Small-Cell Lung Cancers in Patients Who Never Smoked Cigarettes

• Published in: Journal of thoracic oncology 2014-06, Vol.9 (6), p.892-896
• Main Authors: Varghese, Anna M., Zakowski, Maureen F., Yu, Helena A., Won, Helen H., Riely, Gregory J., Krug, Lee M., Kris, Mark G., Rekhtman, Natasha, Ladanyi, Marc, Wang, Lu, Berger, Michael F., Pietanza, M. Catherine
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Antineoplastic Agents - therapeutic use; Chromogranins; Class I Phosphatidylinositol 3-Kinases; DNA Mutational Analysis; Drug Resistance, Neoplasm; ErbB Receptors - genetics; Erlotinib Hydrochloride; Female; Gene Amplification; Gene Rearrangement; GTP-Binding Protein alpha Subunits, Gs - genetics; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Neoplasms, Second Primary - genetics; Never-smokers; Phosphatidylinositol 3-Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-cbl - genetics; Proto-Oncogene Proteins p21(ras); Quinazolines - therapeutic use; ras Proteins - genetics; Receptor Protein-Tyrosine Kinases - genetics; Retinoblastoma Protein - genetics; Retrospective Studies; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - genetics; Small-cell lung cancer; Smoking; Survival Rate; Telomerase - genetics; Tumor Suppressor Protein p53 - genetics
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0000000000000142

We describe clinical, pathologic, and molecular characteristics of never-smoker patients with small-cell lung cancers (SCLCs). We identified cases of SCLCs evaluated at our institution from 2005 to 2012. We collected smoking history, demographic, treatment, and survival data. EGFR, KRAS, PIK3CA, ALK testing, RB protein expression, and next generation sequencing were performed on available samples. Two percent (23 of 1040) of patients with SCLCs were never-smokers. Eighty-three percent (19 of 23) had de novo SCLCs, whereas 17% had SCLC transformation as acquired resistance to erlotinib after treatment for EGFR-mutant lung carcinomas. Median survival from SCLC diagnosis was 23 months. Of de novo SCLCs, ALK rearrangement, KRAS mutations, EGFR mutations, and RB loss were identified in zero of five, zero of eight, two of eight, and six of seven, respectively. Two de novo samples underwent next generation sequencing. One had mutations in p53 and RB1 with amplification in TERT, and a second had mutations in CBL and GNAS with amplification in MYCL1. Two percent of patients with SCLCs are never-smokers. Although transformation to SCLC can rarely occur in acquired resistance to erlotinib, 83% of never-smokers with SCLCs had de novo SCLC. RB loss was noted in 86% of cases. Multiplexed genotyping can be performed on tissues to identify potentially actionable oncogenic drivers.