The Clinical Utility of Next-Generation Sequencing in Childhood and Adolescent/Young Adult Solid Tumors: A Systematic Review and Meta-Analysis.
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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.