OA 06.03 Comorbidity and Competing Causes of Death attenuate outcomes in the NLST

S1758 quit rate of 5% per cessation attempt. Cost-effectiveness was estimated with a lifetime horizon, health system perspective and 1.5% discount rate. Costs are in 2016 CAD. Result: Cessation within a screening program with 60% recruitment and 70% rescreening (adherence) would cost approximately $76 million (undiscounted) per year for 2017-2036 or 8% of the total cost of screening, treatment and cessation. Compared to screening with no cessation, approximately 110 fewer incident cases and 50 fewer lung cancer deaths would occur on average per year for 2017-2036 and cost $14,000/QALY (lifetime horizon). 90% recruitment and 80% rescreening would result in 260 fewer deaths and cost of $24,000/QALY. At a doubled permanent quit rate of 10%, screening with cessation would cost $6,000/QALY. A 50% increase in the cost of the cessation intervention would decrease costeffectiveness to $22,000/QALY. Conclusion: Based on the OncoSim-LC model, a cessation program within an organized LDCT screening program would cost well under $50,000/QALY even over multiple quit attempts. Integrating robust smoking cession initiatives within a LDCT screening program could save lives and be relatively cost-effective.

OA 06.02 Final Report of the INHERIT EGFR Study - 33 Unrelated Kindreds Carrying Germline EGFR Mutations G. Oxnard,1 J. Heng,1 R. Chen,1 D. Koeller,2 K. Shane-Carson,3 R. Morgan,4 G. Wiesner,4 J. Garber2 1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA/US, 2Center for Cancer Prevention and Genetics, Dana-Farber Cancer Institute, Boston, MA/US, 3Clinical Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH/US, 4Genetic Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN/US Background: Anecdotal reports of families carrying germline EGFR mutations force us to reconsider our understanding of inherited lung cancer risk in non-smokers. We launched this prospective trial (NCT01754025; ALCMI-002) to remotely enroll and characterize these rare families. Method: Eligible subjects were recruited at participating cancer centers or through an online referral system. Following consent (in person or by phone), subjects received genetic counseling and sequencing of saliva or blood for germline EGFR mutations. Cancer specimens and CT scans were additionally analyzed when available. Result: Between 12/2012-6/2017, 105 participants were enrolled from 30 US states. Germline EGFR mutations were found in 63% of patients (31 of 49) with EGFR T790M in their lung cancer at diagnosis, and in 62% (16 of 27) and 44% (4 of 9) of first- and second-degree relatives of germline carriers. Pedigrees were available for 32 unrelated kindreds (31 germline T790M, 1 germline R776H): 4 with no family history of lung cancer, 8 with a family history of lung cancer in nonsmokers, 18 with multiple relatives with lung cancer. Characteristics of 31 lung cancer probands: median age of lung cancer diagnosis was 57 (range 28-82); 81% white, 19% black; 52% never-smokers; 65% stage IV at diagnosis; 65% were from states in or bordering the US Southeast. Tumor genotyping revealed somatic EGFR co-mutations in 29 (94%) of probands: 6 exon 19 del, 12 L858R, 6 G719X, 1 exon 19 del & G719R, 1 L861Q, 2 H773R, 1 V774M. Imaging analysis suggests a unique pattern of cancer evolution including an indolent multi-focal nodular phase which then progresses to lymph nodes and then remote metastatic disease. Of 8 probands with sensitizing EGFRco-mutations treated with osimertinib, no unexpected toxicities were seen, and 4 have had durable benefit exceeding 12 months. Of 9 relatives with germline EGFR mutations and CT imaging available, 2 have a lung cancer diagnosis and 6 others have lung nodules. Conclusion: This study confirms the high likelihood of a germline mutation in lung cancer patients with EGFR T790M detected at diagnosis, and suggests a risk of lung nodules and lung cancer in germline carriers. The regional enrichment in the US Southeast suggests a possible founder effect; haplotyping is planned. A registry is under development to continue follow-up of these rare

Journal of Thoracic Oncology

Vol. 12 No. 11S2

individuals. Further investigation of germline risk alleles associated with lung cancer risk in non-smokers is needed. Funding: Bonnie J. Addario Lung Cancer Foundation, Conquer Cancer Foundation of ASCO. Keywords: Germline EGFR mutations, EGFR T790M, familial lung cancer

OA 06.03 Comorbidity and Competing Causes of Death attenuate outcomes in the NLST R. Young,1 R. Hopkins,2 G. Gamble2 1Faculty of Medical Health Sciences, University of Auckland, Auckland/NZ, 2University of Auckland, Auckland/NZ Background: In the National Lung Screening Trial (NLST), annual CT screening reduced lung cancer-specific mortality by 20% and all-cause mortality by 7% relative to chest x-ray (CXR) screening. However, in contrast to other screening approaches, recommendations for CT screening for lung cancer is limited to older heavy smokers, where the risk of death from all smoking-related complications is high, relative to the unscreened population. In the NLST, airflow limitation affects 35% of screening participants and is associated with a 2-4 fold increase risk of lung cancer. We have recently shown that for screening participants with COPD, the reduction in lung cancer-specific mortality with CT screening is only half that seen in those with no COPD (15% vs 28%). We hypothesize that this reduction is due in part to a “competing cause of death” effect. Method: Using 10,054 subjects from the ACRIN-NLST sub-study, the current study aimed to compare disease-specific mortality according to the severity of airflow limitation at baseline to better understand its relationship with dying of lung cancer and dying of other smoking-related diseases. We also examined this relationship according to baseline risk of lung cancer, using the Brock (Lung cancer risk) Model, and outcomes from screening. Result: After 6.4 years of follow-up, there were 699 deaths; 189 (27%) attributed to lung cancer, 166 (24%) to cardiovascular disease, 61 (9%) to respiratory disease and 150 (21%) to other cancers. After stratifying the 10,054 subjects according to severity of airflow limitation (baseline FEV1%predicted and GOLD grade), we found that the risk of dying of lung cancer and risk of dying of other diseases diverged favoring a stronger relationship with non-lung cancer causes. After stratifying the 10,054 subjects according to their risk of lung cancer (tertiles), we found that CT screening in those at highest risk (highest tertile) had only a 12% reduction in lung cancer-specific deaths compared to 23-24% in other lower risk tertiles. This was associated with higher deaths from cardiovascular disease, respiratory disease and other cancers. Conclusion: In a CT screening study, where smokers were followed for a mean of 6.4 years, we found worsening lung function and higher underlying risk for lung cancer was associated with a greater tendency to die of causes other than lung cancer. We suggest smokers at the greatest risk for lung cancer, and those with worse lung function, benefit less from CT screening due to a “competing cause of death” effect. Keywords: lung cancer, Comorbidities, Airflow Limitation

OA 06.05 Socioeconomic Factors Affecting Outcomes in NonSmall Cell Lung Cancer (NSCLC): A Large PopulationBased Analysis Y. Lou,1 B. Dholaria,1 A. Soyano,1 D. Hodge,2 S. Ailawadhi1 1 Hematology and Oncology, Mayo Clinic, Jacksonville, FL/US, 2Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL/US Background: Disparities exist in cancer outcomes. NSCLC outcomes have improved in recent years but effects of socioeconomic factors have not been reported. Method: The National Cancer Database with NSCLC incident cases 2004-2013 was analyzed. Overall survival (OS) was explored by several available factors with a focus on race and