Pathogenic germline variants in small cell lung cancer: A systematic review and meta-analysis

This systematic review and meta-analysis examined the prevalence and clinical impact of germline variants in small cell lung cancer (SCLC). Primary objectives included estimating the prevalence of germline variants in SCLC patients, while secondary objectives focused on their effects on patient outcomes. A comprehensive search was conducted in Ovid MEDLINE, EMBASE, and gray-literature databases (as of July 2024). Studies reporting germline variants in SCLC patients were included. Data were extracted to calculate pooled prevalence and hazard ratios (HRs). Study quality was assessed using the Translating ROBBINs tool, and heterogeneity was evaluated using the I² statistic. Of 6,117 screened studies, 124 met inclusion criteria, with 8% (10/124) reporting pathogenic/likely pathogenic (P/LP) findings. Meta-analysis using a random-effects model estimated the prevalence of P/LP germline variants in SCLC patients at 11% (95% CI: 5%-25%). Gene-level prevalence was estimated for ATM (pooled prevalence = 1%; 95% CI: 0%-5%), BRCA1 (1%; 95% CI: 1%-3%), BRCA2 (1%; 95% CI: 1%-3%), and TP53 (1%; 95% CI: 0%-3%). Patients with P/LP variants in DNA damage repair genes showed a non-significant prognostic survival benefit (pooled HR: 0.8; 95% CI: 0.51-1.29, I² = 8%). We have conducted a comprehensive systematic review of germline variants and their impact on clinical outcomes of SCLC patients. Our meta-analysis identified an estimated prevalence of P/LP variants in SCLC patients, suggesting a rationale for screening in the clinic.