Katz Lior, Ben-Arush Myriam, Blanche Einav, Meir Inbar, Mordechai Oz
Pediatrics, Ruth Rappaport Children's Hospital, Rambam Medical Center, Haifa 3109601, Israel.
Joan and Sanford Weill Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Ruth Rappaport Children's Hospital, Rambam Medical Center, Haifa 3109601, Israel.
Cancers (Basel). 2025 Apr 11;17(8):1292. doi: 10.3390/cancers17081292.
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.
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.
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.
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.
下一代测序（NGS）已成为精准医学中的一种变革性工具，可深入了解可操作的基因组改变，并为儿童及青少年/青年成人（AYA）实体瘤的临床决策提供依据。
我们进行了一项系统评价和荟萃分析，以评估NGS在识别可操作的基因组改变方面的效用及其对临床决策的影响。纳入了涉及0至40岁实体瘤患者的研究。使用Covidence提取数据，并使用随机效应模型计算合并估计值。使用Begg-Mazumdar、Egger和Harbord检验评估偏倚。
在筛选的13624篇参考文献中，24项研究符合纳入标准，包括5278例患者和5359个样本，其中5207个提供了可用数据。可操作改变的合并比例为57.9%（95%CI：49.0-66.5%），几乎没有发表偏倚的证据。21项研究报告了临床决策结果，合并比例为22.8%（95%CI：16.4-29.9%）。11项研究报告的种系突变率合并比例为11.2%（95%CI：8.4-14.3%），与儿童癌症中通常观察到的率一致。由于测序方法、肿瘤类型和采样策略的差异，各研究间观察到显著的异质性。
NGS在识别可操作的基因组靶点和指导儿童及AYA实体瘤的临床决策方面显示出巨大潜力。然而，方法的变异性强调了需要标准化方案和报告实践，以提高可比性和可推广性。这项荟萃分析突出了基因组医学的前景，同时也认识到研究设计异质性带来的挑战。
