Ul Haq Sami, Aamir Aleem, Mighton Chloe, Hueniken Katrina, Philip Vivek, Kim Raymond H, Liu Geoffrey, Sabatini Peter, Bratman Scott V, Lok Benjamin H
Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada; Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2C1, Canada.
Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2C1, Canada; Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Princess Margaret Cancer Research Tower, 101 College Street, Room 9-309, Toronto, ON M5G 1L7, Canada.
HGG Adv. 2025 Apr 29;6(3):100445. doi: 10.1016/j.xhgg.2025.100445.
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 I 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, I = 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.
本系统评价和荟萃分析研究了小细胞肺癌（SCLC）中胚系变异的患病率及其临床影响。主要目标包括估计SCLC患者中胚系变异的患病率，次要目标则聚焦于其对患者预后的影响。我们在Ovid MEDLINE、EMBASE和灰色文献数据库（截至2024年7月）中进行了全面检索。纳入了报告SCLC患者中胚系变异的研究。提取数据以计算合并患病率和风险比（HRs）。使用“转化的ROBBINs”工具评估研究质量，并使用I统计量评估异质性。在6117项筛选的研究中，124项符合纳入标准，其中8%（10/124）报告了致病/可能致病（P/LP）结果。使用随机效应模型进行的荟萃分析估计，SCLC患者中P/LP胚系变异的患病率为11%（95%CI：5%-25%）。估计了ATM基因（合并患病率=1%；95%CI：0%-5%）、BRCA1基因（1%；95%CI：1%-3%）、BRCA2基因（1%；95%CI：1%-3%）和TP53基因（1%；95%CI：0%-3%）的基因水平患病率。DNA损伤修复基因中存在P/LP变异的患者显示出非显著的预后生存获益（合并HR：0.8；95%CI：0.51-1.29，I²=8%）。我们对胚系变异及其对SCLC患者临床结局的影响进行了全面的系统评价。我们的荟萃分析确定了SCLC患者中P/LP变异的估计患病率，为临床筛查提供了理论依据。
