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MA05.06 Diagnosis of Chronic Obstructive Pulmonary Disease in Lung Cancer - A Population Based Study
S366
Journal of Thoracic Oncology
samples and subjected to quantitative and qualitative assessment. Sequencing for EGFR, KRAS, BRAF mutations was performed in adenocarcinoma/non-small cell lung cancer not otherwise specified (NSCLC-NOS) cases. Results: Samples were obtained in 41 patients. Cytological diagnosis was adenocarcinoma/NSCLC-NOS in 25 (61.0%), squamous cell carcinoma in 10 (24.4%), small cell lung cancer in 5 (12.2%), and carcinoid in 1 (2.4%) case. DNA extraction yielded a mean of 4.03mg, well above the minimum required quantity for targeted sequencing of 10ng (Table 1). DNA quality measured by DNA Integrity Number could be calculated in 35 (85%) cases with a mean of 8.9, where >7 is acceptable for sequencing (Table 1). Sequencing results of adenocarcinoma/NSCLC-NOS cases show mutations in EGFR in 6, KRAS in 8, BRAF in 1 case. Wild type was demonstrated in 6 cases. Molecular analysis of the corresponding study samples is proceeding. Table 1. DNA quantity and quality Histological subtype
Cases, n (%)
Mean DNA Mean DNA quantity Integrity (mg) Number (DIN)
Adenocarcinoma/ 25 (61.0) 3.83 NSCLC-NOS Squamous cell carcinoma 10 (24.4) 2.65 Small cell lung carcinoma 5 (12.2) 5.28 Carcinoid 1 (2.4) 16.24 Overall 41 4.03
8.8 9.0 9.0 9.1 8.9
Conclusion: A single EBUS-TBNA yields DNA of quantity and quality sufficient for molecular analysis, and is expected to be adequate for lung cancer genotyping. Keywords: EBUS-TBNA, lung cancer, Molecular
MA05.05 Genomic Profiles of Lung Cancer Associated with Idiopathic Pulmonary Fibrosis
Vol. 12 No. 1S
standardized consensus. However, despite recent progress in the understanding of pathogenesis and the treatment of LC in general population based on the advances in molecular genomics, the pathogenesis or molecular profiles of IPF-LC has been largely unknown to date. Methods: We assessed genomic profiles of IPF-LC using targeted exome-sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling were performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted using CNVkit with focal events determined by GISTIC 2.0, and pathway analysis (KEGG) using DAVID. Results: Germline mutations in TERT (rs2736100,n¼33) and CDKN1A (rs2395655,n¼27) linked with IPF risk were detected in most samples. A total of 410 somatic mutations were identified with an average of 11.7 per tumor including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop, 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C/T transitions despite extensive smoking histories across most study subjects, suggesting more associations with APOBEC3B-related mutagenesis in the process of IPF-LC development, rather than smoking. TP53 (22/35,62.9%) and BRAF (6/35,17.1%) genes were found significantly mutated in IPF-LC. Recurrent focal amplifications in 3 chromosomal loci (3q26.33, 7q31.2, and 12q14.3), and 9p21.3 deletion were identified, and genes associated with JAK-STAT signaling pathway were significantly amplified in IPF-LC (P¼0.012). Conclusion: IPF-LC is genetically characterized by the presence of somatic mutations reflecting viral and immune-related mutagenic processes in the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Keywords: idiopathic pulmonary fibrosis, genomic profile, lung cancer
Ji An Hwang, Deokhoon Kim, Soo Hyun Bae, Sung-Min Chun, Joon Seon Song, Mi Young Kim, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Sojung Park, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang Asan Medical Center, Seoul/Korea, Republic of
MA05.06 Diagnosis of Chronic Obstructive Pulmonary Disease in Lung Cancer - A Population Based Study
Background: Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer (LC) independent of the effect of cigarette smoking. The prognosis of IPF-associated LC (IPF-LC) is known to be worse than the lone IPF or LC mainly due to the complications accompanying LC treatment with no established or
John Goffin,1 Grace Tang,2 Gregory Pond,2 Sophie Corriveau3 1Oncology, Juravinski Cancer Centre, Hamilton/ON/Canada, 2Oncology, Ontario Clinical Oncology Group, McMaster University, Hamilton/ON/ Canada, 3Medicine, St. Joseph’s Hospital, Hamilton/ON/ Canada
January 2017
Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are associated through tobacco. COPD is underdiagnosed in the general population. Patients with lung cancer suffer from dyspnea and hospitalization for respiratory complications, and underdiagnosis of COPD could confer worse symptoms and morbidity. Using Institute for Clinical Evaluative Sciences (ICES) data, we assessed the diagnosis of COPD in the lung cancer population in Ontario, Canada. Methods: Cancer registry, hospital ICD-10 codes, physician billing data, and vital statistics were abstracted in an anonymized manner from ICES. COPD was defined using the validated ICES-derived COPD cohort and spirometry use was assessed through billing codes. Cancer stage was available from cancer registry data. Analysis was conducted using ICES’s confidential, analytic virtual environment using SAS v 9.3 in the population age >39 years. The local ethics board approved the study. Results: From 2004-2014, 90,783 individuals were diagnosed with lung cancer and 608,347 individuals diagnosed with COPD. Of individuals with lung cancer, 52.7% were male, median age at diagnosis was 65-69 years, and 82.8% have died. Of individuals with COPD, 51% were male, median age at diagnosis was 60-64 years, and 24.7% have died. The diagnosis of COPD was made at a rate of 8.7 persons per 1000 person-years. Among individuals having COPD, 48.4% underwent spirometry. 30.2% of individuals with lung cancer were also diagnosed with COPD and 60.8% underwent spirometry at any time. Among those with a diagnosis of both lung cancer and COPD, 73.6% underwent spirometry. For individuals with registry recorded stage data, 12,110 persons had stage I-II lung cancer, of whom 90.7% had spirometry and 55.9% had a diagnosis of COPD. Conversely, among 31,392 persons with stage III-IV lung cancer, 54.6% had spirometry and 46% were diagnosed with COPD (p<0.001 vs early stage for both). Conclusion: The diagnosis of COPD is not based on spirometry in half of cases. More patients with early stage lung cancer underwent spirometry and a higher rate of spirometry was associated with more diagnosis of COPD. Increased use of spirometry may improve the accuracy of a COPD diagnosis and may increase the diagnosis of COPD in advanced stage lung cancer, allowing improved dyspnea management in this population. Keywords: dyspnea, lung cancer, emphysema, spirometry
Abstracts
S367
MA05.07 Identifying Comorbid Disease on Chest CT Scans in a Lung Cancer Screening-Eligible Cohort Elizabeth Regan,1 Barry Make,1 Gregory Kinney,2 Matthew Budoff,3 Debra Dyer,1 Jeffrey Curtis,4 Russell Bowler,1 Meilan Han,4 Terri Beaty,5 John Hokanson,6 Elizabeth Kern,1 David Lynch,1 Edwin Van Beek,7 Edwin Silverman,8 James Crapo,1 James Finigan9 1Medicine, National Jewish Health, Denver/United States of America, 2University of Colorado Denver, Aurora/CO/United States of America, 3Los Angeles Biomedical Research Institute, Torrance/CA/United States of America, 4University of Michigan Health System, Ann Arbor/United States of America, 5Johns Hopkins Bloomberg School of Public Health, Baltimore/MD/United States of America, 6Epidemiology, Colorado School of Public Health, Aurora/CO/United States of America, 7 Clinical Radiology, Queen’s Medical Research Institute University of Edinburgh, Edinburgh/United Kingdom, 8 Brigham and Women’s Hospital, Boston/MA/United States of America, 9Medicine, National Jewish Health, Denver/CO/United States of America Background: Lung cancer screening (LCS) with chest CT scans in high-risk smokers has been demonstrated to save lives. Medicare and private insurers now cover these scans for beneficiaries under specific criteria. However, most smokers will die of comorbid smokingrelated diseases rather than lung cancer itself. Important information about comorbid conditions is available on screening chest CT scans, but the prevalence of these comorbidities has not been comprehensively assessed. Methods: COPDGene subjects from the Phase 1 visit who met USPSTF criteria for LCS (age > 55, >30 pack years smoking, current or former smokers within 15 years of smoking cessation or current smokers) were assessed for coronary calcification, emphysema, gas trapping, airway wall thickening and vertebral bone density on standard dose CT scans. A new diagnosis of emphysema, osteoporosis, or cardiovascular disease was assumed when there was no self-report of diagnosis or medication use. Results: In 76% of CT scans from LCS-eligible COPDGene subjects, we found abnormal emphysema (>5% low attenuation area @-950 Hounsfield units), airway wall thickening or gas trapping (>20% low attenuation area @-856 Hounsfield units). Osteoporosis was identified in 54% of all CT scans, and abnormal coronary artery calcium was present in 51%. In non-COPD
Journal of Thoracic Oncology
samples and subjected to quantitative and qualitative assessment. Sequencing for EGFR, KRAS, BRAF mutations was performed in adenocarcinoma/non-small cell lung cancer not otherwise specified (NSCLC-NOS) cases. Results: Samples were obtained in 41 patients. Cytological diagnosis was adenocarcinoma/NSCLC-NOS in 25 (61.0%), squamous cell carcinoma in 10 (24.4%), small cell lung cancer in 5 (12.2%), and carcinoid in 1 (2.4%) case. DNA extraction yielded a mean of 4.03mg, well above the minimum required quantity for targeted sequencing of 10ng (Table 1). DNA quality measured by DNA Integrity Number could be calculated in 35 (85%) cases with a mean of 8.9, where >7 is acceptable for sequencing (Table 1). Sequencing results of adenocarcinoma/NSCLC-NOS cases show mutations in EGFR in 6, KRAS in 8, BRAF in 1 case. Wild type was demonstrated in 6 cases. Molecular analysis of the corresponding study samples is proceeding. Table 1. DNA quantity and quality Histological subtype
Cases, n (%)
Mean DNA Mean DNA quantity Integrity (mg) Number (DIN)
Adenocarcinoma/ 25 (61.0) 3.83 NSCLC-NOS Squamous cell carcinoma 10 (24.4) 2.65 Small cell lung carcinoma 5 (12.2) 5.28 Carcinoid 1 (2.4) 16.24 Overall 41 4.03
8.8 9.0 9.0 9.1 8.9
Conclusion: A single EBUS-TBNA yields DNA of quantity and quality sufficient for molecular analysis, and is expected to be adequate for lung cancer genotyping. Keywords: EBUS-TBNA, lung cancer, Molecular
MA05.05 Genomic Profiles of Lung Cancer Associated with Idiopathic Pulmonary Fibrosis
Vol. 12 No. 1S
standardized consensus. However, despite recent progress in the understanding of pathogenesis and the treatment of LC in general population based on the advances in molecular genomics, the pathogenesis or molecular profiles of IPF-LC has been largely unknown to date. Methods: We assessed genomic profiles of IPF-LC using targeted exome-sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling were performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted using CNVkit with focal events determined by GISTIC 2.0, and pathway analysis (KEGG) using DAVID. Results: Germline mutations in TERT (rs2736100,n¼33) and CDKN1A (rs2395655,n¼27) linked with IPF risk were detected in most samples. A total of 410 somatic mutations were identified with an average of 11.7 per tumor including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop, 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C/T transitions despite extensive smoking histories across most study subjects, suggesting more associations with APOBEC3B-related mutagenesis in the process of IPF-LC development, rather than smoking. TP53 (22/35,62.9%) and BRAF (6/35,17.1%) genes were found significantly mutated in IPF-LC. Recurrent focal amplifications in 3 chromosomal loci (3q26.33, 7q31.2, and 12q14.3), and 9p21.3 deletion were identified, and genes associated with JAK-STAT signaling pathway were significantly amplified in IPF-LC (P¼0.012). Conclusion: IPF-LC is genetically characterized by the presence of somatic mutations reflecting viral and immune-related mutagenic processes in the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Keywords: idiopathic pulmonary fibrosis, genomic profile, lung cancer
Ji An Hwang, Deokhoon Kim, Soo Hyun Bae, Sung-Min Chun, Joon Seon Song, Mi Young Kim, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Sojung Park, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang Asan Medical Center, Seoul/Korea, Republic of
MA05.06 Diagnosis of Chronic Obstructive Pulmonary Disease in Lung Cancer - A Population Based Study
Background: Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer (LC) independent of the effect of cigarette smoking. The prognosis of IPF-associated LC (IPF-LC) is known to be worse than the lone IPF or LC mainly due to the complications accompanying LC treatment with no established or
John Goffin,1 Grace Tang,2 Gregory Pond,2 Sophie Corriveau3 1Oncology, Juravinski Cancer Centre, Hamilton/ON/Canada, 2Oncology, Ontario Clinical Oncology Group, McMaster University, Hamilton/ON/ Canada, 3Medicine, St. Joseph’s Hospital, Hamilton/ON/ Canada
January 2017
Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are associated through tobacco. COPD is underdiagnosed in the general population. Patients with lung cancer suffer from dyspnea and hospitalization for respiratory complications, and underdiagnosis of COPD could confer worse symptoms and morbidity. Using Institute for Clinical Evaluative Sciences (ICES) data, we assessed the diagnosis of COPD in the lung cancer population in Ontario, Canada. Methods: Cancer registry, hospital ICD-10 codes, physician billing data, and vital statistics were abstracted in an anonymized manner from ICES. COPD was defined using the validated ICES-derived COPD cohort and spirometry use was assessed through billing codes. Cancer stage was available from cancer registry data. Analysis was conducted using ICES’s confidential, analytic virtual environment using SAS v 9.3 in the population age >39 years. The local ethics board approved the study. Results: From 2004-2014, 90,783 individuals were diagnosed with lung cancer and 608,347 individuals diagnosed with COPD. Of individuals with lung cancer, 52.7% were male, median age at diagnosis was 65-69 years, and 82.8% have died. Of individuals with COPD, 51% were male, median age at diagnosis was 60-64 years, and 24.7% have died. The diagnosis of COPD was made at a rate of 8.7 persons per 1000 person-years. Among individuals having COPD, 48.4% underwent spirometry. 30.2% of individuals with lung cancer were also diagnosed with COPD and 60.8% underwent spirometry at any time. Among those with a diagnosis of both lung cancer and COPD, 73.6% underwent spirometry. For individuals with registry recorded stage data, 12,110 persons had stage I-II lung cancer, of whom 90.7% had spirometry and 55.9% had a diagnosis of COPD. Conversely, among 31,392 persons with stage III-IV lung cancer, 54.6% had spirometry and 46% were diagnosed with COPD (p<0.001 vs early stage for both). Conclusion: The diagnosis of COPD is not based on spirometry in half of cases. More patients with early stage lung cancer underwent spirometry and a higher rate of spirometry was associated with more diagnosis of COPD. Increased use of spirometry may improve the accuracy of a COPD diagnosis and may increase the diagnosis of COPD in advanced stage lung cancer, allowing improved dyspnea management in this population. Keywords: dyspnea, lung cancer, emphysema, spirometry
Abstracts
S367
MA05.07 Identifying Comorbid Disease on Chest CT Scans in a Lung Cancer Screening-Eligible Cohort Elizabeth Regan,1 Barry Make,1 Gregory Kinney,2 Matthew Budoff,3 Debra Dyer,1 Jeffrey Curtis,4 Russell Bowler,1 Meilan Han,4 Terri Beaty,5 John Hokanson,6 Elizabeth Kern,1 David Lynch,1 Edwin Van Beek,7 Edwin Silverman,8 James Crapo,1 James Finigan9 1Medicine, National Jewish Health, Denver/United States of America, 2University of Colorado Denver, Aurora/CO/United States of America, 3Los Angeles Biomedical Research Institute, Torrance/CA/United States of America, 4University of Michigan Health System, Ann Arbor/United States of America, 5Johns Hopkins Bloomberg School of Public Health, Baltimore/MD/United States of America, 6Epidemiology, Colorado School of Public Health, Aurora/CO/United States of America, 7 Clinical Radiology, Queen’s Medical Research Institute University of Edinburgh, Edinburgh/United Kingdom, 8 Brigham and Women’s Hospital, Boston/MA/United States of America, 9Medicine, National Jewish Health, Denver/CO/United States of America Background: Lung cancer screening (LCS) with chest CT scans in high-risk smokers has been demonstrated to save lives. Medicare and private insurers now cover these scans for beneficiaries under specific criteria. However, most smokers will die of comorbid smokingrelated diseases rather than lung cancer itself. Important information about comorbid conditions is available on screening chest CT scans, but the prevalence of these comorbidities has not been comprehensively assessed. Methods: COPDGene subjects from the Phase 1 visit who met USPSTF criteria for LCS (age > 55, >30 pack years smoking, current or former smokers within 15 years of smoking cessation or current smokers) were assessed for coronary calcification, emphysema, gas trapping, airway wall thickening and vertebral bone density on standard dose CT scans. A new diagnosis of emphysema, osteoporosis, or cardiovascular disease was assumed when there was no self-report of diagnosis or medication use. Results: In 76% of CT scans from LCS-eligible COPDGene subjects, we found abnormal emphysema (>5% low attenuation area @-950 Hounsfield units), airway wall thickening or gas trapping (>20% low attenuation area @-856 Hounsfield units). Osteoporosis was identified in 54% of all CT scans, and abnormal coronary artery calcium was present in 51%. In non-COPD