Virtual Library

Abstract
Lung cancer risk models and screening protocols are becoming more precise and, consequently, there is an increasing interest in developing new chemoprevention strategies for lung cancer. A number of compounds, among them several phytochemicals, have been proposed as potential lung cancer chemopreventive agents based on studies using rodent models. New preclinical studies involving novel chemopreventive compounds or more efficacious dosing strategies are required and their success will depend in part on the quality of the experimental models. In our presentation we will give an update of the available and newly emerging rodent models for the preclinical study of potential chemopreventive interventions for lung cancer. In order to fully recapitulate the complexities of human lung cancer, different animal models have been developed. These models can be divided into chemically-induced lung cancer and genetically engineered mouse models (GEMMs). Most chemoprevention studies have been performed on mouse models of lung adenocarcinoma (ADC) induced by a number of chemical carcinogens found in tobacco combustion products. The A/J mouse strain has been utilized primarily for these studies since these mice develop lung tumors rapidly after treatment with certain carcinogens such as anthracene, urethane, nicotine-derived nitrosamine ketone (NNK), other nitrosamines, benzo(a)pyrene (BaP), or vinyl carbamate. There are several well established chemically induced mouse ADC models which have been most frequently used in the assessment of the preventive potential of various types of agents: Genetic differences between ADC and squamous cell carcinoma (SCC) are also paralleled in the development of animal models. Skin painting with nitroso-tris-chloroethylurea (NTCU) is the best established protocol to produce lung SCC in susceptible mice and it has already been used for chemoprevention studies. In our lab, we have studied some phenotypic and genetic traits of the NTCU induced SCC, and we have used this model to analyse SCC-specific drug efficacy. GEMMs of lung cancer, mainly leading to adenomas or ADCs have also been used in chemopreventive preclinical studies. A plethora of GEMMs for lung carcinogenesis are available with single or combined genetic alterations in oncogenes or tumor suppressors. Several mouse models of lung cancer have been developed with mutation of Kras as the initiating oncogenic event. In the Kras[LSLG12D/+ ]knock-in mouse model, expression of oncogenic Kras is achieved by intratracheal inoculation with adenoviruses carrying Cre-recombinase The Kras[LSLG12D/+ ]model represents a highly relevant GEMM as it recapitulates many aspects of human ADC oncogenesis, including the full spectrum of lesions from early atypical adenomatous hyperplasia (AAH) to adenocarcinoma, and expresses human NSCLC gene signatures. Interestingly, combined mutant KRAS expression with additional genetic alterations such as p53, PTEN or LKB1 loss results in advanced stages of lung cancer including metastasis. To date, there is only one GEMM leading to pure squamous histology with many human SCC traits, recently developed in kinase-dead IKKα knock-in mice. Some years ago a mouse model for SCLC was developed by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. A newly developed model of SCLC incorporates p130 knockout and accelerates the formation of SCLC. Finally, mouse models for inflammation-driven lung carcinogenesis are helping to understand the role of smoking induced inflammation in lung cancer. We recently found that silica-induced chronic lung inflammation markedly increases the incidence and multiplicity of mouse lung adenomas and ADCs following N-nitrosodimethylamine (NDMA) treatment. These results are in concordance with other animal models that explore the effects of different inflammatory agents in chemically-induced lung tumor promotion. One of the key practical points regarding the relevance of these animal models in developing new chemoprevention strategies is the extent to which they recapitulate human lung cancer multistep progression at the cellular and molecular levels.. The pathological and molecular likes and dislikes between human lung cancer and the most frequently used animal models will be discussed during the presentation. The quantitative assessment of tumor volume progression in cancers affecting internal organs such the lung is more difficult than the assessment of lesions that are superficial (for example, breast or skin). New imaging technologies such as respiratory-gated micro-CT scans for small animals allow performing longitudinal studies on animal models of lung cancer. Micro-CT has been mainly used to monitor tumor growth and to assess the response or the resistance to therapeutic drugs. The potential of micro-CT imaging in lung cancer chemoprevention studies has been already highlighted. Standardization of protocols, improved resolution, more robust and faster image acquisition and, fully automatic and properly validated quantification algorithms need to be implemented before micro-CT imaging can show its full potential in the assessment of chemoprevention therapies.

Abstract not provided

Abstract
The goal of lung cancer chemoprevention is to prevent the development of invasive cancer, but designing early phase intermediate efficacy clinical trials to demonstrate that a strategy is effective remains a “work in progress”. Phase III prevention trials focus on individuals at high risk for cancer and have a lung cancer endpoint. By contrast, phase II trials depend on intermediate endpoints that are surrogates for cancer incidence, in a fashion analogous to shrinkage in tumor size being a surrogate for survival in phase II cancer treatment trials. Examples of such endpoints include premalignant lesions, proliferative indices, and various biomarkers of risk or malignant potential. To be useful, intermediate endpoints should be integrally involved in the process of carcinogenesis, differentially expressed in at-risk vs. normal epithelium, and modulated by effective interventions with little spontaneous fluctuation in expression. Although no intermediate endpoints have been validated as replacements for cancer incidence thus far, the assessment of a variety of such markers can significantly inform drug development and help make decisions regarding subsequent phase III trials. Lung cancer consists of a heterogeneous set of malignancies that presents with diverse molecular and histologic characteristics. The molecular evolution of tobacco related carcinogenesis is not well understood, but histologic evolution of squamous carcinogenesis, with progression from metaplasia through increasing grades of dysplasia and carcinoma in situ, is well described. This allows for a clinical trial design based on pre- and post-treatment bronchial biopsies to assess the response to chemopreventive interventions. Since the rate of progression of dysplasia to invasive cancer is variable, with higher progression rates associated with higher grades of dysplasia, studies assessing dysplasia as an endpoint need to be randomized such that the “spontaneous” reversion rate in the placebo arm can be used as a comparison to account for the effects of the biopsies and for true biologic reversion. This model has been successfully used to study a variety of interventions, including a recent trial of the prostacyclin analogue iloprost that showed improvement in bronchial histology after 6 months of treatment (Keith R et al., Cancer Prev Res 2011;4:793-802). In contrast, the study of the development of adenocarcinomas has been more difficult due to the inability to access tissues from the peripheral lung. The demonstration that helical CT screening reduces lung cancer mortality opens the opportunity to assess the peripheral lung for adenocarcinoma precursor lesions. Veronesi and colleagues (Veronesi G et al., Cancer Prev Res 2011;4;34-42) examined the effect of an inhaled steroid, budesonide, on CT-detected lung nodules, showing nonsignificant modulation of nonsolid lesions only. As persistent nonsolid (ground glass) lesions are more likely to represent lung cancer precursor lesions such as atypical adenomatous hyperplasia or early cancers than solid nodules, future studies should focus on nonsolid lesions only. Alternative designs for trials include a focus on individual biomarkers, panels of biomarkers, or pathways that are deregulated during carcinogenesis. As an example, Gustafson et al. demonstrated that the PI3K pathway is upregulated early during lung carcinogenesis and that an intervention with the drug myo-inositol that resulted in regression of bronchial dysplasia also inhibited PI3K activation in the bronchial epithelium (Gustafson AM et al., Science Trans Med 2010;2:26ra25). These data suggest that upregulated PI3K signaling could potentially identify smokers at increased risk for lung cancer and that pathway inhibition could serve as an endpoint for assessing treatment effect, a hypothesis that requires further testing. The rapidly increasing understanding of the pathogenesis of lung cancer provides an unprecedented opportunity to intervene in the process. Optimization of clinical trial design is required to translate the basic knowledge into clinical realities.

Abstract
Smoking exposes the respiratory mucosa to carcinogens in a “field cancerization” process. Smokers develop bronchial lesions, at the pre-invasive stages, preceding the development of invasive lung cancer. Because of the field of cancerization, these lesions are multiple and occur throughout the bronchial airways, which make complete resection of bronchial premalignant lesions impractical. Chemoprevention aims to prevent the development of lung cancer. The administration of chemopreventive agents may be effective, alone or in association with local treatment, in reducing the risk of developing lung cancer. So far no phase III trial testing chemopreventive agents for lung cancer has shown a consistent and reproducible benefit. Therefore no agent can be recommended currently for the chemoprevention of lung cancer (Szabo et al, Chest, 143 (5), Supplement, 2013, e40S-e60S). Future chemoprevention trials should be conducted based on the knowledge of lung carcinogenesis drivers and pathways (Keith et al, Nature Reviews, 10, 2013, 334-343). This would allow the choice of drugs with a better chance of benefit and the customization of the chemoprevention agents. Personalized approaches based on prediction of response to therapy by biomarkers are integrated in lung cancer treatment, with much higher success rate and reduced useless toxicity. In the context of chemoprevention, no or minimal sides effect must be obtained in the high risk population receiving the drug because of the absence of active disease, the fact that the treatment might have to be taken for many years by a large population at high-risk and consequently, the potential huge impact on public health. Therefore biomarkers could play crucial roles as surrogate intermediate endpoint and as predictors of response to targeted treatment. Lung cancers express lower levels of prostacyclin than normal lung tissues. Prostacyclin prevents lung cancer in a variety of mouse models. A randomized phase II trial comparing oral iloprost (a prostacyclin analogue) to placebo in high-risk subjects demonstrated improvement in bronchial histology but only in former smokers (Keith et al, Cancer Prev Res, 4 (6), 2011, 793-802). This placebo-controlled study offered the opportunity for investigation of other potential intermediate endpoints and predictive biomarkers to incorporate into chemoprevention trials. Matched biopsies (baseline-BL and the same site at follow-up-FU after 6 months of Iloprost or placebo) were obtained in 125 high-risk individuals who completed the trial: 40/35 and 25/25 current/former smokers in the Iloprost and placebo arm, respectively. We analyzed 496 biopsies including 4 matched biopsy pairs per patient: the best and the worst histology at BL and the 2 biopsies from same site at FU. Total RNA was extracted from formalin fixed paraffin embedded sections adjacent to the diagnostic section and 14 selected miRNA previously identified in high-grade bronchial preneoplasia were analyzed by qRT-PCR (Mascaux et al, Eur Respir J, 33, 2009, 352-359). The expression of seven miRNAs was significantly correlated with histology at BL. The expression of miR-34c was inversely correlated with histology at BL (p<0.0001) and with change in histology at FU (p=0.0003), independent of treatment or smoking status. Several miRNAs were also found to be differentially expressed in current smokers as compared with former smokers. In current smokers, miR-375 was up-regulated at BL (p<0.0001) and down-regulated after treatment with iloprost (p=0.0023). No miRNA at baseline reliably predicted a response to iloprost. Thus, miR-34c was inversely correlated with BL histology and with histology changes. Mir-34c changes at FU could be used as a quantitative biomarker to assess histological response in formalin-fixed bronchial biopsies in future lung cancer chemoprevention studies (Mascaux et al, Canc Prev Res, 6 (2), 2013, 100-108). This utility of miR-34c to assess the histological response to chemoprevention needs to be further demonstrated prospectively in other chemoprevention trials. The high-throughput gene expression profiling of bronchial epithelium (Gustafson et al, Sci Transl Med, 2 (26), 2010, 26ra25) and in lung preneoplasia (Mascaux et al, J Thor Oncol, 4 (suppl to 9), 2009, abstract PRS.2, page S282) could allow the discovery of new targets for chemoprevention and the possibility of customized lung cancer chemoprevention, by selecting the agents based on the different molecular profile of the individuals at high risk. Thus future chemoprevention trials should be undertaken based on the biological drivers and pathways of lung carcinogenesis. The chemoprevention trials should include the collection of biological samples to allow testing biomarker for their role as surrogate intermediate endpoint, for the selection of the patients who are at higher risk and for the personalization of the chemoprevention approach, with the purpose of optimizing the benefit and avoiding useless toxicity in high-risk but cancer-free individuals.

Background
Lung squamous cell carcinoma (SqCC) is the second most prevalent type of lung cancer. Currently, no targeted-therapeutics are approved for treatment of this cancer, largely due to a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SqCC, we probed somatic genome alterations of lung SqCC cases from Korean patients.

Methods
We performed whole-exome sequencing of DNA from 104 lung SqCC samples from Korean patients and matched normal DNA. In addition, copy number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.

Results
This cancer cohort is characterized by a very high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of cigarette-smoke exposure. Seven genes demonstrated statistical enrichment for mutation (TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2 and PIK3CA). Comparative analysis between Korean and North American lung SqCC demonstrated similar spectrum of alterations in these two populations, in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SqCC.

Conclusion
These findings provide new steps towards the identification of genomic target candidates for precision medicine in lung SqCC, a disease with a significant unmet medical need.

Background
Previously we reported that the frequency of mutations in EGFR and KRAS in non-small cell lung cancer (NSCLC) is Latinoamerica,finding the frequency of EGFR mutations in Latin-America between Asian (40%) and European (15%) populations. We report the update frequency of mutations in Latin America.

Methods
3606 biopsies of NSCLC patients from Latin-America (Argentina, Colombia, México and Peru) were used by extracted genomic DNA which was used to perform direct sequencing of EGFR gene (exons 18 and 21) and KRAS gene in 2385 samples.

Results
Of all patients the median age was 62.2 ±12.3, 52.6% were women, and 51% had smoking history. Frequency of EGFR mutations in NSCLC was 24.4% [CI 95% 22.7-24.1] (Argentina 14.4%, Colombia 24.9%, Mexico 34.4%, Peru 67.0%). The frequency of KRAS mutations was 7.1%. EGFR mutations were independently associated with gender (29.8% vs 16.3%; p< 0.001), older age (<60 vs >60; p= 0.001), non-smokers 25.9% vs 15.7%; p= 0.001), ethnicity (Hispanic 37.7%, Caucasic 13%, Afro-American 0%, non-determinate 22.9%; p< 0.001), histology (adenocarcinoma 23.8%, squamous 4.4%, large cells 33.3% and non differenced 22.2%) and absence of KRAS mutation. Overall response rate to tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutated patients (n=56) was 62.5% [95% CI 50-75] with a median overall survival of 16.5 months [95% CI 12.4-20.6].

Conclusion
Our findings confirm the high frequency of EGFR Mutation in Latino-america and low frequency of K-RAS mutation, particularly in patients of Hispanic ethnicity. Differences in risk factors associated with lung cancer in our population and ethnic variability could explain these findings.

Background
Approximately 1.2 million people are diagnosed with lung cancer every year. The identification of genomic alteration can impact therapeutics. EGFR mutation status predicts how patients can respond to EGFR tyrosine kinase drugs (EGFR-TKI). EGFR positive patients have an improved response rate to erlotinib or gefitinib; KRAS mutated tumors are not sensitive to EGFR-TKI. Recently, it has been published that patients with mutations inHER2 have a high response rate to trastuzumab. The prevalence of EGFR and KRAS mutations are well known to be associated with sex, histological type of tumor, smoking status and also ethnic origin. HER2, BRAF and PI3K are relevant gene candidates to emerging therapies. Mutation prevalence of the latter genes has not yet been investigated in large populations.

Methods
We have analyzed 1375 consecutive patients with metastatic lung adenocarcinomas having the screening of EGFR, KRAS, BRAF, PI3K and HER2 gene mutational status in the Paul Brousse platform between November 2011 and April 2013. The DNA mutation screening was performed using the HRM technology and their identification were analyzed by allelic discrimination and/or sequencing. Our database included all mutations results as well as anonymous diagnosis and socio-demographic data. The birth location has been self-reported.

Results
Of the 1375 tumors, the frequencies of EGFR, KRAS, BRAF or HER2 mutations were those usually reported in Caucasian population. Mean age was 65.2 years (SD = 11.2), 821 were male and 519 female. Among our population, 140 patients reported of African birth location, 1220 of European birth location and 15 of Asian birth location.

TABLE 1. Mutation prévalance and birth location
	European birth location	African birth location	Asia birth location	Total
EGFR (n/%)	129 (10.6)	13 (9.3)	5 (33.3)	147/1375 (10.7)
KRAS (n/%)	318 (26.3)	21 (15.0)	*	340/1366 (24.9)
BRAF (n/%)	23 (1,9)	1 (0,75)	*	24/1345 (1.8)
HER2 (n/%)	13 (1.1)	4 (2.9)	*	19/1327 (1.7)
PIK3CA (n/%)	20 (2.0)	5 (4,2)	*	25/1159 (2.2)
*Low effective

The percentage of EGFR mutations was higher in Asiatic patients, as previously reported. Interestingly the KRAS mutation rate was significantly lower in the African patients (15.0%, CI: 10.0 – 21.9) than in the European patients (26.3%; I: 23.9 – 28.8; p = 0.004). HER2 and PI3K mutation prevalences were more than doubled in African population compared to European population (Fisher's Exact Test, respectively p = 0.10; p = 0.17).

Conclusion
Our data show different EGFR, KRAS, and HER2 mutation rates according to the geographical birth location of patients. Interestingly, we noted a significant decreased Kras and higher HER2 and PI3K mutations prevalence in African birth location mutation rates compared to the other populations studied. The incidence of these mutations had not been extensively studied in the population of African birth location. That could suggest, especially in this population, the importance of systematic HER2 and PI3K screening to investigate specific targeted therapy.

Background
Treatment paradigms for non–small-cell lung cancer (NSCLC) have shifted from one based only on histology to one that incorporates molecular subtypes involving particular genetic alterations such as activating mutations in EGFR or translocations of ALK. The list of therapeutically targetable lesions is rapidly increasing including mutations in genes such as EGFR, HER2, KRAS, ALK, BRAF, PIK3CA, AKT1, ROS1, NRAS, FGFR1 and MAP2K1. Analysis of these potential targets is becoming a challenge in terms of work load, tissue availability as well as cost. Within the Network Genomic Medicine Lung Cancer (NGM), a regional molecular screening network of the Center for Integrated Oncology Köln Bonn, we aimed to improve on the sequential analysis of a set of 9 target amplicons by Sanger sequencing using bench top ultra-deep parallel sequencing platforms. We aimed to reduce 1) the time requirement for comprehensive molecular diagnostics, 2) the minimal amount of formalin fixed paraffin embedded (FFPE) derived input DNA, 3) while at the same time increasing the number of target regions analysed.

Methods
We established a multiplex PCR to amplify up to 640 lung cancer relevant target regions from at least 20ng of FFPE derived tumor DNA. The amplicon libraries were ligated to adapters encompassing medical identifier sequences that allowed multiplexing of up to 48 patients. The resulting libraries were sequenced on a benchtop Illumina platform (MiSeq). Mutations identified by parallel sequencing were confirmed by Sanger sequencing.

Results
330 patients were analyzed both by traditional single PCR based Sanger sequencing of 9 amplicons and the newly established parallel sequencing protocol. We found that the NGS approach worked reliably, was less prone to sequencing analysis errors and that the time needed to complete the mutation screening was significantly reduced to 7 working days from previously 21 days. A total of at least 300ng of DNA was needed to complete the analysis of 9 amplicons by Sanger sequencing compared to 20 to 100ng of DNA needed for up to 640 amplicons analyzed by parallel sequencing.

Conclusion
Newly multiplex PCR based parallel sequencing allows rapid comprehensive mutation testing in routine molecular pathological diagnostics even on small FFPE embedded transbronchial biopsies.

Abstract not provided

Background
Molecular subtypes of NSCLC are delineated through single driver alterations, although this likely underestimates the extent of inter-tumor heterogeneity. The goal of this study was to evaluate the potential impact of co-occuring mutations and copy number alterations in a series of tumours from both East-Asian (EA) and Western-Europe (WE) origins.

Methods
230 non-squamous non-small cell lung carcinomas (NSCLC) were analysed using the MassARRAY LungCarta™ panel (Sequenom) which examines 214 mutations in 26 oncogenes and tumour suppressor genes. Results were integrated with copy number alterations evaluated using Affymetrix Genome-Wide Human SNP 6.0 arrays and clinical variables.

Results
Out of the 230 tumours tested, 185 mutations were observed, with 138 tumours (60%) with at least one mutation – 97 tumours (42.2%) with a single mutation in a single gene, 36 tumours (15.7%) with two mutations (either in the same gene or two different genes), four tumours (2.2%) with three mutations and one with four mutations. The most frequent mutations were EGFR (38.5% EA;10.1% WE), KRAS (10.9% EA;31.6% WE), P53 (8.8% EA;15.1% WE), MET (14.3% EA;2.2% WE), STK11 (9.9% EA;2.8% WE) and PIK3CA (2.2% EA;4.3% WE). Co-occurring mutations were found in up to 30% of tumors, although the likelihood differed for each gene: KRAS (16/54, 31%), EGFR (18/49, 37%), MET (6/16, 38%), P53 (13/29, 45%), STK11 (8/13, 62%) and PIK3CA (5/8; 62%). Among the eight tumors harbouring PIK3CA mutations, five cases had a co-mutation (four cases with EGFR, one case with KRAS). In EGFR mutant cancers, co-occuring mutations include p53 (10%), PIK3CA (8%), STK11 (6%) and MET (4%). Significant relationships were also detected between EGFR mutation and CNAs on chromosomes 1p, 7p, and 13q. There were also significant relationships between KRAS mutation and CNAs on chromosomes 1q and 3q. For stage I, we found a worse prognosis for patients with at least one mutation. PIK3CA was significantly correlated with poor prognosis. Consistent with recent pooled analysis, KRAS alone is not prognostic but when CNAs and mutation status are combined, patients having both KRAS mutation and the highest related CNA (3q22.3 copy loss) showed a significant poorer prognosis.

Conclusion
This study highlights the wide diversity of mutation profiles within molecularly-defined NSCLCs, revealing co-mutations and associations with numerical chromosomal abnormalities that are clinically relevant. This diversity should be taken into account when designing stratified treatment approaches and underscores the need for customized assays that broadly screen for “actionable” mutations and copy-number alterations.

Background
The European Thoracic Oncology Platform LungScape database contains 2614 cases of primary resected lung carcinoma from 16 centres with patient demographics, pathological tumour data and detailed clinical follow-up. A total of 1281 cases of adenocarcinoma with >2 years clinical follow-up were selected for analysis of ALK status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Test positive cases were matched, in order of importance at ratio 1:2, by stage, gender, smoking status, study centre, year of surgery and age with test negative cases -both for IHC and for FISH testing.

Methods
Testing was performed in all centres using the same protocol (IHC: Novocastra 5A4 clone antibody at 1:10 dilution, Novolink detection system. FISH: Abbott Vysis ALK break-apart probe). Each centre passed an external QA test using unknown cases in a tissue microarray before conducting the LungScape tumour testing. IHC was scored according to three intensity scores (1+, 2+, 3+) using ‘objective’ methodology previously described [1]. Maximum staining intensity was recorded. Any IHC staining was defined as IHC positive result. FISH preparations were assessed according to the Vysis protocol on all 82 IHCpositive cases plus their 164 IHCnegative matches.

Results

	IHC cases, n=1281	FISH positive(264 tested)
IHC negative	1199 (93.6%)	0 (0.0% of 164 controls)	FISH specificity: 100%
IHC 1+	43 (3.35%)	2 (4.6% of IHC 1+)
IHC 2+	16 (1.25%)	6 (37.5% of IHC 2+)
IHC 3+	23 (1.8%)	20 (87% of IHC 3+)
IHC any positive	82 (6.4%)	28 (34.1% of IHC+)	FISH sensitivity: 34.1%

FISH sensitivity was 87% for IHC 3+. IHCpositive/FISHnegative cases (n=54) were mostly IHC 1+ (75.9%), sometimes IHC 2+ (18.5%) and rarely IHC 3+ (5.5%). The frequency of never smokers was higher in the ALK IHCpositive group (29.3%) versus IHCnegative group (18.3%) {p=0.011}. Age, gender and tumour stage did not differ between IHC groups. The hazard of an event for IHCpositive cases decreases by 32% in relapse-free survival {RFS; p=0.03} and by 38% in either time-to-relapse {TTR; p=0.02} or overall survival {OS; p=0.016}. Multivariate models -adjusted for patient and tumour characteristics- indicated that IHC-ALK was a significant predictor for all three time-to-event outcomes (RFS, TTR, OS). In stratified Cox analysis, significantly higher OS was retained in the IHCpositive (HR=0.59, p=0.04) and FISHpositive (HR=0.34, p=0.03) cases in the matched cohorts, while conditional logistic regression yielded non-significant associations with 3-year survival status.

Conclusion
In this large cohort of surgically resected primary lung adenocarcinoma: ALK IHC positivity was 6.4%. IHC 3+ staining (prevalence 1.8%) showed 87% probability of ALK FISH positivity ALK IHC positivity was higher in never smokers and related to better clinical outcome ALK testing can be reliably implemented across multiple laboratories {1} Ruschoff et al. Virchows Arch. 2010;457(299-307).

Background
Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults and comprise 30% of all carcinoid malignancies. They are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors, and are characterized by neuroendocrine differentiation and the potential to metastasize. Relatively little is known about bronchopulmonary carcinoid tumorigenesis, and understanding of these tumors has yet to benefit from the insight of genomic studies. This unfortunately has translated into relatively limited treatment options for these patients and no recent advances in therapy. We aimed to characterize genomic alterations in pulmonary carcinoid tumors under the hypothesis that a better molecular understanding may lead to improved therapeutic approaches and patient outcomes.

Methods
We characterized genomic alterations in pulmonary carcinoid tumors using whole genome, exome, and RNA sequencing, in addition to mRNA expression and SNP genotyping from specimens of normal lung, typical and atypical carcinoid, and SCLC. Fresh-frozen specimens from 54 patients with primary lung neuroendocrine tumors were obtained from our lung specimen registry and clinical data collected. This included a total of 31 typical and 11 atypical carcinoid tumors with associated normal tissue, and 12 SCLC. Whole transcriptome mRNA expression profiling and SNP genotyping for evaluating copy number variation was performed using Illumina array platforms. For a subset of tumors, whole genome sequencing was performed through Complete Genomics, and exome and RNA sequencing performed through BGI and the Mayo Clinic Genomics Facility. These data were correlated with the histologic subtype, stage and survival data available from this cohort of patients.

Results
Gene expression clearly identified distinct profiles differentiating carcinoid tumors from SCLC, though not between typical and atypical carcinoids. Copy number variations (CNV) were widely prevalent in SCLC, less frequent in AC, while TC had the lowest frequency of CNV. Validated sequencing data from exome and WGS platforms revealed a number of novel mutations for pulmonary carcinoid tumors, including ADNP, BRIP1, cyclin B3, CREBL2, GLI3, HERC1, IRAK3, NEDD4L, PRRX2, and ZDBF2, among others. RNA sequencing data did not reveal any novel fusions from analysis to date. Despite a low overall mutation frequency versus other forms of lung cancer, each carcinoid tumor had at least one potential driver mutation, suggesting possible targeted therapy opportunities for a disease where currently none exist.

Conclusion
Despite a low overall mutation frequency and an absence of frequently recurring mutations from the tumors sequenced to date, targeted therapy opportunities may exist through mutation profiling in broncopulmonary carcinoid tumors.

Abstract not provided

Background
Activation of the RET gene by fusion has been described in 1-2% of unselected population of non-small-cell lung cancer (NSCLC) and there is early evidence suggesting that patients with RET activated tumors obtain clinical benefit from RET inhibitors. The major fusion partner is KIF5B, but CCDC6, NCOA4 and TRIM33 have also been reported. The prevalence of RET fusions in different lung cancer subtypes and clinicopathologic characteristics of remain unclear. In this study, we sought to identify RET rearrangements in NSCLC using FISH and to investigate the association with histology and clinical features.

Methods
A 3-target, 3-color FISH probe set [3’RET in red, 5’RET in green, 5’KIF5B in yellow] was developed to simultaneously detect (a) disruption between 3’ and 5’ RET and (b) specific fusion between 5’KIF5B-3’RET. This probe set was used to interrogate a cohort of Caucasian NSCLC patients using tumor microarray. Inclusion of specimens on the tissue microarray was independent of gender, age, smoking history, histology and any known molecular profile and was only based on patient informed consent and tissue availability.

Results
Among 348 evaluable NSCLC patients, 6 (1.7%) were found to be positive for RET rearrangement (RET+): 2 showed typical KIF5B:RET pattern, 2 showed patterns consistent with CCDC6: RET fusion; and 2 had split 3’-5’ without suggestion of the fusion partner identity. The histology was adenocarcinoma in 4, large cell carcinoma in 1 and squamous cell carcinoma in 1. All RET+ tumors were wild type for EGFR and negative for ALK and ROS1 rearrangements. The mean age of RET+ patients at the time of diagnosis was 62 years (49-74) and they were predominantly male (5) and former (4) or current smokers (1). The 10p11-q11 region displayed high level of genomic instability, with RET doublets, KIF5B and RET doublets, unbalanced KIF5B copy number gain, fusion KIF5B with 5’ and 3’RET, and abnormal separation between KIF5B and RET in 8.5%, 5.1%, 9.6%, 2.3%, and 2% of specimens, respectively. These atypical patterns will be further investigated by RT-PCR.

Conclusion
The customized 3-target, 3-color probe set successfully detected KIF5B:RET rearrangements and identified patterns suggestive of RET rearrangements with non-KIF5B partners in small subset of unselected NSCLC. Interestingly, only a minority of RET + patients were never smokers and 1/3 of them had non-adenocarcinoma histology. Despite the benefits of using enrichment strategies based on clinicopathologic variables for molecular testing of NSCLC in search for personalized therapy, these findings argue against using variables such as smoking status and histology for screening selection when the aim is to detect all potential RET+ patients.

Background
The presence of mutations of epidermal growth factor receptor (EGFR) is related to phenotypical characteristics such as ethnicity, gender and smoking status. Such observations led us to explore associations between genetic polymorphisms and EGFR mutational status.

Methods
We set up a set of samples from 677 primary pulmonary adenocarcinoma. We tested two genetic polymorphisms (rs2736100 and rs10937405), which were discovered previously as to be associated with the risk of lung adenocarcinoma. The association between EGFR mutational status and genetic polymorphisms were evaluated using logistic regression analysis.

Results
In 673 patients, four exons (18, 19, 20, 21) of EGFR were completely evaluated. Presence of EGFR mutations were found in 382 (56.8%) patients. In logistic regression analysis, female gender (aOR, 1.7 with 95% CI, 1.0-2.9) and smoking status (ex-smoker, aOR, 0.6 with 95% CI, 0.4-1.1; current smoker aOR, 0.4 with 95% CI, 0.2-0.8) were associated with presence of EGFR mutations. None of two single nucleotide polymorphism (SNP) sites showed significant association. In the analysis of individual type of EGFR mutations, however, we found a significant association between EGFR exon 18 mutations and a SNP rs27366100T/G located in TERT. The G/G genotype showed a 2.8-fold increase in the occurrence of the EGFR exon 18 mutations compared to T/T+G/T genotypes (aOR, 2.8 with 95% CI, 1.2-8.7). Additionally, C/T+T/T genotypes of rs10937405C/T SNP in TP63 showed frequnt occurrences of EGFR exon 21 mutations compared to CC genotype (aOR, 1.5 with 95% CI, 1.0-2.3).

Conclusion
Our findings suggest that the somatic mutations of EGFR may be closely associated with genetic polymorphisms. Further investigation of this field may enable us to identify patients who may get a benefit from EGFR inhibitors.

Background
Chromosomal rearrangements which generate constitutively activated ROS1 receptor tyrosine kinase (6q22.1) have been found in several tumor types, including non-small cell lung cancers (NSCLC). In clinical trials, the oral kinase inhibitor crizotinib has shown promise in treating tumors with ROS1 rearrangements. Currently, fluorescence in situ hybridization (FISH) using dual-color, break-apart (BA) probes is used to detect ROS1 rearrangements in clinical samples; however, further optimization of this method is necessary to ensure patients are accurately diagnosed. This study explores BA FISH assay characteristics in NSCLC samples.

Methods
Tumor sections from 464 NSCLC patients were screened for ROS1 rearrangement using ROS1 BA FISH. Of these samples, 206 were co-screened for ALK rearrangement. The copy number of fused and isolated 3’/5’ signals, as well as the incidence of atypical patterns (doublet and clustered multiple fusions) was investigated. Cells were considered ROS1 positive (ROS1+) when ≥ 15% of nuclei displayed split 5’/3’ signals or single 3’ signals. Specific fusion transcripts in ROS1+ cases were identified by RT-PCR or inverse PCR.

Results
ROS1 rearrangements (ROS1+) were found in 21 patients (5%). The copy number of native ROS1 differed significantly between positive and negative tumors (mean of 1.5 versus 2.5, p<0.0001). The percent of cells with FISH patterns compatible with ROS1 rearrangement ranged from 30% to 100%, with a mean of 81%, in ROS1+ patients. The distribution of positive cells between scored regions within ROS1+ tumors was investigated for 13 cases and found to follow a normal distribution, ruling out intra-tumoral heterogeneity. Among ROS1+ specimens, 71% had a split signal pattern, 19% displayed a single 3’ pattern, and 10% had both a split and single 3’ pattern of positivity. For positive tumors, ROS1 fusion partners were identified as SDC4 (S2;R32 and S2;R34), EZR (E10;R34) and CD74 (C6;R32 and C6;R34). Atypical negative patterns such as fused doublets, clusters, 3’ doublets, 5’ doublets, and single 5’ signals were observed in 4%, 1%, 1%, <1%, and <1% of negative patients. ALK and ROS1 were scored simultaneously in the same cells in 206 patients, including 5 ROS1+ and 10 ALK+; no double positive cases were found. In ROS1 negative specimens, mean native ALK copy numbers were significantly higher than native ROS1 in ALK negative samples (3.2 versus 2.3, p<0.0001).

Conclusion
ROS1+ tumors were detected in 5% of patients in this large NSCLC cohort. Since these patients were subject to various selection strategies, this frequency cannot be transferred to an unselected NSCLC population. The low native ROS1 copy number in the rearranged cells and lack of evidence of intra-tumoral heterogeneity suggests ROS1 rearrangements occur early in tumorigenesis, consistent with their known oncogenic driver role. Data from this sample also show that, in FISH negative cases, ROS1 copy number was lower than native ALK. This suggests ROS1 may exist in a relatively more stable portion of the genome, potentially explaining why ROS1 rearrangements exist at a lower frequency than ALK rearrangements in NSCLC.

Abstract not provided

Background
Lung cancer patients have complex problems and are considered as disadvantaged when compared with other cancer patients. The needs of lung cancer patients during the treatment trajectory still remain to be identified systematically. The present study is part of a Ph.D. study investigating ’Four critical moments’ in daily life during disease and treatment trajectory in operable lung cancer patients. The Ph.D. study is part of the Centre for Integrated Rehabilitation of Cancer Patients – CIRE. The present study aims to explore lived experiences at diagnosis of operable lung cancer patients in order to identify needs of supportive and rehabilitative care.

Methods
A sample of nineteen patients is included in the study. Inclusion criteria are a diagnosis of non small cell lung cancer referred for surgery at department of Thoracic surgery, Rigshospitalet and age above 18. Individual in-depths interviews with a phenomenological approach were conducted approximately seven days following diagnosis. The phenomenological approach is based on the French philosopher Paul Ricoeur. Focus in the interviews is the present and deals with themes of patients’ experiences with the diagnosis and daily life, bodily experiences, smoking and physical activity. Follow-up interviews are performed 14 weeks post surgery focusing on the patients return to daily life.

Results
Through the analysis of the narrative interviews, patients' lived experiences are described in themes such as onset of illness with no symptoms; resilience expressed as managing on their own, used to be strong and not complaining; psychological response expressed as feelings of unreality, trying to push it away and experiences of lack of concentration, lack of energy and excessive thoughts; existential thoughts, expressed as a confrontation with death, anxiety, loneliness, afraid of the unknown and an emotional rollercoaster ride; the continued daily life focusing on continuing with usual activities and patterns; disruptions in the social relations expressed as withdrawal from social situations or experiences of family and friends’ withdrawal from the ill person. Will not be a burden or receive compassion from family and friends and will not express their vulnerability to family and friends; physical activity as a daily activity but not used to exercise; smoking as stress reduction; supportive needs from a patient perspective such as conversations with healthcare professionals about the whole situation, early information about surgery and no need of further written information; confidence in the meeting with the health care system; uncertain but hopeful about the future.

Conclusion
It is important that health care professionals provide patients with opportunities to talk about their fears, concerns and experiences. Through listening to and understanding operable lung cancer patients, nurses can identify appropriate resources and help patients to access them. Results are expected to contribute to the development and initiation of further interventions for lung cancer patients early in the treatment trajectory.

Background
Malignant pleural effusion (MPE) is common in individuals with advanced cancers and has an adverse impact on respiratory function and quality of life (QOL). Research evaluating treatment methods for MPE have focused on medical endpoints such as chest x-ray and there are no studies that have evaluated patient centered outcomes. Taking into consideration the short life expectancy in this patient population at the time of diagnosis, this study aims to determine the effect of any of the currently accepted treatment methods on QOL and hospital length of stay (LOS).

Methods
A prospective study of patients with a radiologically confirmed pleural effusion and an underlying malignancy evaluated patient centered outcomes using the London Chest Activity of Daily Living Scale (LCADL), Functional Assessment of Chronic Illness Therapy –Palliative (FACIT-PAL) and Functional Assessment of Chronic Illness Therapy Treatment Satisfaction (FACIT-TS-G). Cytological confirmation of MPE was obtained in the majority of patients. Treatment of MPE was determined by the attending physician. The study was approved by the institutional REB. Patients who were unable to read or speak English were excluded from the study. After providing informed consent, patients completed the questionnaires (LCADL, FACIT-PAL and FACIT-TS-G) prior to treatment, immediately post treatment and 2 and 6 weeks post treatment. Spearman correlation coefficients were calculated with 95% confidence intervals and p-values were utilized to assess linear relationships between QOL measurements. Mixed model regression analysis was used to estimate linear trends in LCADLS, FACIT-PAL, FACIT-TS Recommendation and FACIT-TS Satisfaction scores in the entire cohort and between treatment groups. Mean QOL scores at measurement time points were plotted in order to assess trends over time for both the entire cohort and for treatment groups.

Results
There were 105 study participants from 4 hospitals with a median age of 61 years (range 26-89 years). Lung cancer was the most common underlying malignancy, followed by breast and gastrointestinal cancers. MPE was treated by chest tube + pleurodesis (n=39), Tenckhoff catheter alone (n=27), VATS + Tenchkoff (n=20) and VATS + pleurodesis (n=17). In analyzing the entire cohort, there was an overall improvement in shortness of breath (p<0.0001), ability to perform activities of daily living (p=0.03) and quality of life (p<0.0001) for all treatments. There was no statistically significant difference between treatment groups. However, individuals treated with chest tube + pleurodesis had a decrease in treatment satisfaction, while individuals who were treated with VATS + Tenckhoff (p=0.03) or Tenckhoff alone (p=0.04) reported improvement in their treatment satisfaction. LOS was longer for individuals treated with chest tube + pleurodesis (median 10 days) and VATS pleuroscopy (median 6 days) when compared to VATS + Tenckhoff (median 3 days) & Tenckhoff catheter alone (median 2 days).

Conclusion
In the management of MPE, patient centered outcomes are most important. All treatment strategies evaluated in this study provided similar improvements in dyspnea, ability to perform activities of daily living and QOL. However, Tenchkoff catheter treatment strategies offer shorter LOS as well as improved treatment satisfaction which is important given the limited life expectancy of patients with MPE.

Background
Cancer patients' satisfaction with their treatment decision has been proven to be associated with improved health outcome, but few studies have been conducted in Japan. Doctor-centered medicine has been prevailing in the area of cancer treatment in Japan. It has been common among Japanese physicians to withhold "bad news" from patients. Several studies have reported that cancer patients were dissatisfied with this situation and desired to participate in the decision -making on their cancer treatments. Such trends led to the enactment of Cancer Control Act in 2006.The purpose of this law was to establish an environment in which cancer patients were informed about their diagnosis ,and allowed to participate in making decision on their treatment. In this study we hypothesized that cancer patients' satisfaction with their treatment can enhance their psychological outcomes. Furthermore, we hypothesized that cancer patients' satisfaction with their treatment was associated with a rapport established by patient-centered communication with their caregivers. We conducted a cross-sectional survey among 576 Japanese cancer patients.

Methods
We conducted cross-sectional questionnaire surveys among patients who had received cancer treatment. One source was inpatients of a Cancer Center Hospital, and the other a website of Japan's biggest newspaper. The questionnaire included demographics, and general self-rated life status such as peace of mind, quality of life, daily activities, family relationships, rapport with attending physician, assessment of physician's explanations and feeling of happiness during the previous week.

Results
Of 576 participants who responded, 383 subjects were satisfied and 193 dissatisfied. The dissatisfied group included more females and fewer mandatory retired subjects than did the satisfied group. The patients in the more satisfied group had a more favorable subjective opinion on their recent life. Assessment of physician's role showed significant differences between the two groups; the patients in the satisfied group felt more than those in the dissatisfied group that the doctor's explanations of treatment were sufficient and were satisfied with the rapport with their doctors. Multiple logistic regression analysis revealed that rapport with their doctors showed a significant odds ratio (3.79, 95% CI, 2.25-6.39).

Conclusion
Cancer patients' well-being is associated with treatment satisfaction. Rapport between physicians and patients is the most important key factor for patients' satisfaction with their treatment decision.

Background
Supportive care needs (SCNs) of people with lung cancer (LC) are highly prevalent; yet, are often unrecognised and unmet. Patient Reported Outcome Measures (PROMs) are a way of identifying the SCNs of people with lung cancer in clinical practice. Objectives: To explore the use of PROM's by lung cancer nurse specialists (LCNS) in the delivery of supportive care to people with LC.

Methods
A mixed-methods study design was used. Patients (N=20) were recruited from 3 sites in Scotland and took part in the study over 3 time-points: baseline (T1), one month (T2), two months (T3). At each time point, patients completed the Sheffield Profile for Assessment and Referral to Care (SPARC) and used the PROM to direct consultations with their LCNS (N=3). End of study interviews explored patients’/clinicians’ experiences of using the SPARC in the delivery of supportive care.

Results
SCNs were highly prevalent at baseline. A significant reduction in overall psychological and spiritual needs from T1-T2, and family/social and treatment concerns from T1- T3 was recorded. The use of the SPARC resulted in patients disclosing needs that they would not have previously raised and promoted them to ask questions about their condition/care. LCNSs perceived that using the SPARC to guide consultations resulted in patients discussing a wider array of SCNs particularly sensitive issues such as death/dying, concerns regarding family/carers, and sexuality.

Conclusion
Our findings demonstrate the feasibility and acceptability of the use of PROMs in the delivery of supportive care to people with LC in clinical practice.

Abstract not provided

Background
The pattern in which functional decline in people living with advanced cancer occurs has been described as an initial period of reasonably stable function, followed by more rapid functional deterioration with a defined terminal phase. However little is known about the more subtle changes in function in the more advanced stages of cancer, and the role that breathlessness plays in functional changes. The aim of this pilot study is to compare the feasibility of conducting a range of standardised assessments at different levels of performance status in people with advanced cancer.

Methods
A consecutive cohort was recruited to a cross sectional study from three large palliative care units in metropolitan Sydney. Participants completed four breathlessness-inducing assessments: Six-minute Walk Test, Two-minute Walk Test, Isometric Upper limb Exercises and Reading Numbers Aloud. Performance status was assessed using the Australian Modified Karnofsky Performance Scale, Eastern Cooperative Oncology Group Performance Scale and Life-Space Assessment. Comorbidity was identified using the Charlson Comorbidity Index. Four scales were used to assess breathlessness in each participant: Medical Research Council Dyspnoea Scale, Intensity and Unpleasantness of Breathlessness Visual Analogue Scales and Numerical Rating Scale for Breathlessness.

Results
The results of the pilot study have allowed a comparison of the four methods of breathlessness-inducing assessments by functional status in 37 people with advanced cancer. Median scores for performing breathlessness-inducing assessments by level of function where ≥80% of people could complete the assessments will also be presented.

Conclusion
This oral presentation will highlight the pilot study results and the feasibility of using these assessments in research and clinical practice, to improve the assessment of functional capacity and breathlessness in people living with advanced cancer. There is currently limited evidence into how function can be assessed in advanced cancer when breathlessness is present. This study adds to the evidence and knowledge base around the assessment of function in people living with advanced cancer.

Background
All cancer survivors should have a personalised assessment and care plan, and support to self manage their condition (UK DoH 2010) The SPARC (Sheffield Profile for Assessment and Referral to Care) is a tool designed to be completed by the patient, with support from carers if needed, and forms the starting point for the holistic needs assessment process. SPARC is a screening questionnaire that explores a variety of issues and may help the patient/carers to reflect on their needs. The SPARC assessment tool was evaluated for its application utilising lung cancer patients who attended the Lung Cancer Clinic in Rotherham from 2011-2012.

Methods
100 patients responses utilising the SPARC assessment tool were analysed at various time points of their pathway including diagnosis, post treatment, disease recurrence and 5 years post discharge.

Results
The results analysed were in the domains of physical symptoms, communication and information issues, treatment issues, psychological symptoms and distress thermometer outcomes. Key results showed that: - all patients suffered with common symptoms from lung cancer; - were mostly concerned about the effect that their illnes was having on their family or other people; - many required input to help with their personal affairs; - psychological symptoms were evident in a significant proportion of patients; - the distress thermometer was an appropriate tool in this clinic. The results will be shown in detail in the poster.

Conclusion
The SPARC assessment tool is an efficient and validated audit tool for assessing patient concerns and to provide feedback to the patients healthcare team. In Rotherhamm the tool will continue to be utilised and evaluated and is offered to all patients at the first post treatment phase and when no further active treatment is planned. The tool is an appropriate audit tool for assessing patient concerns and to provide feedback to clinicians and community health care teams.

Background
Lung cancer patients continue to experience higher symptom distress than others with different cancer types. We assessed changes in the needs and symptoms of advanced lung cancer patients over a 10 year period.

Methods
Consecutive outpatients with advanced lung cancer attending thoracic oncology clinics at a major Canadian cancer centre were invited to complete a 25-item self-administered questionnaire assessing physical and psychosocial symptoms, functional impairment, cancer knowledge and information preferences. Patients were surveyed over 6 months in 2002, and a second cohort surveyed over 3 months in 2012. Summary data and relevant changes over time are presented here.

Results
108 advanced lung cancer patients were surveyed in 2002, and 100 in 2012. Fatigue, cough, and shortness of breath are the most common physical symptoms, affecting over one-third of patients on a frequent or constant basis. Significant anxiety was reported by 27% in 2002, 20% in 2012, and 15% reported depression, unchanged over time. Lung cancer or treatment-related symptoms impair daily activities in approximately two-thirds of patients. More than a third experience significant financial hardship, and 62% believe their lung cancer imposed significant hardship on their family. More patients in 2012 reported receiving advice on symptom management, information on the goals and benefits of cancer therapy, and an understanding of clinical trials. However a quarter of patients still perceived that they received little to no advice on symptom management, and 19% felt uninformed about treatment goals for their advanced lung cancer. Despite advances in palliative care, less than 20% discussed their end-of-life care wishes with their healthcare team, even though ~40% had specific wishes or plans, with no change over 10 years. In 2002, most advanced lung cancer patients preferred to receive information in print media. In 2012, while most would still be interested in print media, significantly more were interested in a telephone helpline (~60%). Half of patients indicated they would not use internet-based resources even if readily available in 2002, but this number did not change over time (46% in 2012).

Conclusion
Advanced lung cancer patients continue to experience a significant burden of physical and psychosocial symptoms, with no decrease in this burden over time despite perceived advances in treatment and support. Patients are more informed about symptom management and treatment goals than a decade ago, although a significant number still require more information. Patients with advanced lung cancer also need greater empowerment and support from their oncology team in advanced care planning. Printed information continues to be preferable to internet-based resources for the majority of advanced lung cancer patients, and a growing number are interested in telephone help-line support.

Background
Lung cancer affects nearly 41, 500 people per year in the United Kingdom (UK) of which 5000 (12%) will undergo major lung resection for primary lung cancer with approximately 15% of all patients having complications post operatively. Once the patient develops a post surgical pulmonary complication mortality increases from 0.5% to 12%, ITU admission rate increases from 1.5% to 26% and the length of stay increases from 5 to 14 days. The UK National Lung Cancer Forum for Nurses have produced a Guideline for Telephone Follow Up for Patients Undergoing Thoracic Surgery . The aim of the Guideline is to help to provide a telephone follow up service to patients to reduce rates of re-admission and to improve patients satisfaction of their care. The guideline was produced following an audit of patients who had undergone thoracic surgery and a consensus of expert opinion within the thoracic surgical speciality.

Methods
In 2012 a retrospective audit of patients who had lung surgery was undertaken by UK National Lung Cancer Forum for Nurses Thoracic Surgical Group (TSG) in 2012 to assess the timing of intervention after discharge and what assessments would be important to patients. Following a literature review, opinions gathered from Thoracic Surgeons (who worked with the TSG members) and other Lung Cancer Nurse Specialists an assessment was made on how best to support patients after lung surgery. The guideline was developed through regular meetings of the TSG and was developed following the audit, literature review and consideration of the expert views provided.

Results
The audit data was collected from 147 patients from across four Thoracic Surgical Centres in the UK and received 439 comments and focused specifically on post-operative care. The data showed that the consensus opinion from patients was that a preferred interval for post-operative assessment by telephone was between two and seven days after discharge and provided information on the aspects of care that were important to them. The aspects of care that were important to patients included wound management, pain, breathlessness, activity, anxiety, constipation, fatigue and sleep. Following the literature review and expert opinion gathered from Thoracic Surgeons and Clinical Nurse Specialists the decision was made to produce the Guideline for Telephone Follow Up for Patients Undergoing Thoracic Surgery for which can be used by any health professional. The guideline includes assessment tools and interventions utilising best available evidence to assist in the identification of concerns or problems that a patient may face after thoracic surgery. The full guideline can be found at www.nlcfn.org.uk

Conclusion
This guideline aims to help support health professionals in the provision of a follow up service to patients after thoracic surgery. The audit of patients who had undergone lung surgery helped to focus on the problems that patients had identified as being important to them and, together, with best available evidence and expert consensus opinion allowed the development of this guideline. The guideline is being utilised in thoracic centres in the UK and could be adapted for use in other countries.

Abstract not provided

Abstract
Malignant mesothelioma (MM) is a lethal cancer whose pathogenesis results from complex interactions between host genetics and environmental carcinogens, such as asbestos and erionite fibers. Recently, BAP1 (BRCA associated protein 1) has been identified as a novel MM tumor suppressor gene. BAP1 is located at the 3p21, a region frequently deleted in MM, and encodes for a deubiquitinase enzyme known to target histones and other proteins. Originally discovered as a BRCA1 interacting protein, BAP1 appears to exert its anti-tumor activities mainly in a BRCA-independent manner, through its association in multi-protein complexes with diverse functions. For example, when associated to the Polycomb protein ASXL1, BAP1 is important for the regulation of the cell epigenome, via modulation of histone H2A ubiquitination and thus chromatin accessibility. In complex with other proteins (e.g. HCF-1, OGT, and YY1), BAP1 is also important in the transcriptional regulation of several genes and in the stability of target proteins such as PGC-1α. Recent reports also suggest a possible involvement of BAP1 in DNA repair pathways. However, the relevance of BAP1 to the biology of normal and cancer cells remains largely unexplained, in fact manipulation of BAP1 in cancer cells has often yielded unexpected or even contradictory results. For example, silencing of BAP1 in MM and uveal melanoma cell lines resulted in reduced cell growth (Bott et al; Matatall et al). We discovered that germline BAP1 mutations cause a novel cancer syndrome characterized by a significant excess of both pleural and peritoneal MM, uveal and cutaneous melanoma and possibly other tumors. In the same study, we reported that 22% sporadic MM tumors harbored somatic BAP1 mutations (Testa et al). In a separate study using 53 primary pleural MM collected in the USA, 42% of tumors harbored either BAP1 loss, BAP1 somatic mutations (detected in 23% of the samples), or both. Moreover, another 25% of tumors showed no BAP1 staining by immunohistochemistry (IHC) despite apparently normal BAP1 status, raising the possibility of post-translational deregulation of BAP1 in a subset of cases. In this MM cohort, there was a significant association between BAP1 status and patients’ age (66.7 years in mutant BAP1 compared to 58.6 years in wild-type BAP1), but there was no significant correlation with other variables such as sex, overall survival, histological subtype or asbestos exposure (Bott et al). In a recent meeting, using a bigger sample size, the same group confirmed that somatic BAP1 mutations occur in about 20% of pleural MM. They reported that the only clinical variable significantly different among those with and without BAP1 mutations was smoking (former or current), with BAP1 mutations more prevalent among smokers (75% vs. 42%). A Japanese study reported BAP1 gene alterations (either deletions or sequence-level mutations) in 61% of their 23 MM samples (Yoshikawa et al). Their data, but not those reported by Bott et al, also suggested an association between BAP1 mutations and the epithelioid histological MM subtype. Whether this discrepancy results from the different methodologies in sample preparation and detection of BAP1 mutations or it is an intrinsic difference between the two populations (e.g. due to ethnicity) has still to be determined. A third recent study, with a separate cohort of 52 pleural MM, reported absence of BAP1 IHC staining in 60% of pleural MM, confirming previous results (Arzt et al). The Authors also confirmed the absence of a correlation between BAP1 expression and asbestos exposure, and suggested that expression of BAP1 in tumor samples is inversely correlated to survival. The discovery of BAP1 germline and somatic mutations has renewed after decades the interest in MM genetics. Because germline BAP1 mutations predispose to multiple cancers and because BAP1 loss of heterozygosity is frequent in different tumor types, BAP1 would appear to act as a classical tumor suppressor. However, this definition is unsatisfactory because manipulation in vitro of BAP1 expression has often given unexpected and paradoxical results, complicating our understanding of its mechanisms of action. BAP1 absence (due to genetic, genomic, epigenomic or post-translational causes) was reported in about 60% of pleural MM. No studies so far have thoroughly investigated BAP1 expression in MMs arising from other sites. BAP1 expression is not associated to asbestos exposure, suggesting that its role in MM pathogenesis may be independent from the known asbestos-related pathways. Other clinicopathological associations are at this moment too weak to be conclusive, possibly due to limited tumor sample sizes, methodological differences in the studies or finally ethical differences of the analyzed populations. It appears, but remains unproven, that patients with germline BAP1 mutations have less aggressive MMs compared to sporadic MMs in which BAP1 mutations do not appear to influence prognosis. More experiments are urgently required to see whether BAP1 expression could be use in diagnostic, prognostic, or therapeutic settings. In fact, defining a therapeutically accessible synthetic lethal target in the setting of BAP1 loss could eventually benefit the approximately 40-60% of patients with BAP1 negative MMs. Even more speculatively, the same synthetic lethal target could be studied as chemoprevention drug targets in individuals with germline BAP1 mutations. The impact of this work obviously extends to other cancers with BAP1 mutations.

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Abstract
We have developed a novel transgenic mouse (MexTAg) where cellular transformation is driven by the SV40 (simian virus 40) large T antigen (TAg). In these mice, TAg is specifically targeted to the mesothelial compartment because it is expressed under the control of a tissue specific promoter. MexTAg mice uniformly develop mesothelioma after exposure to asbestos, with no spontaneous formation of other tumours. The key differences between MexTAg and wild type animals are the higher incidence and the shorter latency of the disease. Survival after diagnosis is not different suggesting that TAg does not drive a more aggressive disease. The model is comparable to human mesothelioma because of the eliciting carcinogen and because the location, pathology, molecular lesions and tumour response to therapy are similar (Robinson et al., 2006; Robinson et al., 2011). It is thought that asbestos fibres drive cellular transformation via the production of reactive oxygen species and the induction of chronic local inflammation. Accordingly, we have begun to test antioxidants and anti-inflammatory drugs as potential cancer prevention agents. We have reported that dietary supplementation with the antioxidants, vitamins A, E and selenium does not affect overall survival nor the time to progression of asbestos-induced mesothelioma in MexTAg mice (Robinson et al., 2012). We have extended our analysis to vitamin D and compared survival of asbestos-exposed MexTAg mice provided with diets supplemented (4500 IU/kg feed) or deficient in vitamin D (cholecalciferol). Survival of supplemented mice was significantly shorter than mice given standard diet (median survival, 29 and 32.5 weeks respectively). Mice deficient in vitamin D developed mesothelioma at the same rate as control mice. We conclude that vitamin D is unlikely to moderate the incidence of disease in asbestos exposed populations or to ameliorate the pathology in patients with established mesothelioma. Mesotheliomas in MexTAg mice respond to cytotoxic chemotherapy. Gemcitabine treatment from week 16 prolonged survival of asbestos-exposed MexTAg mice increasing the median survival from 33 weeks to 48 weeks. Interestingly, latency was not significantly prolonged, but animals survived for longer after the first signs of disease were noted. To understand the importance of the immune system in the pathogenesis of mesothelioma, we crossed MexTAg mice with immune deficient RAG KO mice. Perhaps surprisingly, MexTAg mice with no acquired immunity lived longer with a more indolent disease than their immunocompetent sibs. We compared cell lines derived from mesotheliomas from MexTAg mice and cell lines from wild type mice with human mesothelioma cell lines by expression array. TAg expressing mouse tumours were 90% identical to wild type mouse tumours. The key pathway that was different was cell cycle-associated. Human mesotheliomas commonly have a deletion of the cdkN2 locus, encoding the tumour suppressor genes p16 and p15. While wild type mouse tumours carried a homologous p16 deletion, TAg tumours did not. We hypothesize that TAg expressing mice develop tumours in an accelerated way following asbestos exposure because they are not dependent on deletion of p16 for tumourigenesis. Robinson, C., I. van Bruggen, A. Segal, M. Dunham, A. Sherwood, F. Koentgen, B.W. Robinson, and R.A. Lake. 2006. A novel SV40 TAg transgenic model of asbestos-induced mesothelioma: malignant transformation is dose dependent. Cancer Res 66:10786-10794. Robinson, C., A. Walsh, I. Larma, S. O'Halloran, A.K. Nowak, and R.A. Lake. 2011. MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma. Eur J Cancer 47:151-161. Robinson, C., S. Woo, A. Walsh, A.K. Nowak, and R.A. Lake. 2012. The antioxidants vitamins A and E and selenium do not reduce the incidence of asbestos-induced disease in a mouse model of mesothelioma. Nutrition and cancer 64:315-322.

Abstract

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Abstract
Malignant mesothelioma (MM) represents a significant clinical challenge. Not only can this tumour be difficult to diagnose but treatment options are limited. There is a desperate clinical need for biomarkers that can aid the diagnosis of MM, and/or predict survival and measure disease response to treatment. MM diagnosis is challenging as phenotypic differentiation of malignant mesothelial cells from benign reactive ones is notoriously difficult. No immunohistochemical marker(s) can uniformly define the cancer either. Invasive pleural tissue sampling for MM is more frequently negative than in any other cancer type [1]. A reliable diagnostic marker will present a major aid to clinicians. The median survival for the MM population is less than 12 months, however about 5% of patients live for several years and unusually long survivals of over 10 years have also been seen. But no reliable prognostic algorithm exists to predict survival in individual cases – a question of utmost concern for patients and their families. There is no cure for MM. Chemotherapy may improve survival, but only 30 to 40% of patients respond [2]. Thus finding a biomarker that may reflect disease burden and response to therapy, and hence prognosis, will be a significant advance. It has been nearly a decade since mesothelin [3] and MPF [4,5]were reported as candidate biomarkers for MM, both providing similar diagnostic accuracy [6]. A recent meta-analysis of serum mesothelin in the diagnosis of MM determined that having a sensitivity of 32% at a 95% specificity was too low for diagnostic use and highlighted the need for ongoing research for better biomarker(s) [7]. However, studies world-wide on a range of soluble markers including osteopontin, hyaluronic acid, CA125, CA15-3 and others have failed to improve upon diagnostic accuracy. More potential biomarkers such as fibulin-3 and the SOMamer panel have recently been identified [8,9]and the search to discover novel biomarker(s) for this disease using a variety of genomic, proteomic and immunologic approaches continues. For these candidate MM biomarkers to attain their professed clinical potential, independent externally validated studies with large, representative patient cohorts will be required. The next stage will then need studies to determine how to integrate promising markers into clinical diagnostic and/or management algorithms, a process essential to improve outcomes for MM patients. 1 Davies, H. E. et al. Outcome of patients with nonspecific pleuritis/fibrosis on thoracoscopic pleural biopsies. Eur J Cardiothorac Surg 38, 472-477, (2010). 2 Nowak, A. & Bydder, S. Management of malignant pleural mesothelioma: a review. Asia Pacific J clin Oncol (2007). 3 Robinson, B. W. et al. Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 362, 4 Onda, M. et al. Megakaryocyte potentiation factor cleaved from mesothelin precursor is a useful tumor marker in the serum of patients with mesothelioma. Clin Cancer Res 12, 4225-4231 (2006). 5 Shiomi, K. et al. Novel ELISA system for detection of N-ERC/mesothelin in the sera of mesothelioma patients. Cancer Sci 97, 928-932 (2006). 6 Hollevoet, K. et al. Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma. Am J Respir Crit Care Med 181, 620-625, (2010). 7 Hollevoet, K. et al. Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis. J Clin Oncol 30, 1541-1549, (2012). 8 Ostroff, R. M. et al. Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool. PLoS One 7, e46091, (2012). 9 Pass, H. I. et al. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med 367, 1417-1427, (2012).

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Abstract
Novel therapeutic targets have been revealed in lung cancer through the use of systematic large-scale sequencing approaches. While some of these are already part of routine clinical care, others still await confirmation in clinical trials. I will discuss basics of lung cancer genomics, differences in targets and target candidates in lung adenocarcinoma, squamous cell lung cancer and small cell lung cancer and problems arising during the path of translating basic discoveries into clinical practice.

Background
In order to improve prognosis and quality of lung cancer care the Danish Lung Cancer Group has developed a strategy consisting of national clinical guidelines and a clinical quality and research database. In 1998 the first edition of guidelines was published and a registry was opened for registrations in the year 2000. This abstract describes the methods used and the result obtained through the collaborative work and discusses how to improve the quality of lung cancer care through the development and monitoring of indicators.

Methods
A wide range of indicators was established, validated and monitored. By registration of all lung cancer patients since the year 2000, more than 40.000 patients have been included in the database. Results are reported periodically and submitted to formal auditing on an annual basis.

Results
Improvements in all outcome indicators are documented and statistical significant. Thus the one year overall survival has between 2003 and 2011increased from 36.6 % to 42.7 %; the 2 year survival from 19.8 % to 24.3 % and the 5 year survival from 9.8 % to 12.1 %. 5 year survival after surgery has increased from 39.5 % to 48.1 %. Improvements in waiting times, accordance between cTNM and pTNM and in resection rates are documented.

No	Indicator	Threshold (%)	2003 (%)	2004 (%)	2005 (%)	2006 (%)	2007 (%)	2008 (%)	2009 (%)	2010 (%)	2011 (%)	2012 (%)
Ia	Patients surviving 1 year from date of diagnosis	42	36,6	37,4	37,3	37,2	39,3	38,2	38,3	40,2	42,7
Ib	Patients surviving 2 years from date of diagnosis	22	19,8	20,5	20,7	20,9	22,9	21,8	23,0	24,3
Ic	Patients surviving 5 years from date of diagnosis	12	9,8	9,6	10,4	10,5	12,1
IIa	Patients surviving 30 days from date of operation	97	93,7	98,4	96,9	96,7	96,8	97,5	97,8	98,0	99,0	99,0
IIb	Patients surviving 1 year from date of operation	75	73,8	76,4	79,7	80,7	83,8	82,2	86,1	85,9	88,6
IIc	Patients surviving 2 years from date of operation	65	60,5	58,9	64,3	67,2	70,6	66,6	73,6	75,5
IId	Patients surviving 5 years from date of operation	40	39,5	38,8	44,5	46,9	48,1
IIIc	Rate of patients starting chemo within 42 days after referral	85	62,9	51,1	50,3	56,0	59,8	73,4	72,7	74,7	80,8	82,9
IV	Rate of patients with accordance between cTNM and pTNM	85	68,2	70,2	77,0	72,7	79,8	77,6	80,1	83,3	86,4	91,3
V	Rate of patients with NSCLC who had a resection	20						18,7	18,9	19,8	20,4	19,8

Conclusion
The Danish experience shows that a national quality management system including national guidelines, a database with a high degree of data quality, frequent reports, audit and commitment from all stakeholders can contribute to improve clinical practice, improve core results and reduce regional / geographic differences.

Background
One goal of the current French National Cancer Plan is to reduce health inequities in cancer control. In this study, an underprivileged population was investigated to analyze exposure to lung cancer risk factors and health care access in order to highlight ways to improve lung cancer control in that population.

Methods
Within the nationwide observational study EDIFICE 3, conducted by phone interviews among a representative sample of 1603 subjects aged between 40 and 75 years old, we used the “EPICES” validated questionnaire to examine the association of underserved status with lung cancer risk factors, beliefs, and health care access.

Results
Based on the EPICES score, underserved subjects represented 33% of the sample. These subjects subjectively perceived a higher risk of cancer compared to subjects in the served population (21% vs. 14% respectively, p<0.01). Among people with cancer, underserved subjects have a higher rate of lung cancer (10% of cancers vs. 1%, p<0.05). They also have more cancer risk factors: a high BMI (26.0 vs. 24.8, p<0.01), are active smokers (38% vs. 23%, p<0.01) with a higher consumption of cigarettes (16.0 cigarettes/day vs. 10.1, p<0.01) and for a longer period (29.4 years vs. 26.3, p<0.01), and also practice less sport (42% vs. 77%, p<0.01). They have more comorbidities: on average (2.2 vs. 1.8, p<0.01), at least one (76% vs. 65%, p<0.01), hypertension (24% vs. 19%, p<0.05), cardiovascular disease (13% vs. 9%, p<0.05) and respiratory disease (13% vs. 7%, p<0.01). Access to healthcare is not an issue (consultations with a general practitioner are more frequent for the underserved group: 5.4 vs. 3.7 per year, p<0.01). They trust the national health system less (an average score from 1 to 10; 6.0 vs. 6.3, p <0.05). However, 85% of underserved subjects think that lung cancer can be efficiently screened vs. 78% of the served population (p<0.01).

Conclusion
In order to reduce inequities in lung cancer control, the effort of upstream interventions should be focused on prevention, as healthcare access does not discriminate. Underserved subjects have a high level of trust in lung cancer screening but a riskier behavior in terms of smoking. This constitutes new targets for specific communication campaigns and Health authorities’ interventions.

Background
Lung cancer results from the combined effects of smoking exposure and genetic predisposition. Recent studies have shown that susceptibility to chronic obstructive pulmonary disease (COPD) is also relevant to a predisposition to lung cancer. The latter may be mediated in part through exaggerated systemic inflammation secondary to smoking exposure and the innate response to smoking in genetically susceptible people. Recently a large population based study reported that statin therapy was associated with a reduction in mortality from cancer (Nielsen et al. Statin Use and Reduced Cancer-Related Mortality, NEJM 2012; 367: 1792-1802). The aim of this study was to examine the cancer specific effect of statins on mortality.

Methods
Using the raw data from the Nielsen study, we calculated the estimated number of lives saved from statin therapy use according to type of cancer and then estimated the absolute numbers of lives saved.

Results
When we examined the raw data showing hazard ratios according to statin use in each of the cancers described, we found that except for lymphoma, the mortality reductions were significant for smoking related cancers (lung, pharynx, oesophagus, urinary) and obesity-related cancers (colon, prostate, breast - see Figure 1). When we calculated the number of lives saved according to specific cancer type, we found that of all lives saved, 43% could be attributed to a reduction in lung cancer deaths (Table 1). Importantly, mortality for many of these cancers (lung, colon, breast and prostate) has been associated, in large prospective studies, to elevation of the C-reactive protein, a marker of systemic inflammation. Figure 1Figure 2

Conclusion
We conclude that the reduction in cancer mortality attributed to statin therapy by Nielsen et al. is seen almost exclusively in cancers where smoking and/or systemic inflammation is thought to be of significant pathogenic importance. Significantly, the single largest reduction can be attributed to lung cancer where both smoking and systemic inflammation are strongly implicated. We suggest that a reduction in systemic inflammation by statins may be one mechanism underlying the reduction in mortality reported by Nielsen and colleagues.

Abstract not provided

Background
Smokers with a family history of cancer are at higher risk for developing cancer. A diagnosis of cancer within the family may provide an opportunity for smokers to adopt health-promoting behavior. This study examined associations between having a first-degree family history of cancer and smoking status.

Methods
Data from the 2009 California Health Interview Survey (CHIS) on 47,331 adults were used in this cross-sectional study. Sample weights were applied to account for the complex survey design with results generalizable to non-institutionalized adults in California (27.4 million). Smoking status was classified as current, former, or never-smoker. Family cancer history was defined as blood relatives that include biological father or mother, full brothers or sisters, or biological sons or daughters. Demographic characteristics included age, gender, race/ethnicity, marital status, poverty level, education level and health insurance coverage. General health status, physical activity, body weight status and binge drinking status were also included. CHIS defined binge drinking status as ≥5 alcoholic drinks for males or ≥4 alcoholic drinks for females in a single episode in the past year. Body weight status was defined by body mass index as underweight <18.5 kg/m2, normal = 18.5–24.9 kg/m2, overweight = 25.0–29.9 kg/m2, and obesity ≥30.0 kg/m2. Multinomial logistic regression was used to analyze the association between first-degree family history of cancer and smoking status.

Results
In 2009, 13.6% (3.7 million) of the 27.4 million adults were current-smokers, 23.0% (6.3 million) former-smokers and 63.4% (17.4 million) never-smokers. Thirty-five percent (9.6 million) had a first-degree family history of cancer (Table 1). Among those with a first-degree family history of cancer, 13.5% (1.3million) were current-smokers, 29.7% (2.8 million) were former-smokers and 56.8% (5.4 million) were never-smokers. Adults with a first-degree family history of cancer were more likely to be former-smokers compared with adults without a first-degree family history of cancer (29.7% vs. 19.3%, p<.001). Controlling for demographic factors and other risk characteristics (binge drinking, obesity, physical activity), having a first-degree family history of cancer was significantly related to being a current-smoker (OR=1.16; 95% CI=1.01-1.34) and former-smoker (OR=1.17; 95% CI 1.05-1.30).

Table 1: Characteristics of California Health Interview Survey participants, 2009

Characteristics	Unweighted sample size	Weighted percentages (95% CI)
Smoking Status
Current smokers	5,528	13.6 (12.8-14.4)
Former Smokers	14,487	23.0 (22.1-23.8)
Never smokers	27,317	63.4 (62.5-64.3)
Family Cancer History
Yes	22,286	35.0 (34.1-35.8)
No	25,045	65.0 (64.1-65.8)
Age
18-25	2,826	16.0 (15.6-16.4)
26-34	3,446	15.6 (15.0-16.0)
35-49	10,484	30.2 (29.7-30.5)
50+	30,575	38.2 (38.1-38.2)
Gender
Male	19,280	49.0 (49.0-49.1)
Female	28,051	51.0 (50.0-51.0)
Race/Ethnicity
Hispanic	8,281	32.5 (32.4-32.5)
Non-Hispanic White	30,951	46.4(46.4-46.5)
Non-Hispanic Black	1,839	5.6 (5.6-5.7)
Non-Hispanic Asian	4,833	12.8 (12.8-13.0)
Non-Hispanic Other	1,427	2.6 (2.5-2.6)
Marital Status
Married	27,079	61.3 (60.5-62.2)
Not-married	20,252	38.6 (37.8-39.5)
Federal Poverty Level (FPL)
< 100% FPL	5,747	16.0 (15.3-16.8)
100-199 % FPL	7,950	18.0 (17.2-18.7)
200-299 % FPL	6,478	13.7 (13.0-14.5)
≥ 300% FPL	27,156	52.2 (51.3-53.1)
Education Level
< High-school	4,795	16.3 (16.1-16.4)
High-school graduate	10,345	26.0 (25.8-26.0)
Some college	12,858	23.7 (23.0-24.5)
College or more	19,333	34.0 (33.3-34.7)
Health Insurance
Currently insured	42,186	82.0 (81.0-82.8)
Not insured	5,145	18.0 (17.1-19.0)
General Health
Excellent/Very Good	24,554	52.0 (51.0-52.8)
Good	13,588	29.8 (28.4-30.8)
Fair/Poor	9,189	18.2 (17.4-19.0)
Body Weight Status
Underweight	1,051	2.2 (2.0-2.5)
Normal	19,689	41.3 (40.4-42.3)
Overweight	16,078	33.7 (32.8-34.5)
Obese	10,513	22.7 (21.8-23.5)
Physical Activity
Sedentary	16,936	34.6 (33.6-35.7)
Some activity	20,838	43.4 (42.3-44.5)
Regular activity	9,557	21.8 (21.0-22.7)
Binge drinking status
Yes	11,049	31.4 (30.5-32.3)
No	36,282	68.5 (67.6-69.4)

Conclusion
In California, many adults with a first-degree family history of cancer still smoke which places them at higher risk for poor health outcomes. Smokers with a first-degree family history of cancer may be an important target population for smoking cessation interventions.

Background
Australia established its first national quitline service in 1997 as part of the Australian National Tobacco Campaign (NTC). In 2005 our hospital, an Australian tertiary specialist cancer centre, commenced a multidisciplinary smoking cessation program which included the provision of counselling and behaviour techniques as well as free access to pharmacological smoking cessation agents. In 2007 the hospital went totally smoke free and in 2009 all new patient registrations included collection of information pertaining to smoking behaviours. Cancer patients are known to withhold and underreport details regarding current and previous smoking behaviours however there is limited data on the impact of non-disclosure on the ability to implement interventional smoking cessation programs in the oncology setting. Five years after initiation of an interventional smoking cessation program we present previously uncollected and unreported hospital wide smoking behaviour data (prevalence, magnitude and willingness to report) of cancer patients. We also evaluate our multidisciplinary smoking cessation model including recruitment and quit rates for cancer patients at a specialist oncology centre.

Methods
For the two year period 2009-2011 self-reported smoking behaviors were obtained from hospital registration datasets. A retrospective single arm cohort study, including patients with a cancer diagnosis who accessed the smoking cessation program within the same two year period, was also conducted. Patients and family members are recruited to the program via a multidisciplinary referral system and have access to nurse led counselling and behaviour modification consultations as well as provision of free pharmacological smoking cessation aids. Evaluation of the program was undertaken through and audit of medical and pharmacy records for all patients who participated in the program (n=312) and by phone interviews with a subset of patients (n=30) and compared to data from a previously published study at our institution[1].

Results
50% (n=10,401) of patients newly registered to the hospital identified as having ever smoked with 12% (n=2448) current smokers. Recruitment of self-identified active smokers into the smoking cessation program was low (7.3%). 43% (n=134) of patients enrolled into the program had not disclosed their smoking status at hospital registration. Magnitude of smoking was high; average pack-years of patients who have ever smoked was 22.6 and for current smokers was 27.8; 155 patients reported smoking magnitude as greater than 100 pack years. Provision of free pharmacotherapy equated to a net expenditure of AUD$22,042. Point prevalence smoking cessation rate among patients who participated in follow-up interviews (n=30) was similar to that previously reported following participation in our multidisciplinary smoking cessation program, 33% compared to 37%[1]. 66% of patients reported successful outcomes (cessation or reduction in consumption).

Conclusion
Patient-reported smoking behaviours were grossly underreported impacting on the ability to actively enrol patients into established interventional cessation programs. Despite low recruitment rates and high magnitude of smoking, the multidisciplinary model was able to achieve successful outcomes at minimal cost in this vulnerable patient cohort. Improving disclosure practices may enable future targeted recruitment of patients by health-care professionals and increase the participation of smokers in proven healthcare interventions.

Background
Lung cancer screening programs provide unique opportunities to facilitate smoking cessation in smokers who participate in these programs. However, the effects of screening on motivation to quit might be mediated or modified by other variables. Identifying the participants more likely to quit will allow rapid application of smoking cessation resources to these participants, while those least likely to quit can be afforded experimental interventions. The aim of our study was to assess the impact of lung cancer screening on smoking cessation in current smokers at the time of enrollment and to identify factors that were associated with quitting smoking in this screening population.

Methods
Using data collected from the Pan-Canadian Study of Early Detection of Lung Cancer, both univariate and multivariable logistic regression analysis was used to identify predictors of smoking cessation among current smokers at enrolment. Smoking cessation was defined as quitting for at least a 6 month period, occurring anytime after enrolment.

Results
We analyzed baseline and follow-up questionnaires of 2320 participants, of which 1419 were current smokers. Of these 1419 patients, 392 (27.8%) met the definition of smoking cessation during a median of two annual follow-up visits. In both univariate and multivariable (MV) analysis, greater smoking cessation was associated with four factors: (i) having a diagnosis of lung cancer at any time during the screening process, with a MV Odds ratio (OR) of quitting of 2.4 (95%CI: 1.1-5.0); (ii) lower and medium nicotine addiction as assessed by the Fagerström Nicotine Dependence Scale Score, with MV-ORs of 3.2 (95%CI: 2.2-4.6) and 1.4 (95%CI: 0.9-2.0), respectively; (iii) having higher education, with MV-OR: 1.4 (95%CI: 1.1-1.9); and (iv) having an earlier age of onset of regular alcohol intake, with MV-OR of 1.11 (95%CI: 1.02-1.21) per 5 year decrease in age. Smoking cessation was also associated with (i) previous attempts of quitting [UV-OR 1.8 (95%CI: 1.2-2.7)], willingness to quit smoking within the next month (at baseline screening) [UV-OR 2.2 (95%CI: 1.8-2.9)] or within the next 6 months after baseline screening [UV-OR 1.8 (95%CI: 1.3.-2.4)]. Second-hand smoking exposure, including exposure as a child, or as an adult at work, at home, privately with friends, or in public settings, or a cumulative index of these different exposures, was not associated with smoking cessation. Presence of potential index symptoms for lung disease, including shortness of breath, cough (both dry and productive), hoarseness, audible wheezing or even chest pain, was not associated with an increased chance of smoking cessation.

Conclusion
The diagnosis of a new lung cancer had a major positive impact on screening participants quitting smoking, as were factors such as lower nicotine dependence, higher education, earlier starting alcohol drinking age, and willingness to quit. Whether a new lung cancer diagnosis triggered additional efforts by clinicians to help the person quit will be explored further. Individual lung symptoms and secondhand smoke exposure were not associated with smoking cessation. (Geoffrey Liu and Martin Tamemmagi are co-senior authors)

Abstract not provided

Background
A projected 75% increase in cancer deaths are expected in Low and Middle Income Countries (LMIC) by 2020. As successful battles against infectious disease and malnutrition deaths are waged, the demands on poor healthcare systems to create affordable oncology infrastructure will become ever more acute. Effective and efficient collaborative technologies that permit presentation of cases from resource limited environments to healthcare professionals in the developed world can aid in decision making, treatment planning and education. In this trial a novel clinical platform was launched in Haiti and we present a case of a chest wall malignancy demonstrating the platform's capacity for collaboration and clinical management between a resource limited community hospital in Haiti and Academic Medical Centers in the United States.

Methods
An Extensible Markup Language (XML) based system was built according to specifications of clinicians in the Thoracic Oncology Service of University of California San Francisco Medical Center. In a community hospital in Saint Marc, Haiti 30 cases involving a variety of clinical conditions across adult and pediatric oncology and traumatic disease were presented to Academic Medical Center volunteer physicians in the United States on a web-based asynchronous clinical collaboration system. The infrastructure required transfer over a wireless network in Haiti followed by secure transmission via internet to the dedicated servers in the United States.

Results
Case 1: A 32 year old Haitian Male presented to the Hopital Saint Nicholas in Saint Marc, Haiti with posterior chest and shoulder pain and a chest wall mass extending to the scapula. X-rays revealed a destructive lesion of the chest wall without frank mass within the pulmonary parenchyma. An open biopsy was performed and the specimen transferred for pathologic evaluation at The University of California San Francisco. Clinicians from 3 medical centers in the US came to a consensus opinion regarding diagnosis (unicentric plasmacytoma of chest wall) and treatment strategy within 3 days. Digital images of Immunohistochemical staining, X-rays uploaded to the collaboration platform via a smartphone photo app and literature reviews of the case were transmitted to Haitian physicians including a treatment plan recommendations . 29 additional patients have been offered evaluation in a web based environment and will be discussed.

Conclusion
Oncology cases in the developing world are increasingly prominent in light of advances in combating infectious disease and poverty related malnutrition. However resource limited environments may not have access to clinical decision tools, diagnostic measures or treatments commonplace in fully developed countries. Inexpensive collaborative technologic tools as demonstrated in this pilot can serve as a bridge between developed and developing countries in combination with the will to improve health among the planet's poorest communities

Background
Lung cancer remains the United Kingdom's commonest cause of cancer death and accounts for 1 in 14 of UK deaths from cancers. Approximately 41,428 new cases of lung cancer and 2500 new cases of mesothelioma are diagnosed in the UK (CRUK : Cancer Research UK 2009.) Evidence shows eighty per cent of people will present with advanced disease and the majority of these will die within a year of diagnosis (CRUK 2009.) There is a large amount of evidence in existence to support end of life care but this is very generic in nature. Consensus opinion from the National Lung Cancer Forum for Nurses recognised the need for specialist guidance for lung cancer and mesothelioma patients to enhance their end of life experience and to inform health care professionals who are caring for this group of patients. The focus of the project was to develop guidance driven by evidence from patients and carers, to focus on issues highlighted by them that were important. Previous guidance produced had not had this direct focus.

Methods
This guidance has been developed over an eighteen month period by a dedicated working party with expertise in caring for lung cancer and mesothelioma patients and carers and incorporating current evidence and guidance which was reviewed extensively. The document provides detailed supportive and palliative care specialist interventions to assist any health care professional who is caring for a patient with advanced lung cancer or mesothelioma. The guidance is focused around nine key elements that were identified in work carried out by the Health Experience Research Group at the University of Oxford. Cancer patients identified nine key areas of their care that were important to them or that they found to be lacking. Holistic approach to care. Getting the bad news. Care co ordination. Responsiveness and ease of access to benefits and support. Pain control and symptom management. Staff attitudes and empathy. End of life choice and the actual experience. Carer focus. Each of these nine key elements are addressed within the guidance. Recommendations are made based on evidence and specialist experience. Good practice examples are included collected from a wide range of lung cancer services across the United Kingdom to assist users to develop their own practice.

Results
The guidance was completed and published in Novmber 2012. The guidance provides a usable document with evidence and practice examples to assist health care professonals to improve supportive and palliative care within their area. The document is being diseminated locally by specialist lung cancer nurses and nationally via the National Lung Cancer Forum for Nurses.

Conclusion
Although recently published and to date has not been formally evaluated, this guidance has been well received by health care professionals and organisations associated with the care of lung cancer and mesothelioma patients. References 1. Cancer Research UK (2009) : Incidences of Lung Cancer (online) Cancer Research UK. Available from 2. Health Experience Research Group (HERG) University of Oxford, GC Associates, Unpublished.

Background
Lung cancer is the leading cause of death from cancer in Australia with the majority of patients diagnosed with late stage incurable disease. Although there is evidence of patient benefit from early involvement with specialist palliative care, this may not translate into clinical practice. The aim of this study was to explore clinicians’ perceptions and attitudes to Palliative Care referral.

Methods
A modified validated self-report palliative care referral questionnaire (Johnson, 2008) was given to doctors and nurses working in the multi-disciplinary lung cancer teams at three teaching hospitals in metropolitan Melbourne. Participants were asked whether listed items had contributed to referral (9 triggers) or non referral (15 barriers) of their patients. Level of agreement with 22 attitudinal and perception items explored clinicians’ views about palliative care.

Results
55 questionnaires were distributed and 42 completed (76% response rate). Respondents had a median of 6 years (interquartile range 3-12) of experience practicing in their specialty. One-third (14/42) were doctors working in Medical Oncology, 26% (11/42) in Respiratory Medicine, 19% (8/42) in Radiation Oncology, and 12%, (5/42) in Surgical Oncology, plus two oncology nurses and one physician trainee.93% of respondents agreed that early referral to Palliative Care is beneficial to patients and 95% agreed that Palliative Care can benefit patients receiving active treatment. The majority (69%) of clinicians believe that their relationship with the patient continues when she/he elects to have specialist palliative care. 71% indicated that it is not difficult to refer a patient they have cared for a long time and have a close relationship with. Almost two-thirds (64%) disagreed that when they first bring up palliative care patients give up hope. However, only 60% of respondents agreed that all advanced cancer patients should be referred to Palliative Care. The most frequently cited reasons for referral were for physical symptoms. The majority reported that Palliative Care is either very important or important for patients with psycho-social issues or foreseeable future psycho-social issues, yet only half of respondents agreed that psycho-social issues would trigger a referral to Palliative Care. When asked for the main reasons for not referring to Palliative Care, 60% agreed they do not refer when the patient has no symptoms and 60% also agreed they do not refer if they can manage the patients’ symptoms themselves. However, only 38% of clinicians reported they were well trained to take care of the symptoms of advanced cancer patients. Issues related to patients not understanding or accepting their prognosis were cited as barriers to referral by more than a third of clinicians.

Conclusion
Clinicians involved in the care of patients with incurable lung cancer have positive perceptions and attitudes to Palliative Care but this may not translate into routine referral of all patients with incurable lung cancer. In order to make referral routine, we need education around the perception that only patients with unmanageable symptoms benefit from referral to Palliative Care. Furthermore, additional training of oncologists about symptom management appears desirable since a significant proportion reported a deficiency in this area.

Abstract not provided

Background
Palliative radiotherapy to the thorax is very effective at managing symptoms and improving quality of life but can also have significant toxicity. Dosing decisions are a balance between potential benefit and toxicity in patients whose prognosis and performance status is poor and who are likely to have multiple co-morbidities and complex causation of symptoms. Observations made by the members of the Uinted Kingdom National Lung Cancer Forum for Nurses (NLCFN) raised concerns that this group of patients may not be receiving optimal intervention and support following palliative radiotherapy. The NLCFN has therefore produced Guidance for the Assessment of Patients following Palliative Radiotherapy for Lung Cancer to aid Lung Cancer Nurse Specialists (LCNS) in the assessment and intervention of patients undergoing low dose palliative radiotherapy for symptoms related to lung cancer and side effects from treatment.

Methods
A NLCFN working group was created to analyse the observation of sub-optimal care following palliative radiotherapy. A literature review was undertaken to identify current best evidence and practice. A survey was undertaken to question LCNS, Clinical Oncologists, as well as Radiographers who could provide whether there was a need for such a guideline. 53 responses were received. Following analysis of the survey and discussion within the working group the Guidance for the Assessment of Patients following Palliative Radiotherapy for Lung Cancer was produced. The guidance aims to aid LCNS in the assessment and intervention of patients undergoing low dose palliative radiotherapy for symptoms related to lung cancer and side effects from treatment. Table 1 Figure 1Figure 2Figure 3

Results
Following the literature review, although there was significant evidence of toxicity profiles and effects of treatment, there were no examples of how to address the support needs of patients following palliative radiotherapy to the thorax. Of the 53 responses, 75% said that there was a need for the service, 54% were not aware of current practice in radiotherapy follow up support, with 55 % stating that a review should take place between 1 and 2 weeks after treatment. The working group produced the guideline following discussion in relation to these outcomes.

Conclusion
The Guidance for the Assessment of Patients following Palliative Radiotherapy for Lung Cancer aims to guide LCNS and the treating teams in the assessment and intervention of patients undergoing low dose palliative radiotherapy for symptoms related to lung cancer. The guideline contains flow charts with recommended interventions together with documentation proforma and Common Toxicity Criteria. In the UK patients are treated in Cancer Centres and often repatriated to secondary care for review and follow-up. The formal assessments provided in the Guidance can be implemented either in the clinic, telephone or home visit. The guideline could be adapted for use in other health care systems other than the UK and can be found at http://www.nlcfn.org.uk/NLCFN-guidelines.htm

Background
Between 01/01/2006 and 31/12/2011, 1070 cases of non-small cell lung cancer (NSCLC) were registered in the Illawarra Shoalhaven Local Health District (ISLHD) Clinical Cancer Registry (ClinCR); having been diagnosed and/or received a cancer directed treatment (including end-of-life palliative care) in an ISLHD public facility. A retrospective study was undertaken to determine the impact palliative care involvement had on the place of death for patients in this cohort who were known to be deceased.

Methods
A retrospective study was undertaken using data recorded in ClinCR. Data items include date of death, name of public facility where death occurred, palliative care status and date of referral to palliative care. Patients who did not die in public hospital had the place of death recorded in a free text box in ClinCR if it was documented in one of ISLHD’s electronic medical records: PowerChart, iPM, CHIME or MOSAIQ.

Results
Of the 1070 cases, 936 (87.5%) patients were known to be deceased, with 93% (872n) of those patients dying locally: palliative care facility 52% (454n); hospital 27.5% (240n); home 14.5% (127) and RACF 6% (51n). The remaining 7% died out of the Area (12n) or had “unknown” recorded for place of death (52n). 87% of those known to be deceased were referred to palliative care. Of the deceased patients not referred to palliative care, 45% died in an acute hospital, compared to 14% of those who were referred to palliative care. Home was the second most frequent place of death (15% 121n) for patients referred to palliative care.

Conclusion
This study shows the impact palliative care involvement had on the place of death for non-small cell lung cancer patients in ISLHD. Although more than 50% died in a dedicated palliative care ward/facility, the data shows that patients with palliative care intervention are more likely to die in their home, and less likely to die in an Acute Hospital. Patients with respiratory cancers may require hospital admissions due to local complications which may not occur in other cancers; making a comparison between this and another tumour stream a worthwhile exercise.

Background
Data from the Ontario Cancer System Quality Index demonstrate a high use of Emergency Department (ED) services by lung cancer patients in the last three months of life. There is a need to better understand the resource utilization of lung cancer patients during this time period.

Methods
A retrospective cohort study was undertaken to evaluate resource utilization in the last three months of life for new patients with lung cancer seen at the Juravinski and Walker Family Cancer Centres between January and June 2011and deceased prior to July 2012. Data abstracted from patient records included demographics, staging, treatment, referral to palliative care, use of community services, visits to the cancer centre and family doctor, visits to the emergency department and hospitalizations in the last three months of life. The primary outcome was the proportion of patients using the ED in the last three months of life. Secondary outcomes include the proportion of patients hospitalized, place of death, and the use of community and palliative care services.

Results
There were 323 new patients seen during the six month period and 162 were deceased at the time of data cut-off. There were 86 men (53%) and 76 women (47%), with a median age at diagnosis was 68.9 years (range 38-90). The majority were married (66%), but 20% were living alone. Twenty percent of patients had SCLC, 73% NSCLC and 7% did not have tissue diagnosis. Most patients (n=141, 87%) were treated with palliative intent from the outset. Chemotherapy was administered to 63 patients (39%) with 11 (7%) receiving chemotherapy within the last 2 weeks of life. A greater proportion of patients received radiation therapy (n=111, 69% [10% radical, 90% palliative]). The median overall survival was 4.1 months (95%CI 3.4-4.8m). The majority of patients (n=132, 82%) were referred to community care services (CCAC) and most of these received community palliative services (n=113, 70%). The median time from CCAC referral to death was 2.5 months (0.3 – 31 months). There was documentation about a change in goal from active treatment to supportive care in 38% of patients and documentation of end of life discussion in 66% of patients. Place of death was: hospital (51%), home (21%), hospice/palliative care institution (20%), unknown (8%). During the last three months of life 93% visited the cancer centre (median visits 2, range 0-10) and 67% made calls to the cancer centre (median 1, range 0-19). Visits to the ED were made by 118 patients (73%, median visits 1, range 1-9) and 36 patients were hospitalized (22%, median 1, range 1-5). Patients referred to CCAC were less likely to visit the ED (72% v 83%, p=0.2).

Conclusion
Lung cancer patients use considerable range of services during the last three months of life. Use of acute care services such as the ED and hospitalizations are common. CCAC referral has a small impact on the use of acute care services.

Abstract not provided