a willing partner/ carer. This may raise practical challenges regarding how applicable the results of the main trial will be to clinical practice especially with regard to quality of life and thus compliance. We conducted a longitudinal quality of life study to explore the experiences of patients participating in the FRAGMATIC trial to better inform the patient journey and practicalities of applying results to clinical practice.

Methods
Semi-structured interviews were held at up to three time points, with two groups of patients recruited from the intervention (n=4) and control (n=6) arms of the FRAGMATIC trial.A total of twenty interviews were analysed using Interpretative Phenomenological Analysis to identify emergent themes that reflect participants' lived experience. We report data focusing on participant views and experiences of self injection for six months.

Results
No discernable difference in quality of life was identified between patients in the control or intervention arm who reported similar experiences of the cancer journey and its treatments. Patients on the intervention arm found daily Fragmin injections to be acceptable and a small consequence of having additional treatment as they saw it. Patients developed processes in order to administer Fragmin at similar times and described adaptive techniques to reduce discomfort and bruising. Minimal training was required to be able to inject Fragmin and few side effects were reported. The most common side effect was stinging which was short lived and bruising around injection sites. Patients reported these events did not impact upon quality of life. Overall, Fragmin was found to be an acceptable intervention, which did not pose any compliance problems.

Conclusion
The FRAGMATIC trail will report the impact of daily subcutaneous LMWH on overall survival in lung cancer. In this trial 1100 patients self injected Fragmin or had it administered to them. Based on qualitative interview data, Fragmin injections were well tolerated and the experiences of patients suggest that it would be relatively simple to introduce self-injecting into standard lung cancer therapy should the results of the FRAGMATIC study demonstrate a survival benefit.

Background
A previous 2010 audit at the Royal Adelaide Hospital (RAH) found delays in treatment initiation when compared to targets set in the United Kingdom (UK) National Cancer Plan. The aim of this study was to review our performance in 2011 and to explore the impact of curative or palliative treatment intent and rural or urban based location, in order to guide future improvement.

Methods
Using a pathology database, we retrospectively reviewed 128 case notes of patients referred to the RAH in 2011 with new histologically confirmed lung cancer. We identified treatment intent, patient location and key dates in diagnosis and treatment by radiation oncology, medical oncology, cardiothoracic surgery or palliative care before calculating median intervals between these points.

Results
Figure 1 52% of patients were urban and 48% rural. 45% of patients were treated with curative intent and 55% with palliative intent. Pertinent median intervals include: referral to appointment (appt): 4 days (inpt: 0 days, outpt: 7 days); appt to diagnosis (a) rural outpt :16 days, urban outpt: 10 days (p=0.58); (b) surgical: 21 days, curative outpt CH-R: 7 days (P<0.001); (c) surgical rural 30.5 days, surgical urban 13 days (p<0.001); referral to treatment: 41 days (UK 2006: 41 days, RAH 2010: 48 days, (a) outpt: 54 days, inpt: 21 days (p<0.0001), (b) surgical: 62 days, outpt curative CH-R: 34 days (p=0.81), curative outpt CH-R: 34 days, palliative outpt CH-R: 46.5 days (p=0.79)). Inpts met both UK targets. There are a number of factors contributing to the delays in surgical cases including a higher proportion of cases needing multiple biopsy attempts and requiring CT-FNA, which takes twice as long to obtain as a bronchoscopy. Rural location did not impact on overall time to treatment but delays seen in appointment to diagnosis, in particular the surgical cases.

Conclusion
For 2011, the RAH achieved the first UK targets for first appointment to a specialist but did not meet the target set for referral to commencing treatment. Delays were seen in some rural subgroups, necessitating the need for a streamlined rural pathway to assist in managing investigations and appointments. In turn, this will also reduce the number of rural elective admissions. Initiatives to improve time to treatment with curative intent include pre-booking investigations, utilising EBUS for staging and improving access to CT-FNA. A follow up audit including analysis of mortality is being conducted.

Background
Locally advanced non-small cell lung cancer has poor prognosis with less than 20% probability of 5-year survival despite the use of concurrent chemoradiotherapy. Last generation chemotherapy regimen, high dose of radiotherapy, and surgery if feasible are options to achieve better outcomes in highly selected cases.

Methods
A case report of a 25-year woman with non-mutated adenocarcinoma of the right lung is presented in this work.

Results
The young woman, age 25 years, smoker of 1 pack/day since the age of 18 years, without family cancer history presented with right lung perihilar mass. CT scan showed tumor infiltration of the right upper lobe of 73x65x80 mm involving mediastinum as well as enlargement of right hilar and mediastinal lymph nodes. Suspicion of left aortic arc lymph nodes infiltration was described on FDG-PET/CT but no distant metastases were seen. Transbronchial biopsy confirmed adenocarcinoma. EGFR mutation and ALK translocation were not found. TNM stage (UICC7) was T4N2-3M0 – clinical stage IIIB. Performance status 1, cough, dyspnoea and mild weight loss at time of diagnosis were noted. Treatment consisted of 5 cycles of chemotherapy with cisplatin and pemetrexed in standard doses every 3 weeks and concurrent radiotherapy given in the dose of 72Gy/36 fraction/7.5 weeks during 3-5th cycle. Restaging after CRT showed substantial partial remission with negative mediastinal lymph nodes on PET/CT scan, therefore surgery was proposed, resulting in right upper lobectomy and mediastinal lymphadenectomy. The histology showed residual adenocarcinoma 35x20x45mm with regressive signs, stage ypT2 ypN0. Whole-body and brain FDG-PET/CT two months after surgery confirmed complete remission. No additional chemotherapy nor prophylactic cranial irradiation were indicated but close follow-up has been planned because of the high risk of recurrent distant metastases.

Conclusion
This case report showed successful multimodal therapy of advanced NSCLC in a very young woman whose age and good PS warranted aggressive treatment approach. This abstract was supported by a grant from the Ministry of Health of the Czech Republic – IGA MZ CR NT12331-5/2011 and by a grant from the Charles University Prague PRVOUK - P27.

Background
Photodynamic therapy (PDT) is a unique combination of photosensitizing drug and laser light for drug activation which results in tissue destruction by direct cellular damage and small vessel thrombosis. We have utilized PDT to manage airway malignancies since 1998. This large, single institution case series will describe technical considerations of airway PDT,incorporation of PDT into multi modality therapy, patient selection, patient management and clinical outcomes.

Methods
All patients receiving PDT were entered into an IRB approved outcomes registry. Data was abstracted from the medical record and the cancer registry. Photofrin was used as the photosensitizer at a dose of 2 mg/kg IV . Light dosimetry ranged from 100 - 200 J. Light was delivered at 630 nm. All patients were treated under general anesthesia for light application and airway debridement. Autofluorescent bronchoscopy was used to delineate extent of endobronchial disease.

Results
Between 1998 and 2013, we have performed PDT on 910 patients; 519 procedures (57%) have involved the tracheobronchial tree. The average age was 62 years with a range of 18 -92 years.The cell types managed by PDT included NSCLC, SCLC, carcinoid, and metastases to the airway. Indications for tracheobronchial PDT included symptom management/ palliation (63%), induction therapy (27%), and definitive therapy with curative intent (10%). Dyspnea and post obstructive pneumonia from airway obstruction were the most common symptoms. Photosensitivity rate was < 2%. There were no perforations of the tracheobronchial tree. There was a single stricture in this cohort; this occurred in a patient who had been previously resected.

Conclusion
PDT for primary or metastatic lesions to the tracheobronchial tree is safe. Early and advanced lesions can be treated. PDT can be used prior to surgical resection and may increase resectability by reducing endoluminal disease. PDT may be used after radiation therapy with good efficacy. PDT can be utilized during multiple courses of treatment to palliate obstructing or bleeding lesions. Photosensitivity is an infrequent complication. Our experience demonstates the utility of PDT across all stages of NSCLC when there is a visible endoluminal component. In order to more specifically define the utility of PDT in NSCLC, we have established a prospective multi center registry to delineate indications, contraindications and the role of PDT in treatment algorhythms for airway malignancies.

Background
A number of studies have demonstrated that early palliative care involvement in the care of metastatic non-small cell lung cancer patients leads to significant improvements in quality of life, symptom control, and survival. Most studies, however, were performed in large centres where palliative care service is readily available. The North West Cancer Centre is a comprehensive rural Australian cancer centre. In this study, we reviewed our patterns of palliative care involvement, seeking to examine the current practices in the light of our limitations.

Methods
Retrospective analysis of patients with metastatic adenocarcinoma of the lung in the North West Cancer Centre between January 2008 to December 2012.

Results
We identified 35 patients with stage IV adenocarcinoma of the lung. The median duration to first review by palliative care is 126 days (range 28 - 669 days). Median duration from first review by palliative care to time of death is 22 days (range 11 - 152 days). Both are calculated from time of first review in medical oncology clinic. Further analysis revealed only 10 patients reviewed by a palliative care physician, with a median duration to first review of 227 days (range from 76 to 670 days). 25 patients were reviewed by specialist palliative care nurses, with a median duration to first review of 382 days (range from 76 to 676.5 days). 30 patients required inpatient palliative care, however only 7 were admitted under a specialist palliative care unit. 8 patients are currently alive. 5 patients received no palliative care input.

Conclusion
Lung cancer patients in rural and remote communities are known to have poorer prognosis compared to their urban counterparts. Our study further highlights this disparity. Early palliative care is becoming a standard of care. However, there are unique challenges facing a rural cancer centre that limits feasibility of early palliative care involvement in rural and remote lung cancer patients. A limited number of specialist palliative care health care providers service a large area (map). Currently we have 1 part-time specialist palliative care physician and 2 specialist palliative care nurses, catering for inpatient, ambulatory, and community palliative care patients. Our study found significant involvement of non-palliative care specialist health care providers assisting in provision of palliative care services. It is our impression that increasing awareness and education of the supporting health care providers is imperative to improving delivery of palliative care in a rural setting.

Background
Docetaxel is an accepted second line drug for NSCLC not used frequently for its side effects. VT-122 (propranolol and etodolac) which has anti-angiogenic COX-2 inhibition properties. Modifying the tumor-microenvironment and sympathetic system has anticancer activity as well as ameliorates toxicity of anticancer drugs. Docetaxel efficiency can be improved with VT-122 which possesses the above property. To increase efficacy of docetaxel and safety profile using VT-122.

Methods
20 (10 in each arm) patients (55-65 years) were treated with docetaxel (75mg/m[2]) with or without VT-122. VT-122 was started 7 days before giving docetaxel. Propranolol doses were titrated to maintaining heart rate around 60. Etodolac was titrated on the basis of CRP to a maximum of 1200mg.

Results
Overall Response seen in 4 patients (VT-122 arm) and 2 patients (docetaxel arm). 6 patients in VT-122 arm completed 6 cycles of docetaxel while in non-VT-122 4 patients completed the 6 cycles. 1 year survival was 30% vs 10%; p=0.025. Grade III/IV hematologic toxicity was decreased by 50% ie 6 cases in docetaxel arm and 3 in VT-122. In non-hematological toxicity this trend was seen for asthenia, neuropathy, skin and nail changes and weight loss.

Conclusion
Addition of VT-122 (propranolol and etodolac) increases efficacy of docetaxel and is cost effective.

Background
Fatigue, depression, sleep disturbance, and dyspnea are symptoms frequently reported by patients with non-small cell lung cancer before anti-cancer treatment. The purposes of this study were to identify latent subgroups of patients with NSCLC using the above four symptoms assessed at pre-chemotherapy and to determine whether different patient subgroups based on their symptom profiles can predict their survival.

Methods
Patients with stage III or IV NSCLC were recruited from a large teaching hospital located in northern Taiwan. Fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was used to measure fatigue. The Hospital Anxiety and Depression-Depression subscale was used to measure depressive symptom. The Pittsburg Sleep Quality Index (PSQI) was used to measure sleep disturbance. Four items from EORTC QLQ-C30 and QLQ-LC13 was used to measure dyspnea. All patients were followed up until the end of the study. The follow-up time ranged from 10 to 30 months. Latent class analysis was used to identify patient subgroups. Cox regression was used to examine the effect of patient subgroup on survival after adjusting the effect of covariates.

Results
The study sample consisted of 127 NSCLC patients. Two distinct patient subgroups were identified. The first group (30%) was characterized with high severity on all four symptoms (high symptom group), the second groups (70%) showed low severity on all four symptom (low symptom group). Before adjusting covariates, the “high symptom group” had significantly shorter survival time (median = 11.1 months) than the “low symptom group” (median = 21.1 months) (P = 0.016). After controlling for gender and disease stage, the group membership remain significantly associated with survival time (P=0.047). The risk of early death was 1.81 times higher in the “high symptom group” as compared to the “low symptom group” (HR=1.81, 95% CI=1.01 to 3.23).

Conclusion
The finding suggests that pre-treatment symptom profile has additional prognostic prediction in patients with advanced NSCLC. Early symptom assessment is recommended.

Background
The incidence of lung cancer in the Czech Republic has been unacceptably high for decades. It has reached 91/100 000 in men and 31/100 000 in women. Bronchoscopy plays an important role in the diagnostic process. To assess the quality and density of the bronchological net and to determine the current situation in the implementation of bronchoscopy in the Czech Republic we decided to carry out a national survey.

Methods
A bronchological questionnaire was sent by e-mail to every pneumologist performing bronchoscopy. With the help of repeated e–mails and additional telephone interviews we achieved a response rate of more than 95%.

Results
In 2012 there were 56 centers performing bronchoscopy in adults and 9 in children in the Czech Republic. The bronchological units of adult clinics employed 169 bronchologists using 231 fiberscopes, out of which 88 were video bronchoscopes and 79 rigid bronchoscopes. Altogether 30 354 bronchoscopies were performed in adults. General anesthesia was used in 2 146 cases, the rest was carried out under local anesthesia. The total number also includes 1767 bronchoscopies performed using rigid instrumentation. Cytological examination of the material obtained during bronchoscopy was carried out by a pathologist (Department of Clinical Pathology) at 34 centers, by a pneumologist trained in cytology at 13 centers and by both the pathologist and the pneumologist at 9 centers. Interventional bronchoscopic procedures (laser, electrocautery, stenting, brachytherapy, cryocautery and the introduction of endobronchial valves) were used in 17 departments. Altogether the above mentioned procedures were performed 654 times during one year. All 9 children's bronchological departments employed 12 bronchoscopists, using a total number of 29 fiberscopes, out of which 17 were video bronchoscopes. Seven pediatric bronchoscopy centers also used rigid instrumentation. The total number of pediatric bronchoscopies performed in 2012 was 682, the majority of them (621) under general anesthesia. Out of all bronchoscopies, the rigid bronchoscopy was performed in 32 cases. At five centers cytology examination was performed by a pathologist, at 3 centers by a pneumologist trained in cytology and at one center by both specialists together. Further analysis of the specialized bronchological procedures (endobronchial ultrasound, autofluorescence), including a comparison with previous surveys will be given in the lecture or on the poster.

Conclusion
The level of bronchological service offered in the Czech Republic is comparable with the most developed countries and serves a prompt and exact diagnostics of patients with respiratory disorders including lung cancer. "Supported by Projects (Ministry of Health) of conceptual development of research organization 00064203 (FN Motol, Prague, Czech Republic)".

Background
Dosing of many chemotherapy drugs is currently based on body surface area (BSA), which is partly derived from body weight. However, BSA has been shown to result in large inter-patient variability in drug exposure. Another measurement of body composition is fat free mass (FFM), which includes hepatic, renal and muscle metabolic tissue. Depletion of FFM is termed sarcopenia, which in breast and renal cancer populations is associated with increased chemotherapy toxicity and time to disease progression. Sarcopenia can occur regardless of weight or BSA. In order to explore the value of FFM assessment in lung cancer patients undergoing chemotherapy, we performed a systematic review to explore this relationship. We present an analysis of relationships between sarcopenia, body weight, BSA, chemotherapy toxicities and outcomes in lung cancer patients.

Methods
Two search strings (‘muscle mass loss’ AND ‘lung cancer’) were used as a basis for formulating specific literature search strategies in five databases. We included all publication types and the search was limited to articles written in English. From this larger review, we then narrowed our focus to chemotherapy-specific studies.

Results
Our systematic review of FFM loss in lung cancer consisted of 29 studies, from which 7 studies considered specifically the relationship between FFM and chemotherapy. One study of 250 obese patients found 15% were sarcopenic, FFM poorly correlated with BSA (r[2]=0.37), and variation in FFM per unit of BSA could account for up to three-times variation of chemotherapy volume of distribution, potentially indicating increased risk of chemotherapy toxicity. A further population-based study (N=441) found 46.8% were sarcopenic, despite only 7.5% being underweight. A further two smaller studies (N=40, 41) found the prevalence of sarcopenia to be 61% and 46% (despite approximately half being overweight or obese). Prospective evaluation of the effect of chemotherapy on FFM in 3 small studies (N<22) showed no significant change. Sarcopenia was also associated with poorer performance status and reduced median survival.

Conclusion
A more refined understanding of body composition is needed in lung cancer patients, in order to minimise toxicities of chemotherapy, whilst ensuring optimal chemotherapy dosage. The current literature suggests that a more detailed prospective study is required in order to explore the validity and advantage of measuring FFM rather than BSA in lung cancer patients, in the work-up to chemotherapy. It also suggests that targeting sarcopenia may offer a novel approach to improving chemotherapy tolerance and overall survival.

Background
The presence of EGFR activating mutations in NSCLC and sensitivity of these tumours to EGFR tyrosine kinase inhibitors (TKI) was first described in 2005. For NSCLC patients harbouring an activating EGFR mutation the treatment of choice is an EGFR TKI which is better tolerated and easier to administer than chemotherapy. However, questions remain about duration of therapy and optimal management on radiological progression.

Methods
A retrospective case note review was undertaken with the aim of establishing current practice in prescription and discontinuation of EGFR-TKIs, subsequent therapies and clinical outcomes. We identified consecutive patients from the database of the genetic testing laboratory (from Q4 2009 when routine testing commenced to a cut-off point of February 2013). 171 case- notes were reviewed for demographic and clinical data including survival.

Results
Of 171 cases 116 (69%) had received treatment with an EGFR TKI (Gefitinib 79%, Erlotinib 19%, both 2%). The reasons for not receiving treatment included: patient received radical therapy, patient died before oncology assessment and patient preference. 63% of patients were female, 26% never smokers, 44% ex-smokers, 6% current smokers and smoking history was not documented in 23%. 76% of patients had Stage IV disease and performance status was 0-1 in 47%, 2 in 22%, 3 in 7%, 4 in 2% and not documented in 23%. The average length of treatment on EGFR TKI was 10.5 months (range 0.5-40) and 36 (31%) patients were still on treatment at the time of analysis. Disease progression on the EGFR-TKI (PD) had occurred in 82 (71%) of patients and 28 (34%) of these continued EGFR TKI treatment beyond PD. The average length of time on treatment beyond PD was 5.6 months (range 1-16) and TKI treatment was ongoing in 9 of the 28 patients. 25 of the 73 patients (34%) with PD who had stopped EGFR TKI went onto receive a second line systemic treatment: pemetrexed and platinum 60%, gemcitabine and carboplatin 20%, single agent pemetrexed 8%, vinorelbine 8%, gemcitabine 4%. Third line therapy was received by 40% of those who had received 2[nd] line treatment.

Conclusion
Patients with EGFR activating mutations often derive a significant clinical benefit and marked reduction in tumour burden with oral EGFR TKI therapy, which results in a reluctance, from both patients and clinicians, to stop therapy at the time of radiological progression if the patient is still experiencing symptomatic improvement. Our results show that treatment beyond disease progression is common (34%) in ‘real –life’ clinical practice with some patients continuing to derive benefit for more than a year beyond the time of disease progression. .

Background
Patients with advanced lung cancer presenting with ECOG 2 at diagnosis trend to be no longer included in large, randomized, registration trials and then recommendations for their treatment are more difficult. Nonetheless, they account for a significant percentage of the cases attended in a Medical Oncology Department. We describe their characteristics and outcomes in our experience.

Methods
Medical records of lung cancer patients with ECOG 2 that were seen in our Department between april 2009 and april 2013 have been reviewed.

Results
124 patients (p) were found. They account for a 15.3% of the overall number of lung cancer patients attended. 106p were male (85.5%). Median age 66 years (44-83). By histology: adenocarcinoma 41p (33.1%), EGFR+ adenocarcinoma 4p (3.2%), squamous 36p (29.0%), small-cell 23p (18.5%), other 19p (15.3%), no histologic diagnosis 1p (0.8%). By stage: III 39p (31.5%), IV 85 (68.5%). By the time of analysis, 76p (61.3%) hade died, other 31p (25.0%) continued palliative care and 17 (13.7%) were still on active therapy. Initial intention of therapy was palliative in 94p (75.8%), radical/adjuvant in 9 /.3%) and 21p did not receive any active therapy beyond supportive care. Drugs administered at first line: carboplatin 43p (34.7%), cisplatin 12p (9.7%), EGFR-TKI 6p (4.8%), non-platinium chemotherapy 39p (31.5%), no Chemotherpy 24 (19.4%). No differences by gender existed in the drugs given, except for TKI which were more frequently given to women (5/6). Median overall survival was 34 weeks (IC: 26.0-41.9). No differences existed by gender (male 32 weeks, female 39 weeks) or stage (III 30 weeks, IV 36 weeks) but they differed by histology: adenocarcinoma 34 weeks, squamous 22 weeks, EGFR+ aenocarcinoma Not Reached, small cell 59 weeks.

Conclusion
A significant percentage of lung cancer patients are diagnosed with ECOG 2 performance status in every histological subtype. Minor differences existed with respect to clinical characteristicas and they benefit from receiving active therapy. This advantage seemed to be lesser in squanous carcinoma.

Background
Erlotinib (E) is a EGF-receptor tyrosine kinase inhibitor (TKI) approved for the treatment of NSCLC after progression to first-line chemotherapy irrespective of EGFR status. Currently EGFR mutation is usually performed upfront upon diagnosis and most mutated patients are treated with first-line TKI's. Nowadays, patients candidates for second line therapies are EGFR-wild-type.

Methods
Medical records of EGFR-wild-type patients treated with E in second or further linesbetween March/2008 and March/2013 were reviewed.

Results
85 patients (p) were found. Characteristics: Median age 61 years (38-83), 76.5% were male. Tobacco: 42.4% were smokers and 45.9% former smokers. PS 0, 16p; 1, 50p; 2, 19p; by stage: IIIb 27p, IV 58 p. Histology: adenocarcinoma 48p, squamous-cell 25p, undifferentiated or non-specified 11p, adenosquamous 1p. E was given: 40% as second, 44.7% as third and 15.3% as fourth or subsequent line. Effectivity: Partial response 9.4%, Stable disease 48.2%, Progressive disease 41.2%, Not assessable 1%. Overall Survival (OS): median 22 weeks (w) (95% CI, 17.4-26 .7), progression free survival (PFS) 12w (95% CI ,9.8-14 .2). In smokers PFS was 12w also. In squamous carcinomas 10w. In males 11w (these differences were non significant). Toxicity: 92.9%p presented some side-effect: 70.5% rash (49p, G1; 11p, G2); diarrhea 34.1%p (25p, G1; 3p, G2; 1p, G3); asthenia 29.4%p (12p, G1; 6p, G2; 7p, G3); ocular 2.4%p (2p, G1) and digestive 9.5% (2p, G1; 1p, G2; 1p, G3). Dose was reduced in 12.9%p (7p 100 and 4p 125 mg/day). Treatment was interrupted in 7.1%p (median 14 days (range 7-23)); most common causes were G3 skin rash and diarrhea.

Conclusion
We described the efficacy of Erlotinib in day-to-day clinical practice when was given beyond the first-line treatment in advanced and metastatic NSCLC without EGFR mutation. Our results are in accordance with has been reported from clinical trials and may reflect its efficacy in clinical practice.

Background
Creative art therapy (CAT) consists in the use of artistic activities to help patients manage physical and emotional problems in a therapeutic setting. In oncology, CAT has mostly been practiced in palliative-care units. CAT has not been used in lung cancer patients so far, especially when chemotherapy treatment is still delivered. Our objectives were to prospectively assess the feasibility of integrating CAT in the management of patients with metastatic lung cancer treated with chemotherapy.

Methods
From 2011/11 to 2013/05, CAT was offered to in- and out-patients who received chemotherapy for metastatic lung cancer in our department. Creative activities included the production of paintings, drawings, and/or sculptures. Patients were assessed by a trained art therapist for anxiety levels, self-awareness and satisfaction, before and after each art session.

Results
84 patients were included in the study, among whom 41 (55%) accepted CAT and received a mean number of 3 sessions. In this cohort of 13 men and 28 women, 31 (75%) and 17 (41%) patients reported improvements in anxiety levels and cancer-related symptoms after the art session, respectively. CAT gave satisfaction to 37 (90%) patients. These benefits were transient in all cases. Main reasons for refusing CAT in the remaining 33 patients included fatigue and lack of interest for arts. Painting and drawings from lung cancer patients along the disease management will be presented at the meeting.

Conclusion
Our study reports on the feasibility of CAT in lung cancer patients receiving chemotherapy. CAT may be considered part of the multimodal supportive care management of lung cancer patients. This study was supported by an unrestricted grant from Hoffmann-La Roche.

Background
The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by imaging features consisting of the association of centrilobular and/or paraseptal emphysema and pulmonary fibrosis, associated with subnormal spirometry, contrasting with severe impairment of gas exchange with strong decrease in carbon monoxide diffusing capacity, and hypoxaemia at exercise. Virtually all patients presenting with CPFE are smokers and may be at high-risk to develop lung cancer; limited data have been made available on such association, mostly from Japanese cohorts.

Methods
This retrospective multicentre study was conducted by the Groupe d’Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires (GERM”O”P), a collaborative group of about 200 French physicians dedicated to the study of rare pulmonary diseases. Patients presenting with CPFE syndrome and lung cancer at the referring centers from 2003 to 2012, were included. The clinical, pathological, and therapeutic features, as well as the outcome of patients, were collected and analyzed.

Results
A total of 47 patients presenting with lung cancer and CPFE syndrome were identified. All patients but one were men, with a mean age of 68 years. All patients were smokers, with a mean of 47 pack-years. The CPFE syndrome was diagnosed synchronously with lung cancer in 27 (57%) patients. Detection of lung cancer was incidental in 22 (47%) patients. The tumour was diagnosed at an early-stage, i.e. stage I-II, in 55% of cases. A pathological diagnosis of lung cancer was obtained for only 38 (81%) patients. Histological type was squamous cell carcinoma in 17 (36%) patients, adenocarcinoma in 14 (30%) patients, non-small cell lung cancer not otherwise specified in 3 (6%) patients, small cell lung cancer in 3 (6%) patients, and sarcomatoid carcinoma in one (2%) patient. There was no significant relation between tumor histology and location in the lung parenchyma (p=0.32). Overall, 20 of the 47 patients could not receive standard-of-care treatment for lung cancer, as per international recommendations and guidelines; this limitation was considered to be directly related to the CPFE syndrome in 8 (40%) cases. After a mean follow-up of 17 months, 35 patients were dead, and 12 patients were alive. Causes of death included locoregional or systemic tumor progression in 5 (14%) and 17 (49%) patients, respectively, respiratory failure in 8 (23%) patients, treatment-induced toxicity in 4 (11%) patients, and post-operative exacerbation of pulmonary fibrosis in 1 (3%) patient.

Conclusion
Lung cancer in patients with CPFE syndrome represents a specific entity characterized by very strong association with tobacco-smoking and male gender, peculiar histological-radiological presentation, poor prognosis due to major limitations and risks to conduct standard-of-care diagnostic and therapeutic interventions in a significant proportion of patients, and possible interest of screening. Lung cancer in CPFE syndrome further represents the most characteristic and severe model of tobacco-related disease.

Background
Maintenance treatment, with either bevacizumab or pemetrexed, has been shown to increase PFS and overall survival. Two trials have compared double maintenance (DM) therapy (pemetrexed + bevacizumab), to single drug maintenance (bevacizumab in AVAPERL and POINTBREAK studies). Conflicting results were found. Before definitive conclusions can be driven from these studies and other ongoing study (ECOG 5508), the purpose of our retrospective study was to determine in real world setting the frequency of double maintenance discontinuation for adverse event, and to describe the main toxicities occurring during double maintenance.

Methods
All patients who received at least one cycle of pemetrexed and bevacizumab as maintenance treatment were identified from the Oncology Pharmacy database of participating centers since year 2011. All the charts were analyzed retrospectively to obtain clinical data. Lab results were noted for haemoglobin, creatinine and liver enzymes before starting and after receiving multiple doses of pemetrexed and bevacizumab.

Results
Included were 87 patients treated with two to six cycles of induction chemotherapy (median 4), combining platinum with pemetrexed and bevacizumab, followed by at least one cycle of bevacizumab and pemetrexed as maintenance treatment. All patients received supplementation of vitamin B12 and folic acid during chemotherapy. Baselines characteristics (%): male 54: stage IV 96,5; adenocarcinoma 96,5; median age 58 yr. 57,8% of patients had objective response after induction chemotherapy, and 42,2% had stable disease after induction chemotherapy. At cut off date: treatment was still ongoing for 17 patients (19,8%); 40,6% of patients stopped DM for progressive disease; 33,3% of patients stopped DM for toxicity (out of these 33% of patients, 42% went on single maintenance with Pemetrexed and 58% with Bevacizumab); 11,6% of patients stopped DM for patient/physician decision, and 14,4% for other reasons. The most common toxicity responsible for DM discontinuation was renal failure (52%).

Reason for discontinuation (%)	POINTBREAK	AVAPERL	This study
Progressive disease	61,0	54,7	40,6
Adverse event	13,7	21,6	33,3
Others reasons	19,8	23,5	25,8

Conclusion
This retrospective study suggests that in real world setting, double maintenance is frequently discontinued for adverse event (33,3% of patients). The most frequent adverse event was renal failure (half of the cases). Further analyses are ongoing in order to identify any predictive factors for renal failure occurrence and will be presented at meeting. These results suggest that particular caution should be taken in order to preserve renal function whenever double maintenance (pemetrexed + bevacizumab) is considered in a patient with stable or responding tumour after induction chemotherapy consisting in platinum, pemetrexed and bevacizumab.

Background
Multidisciplinary team (MDT) meetings are seen as vital to delivering a coordinated approach to the care of patients who have been diagnosed with cancer. Use of an MDT model of care has been shown to increase patient recruitment to clinical trials, ensure a shortened patient journey from diagnosis to treatment, and result in a higher likelihood that the patient receives evidence-based treatment, ensuring better survival outcomes. Additionally, MDT’s are essential in ensuring correct diagnosis and staging, appropriate treatment modalities, and timely referrals to different disciplines within the team. The aim of this study was to analyse the reasons why respiratory cancer patients diagnosed within the Illawarra Shoalhaven Local Health District (ISLHD) have repeat presentations at MDT meetings.

Methods
Patients diagnosed with lung cancer (diagnosis included Small Cell Lung Cancer (SCLC), Non Small Cell Lung Cancer (NSCLC) and Mesothelioma) and discussed in the Lung Cancer MDT meeting in the ISLHD between 1st January 2006 and 31st December 2011 were identified. These identified patients were then cross-referenced against MDT meeting data stored in patient records. Patients identified as having been discussed more than once at an MDT meeting were analysed in relation to the documented reason for re-discussion.

Results
There were 533 patients presented in an MDT meeting within the six year period analysed. 463 were discussed once; 57 twice; 12 three times; and 1 four times. Of those discussed more than once, 10 had pathological diagnosis confirmed after the initial MDT presentation, and were re-presented to discuss these results and formulate a treatment plan. Of the 10 patients, reasons for presentation without pathological diagnosis included: non-diagnostic tissue sample or origin not specified (4); issues around comorbidities and most appropriate avenue for obtaining diagnosis (3); and protracted inpatient stay prior to pneumonectomy (1). Two patients were discussed prior to pathological diagnosis for no apparent reason. 31 cases were re-presented, as initial discussion recommended further investigation/staging. Of these, 18 had initial diagnosis/presumed stage confirmed, 8 were up-staged. After initial treatment was completed, 13 patients were rediscussed with regard to future treatment/monitoring, 10 due to an increase in symptoms and 15 due to disease progression. 50 of the cases discussed more than once resulted in the patient being referred to additional Specialists.

Conclusion
A review of five years of Lung Cancer MDT data has shown that the MDT meeting is performing its role as a central point for discussion of treatment options for lung cancer patients. In a small number of cases (1.9%) pathological diagnosis had not been confirmed prior to the MDT. For the majority of these patients (8), the meeting provided expert guidance in regards to the most appropriate timing and procedure to obtain tissue diagnosis. The MDT may benefit from the development of a template/pathway to ensure a reduction in the number of patients presented without pathological diagnosis and avoid discussion of some of the patients recommended for further investigation/staging. A template/pathway may enable the MDT to have a more complete picture of the patient’s diagnosis and reduce re-presentation/delays in treatment.

Background
Treatment with inhibitors of the Epidermal Growth Factor Receptor (EGFR) commonly results in rash, which causes patients significant symptoms and embarrassment, and is not always easy to manage with existing treatments. BN83495 is a first in class inhibitor of steroid sulphatase (STS), which has been used in early phase studies as treatment for steroid-dependent cancers such as breast, prostate and endometrial cancer, with one side-effect noted to be dry skin. STS converts oestrone sulphate to oestrone, a precursor of oestradiol; and dehydroepiandrosterone sulphate (DHEA-S) to dehydroepiandrosterone (DHEA), a precursor of adrenal testosterone. Blocking these pathways can be helpful in the treatment of acne, and patients with X-linked ichthyosis, who have an inherited deficiency of STS, do not get acne. Hence we hypothesized that use of BN83495 could help to treat EGFR-associated rash.

Methods
Eligible patients had histologically proven, locally recurrent or metastatic NSCLC and were continuing to experience rash during treatment with an EGFR-TKI (Erlotinib or Gefitinib), despite standard management. Patients were treated with BN83495 at a dose of 40 mg/day orally for a period of 12 weeks and able to continue on standard treatment for rash such as topical steroids or antibiotics. For patients with no or minimal toxicity and minimal or no rash at 12 weeks, treatment with BN83495 could continue for an additional 3 months before being discontinued. If rash worsened on discontinuation of treatment at 6 months BN83495 could be resumed. The primary objective was to describe changes in the frequency and grade of EGFR-related rash and other cutaneous side-effects of the EGFR-TKI with the combination. A pragmatic sample size of 20 patients was proposed.

Results
Nine patients were registered but 2 withdrew prior to commencing BN83495. All patients had grade 2 rash at study entry. Of the 7 patients who commenced study treatment, 5 had an improvement in rash by one CTC grade. Patients received BN83495 for a median of 12 weeks (range 1 – 52) with 2 patients recommencing drug after rash worsened when BN83495 was stopped after 6 months of treatment as per protocol. BN83495 was generally well tolerated with no grade 3 or 4 toxicity. However, all participants experienced grade 2 dry skin related to BN83495 which was generally manageable with moisturizers, but 2 patients stopped study drug early for this reason. 3 patients discontinued study drug when the EGFR-TKI was stopped due to disease progression, and 2 other patients elected to cease the drug at 3 and 6 months respectively because rash was mild. The study was closed early due to poor accrual as many patients were not keen to enter a study which involved treating rash by taking an additional tablet.

Conclusion
Treatment of EGFR-TKI related rash with the steroid sulfatase inhibitor BN83495 improved the severity of rash in the majority of patients but commonly resulted in grade 2 dry skin. Accrual to a study which involved treating rash with an additional oral medication proved challenging. Alternative approaches such as topical use of a steroid sulfatase inhibitor could be considered for further investigation.

Background
Comorbidity, such as diseases of the cardiovascular, pulmonary, and other systems may influence prognosis in lung cancer as well as complicate its treatment. The performance status of patients, which is a known prognostic marker, may also be influenced by comorbidity. Due to the close link between tobacco smoking and lung cancer, and because lung cancer is often diagnosed in advanced ages (median age at diagnosis is 70 years), comorbidity iwill be present in a substancial proportion of lung cancer patients.

Methods
Patients with any stage lung cancer who did not have surgical treatment were identified in the Danish Lung Cancer Registry (DLCR). DLCR collects data from clinical departments, the Danish Cancer Registry, Danish National Patient Registry (DNPR) and the Central Population Register. A total of 22,999 patients with lung cancer were identified. Due to missing variables, 19,561 patients were available for analysis. Comorbidity was sought in the DNPR which is a register of all in and out patient visits to hospitals in Denmark. By record linkage, all lung cancer patients who had previously been diagnosed with any of a number of comorbid conditions was recorded using the Charlsson comorbidity score CCS. First treatment was categorized as chemotherapy, chemo-radiotherapy, radiotherapy or no therapy. Data on CCS, performance status, age, sex, stage, pulmonary function (Fev1), histology and type of first treatment (if any) were included in univariable and multivariable Cox proportional hazard analyses.

Results
For patients receiving chemotherapy as first treatment for lung cancer, survival was increasing worsened by increasing comorbidity (HR=1,00,1.10, 1.17, 1,15 for CCS scores 0, 1, 2, 3+ respectively). After adjustment for potential confounders, risk estimates was reduced somewhat (HR: 1.00, 1.05, 1.11, 1.11 for CCS scores 0, 1, 2, 3+ respectively). For patients receiving radiotherapy as first therapy, a different pattern was seen with better survival for patients with comorbidity (HR=1.00, 0.99, 0.94, 0.87 for CCS scores 0, 1, 2, 3+ respectively). After adjustment, this effect disappeared and survival was unaffected by CCS. For patients receiving combined radio/chemo therapy there was no significant association between CCS and survival.Throughout the analysis, performance score remained a strong and highly significant risk factor for survival, and was robust in multivariate analysis (HRunivariate, all patients= 1.0, 1.40, 1.95, 3.23, 5.91 for ECOG performance score 0,1,2,3 and 4 respectively).

Conclusion
Comorbidity has a limited effect on survival and only for patients treated with chemotherapy. It is rather the performance of the patient at diagnosis than the medical history that prognosticates survival in this patient group.

Background
In 2007, lung cancer was the leading cause of cancer-related mortality and morbidity in Australia for both men and women. Only 14% of those diagnosed with lung cancer survive five years beyond their diagnosis. People living in rural areas, those from lower socio-economic status or from certain cultural and linguistic backgrounds have poorer outcomes. Factors contributing to differences in survival and outcomes are varied. Cancer Australia is developing a best practice model of care for the management of lung cancer that has national relevance and can be implemented locally, with the aim of achieving consistency in approach and improving lung cancer outcomes. This abstract describes how the evidence base has been built to inform the model of care.

Methods
A systematic review of international and national literature on patterns and models of care for lung cancer informed themes explored through qualitative and quantitative research. A tiered approach to data collection included: (i) mapping of lung cancer services across Australia; (ii) health service consultation through interviews and site visits; and (iii) consumer consultation through a national survey and targeted interviews. Findings were presented and discussed at a national workshop with clinical leaders, consumers, researchers and service delivery experts to review and define principles and elements of best practice care.

Results
The patterns of care literature for lung cancer identified variations in time to diagnosis, access to active treatment, re-treatment and palliative care. Service delivery themes identified through the review and research included multidisciplinary care, specialist involvement in diagnosis and treatment, care coordination, early integration of palliative care, uptake of guidelines and quality measures, involvement of primary care and consideration of supportive care needs. Lung cancer service mapping identified 192 services across Australia providing some elements of lung cancer care. Approximately two-thirds were public and one third private. Multidisciplinary teams were identified in 58 services (30%), the majority in metropolitan locations (n=41, 71%). Consumer consultation identified variations in time to first specialist appointment (two weeks to two months), definitive diagnosis (two weeks to three months); and treatment (one week to two months). Consumers identified that improvements could be made in the way information about lung cancer is communicated across all stages of lung cancer. Health service consultation highlighted challenges and best practice approaches along with a range of systemic issues that influence how care is delivered. Challenges included streamlining a complex diagnostic pathway, managing multidisciplinary teams that include cancer and non-cancer specialists, early referral to palliative care, coordinating care, involvement of primary care, and a lack of standard guidelines for follow-up care. Best practice examples were identified across the diagnostic and treatment pathway. Results informed a set of national principles including: patient-centred care; timely diagnosis and staging; multidisciplinary care; appropriate treatment and supportive care; coordinated care; and collection and monitoring of data.

Conclusion
This research identified gaps and variations in the delivery of lung cancer care and has built the evidence base to inform the development of best practice approaches to support the consistent diagnosis and management of lung cancer in Australia.

Background
There are limited data on the relative effectiveness of biosimilar ESAs and other available ESAs for the treatment of CIA. In addition, it is unclear whether the most recent recommendations for more conservative use of ESAs to treat CIA are reflected in real-world clinical practice

Methods
We analysed 73 patients with NSCLC who were included in a retrospective audit of CIA treatment with ESAs in a large oncology centre in Spain, with patients treated by multiple physicians. The patients were treated for CIA with Binocrit[®] 40,000 IU QW (n=12), Binocrit[®] 30,000 IU QW (n=6), darbepoetin alfa 500 μg Q3W (n=36) or darbepoetin alfa 150 μg QW (n=19). In addition to overall haemoglobin (Hb) outcomes, comparisons were performed according to the different ESA treatments given

Results
The mean overall haemoglobin (Hb) at start of ESA treatment was 9.4 g/dL; the mean overall Hb level at the end of treatment was 10.6 g/dL. 36/73 patients (49%) achieved a Hb increase of at least 1 g/dL. There were no significant differences (p>0.05) between the groups in terms of Hb levels at the start of ESA treatment. At the end of treatment, however, the mean Hb level in the group treated with darbepoetin alfa 500 μg Q3W was significantly lower than that in the other three groups (Table). No drug-related adverse events were recorded

ESA	Mean treatment duration (weeks)	Mean Hb at start of treatment (g/dL)	Mean Hb at end of treatment (g/dL)
Darbepoetin 150 μg QW	4.16	9.2	11.3
Darbepoetin 500 μg Q3W	4.59	9.4	10.1
Binocrit 30,000 IU	3.50	9.4	11.1
Binocrit 40,000 IU	3.67	9.5	10.7

Conclusion
Our data indicate that Hb outcomes in a real-world clinical practice setting are similar for the ESA treatments used with the exception of Darbepoetin 500 μg Q3W, which achieved a significantly lower Hb at the end of treatment. We consider the use of ESAs in our centre to be conservative and safe, and to reflect the most recent change in ESA prescribing information and recommendations for more moderated use in patients with CIA (that is, use the lowest possible dose and duration of treatment necessary to avoid transfusions)

Background
Background: Lung cancer patients have a higher level of disease burden, higher unmet psychosocial needs and lower uptake of psychological services compared with other cancer groups. The Department of Clinical Psychology, in collaboration with the lung cancer service at PeterMac, revised the model of psychological care to optimise access and improve psychosocial well-being.

Methods
Method: This revised model of care involved realigning the Psychology Outpatient Clinic to run in parallel with the Lung Outpatient Clinic. The aims were to: 1) provide a timely and early intervention service; 2) increase patient access to psychology services; 3) reduce the burden of accessing psychology services; and 4) assess psychological needs of patients and provide appropriate psychological interventions. Patient demographics, uptake, referral information and session data were collected for a three month period and compared to data from the same period in the previous year.

Results
Results: Our sample included a total of 37 patients with lung cancer. The results indicated that the revised model of service delivery led to: a 21% increase in new lung patient referrals for psychology services; an almost 100% uptake of services; and a 186% increase in the number of scheduled sessions attended by lung patients. The main reasons that patients attended sessions were to address mood fluctuations, loss and grief issues, relationship and existential concerns.

Conclusion
Conclusion: The revised model made a significant impact on meeting the previously unmet needs of this patient group through providing timely assessments and interventions. This highlights the potential effectiveness of integrating psychology services within medical cancer streams. We received no funding and there was no duality or conflict of interest

Background
Pleurodesis is a palliative procedure which main purpose is to alleviate respiratory symptoms of patients with malignant pleural effusion. Nevertheless, quality-of-life is an outcome rarely explored in literature. The main purpose of this study was to evaluate the quality-of-life before and 30 days after pleurodesis in patients with malignant pleural effusion. The secondary objective was to identify predictors of quality-of-life improvement after pleurodesis.

Methods
Retrospective study including all patients with recurrent malignant pleural effusion who underwent pleurodesis at Hospital das Clinicas (University of Sao Paulo) and Hospital Aristides Maltez from 2008 until 2012 and who filled out quality-of-life questionnaires before and 30 days after the procedure. In both institutions the World Health Organization-bref general quality-of-life questionnaire has been regularly applied to all patients undergoing pleurodesis since 2007. Paired T-test was used to compare before and after scores and multivariable regression models were used to identify predictors.

Results
During the study period 132 patients were included (26 men, 106 women, mean age 58.1 +- 11.8). The primary tumors were: breast (84), lung (25), ovary (4), lymphoma (11) and other (8). The mean prepleurodesis quality-of-life scores were: physical domain 35.8+-17.7, psychological domain 58.8+-17.7, social domain 52.8+-14.8, and environmental domain 65.4+-18.8. Thirty days after pleurodesis, the physical aspect (8.1 pts, p=0.0001) and the environmental domain (3.6 pts, p=0.008) improved significantly while the other two domains remained unchanged. Predictors of improvement of quality-of-life in this sample were: ovary cancer (p=0.015), pleural fluid glucose (p=0.012), and low physical aspect score before pleurodesis (p=0.001).

Conclusion
All aspects of quality-of-life are deeply compromised in patients with recurrent malignant pleural effusion. Pleurodesis improves quality-of-life thirty days after the procedure particularly in patients with ovary cancer and with very low physical status scores.

Background
Patients with advanced lung cancer suffer from a high burden of tumor-related symptoms. Thus palliative care is an important treatment modality in these patients. Palliative care units have been established in many comprehensive cancer centers in order to achieve this. Here we report on the experience we have obtained at the Palliative Care Unit of the Medical University of Vienna in the management of patients with advanced lung cancer.

Methods
We retrospectively reviewed medical records of 86 patients with advanced lung cancer who were treated at our Palliative Care Unit between June 2010 and March 2013. We determined reasons for admission, duration of hospitalization, non-invasive as well as invasive medical interventions, and clinical outcome.

Results
We report on 86 patients with advanced lung cancer (74 % NSCLC, 26 % SCLC) who had been admitted to our Palliative Care Unit within a period of 34 months. Lung cancer patients comprised the largest group of cancer patients who are admitted to our unit. Reasons for admissions were deterioration of performance status (41 %), dyspnea (13 %), pain (38 %), psychosocial reasons (7 %), and other (1 %). Re-admissions occurred in 20 % of all patients. The patients had the following characteristics: median age 62 years (range 42-85 years), 38 % females and 62 % males, ECOG performance status 0-2 38 % and >2 62%, median body mass index (BMI) 24 (range 14-39). Median duration of hospitalization was 16 days (range 1-101 days). The following treatments were delivered during hospitalization: analgesic treatment according to the WHO I-III ladder (85 %), palliative radiotherapy (31 %), palliative chemotherapy (7 %), and invasive procedures (such as thoracocentesis, pleurX drainage system, pleurodesis, bronchial stenting, invasive neurolysis and other in 26%). Antibiotic therapy was delivered in 33 % and antipressants or antipsychotropic drugs in 38 % of all patients. Palliative sedation by means of a continuous intravenous or subcutaneous infusion with midazolam was administered in 25%. Dietary counseling and spiritual as well as psychosocial support was offered to all patients and accepted by most of them. 77 % of all patients died during their stay, mostly due to disease progression. The remaining 23 % of all patients were discharged with improvements in their tumor related symptoms or stable disease and were offered home care or hospice access.

Conclusion
Patients with advanced lung cancer did benefit from admission to the Palliative Care Unit. Medical as well as non-medical interventions resulted in improvements of cancer-related symptoms and better coping with the disease. Thus Palliative Care Units should be part of the multidisciplinary management of patients with advanced lung cancer. Schur S and Masel EK contributed equally to this work

Background
Non-small cell lung cancer is associated with a higher risk of thromboembolic events in comparison with SCLC. Adenocarcinoma represent roughly 75% of NSCLC patients. Lung adenocarcinomas harboring EGFR and KRAS mutations as well as EML4/ALK rearrangements represent distinct subsets of this disease. No data are available concerning the prevalence of pulmonary embolism in lung adenocarcinoma patients with these mutations. The aim of the study was to evaluate the prevalence of pulmonary embolism in patients with stage IIIB and IV lung adenocarcinomas harboring EGFR and KRAS mutations as well as EML4/ALK traslocations.

Methods
Patients with stage IIIB or IV NSCLC referred to Division of Medical Oncology at the Hospital of Perugia between 2008 and 2012 were included in the study. In these patients, contrast-enhanced CT scans of the chest were reviewed for the presence of pulmonary embolism by a panel composed by three radiologists. In the same patients, data regarding the molecular characteristics (EGFR exons 18-21 and KRAS exon 2 mutations as well as EML4/ALK traslocations) were collected.

Results
A total of 209 patients with stage IIIB or IV NSCLC were included in the study. A histologic diagnosis of lung adenocarcinoma was done in 173 patients (82.7%). In 127 of these patients sequence analysis for known EGFR (exon 18-21) and KRAS (exon 2) mutations was performed. In this population 31/173 patients were EGFR mutated (17.9%), 27/173 were K-RAS mutated (15.6 %) and 17/173 were EML4/ALK positive (9.8%). 41 patients with lung adenocarcinoma had a diagnosis of pulmonary embolism at CT scan (23.7%). Of these, 34.1% had no oncogene mutations in comparison with 28.8% of the patients without pulmonary embolism. Of the 41 patients with a diagnosis of pulmonary embolism 12.1% had an EGFR mutation and 12.1% a KRAS mutation, in comparison with 19.7% and 16.6% of patient without pulmonary embolism, respectively. In patients with lung adenocarcinoma, EML4/ALK rearrangements was observed in 19.5% among patients with pulmonary embolism and in 6.8% among patients without it. The risk of pulmonary embolism was 3.3-fold higher in presence of EML4/ALK rearrangements in comparison with no EML4/ALK rearrangements [OR: 3.3 (95%CI 1.2-9.2)].

Conclusion
In lung adenocarcinoma patients, the presence of EML4/ALK traslocation seems to be associated with a high risk of pulmonary embolism and could help in identifying patients at particular high risk who might benefit from an antithrombotic prophylaxis. These preliminary data need to be confirmed by further studies.

Background
Nitrogen-containing bisphosphonates(N-BPs) are usually administered to patients with advanced cancer harboring bone metastases to prevent skeletal related events(SREs). Preclinical studies have demonstrated the anticancer activity of N-BPs in vitro and in vivo. Zoledronate (ZOL) is a type of N-BP, and clinical trials of ZOL have demonstrated survival benefits in breast cancer and multiple myeloma. However, the benefit of ZOL to overall survival for lung cancer patients is still controversial. The first administration of intravenous N-BPs are occasionally induced fever, which is due to the activation of γδ T cells. γδ T cells are a small subset of T lymphocytes that play an active role in the immunosurveillance against infections and tumors as components of innate immunity. However, the significance of ZOL-induced fever is not clear in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to estimate the prognostic value of fever after N-BP administration in advanced NSCLC patients.

Methods
We retrospectively reviewed 46 patients with advanced NSCLC who recerved ZOL treatment from March-2009 to March-2011 in the department of respiratory medicine in Tottori University hospital. ZOL-related fever was defined as body temprature more than 37.5℃ within 48 hours after the first administration of ZOL. Fever that persister for > 2 days, or treated with antibiotics were not defined as ZOL-related fever. Even if there were records of ZOL administration, we excluded the case with no record in terms of fever after treatment with ZOL. We analysed patients who had Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≦ 1. Clinicopathological factors such as age, gender, smoking history, disease stage, histological type, and epidermal growth factor receptor (EGFR) mutation status were analyzed using univariate and multivariate analyses, and these factors were compared between the fever group and non-fever group.P-value of < 0.05 were considered statistically significant.

Results
Fifteen out of 46 patients (32.6%) experienced fever after the first administration of ZOL. No significant differences in clinicopathological characteristics were seen between the two groups. The mean survival time (MST) observed in the fever group [MST 1003 vs. 471 day, hazard ratio (HR) 2.15, p=0.04] was significantly longer than the non-fever group. Univariate analyses for the probability of overall survival indicated that a positive EGFR mutation status (p=0.016), non-squamous type of cancer (p=0.02), no smoking history (p=0.001), and female gender (p=0.036) were predictors of significantly longer survival time. Comparatively, the presence of fever after ZOL administration [HR, 2.73; 95% confidence interval (CI) 1.17-6.34, p=0.020] and having no smoking history [HR, 0.13; 95%CI 0.20-0.85, p=0.033] were still significant predictors for longer survival time in multivariate analyses.

Conclusion
Fever after the first administration of ZOL was an independent prognostic factor in patients with advanced NSCLC.

Background
Lung cancer is the main cause of cancer death for both men and women in Australia. Non-small cell lung cancer (NSCLC) usually presents late in the disease when treatment options are limited. Surgery remains the main stay of curative treatment with definitive radiotherapy or chemoradiotherapy used in some patients unfit for surgery or with locally advanced disease. Increasing use of chemotherapy with introduction of new targeted therapies has broadened the therapeutic choices for patients. We wished to look at what happened to patients with NSCLC in our hospital (RHH)

Methods
An audit was performed of patients presenting at our MDT (at which all patients with lung cancer in southern Tasmania are discussed) in 2010 and 2011 with a diagnosis of NSCLC. We looked at the type of therapy assigned (or not) and where they had chemotherapy the number of lines and types of treatment given.

Results
177 patients presented with NSCLC. Histology showed 99 adenocarcinomas, 48 squamous cell, 20 NSCLC-NOS, 5 large cell neuroendocrine, 3 adenosquamous cell and 2 with synchronous primaries. 48 (27%) patients received no treatment beyond palliative care. Mostly this was due to comorbidities or patient wishes (8) but 13 (7%) patients died around the time of diagnosis. 38 (21%) patients underwent surgery (3 pneumonectomies, 31 lobectomies and 4 wedge resections). 3 had adjuvant radiotherapy and 5 had adjuvant chemotherapy. 79 (45%) patients under went radiotherapy: 59 had palliative radiotherapy, 12 chemoradiotherapy, 4 definitive radiotherapy, 1 brachytherapy and 3 had adjuvant radiotherapy to surgery. 84 (47%) were reviewed by medical oncologist of whom 56 (32% of total, 67% of those reviewed) received some form of 1[st] line chemotherapy. There were 13 different regimens of first line therapy, most common being carboplatin/gemcitabine (n=19) and carboplatin/vinorelbine (n=10). The reason for choice of therapy was not usually stated and varied between specialists but individual specialists also varied regimens used. 22 patients had 2nd line therapy, 12 patients had 3[rd] line and 5 patients had 4[th] line. 16 patients had pemetrexed maintenance therapy (1 in combination with carboplatin) of which 9 received 3 or less cycles, 1 patient received 26 cycles. 13 (7%) patients received erlotinib. The patients were reviewed by 7 different specialists (3 were seen elsewhere in the state) with one specialist seeing 36 patients but 4 seeing less than 10 over the 2 year period.

Conclusion
The majority of our patients received some form of therapy. Our radiotherapy usage is below expected numbers and chemotherapy usage is particularly low. This may reflect our patients’ demographics. The wide variety of first line regimens used makes over all conclusions about the effect of chemotherapy difficult. A number of medical oncologists treat less than 5 patients with lung cancer a year. Consolidation of care to a smaller number of specialists should be considered.

Background
Cicatricial fibromatosis arises in a surgical scar is a well-known clinical condition. However, its occurrence after thoracic surgery, especially at bronchial stump. is extremely rare.

Methods
42 years old male patient had undergone video assisted thoracoscopic right lower lobectomy 18 months earlier for primary lung cancer. There was no evidence of recurrence in last chest CT examination until 9 months ago. A 33mm sized mass was found beside right lower lobe stump margin in subcarinal space in chest CT examination. It had increased uptakes (SUVmax 6.5) in F-18 FDG PET/CT imaging. There were not any findings of distant metastasis in chest CT and F-18 FDG PET/CT imaging. Therefore we thought it would be a local recurrence of lung cancer at bronchial stump site. We performed biopsy of a mass using EBUS and EUS to confirm the diagnosis. The results were only fibrotic tissue without evidence of malignancy. So he had undergone a complete excision of subcarinal mass through thoracotomy. It was very hard and tightly adhesive to surrounding tissues, as bronchus and esophagus. Figure 1

Results
Pathologic report was that it was myofibroblast proliferation with infiltrative margin, which was diagnosed as cicatricial fibromatosis.

Conclusion
In this case, Cicatricial fibromatosis beside bronchial stump margin were suspected to a local recurrence. It has increased uptakes in PET-CT imaging, like as cancer recurrence. It should be completely excised as soon as possible because it is growing infiltrative to surrounding tissues and it would recur sometimes.

Background
Endothelial Growth Factor Receptor (EGFR) mutation testing is now recommended practice for lung adenocarcinoma. Those patients with EGFR mutations are eligible for targeted agents which offer survival and quality of life advantages with reduced toxicity in some. Several reports have suggested particular samples are more likely to give reliable EGFR mutation results than others. We were interested in investigating the types of samples locally that were viable for testing and to assess the population rate of EGFR mutation positivity in adenocarcinoma for which there is little published data in Australian (mainly Caucasian) populations.

Methods
Data was systematically collected for tissue samples sent for EGFR mutation testing over a three year period. Basic demographic data, sample type and test results were recorded. Testing was performed as part of the routine workup for patients with lung adenocarcinoma. Chart review was undertaken to clarify sampling methods and test results if required.

Results
214 sequential specimens from patients with proven adenocarcinoma were sent for analysis of the presence of EGFR mutation. 197 specimens were of adequate quality for analysis (>20% of specimen composed of tumour cells). There were 22 positive tests for EGFR mutations (16 female; 11 non- or never-smokers). Table 1 outlines the types and adequacy of specimens collected for testing. There was no association between specimen type and adequacy for analysis. 27 specimens were unable to be analysed. Of these 12 were labelled failed tests and 15 returned incomplete results for at least one of four exons. 17 specimens were labelled inadequate for testing; 9 of those were reported as negative for EGFR mutations despite being reported as having less than 20% tumour cells in the specimen. 6 of 12 failed tests were adequate for testing. 14 of 15 incomplete tests were adequate for testing.

Specimen Type	Number collected (% of total)	Number of specimens with >20% of tumour cells in specimen (% of number collected)	Number of failed or incomplete tests
Image guided FNA Bx	27 (12.5)	25 (93)	5
Image guided core Bx	16 (7.5)	15 (94)	3
Bronchial Bx/TBNA/EBUS/TBLB (bronchoscopy)	89 (42)	78 (88)	11
Lung/Pleura/Pericardium/ Mediastinal LN Bx (surgical)	49 (23)	48 (98)	5
Pleural fluid	9 (4)	8 (89)	0
Surgical LN Bx	4 (2)	4 (100)	0
Abdominal/oesophageal node	3 (1.5)	3 (100)	0
Brain/ cerebellar metastasis	11 (5)	10 (91)	1
Musculoskeletal metastasis (surgical)	6 (3)	6 (100)	2
	214 (100)	197 (92)	27 (13%)

Conclusion
In our population (majority Australian born Caucasians), the percentage and profile of EGFR positivity is similar to that reported in other studies. Representative samples can be obtained from many different types of tissue, in particular, fine needle aspirates and core biopsies of lung parenchyma and lymph nodes as well as from pleural fluid.

Background
Lung cancer is the most common cancer related death and the fourth most common cause of death in Germany. The five-year survival rate in European and North American countries is in between 5,5% and 15,7%. In the last couple of years though, significant progress has been made concerning personalized medicine in this disease entity. Novell targeted therapies with tyrosin kinase inhibitors (TKI) for patients with a mutation in the EGFR gene offer a new treatment option.

Methods
A 78-year old male patient was referred to the Thoraxklinik Heidelberg with atypical thoracic pain after cardiologic assessment. In 2001 he was given the diagnosis of pulmonary adenocarcinoma of the right upper lobe in the Asklepios Hospital Munich-Gauting. Because of his overall good clinical condition the patient had declined any treatment to this point. A new PET- CT was conducted and compared to the computer tomography of 2001 revealed a significantly grown lesion in the right upper lobe as well as new, small bipulmonar lesions suspicious of lung metastasis.

Results
A new histological assessment was performed on an endobronchial forceps biopsy of the now occluded right upper lobe. The diagnosis of a partial lepidic differentiated adeno-carcinoma was consistent with the diagnosis as well as the preserved specimens of 2001. We were able to perform an EGFR mutation analysis of the 2001,- as well as of the new tumor specimens through PCR-amplification and bidirectional sequencing of exons 18, 19 and 21. In each of the probes we detected a deletion combined with an insertion c.2127_29del (p.E709_T710delinsD) in exon 18.

Conclusion
The above mentioned mutation has already been described in the literature but there is no information concerning the responsiveness of tyrosine kinase inhibitors in this particular mutation. Now that the cancer had spread we decided to start treatment with erlotinib. Due to cutaneous side effects the patient decided to discontinue this therapy. Since then he has been in regular follow-up showing a stable disease and good general state of health.

Background
Lung cancer is one of the most appalling diagnoses, associated with significant patient distress, poured quality of life and often limited survival. Moreover, the current literature emphasizes the effect of distress level on survival rates. The purpose of this study was to explore the survival curve, considering the distress level reported by patients with advanced NSCLC cancer at the beginning of the treatment.

Methods
A sample of 24 patients with newly diagnosed stage IV NSCLC, answered the Distress Thermometer (DT) and the Problem List (PL) before start the first chemotherapy infusion. They treated at a private cancer center, located at Brasília, Brazil. Survival was calculated from time of the histopathological diagnosis. The data was analyzed with descriptive evaluation, followed by Kaplan-Meier models, to test associations with survival and distress.

Results
Figure 1Of those patients, 58.3% were male. They were between 54-81 years old (M = 66.2; SD = 6.6); 62.5% were married; 54.2% had at least college degree. The NSCLC were 87.5% adenocarcinoma and 12.5% epidermoid. The survival rate was 10.7 months for all patients (range from 1 to 50 months; SD = 10.7); being 6.4 months for moderate to severe distress and 14.2 for mild distress. Seven types of chemotherapy regimen were prescribed: Cisplatin+Gemcitabine (45.8%); Alimta+Carboplatin (16.7%); Carboplatin+Taxol+Avastin (8.3%); Erlotinib (8.3%); Taxol+Carboplatin (8.3%); Cisplatin+Alimta (8.3%); Cisplatin+Gemcitabine+Avastin (4.2%). Half of patients (54.2%) reported moderate to severe distress (DT ≥ 4). The most problems reported at PL were worry (70.8%), sadness (66.7%), fears (45.8%), sleep (70.8%), fatigue (66.7%), pain (58.3%), eating (50%) and breathing (50%). Considering the survival curves, patients with mild distress showed better survival rate than patients with moderate to severe distress (x[2] = 4.16; p = .04).

Conclusion
Despite the limited sample size, the data suggest that mild distress is a prognostic factor in survival rate. The high prevalence of patients with moderate to severe distress, as well as, the problems-related distress, highlighted the importance of the distress screening and also to create an advanced care planning for patients with lung cancer, from the time of diagnosis until the last phase of illness, helping them to cope with this reality. More studies are thus needed to investigate the implication of distress level at diagnosis as a prognostic factor, increasing and diversifying the sample in order to make the data more generalizable.

Background
Although lung resection still provides the best long-term outcome for lung cancer, it is also associated with a considerable decay of physical and psychosocial health status. Physical activity (PA) is considered beneficial for post-surgery recovery, and patients often are encouraged to increase PA in daily life. Surprisingly, only few studies objectively assessed daily PA in lung cancer patients, and none of these studies examined possible associations between daily PA and recovery of health status following lung resection. Therefore, our study aims to explore the relationship between daily PA and recovery of physical and psychosocial health status in lung cancer patients treated with lung resection.

Methods
Lung cancer patients undergoing curative lung resection at the Nederlands Canker Institute-Antoni van Leeuwenhoek Hospital in Amsterdam are enrolled in the study before surgery (T0). Follow-up measurements are scheduled at 1 (T1), 3 (T2) and 6 months (T3) post-surgery. PA levels are measured for three days on all occasions using a triaxial accelerometer and expressed as amount of activity in counts per minute. Secondary outcome measures include VO~2~max, pulmonary function, six-minute-walking-distance, times standing on the 30-seconds-chair-stand test, quality of life, mental distress, fatigue, and pain. The aim is to include 60 patients by October 2015.

Results
So far, fourteen lung cancer patients (6 male; mean age 65.4±10.4 yrs) are included in the study. Ten patients underwent lobectomy, four segment resection, while no patients underwent pneumectomy. Four patients dropped out due to comorbidity (n=1), disinterest (n=1), and inability to perform the measurements (n=2). First analyses show that both physical and psychosocial health are worse one month post-surgery, but improve during the following five months (table 1). Activity patterns from pre-surgery to 6 months post-surgery of the included patients are being analysed at the moment. Figure 1

Conclusion
As was expected from earlier research, physical and psychosocial outcome measures worsened following lung resection, but returned to baseline levels at 6 months post-surgery, except of VO2max. At this moment, we cannot calculate associations between daily PA and secondary outcome measures yet. However, patients are actively recruited and enrolled, and at the time of the conference we will be able to draw more firm conclusions about possible associations between daily PA and recovery of health status following lung resection.

Background
Use of tyrosine kinase inhibitors is a attractive option due to its predicatble profile of side effects & it been a oral tablet. Its efficacy and toxicities have been well described in both east asian and western population. However not much literature is available on its use from India. The aim of this paper was to audit the population which received TKI (Erlotinib or Gefinib) in a tertiary cancer center in India.

Methods
All patients who received TKI in lung cancer were identified from our OPD database. There case records, electronic medical records & our OPD databases were utilized. The demographic profile, the staging details , details of EGFR mutations, the RECIST response rates, the toxicities, progression free survival (PFS) & overall survival (OS). SPSS 16 was used for statistical analysis.

Results
Total of 105 patients were identified with a median age of 58 years (35-77 years). There were 56 females (52.8%). The 15.2 % (16) of patients were smokers & 22.3 % (18) were tobacco chewers. The median duration of smoking & tobacco chewing was 25 & 15 years respectively. All patients had stage IV disease. There were 2 cases of squamous cell carcinoma (1.9%)& rest all were adenocarcinomas. (98.1%) Extrathoracic disease was present in 42 patients (39.6 %) The EGFR mutation invoved exon 19 , 21 & 18 in 25, 72 & 8 patients respectively. The ECOF PS was 0 & 1 in 14 (13.2%) & 51 (48.1%) patients respectively.The incidence of any grade skin and mucosal toxicites were 53% & 38% respectively. The median PFS & OS overall were 11.1 & 21 months respectively. The PFS & OS were not affected by the performnce status, comorbidities & sites of metastasis

Conclusion
Use of TKI in Indian population had similar toxicity & efficacy as reported in literature.

Background
SBRT is an emerging technique, with numerous advantages over classical radiotherapy, namely in high surgical risk patients.

Methods
Critical review of a clinical case

Results
The authors report the case of a 37 year-old man, type 1 Neurofibromatosis patient, with dorsal paraplegia secondary to paravertebral tumours, severe kiphoscoliosis, and chronic hypercapnic respiratory failure requiring continuous non-invasive ventilation (NIV) since 2007. He was also medicated with Baclofen 125mg/day and botulinum toxin for severe spasticity, with poor response. In May 2010, he was diagnosed with testicular malignancy, which has undergone radical resection under local anaesthesia. In June 2010 he was submitted to a follow-up CT scan, which revealed a 9mm pulmonary nodule on the right upper lobe that remained under supervision, due to the risks of invasive diagnostic procedures. In January 2012, because of a significant size increase, a CT scan-guided biopsy of the lesion was performed, which revealed a lymphoepithelioma-like carcinoma. Subsequent CT-scans demonstrated progressive growth of the neoformation (4.9cm in July 2012) with invasion of the thoracic wall, and the PET/CT scan revealed FDG-F18 hyper fixation. Due to the comorbidities, and the need for continuous NIV, he had no surgical, chemotherapy or classical radiotherapy conditions. The remaining treatment option was SBRT. Therefore, a planning 4D-CT scan with a vacuum mattress for immobilization was performed, and a therapy plan was defined to deliver a total dose of 48Gy, in four fractions of 12Gy, in alternate days, with support of Image-Guided Radiation Therapy (IGRT) technology. There was a good clinical and haematological tolerance, no acute or late complications were referred, and the 6 months follow-up CT-scans showed partial response, according to RECIST criteria.

Conclusion
SBRT is nowadays a valid alternative for lung cancer treatment in patients with medical contraindications to surgical treatment, demonstrating a high local control of the lesion, associated with low toxicity effects. Figure 1Figure 2

Background
Discussion of patients at multidisciplinary meetings (MDMs) is now considered the standard of care for management of thoracic malignancies. However, there is limited evidence regarding concordance of decisions made at MDMs with subsequent actual treatment. This study aimed to assess the concordance between MDM outcomes and subsequent treatment received by patients with thoracic malignancy at our centre, and to identify factors that contributed towards any deviation from the MDM management plan.

Methods
In this retrospective audit, patients discussed at 12 Auckland City Hospital MDMs between 1[st] May and 31st July 2012 were identified, using the MDM lists for each session and chairperson summaries of discussion and decisions. The electronic cases records of these patients were then reviewed for demographical data, information on the MDM outcome and to ascertain the eventual treatment received by these patients. Any discrepancies between MDM recommendations and eventual patient management were noted, and the reasons stated for this.

Results
There were 121 cases identified from 138 documented patient presentations; 17 patients were re-presented within the study period, and the presentation at which anti-cancer treatment was determined was analysed (if achieved). Of the 121 cases, 93 included a pathologically confirmed diagnosis (80 primary lung or pleural tumours, 13 other tumours or pulmonary metastases), and 28 did not, including 4 with suspected malignant pleural effusions. A decision for radical therapy was made for 22 cases at the MDM. 18 of these cases received treatment as determined at MDM: 13 of 15 surgical resection, 1 of 3 radical radiotherapy, 3 of 3 radical chemo-radiotherapy, and 1 was deemed not to need adjuvant chemotherapy. A decision for one or more palliative treatments was made for 72 cases. Of these, the MDM determined treatment was actually received in 41 (57% of cases): 5 of 7 palliative surgery cases (1 died pre-op, 1 patient declined), 18 of 28 chemotherapy as initial treatment, and 13 of 23 radiotherapy as initial treatment. In 14 cases with an MDM decision recorded recommending both palliative chemotherapy and radiotherapy, 5 received both modalities, 7 radiotherapy alone and 2 neither. Reasons for discordance between MDM decision and treatment included patient deterioration or poor performance status (n=14), patient choice (n=8), patient and doctor agreed choice (n=5) and did not attend/lost to follow up (n=4) In the remaining 27 cases, best supportive care was recommended in 7 and no definitive treatment decision was able to be made in 20.

Conclusion
This study demonstrated excellent concordance between decisions made for radical therapy at the MDM and actual treatment. Concordance was less for palliative therapies, and this is likely to reflect on the poorer performance status of these patients at presentation and the perceived benefit versus adverse effects of palliative measures to the patient and the clinician. Since this study, a standardised electronic MDM template has been introduced to ensure accurate and complete information is available.

Background
Lung cancer is the second cause of cancer death in Vietnam. Most of patients with lung cancer are non small cell (90%) and present at advanced stage. Erlotinib was the first EGFR TKI permitted to be used for advanced stage non small cell lung cancer in Vietnam since 2007. Safety and efficacy of this treatment has never been reported in Vietnamese patients. We present the first case report of erlotinib in Vietnamese advanced-stage non small cell lung cancer patients to study the safety and the efficacy of this treatment.

Methods
From 12/2007 to 12/2011 advanced stage (wet IIIB and IV) non small cell lung cancer patients diagnosed at Cho Ray hospital were prescribed erlotinib as (1) second/third line treatment or as (2) first line treatment only if they could not use standard, state of the art chemotherapy after well informed about different treatment options.

Results
High overall response 35.5%, median progression free survival of 7 months, median overall survival of 11 months and 1 year survival rate 50% were seen in 31 patients using erlotinib. These results were similar to East Asia patients but better than ones of Caucasian patients. Common adverse events were rash and diarrhea, severe adverse events were rare.

Conclusion
Erlotinib had high efficacy and low toxicity in Vietnamese patients like East Asian patients.

Background
VATS lobectomy for Non-small cell lung cancer usually can be performed using one working window, and two or more ports for endoscopic instruments. The working window are made on the intercostal space space. However, these narrow Intercostal space could be the obstacle for the extraction of congested or huge resected lung lobe. So, we performed VATS lobectomy using 3 interocostal ports and the 3 cm subcostal incision.

Methods
Since March 2012, In Korea University Ansan Hospital, 20 VATS lobectomies was done for lung cancer. Of 20, we performed 4 cases of subcostal incision VATS lobectomy. At first, we performed entire procedure through the intercostal ports (10mm). After resection of lung, the subcostal incision (3cm ) was made anterior to the 10th rib. Because the 11th costal cartilage is abscent, there is no limitation during spreading the 10th intercostal space for the extraction of resected lung (Fig 1). And then, we dissect mediastinal lymph nodes systemically. During the subcostal incision, rectus muscle is resected partially. And the chest cavity was entered through the costophrenic junction. So,at the end the repair of diaphragm is needed. The chest tube can be placed properly through one of the intercostal ports.

Results
The characteristics of patients is summerized in Table 1.Of 4 cases of subcostal incision lobectomy, one case should be conversed to the anterior thoracotomy.That case was 6.5cm sized right middel lobe tumor.In the third case, we used two intercostal ports and one subcostal incision. In the question of post operative intercostal pain at operation day, patients did not complain severe pain (more than VAS score 5). However, we did not compare the pain score after this operation with conventional VATS lobectomy.

Talble 1.The patient's characteristics

Case No.	G/A	Lobe	Tumor size	LND	pTNM	3 ports	subcostal
1	M/67	LLL	3.5cm	30	T2aN0M0	5th/6th/7th	3cm
2	M/62	LUL	3.5cm	16	T2aN0M0	4th/6th/6th	3cm
3	F/69	RUL	1.8cm	47	T1aN1M0	5th/6th	3cm
4	F/43	RML	6.5cm	29	T2bN2M0	5th/6th/6th	1cm

Figure 1 Fig 1. Three intercostal ports (10mm) and one Subcostal incision (3cm)

Conclusion
The subcostal incision for extraction of lung specimen was useful in VATS lobectomy.

Background
Ranking hospitals, publishing reports of high and low performing facilities, and altering reimbursement for outlier sites is becoming common in many areas of healthcare. We explore challenges of profiling hospitals on appropriate use of advanced imaging in lung cancer care.

Methods
We identified 17,325 patients with newly diagnosed lung cancer over a 4 year period from the Veterans Health Administration’s Central Cancer Registry, of whom 5,424 (31%) were Stage IIB, IIIA, or IIIB and treated in one of 84 VA Medical Centers. Imaging was assessed 180 days pre and post diagnosis per National Comprehensive Cancer Network guidelines and American College of Radiology Appropriateness Criteria for Imaging. Risk-adjusted hospital rankings were estimated using a hierarchical logistic modelling approach.

Results
Recommended imaging was performed in 70% of patients overall for brain imaging and 51% of patients for positron emission tomography (PET). Overutilization, with combined bone scintigraphy and PET (BS/PET), occurred in 20% of patients. Widespread variation in non-adherence to guidelines was observed, with distinct geographic patterns. The New England region of the U.S. had imaging rates that were 27 percentage points higher than the Great Plains area, which had the lowest use of imaging. Receipt of recommended imaging ranged from a low of 61% of patients in one facility, to 94% in the best performing facility. Models calculating traditional observed-to-expected ratios identified 6 (7%) underperforming facilities, while hierarchical logistic models recommended by Centers for Medicare and Medicaid for hospital profiling, identified 14 (17%) underperforming facilities.Figure 1.

Conclusion
A significant proportion of patients do not receive recommended imaging, while other patients appear to undergo excessive imaging for lung cancer. These observations are hallmarks of poor quality. Hospital ranking and assessment of performance is sensitive to statistical approach. Lung cancer care providers should engage in developing uniform approaches to reporting and monitoring quality of care, and work to identify opportunities to improve efficiency and reduce waste.

Background
Five full-time doctors are sent to 5 affiliated hospitals from University Hospital of Kyoto Prefectural University of Medicine. To conduct a surgery in the affiliated hospitals, a doctor is sent from the university, for ensuring an efficient and secure medical care with limited members. Until now, each hospital performed surgeries in its own way. However, to perform safer and efficient surgery with a limited number of operating room nurses and thoracic surgeons, they need to work as one team. We report the standardization of thoracic surgery procedures.

Methods
First, to understand the current situation at each affiliated hospital, we survey all aspects of surgical procedures. Subsequently, we held 5 meetings among the group and standardized the surgical procedures. A thoracic surgeon and 3–4 operating room nurses from each hospital joined in the discussion. The topics of the discussion covered all aspects of surgery and methods from each hospital were analyzed and standardized. We have already standardized the thoracoscopy system and energy device in all hospitals. We also standardized the main surgical instruments and methods in these meetings. The content of the standardized main surgical procedure was thoroughly explained in a video distributed to each hospital in DVD format. We evaluated the frequency of use of the surgical instruments and excluded rarely used items. To increase the understanding on automatic suture instruments and energy device, the important usage points were shared in the meeting. Nurses were trained on the usage. In the 6[th] affiliated hospital meeting, a questionnaire was conducted to survey the awareness of this approach.

Results
The amount of time required from entering the operating room to starting the surgery was shortened from 62 to 55.5 minutes (average). The time required from the end of surgery to exiting the operating room was also shortened from 46.1 to 38.7 minutes (average). The difference among hospitals was successfully reduced. Because the main surgical instruments and methods were standardized, almost the same level of surgery could be performed in each hospital. Surgical instruments were reduced from 48.3 to 41.1 types (average). Total number of surgical instruments was successfully reduced from 91.8 to 73.5 items (average). In the questionnaire, all members referred to other hospitals devices, and they will attempt productions of their own device. All members confirmed improved understanding on thoracic surgery and 88% confirmed increased interest in thoracic surgery．

Conclusion
Standardization of the surgical procedures improved the workflow, enabled safe and efficient surgery among the affiliated hospitals, and increased awareness of the importance of workflow improvement. Change in awareness toward thoracic surgery was observed among participating members, suggesting that the present approach is highly useful.

Background
Background Radiation induced oesophagitis (RIO) is a significant toxicity of lung cancer treatment that has profound clinical, social and economic implications. The literature suggests there is minimal evidence to support current analgesic regimes with the exception of systemic analgesia. More information is required to better understand the patient experience of RIO and how it can be managed. Aim To identify the properties and characteristics of RIO experienced by patients having radiotherapy to the chest for lung cancer.

Methods
Methods A qualitative exploratory study conducted with patients with lung cancer receiving radiotherapy to the chest. Patients participated in semi-structured interviews exploring their experience of RIO. Interviews were recorded, transcribed and content analysed.

Results
Results Twenty six patients participated: six with grade 1; 14 with grade 2 and eight with grade 3 RIO. Patients were interviewed following recovery from grade 3 RIO. Four key domains were identified: 1.Pain descriptors such as “feels raw “, “burning”, “like reflux but worse” were reported 2. Swallowing difficulties varied over time and were described as “felt like there was a blockage, “afraid I would choke,” “unable to get anything through”. 3. Self care efforts employed by the patients to manage these difficulties ranged from diet modification, allowing food and drinks to go cold before eating and eating slowly. 4. An aversion to taking regular analgesia was also evident. The overall impact on participants’ lives was often understated, even in the context of hospital admissions, insertion of nasogastric tubes and poorly controlled pain.

Conclusion
Conclusions This study demonstrates the complexity of RIO and suggests clinicians may underestimate the effect and severity of RIO. Given patients appear to continue to experience problems, despite treatment, better prophylaxis and management regimes are required.

Background
AUY922 is an HSP90 inhibitor that degrades client onco-proteins including mutant EGFR. Preclinical studies utilizing cell lines and xenografts harboring EGFR T790M demonstrate that HSP90 inhibition is effective in models of AR. This phase II study combines AUY922 and E for the treatment of patients with EGFR-mutant lung cancer and RECIST-progression on EGFR TKIs.

Methods
Eligible patients had EGFR mutations and developed AR (per Jackman, JCO 2010) after treatment with EGFR TKIs. Patients underwent tumor biopsies after developing AR and prior to study entry. Tumor tissue from re-biopsy was analyzed for EGFR T790M and other mechanisms of resistance. Patients received AUY922 70 mg/m[2 ]IV weekly and E 150 mg oral daily in 28-day cycles. Response assessment was done at 4 weeks (wks), 8 wks, and every 8 wks thereafter. The primary objective was overall response rate (ORR, CR+PR) at 8 wks. A Simon mini-max design determined sample size (stage I: 16 pts (≥2 responses needed to proceed to stage II), stage II: 9 pts; α=10%, β=10%, p0=10%, p1=30%).

Results
The trial has completed accrual, and twenty-five patients have been treated (18 women, median age 59 (range 42-76)). The median time on EGFR TKI prior to the development of AR was 11 mo (range 3-26 mo). Ten patients (40%) had EGFR T790M identified by tumor re-biopsy. In the 25 patients evaluable for response, ORR was 4/25 (16%, 95% CI 6-35%). Three of four patients with PR had EGFR T790M. An additional four patients had stable disease for at least 8 weeks. To date, four patients were on study drug for ≥ 4 cycles, and four patients currently remain on study. Adverse events reported in ≥ 20% of patients were diarrhea, fatigue, myalgias, nausea, mucositis, and night blindness. Sixty-eight percent (17/25) experienced night blindness (grade 1-2 only), and three patients came off study due to eye-related toxicity. Grade 3 toxicities included elevated liver function tests, diarrhea, fatigue, constipation and anemia.

Conclusion
AUY922 and E is an active, well-tolerated regimen for patients with EGFR-mutant lung cancer. Visual disturbances, particularly night blindness, were common, but resolved with drug discontinuation. AUY922 and erlotinib demonstrate activity as combination therapy for patients with EGFR mutant lung cancers and AR to EGFR TKI. Activity is not limited to patients with EGFR T790M. Supported by Novartis, Inc.

Background
Dacomitinib is an oral, irreversible small molecule inhibitor of all active members of the HER (human epidermal growth factor receptor) family of tyrosine kinases: EGFR (HER1), HER2 and HER4. Dacomitinib has shown superior activity to the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib in preclinical studies of lung cancer cell lines with sensitive and resistant EGFR mutations, and superiority to gefitinib in cell-line models with a HER2 insertion mutation or amplified HER2. As part of dacomitinib’s phase II testing, we studied a cohort of patients with HER2-mutant or -amplified lung cancers.

Methods
As a cohort of a larger phase II study, we enrolled patients who had stage IIIB/IV lung cancers and either HER2 mutations or HER2 amplification ([centromere of chromosome 17]; ratio >2), any number of prior systemic chemotherapies, but no prior HER2-targeted treatment. Dacomitinib was administered at 45 mg once daily continuously, or 30 mg if the patient had no prior systemic therapy, with the option to escalate to 45 mg. Patients were evaluated every 28 days. Endpoints included progression-free survival (PFS) rate at 4 months (PFS4m), PFS, objective response rate by RECIST, duration of response, overall survival (OS), and toxicity.

Results
30 patients with HER2-mutant (n=26) or HER2-amplified lung cancers (n=4) were enrolled. Characteristics: 15 female; 18 never smokers (60%); 11 (37%) former smokers. 25 received a 45 mg starting dose; 5 patients received 30 mg. 10 patients had received ≥3 prior systemic therapies. 73% of patients had a PFS event. PFS4m overall was 27% (95% CI: 11%–46%; HER2-mutant subgroup: 21% [95% CI: 6%–43%]). Median overall PFS was 3 months (95% CI: 2–4; HER2-mutant subgroup: 3 months [95% CI: 2–4]). Of 25 patients in the HER2-mutant subgroup evaluable for response, 3 (12%; 95% CI: 3%–31%) experienced a partial response, all with 9 base-pair insertions in HER2 exon 20. The partial response durations were 3+, 11, and 11+ months. The preliminary estimate of median OS was 10 months (95% CI: 7–21; HER2-mutant subgroup: 10 months [95% CI: 7–21]). Among the 4 patients with HER2 amplified lung cancers, no partial responses were seen and the PFS ranged from 1–5 months. Of 29 patients evaluable for toxicity, the most common treatment-related adverse events were diarrhea (90%; grade 3/4: 21%/3%), dermatitis (72%; grade 3/4: 3%/0), fatigue (52%; grade 3/4: 3%/0), and dry skin (48%; grade 3/4: 0/0). 10% of patients discontinued treatment due to adverse events.

Conclusion
Dacomitinib demonstrated an overall 12% objective response rate in patients with HER2-mutant lung cancers. All 3 responding patients had 9 base-pair HER2 exon 20 insertions. No responses were seen in the 4 patients with HER2-amplified lung cancers. Dacomitinib was well tolerated with manageable toxicities, consistent with the class effects of EGFR TKIs.

Background
The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation upon interaction with its ligands, PD-L1 and PD-L2. In a Phase 1 dose-escalation/cohort expansion study (CA209-003; NCT00730639), nivolumab, a fully human PD-1 receptor blocking antibody, delivered durable responses in patients with solid tumors, including advanced NSCLC. Immunohistochemistry (IHC) analysis of tumor samples from this study suggested an association between pre-treatment tumor PD-L1 expression and clinical response to nivolumab in patients with melanoma (Grosso JF J Clin Oncol. 2013;31(suppl):abs 3016; Topalian SL NEJM 2012;366:2443-54). Here we investigate the association between PD-L1 expression by IHC and response to nivolumab in patients with NSCLC, and patient response with pre-/post-dose absolute lymphocyte counts (ALC) and selected lymphocyte cell subsets.

Methods
129 patients with NSCLC from the CA209-003 trial received nivolumab between 2008 and 2012 (1–10 mg/kg IV every 2 weeks) during dose escalation and/or cohort expansion. Archived formalin-fixed paraffin-embedded pre-treatment tumor tissue and pre-treatment and on-treatment peripheral whole blood samples were analyzed to explore potential pharmacodynamic/predictive biomarkers associated with nivolumab therapy. Pre-treatment tumor PD-L1 expression was evaluated by IHC using an automated assay developed by Dako based on a sensitive and specific anti-PD-L1 monoclonal antibody (28-8). Tumors were defined as PD-L1 positive (PD-L1+) when ≥5% of the tumor cells had membrane staining at any intensity. Lymphocyte subsets in the periphery were measured using flow cytometry.

Results
Tumor membrane PD-L1 expression was measured in 63 patients with NSCLC (29 squamous; 34 non-squamous). 31/63 (49%) NSCLC biopsies were PD-L1+. There was no apparent association between PD-L1 protein expression and NSCLC histology: for squamous and non-squamous tumors, 52% (15/29) and 47% (16/34) were PD-L1+, respective. Objective response rates for PD-L1+ and PD-L1- NSCLC patients with non-squamous and squamous histology are shown in the Table. Objective responses were observed in patients with squamous and non-squamous NSCLC who were negative for PD-L1 expression. Since increases in on-treatment ALC and activated T-cell phenotypes have been shown to positively associate with favorable clinical outcomes in ipilimumab monotherapy (Ku GY Cancer 2010;116:1767-75; Carthon BC Clin Cancer Res 2010;16:2861-71), results from an analysis correlating patient response with pre-/post-dose ALC and T-cell populations in patients with NSCLC receiving nivolumab will be presented.

Table. Patient response according to PD-L1 expression status in patients with NSCLC

Tumor type	PD-L1 expression status	Objective response rate, n/N (%)
NSCLC (all patients)	+	5/31 (16.1)
	–	4/32 (12.5)
NSCLC (squamous)	+	2/15 (13.3)
	–	3/14 (21.4)
NSCLC (non-squamous)	+	3/16 (18.8)
	–	1/18 (5.6)

Conclusion
Further evaluation of PD-L1 as a molecular marker of nivolumab therapy is required. Association of PD-L1 protein expression with clinical outcome is currently being prospectively assessed in ongoing Phase 3 trials. Clinical Trial Registration Number: NCT00730639

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Abstract
Cancer is the leading cause of death in the world, accounting for approximately 7.6 million deaths in 2008. Lung cancer accounted for 1.37 million of those deaths.Identification of molecular markers in lung cancer has lead to the development of targeted therapies resulting in improved survival in selected groups of lung cancer patients. Despite the advancements in treatments, the survival for patients with lung cancer, particularly in the metastatic or locally advanced patients (stage IIIb/IV), is generally poor with a 5-year survival of only 6%. The current poor prognosis and latest advances made in the field of lung cancer highlight the importance of clinical trial development, participation and analysis. Participation in clinical trials for the general cancer patient’s is low, between 5-9%. This low percentage is similar to those seen for lung cancer patients. Early stage clinical trials have a smaller number of participants by design and are aimed at establishing a maximum tolerated dose of a drug or treatment, not establishing efficacy.These clinical trials are not designed with curative intent but rather are designed to evaluate drug absorption, distribution, metabolism, excretion and mechanism of action. Only a small number of cancer patients and even a smaller number of advanced stage lung cancer patients enroll into phase I clinical trials. The number of international clinical trials has seen a rapid increase over the past decade. Recently the Office of Inspector General (OIG) reported that as of 2008, 80% of marketing applications for drugs and biologics approved by the US Food and Drug Administration (FDA) contained data from US clinical trials conducted outside of the USA. Despite the importance and availability of clinical trials for lung cancer, participation in early stage clinical trials by advanced stage lung cancer patients remains very low. There are multiple barriers that contribute to these low numbers of participants, some of which include: (1) fear of unknown benefit from the investigational treatment, (2) negative family and family physician influence, (3) logistical and attitudinal constraints – too cumbersome to participate and not willing to be the subject of “experiments”, (4) lack of knowledge, understanding and fear of the complexities of the clinical trial, (5) risk of inability to tolerate related investigational drug / treatment toxicity due to more weaken condition and (7) financial and insurance barriers.Identifying and overcoming the barriers that exist for each patient early in their diagnosis has the potential to improve both the quality and quantity of their lives and potentially help others with the same barriers in the future. Another significant barrier is the real and perceived conflict that exists between the need for palliative and/or Hospice levels of care for advanced stage lung cancer patients. The need for Hospice benefits and palliative care can and does have a significant impact on the decision to participate in early stage clinical trials to the point that participation may not even be an option. Funding and other system related issues act as barriers to participation in early stage clinical trials as well as the philosophical basis of the hospice/palliative care approach to treatment/care. Over the past decade the availability of symptom management and palliative care clinical trials has increased the awareness of this barrier and in many respects further clouded the issue for patients, their families and their healthcare providers. The primary ethical concern is does enrollment into clinical trials interfere with the spirit of hospice care or does it offer hope to a dying patient? Identifying issues that exist globally may help to increase enrollment by advance stage patients while at the same time moving early phase clinical trials forward and onto the phase II/III stage of study. Phase I trials are not designed with curative intent and phase I agents are not likely to prolong life or change the course of a disease. The life expectancy of phase I cancer patients’ averages between 5-6.5 months. Hospice providers and research investigators are in agreement that phase I clinical trials should be open and available to advanced stage lung cancer patients who are concurrently enrolled in hospice care. Overcoming the barriers and obstacles for advanced stage lung cancer patients to participate in early stage clinical trials can only happen in the setting of a committed multidisciplinary research team.Methods to utilize in an effort to move toward that goal include: (1) recognizing the importance of patient and family education, (2) recognizing the importance of healthcare provider education and awareness, (3) careful review and reinforcement of the informed consent process, (4) identifying and recognizing the potential benefit of phase I clinical trial enrollment for advanced stage lung cancer patients – clinical and altruistic, (5) recognizing and assisting patients and families with individual barriers and obstacles to participation and (6) employing effective marketing, recruiting and screening methods that are multidisciplinary in approach. Thoracic Oncology Nurses are well suited to serve as educators, advocates, resources, facilitators, and intermediaries. Nurses traditionally spend a greater amount of time in direct patient care and family interaction. Expanding and clarifying clinical information patients receive from their treating physicians is a vital role nurses play in ensuring patients are well informed and compliant with their plan of care. This is a model that can and has been extended into the realm of clinical trial work.Studies have shown that nurses play an important role in educating and recruiting cancer patients in clinical trials.A randomized clinical trial compared nurses with surgeons recruitment of patients into a clinical trial for prostate cancer and the results indicated that surgeons and nurses were equally as effective in their recruiting and educating abilities and effectiveness. With the proper education about early stage clinical trials, the conduct of clinical research, knowledge of the disease process of advance stage lung cancer and a high degree of self-motivation, thoracic oncology nurses are well suited to improve access and enrollment of advanced stage lung cancer patients into early phase clinical trials.

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