Retrospective database-analysis of the genomic landscape of small cell lung cancer in never-smoking patients

Small cell lung cancer (SCLC) predominantly develops in patients with smoking history, and patients who have no history of tobacco exposure remain understudies. Retrospective analysis of the Tempus clinicogenomic database investigated the genomic landscap of SCLC in never-smoking patients (NS; n=54) compared with that in current/former smoking patients (C/FS; n=608). Compared with CF/S patients, NS patients were more likely to be female (70% versus 55%). Tumors of NS patients had lower prevalence of TP53 mutations (59% versus 85%), no significant difference in RB1 mutations (57% versus 63%) , and higher prevalence of EGFR (26% versus 2.6%), PIK3CA (15% versus 3.6%), and OS9 (5.6% versus 0) mutations. Similar findings were observed even after removing cases of transformation from non-small cell lung cancer or combined SCLC-NSCLC presentations. In addition, tumors of NS patients had a lower tumor mutational burden and decreased immune cell infiltration. The authors conclude that the mutational landscape of SCLC in NS patients significantly differs from that of C/FS patients, suggesting that SCLC in NS patients may represent a distinct genomic entity.