(P 275) NEXT GENERATION SEQUENCING IN ADOLESCENT AND YOUNG ADULT (AYA) SARCOMAS: CLINICAL IMPACT, DIAGNOSTIC UTILITY, AND IMPLICATIONS

Objective: To evaluate the clinical utility of next-generation sequencing (NGS) in adolescent and young adult (AYA) sarcomas, focusing on diagnostic refinement, identification of actionable alterations, germline mutation prevalence, and implications for treatment and clinical trial access.

Methods: We conducted a narrative review of five peer-reviewed studies and two conference abstracts encompassing approximately 360 AYA sarcoma patients (ages 15–39) who underwent comprehensive molecular profiling (CMP). Sequencing platforms included RNA sequencing, hybrid-capture NGS panels, and whole-genome sequencing. Key metrics assessed were the frequency of actionable alterations, diagnostic reclassification, germline mutation rates, turnaround time, and downstream clinical impact.

Results: About 48-81% of AYA patients with sarcoma received treatment recommendations from CMP findings. CMP and central pathology review also aided enrollment into clinical trials, reclassifying the diagnosis in multiple cases. On average, 3 genomic alterations were identified per tumor, with common mutations in TP53 (~25%), RB1, CDKN2A, LMNA-NTRK1, and EWSR1. Germline pathogenic variants were detected in 10–14% of patients, most frequently in TP53, BRCA2, and CHEK2, prompting changes in surveillance and family counseling. NGS findings expanded clinical trial eligibility in 20–30% of patients, particularly for mutation-driven basket trials. The median turnaround time was 28–45 days, with >95% assay success rates and no major biopsy-related complications reported.

Conclusion: NGS is a feasible and impactful tool in the clinical management of AYA sarcomas. It enables identification of actionable genomic alterations, enhances diagnostic precision, and broadens access to targeted therapies and clinical trials. To fully realize the potential of precision oncology in this age group, expanded access to molecular profiling and inclusive trial designs are essential. Rapid turnaround time in AYA sarcomas is required to meet these goals and combat these aggressive malignancies.