Background: Next-generation sequencing (NGS) has emerged as a transformative tool in precision medicine, offering insights into actionable genomic alterations and informing clinical decision-making in childhood and adolescent/young adult (AYA) solid tumors. Methods: We conducted a systematic review and meta-analysis to assess the utility of NGS in identifying actionable genomic alterations and its impact on clinical decision-making. Studies involving patients aged 0–40 years with solid tumors were included. Data were extracted using Covidence, and pooled estimates were calculated using a random-effects model. Bias was assessed using Begg–Mazumdar, Egger, and Harbord tests. Results: Out of 13,624 references screened, 24 studies met eligibility criteria, comprising 5278 patients and 5359 samples, of which 5207 provided usable data. The pooled proportion of actionable alterations was 57.9% (95% CI: 49.0–66.5%), with minimal evidence of publication bias. Clinical decision-making outcomes were reported in 21 studies, with a pooled proportion of 22.8% (95% CI: 16.4–29.9%). Germline mutation rates, reported in 11 studies, yielded a pooled proportion of 11.2% (95% CI: 8.4–14.3%), consistent with rates typically observed in childhood cancers. Significant heterogeneity was observed across studies due to differences in sequencing methodologies, tumor types, and sampling strategies. Conclusions: NGS demonstrates considerable potential in identifying actionable genomic targets and guiding clinical decision-making in childhood and AYA solid tumors. However, the variability in methodologies underscores the need for standardized protocols and reporting practices to enhance comparability and generalizability. This meta-analysis highlights the promise of genomic medicine while acknowledging challenges posed by heterogeneity in study designs.
背景：下一代测序（NGS）已成为精准医学领域的一项变革性工具，能够揭示可操作的基因组改变，并为儿童及青少年/年轻成人（AYA）实体瘤的临床决策提供依据。方法：我们进行了一项系统综述与荟萃分析，以评估NGS在识别可操作基因组改变方面的效用及其对临床决策的影响。研究纳入了年龄在0-40岁、患有实体瘤的患者。使用Covidence软件提取数据，并采用随机效应模型计算汇总估计值。使用Begg–Mazumdar、Egger和Harbord检验评估偏倚风险。结果：在筛选的13,624篇文献中，24项研究符合纳入标准，共涉及5278名患者和5359份样本，其中5207份提供了可用数据。可操作改变的汇总比例为57.9%（95% CI: 49.0–66.5%），发表偏倚证据极少。21项研究报告了临床决策结果，汇总比例为22.8%（95% CI: 16.4–29.9%）。11项研究报告了胚系突变率，汇总比例为11.2%（95% CI: 8.4–14.3%），与儿童癌症中通常观察到的比率一致。由于测序方法、肿瘤类型和采样策略的差异，各研究间存在显著的异质性。结论：NGS在识别可操作的基因组靶点以及指导儿童和AYA实体瘤的临床决策方面显示出巨大潜力。然而，方法学的差异性凸显了标准化方案和报告实践的必要性，以增强结果的可比性和普适性。本荟萃分析在强调基因组医学前景的同时，也指出了研究设计异质性带来的挑战。
肿瘤(癌症)患者之家