Subgroup of Patients with Small Cell Lung Cancer Defined
Contact: Rob Mansheim
IASLC Director of Communications
DENVER – The definition of distinct subgroups has not been as successful in small cell lung cancer (SCLC) as it has been in non-small cell lung cancer (NSCLC). Investigators have now described the clinical, pathologic, and molecular characteristics in a subgroup of SCLCs in never-smoking patients.
In a retrospective review of 1,040 patients with SCLC at Memorial Sloan-Kettering Cancer Center, Anna M. Varghese, MD, and colleagues found that 23 of the patients (2%) were never-smokers. Of particular note, 83% of the patients had de novo SCLC, and 17% had SCLC transformation as acquired resistance to erlotinib after treatment for epidermal growth factor receptor (EGFR)-mutant lung cancer. Previous research has shown that most SCLCs in never-smokers have developed as a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). The findings of the study are published in the June issue of the Journal of Thoracic Oncology (JTO), the official journal of the IASLC.
Of the 19 de novo SCLCs, 15 were pure SCLC, one was mixed SCLC and large cell neuroendocrine carcinoma, one was SCLC and spindle and giant cell carcinoma, and two were mixed SCLC and adenocarcinoma. Among eight de novo SCLCs that had EGFR testing, two harbored an EGFR mutation; ALK rearrangements and KRAS mutations were not found in any of the de novo SCLCs tested, and six of seven of the tumors had RB loss. Next generation sequencing was done on two de novo SCLC samples; one had mutations in p53 and RB1 with amplification in TERT, and the other had mutations in CBL and GNAS with amplification in MYCL1.
"SCLCs in never-smokers represent a clinically and pathologically distinct subgroup because they bear little similarity to NSCLCs among never-smokers. Their molecular characteristics are unique compared with never-smoking patients with adenocarcinomas," says senior author M. Catherine Pietanza, MD, of Memorial Sloan-Kettering Cancer Center, New York, and an IASLC member. "The findings of our study further support the need for comprehensive, multiplexed genotyping to improve our ability to provide optimal care and facilitate research in unique populations with SCLC."
In an editorial accompanying the article, Afshin Dowlati, MD, and Gary Wildey, PhD, of Case Western Reserve University and University Hospitals Seidman Cancer Center and the Case Comprehensive Cancer Center, Cleveland, present several potential explanations for the occurrence of SCLC in never-smokers, including a so-called extrapulmonary SCLC; the presence of combined SCLC, with only the SCLC part identified on a small biopsy specimen; or Askin tumor, a primitive neuroectodermal tumor of the Ewing family tumors. As well, “a simple explanation may be related to the use of self-administered smoking history questionnaires, which have always been criticized,” write the authors of the editorial.
Coauthors of the study include IASLC members Maureen F. Zakowski, MD; Helena A. Yu, MD; Gregory J. Riely, MD, PhD; Lee M. Krug, MD; Mark G. Kris, MD; and Marc Ladanyi, MD.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association’s membership includes more than 3,800 lung cancer specialists in 80 countries. To learn more about IASLC please visit www.iaslc.org.