Impact of Initial Treatment Setting on Survival in Relapsed Pediatric and AYA Bone Sarcomas: A Secondary Analysis of a Prospective Clinical Trial.

Abstract

Background: Outcomes in relapsed or refractory pediatric and AYA bone sarcomas remain poor, and the impact of early referral to specialized sarcoma centers on survival is unclear. Early centralization of care may improve local and systemic treatment quality, but evidence in this population is limited.

Methods: This secondary analysis of a prospective single-center regorafenib trial in children and adolescents/young adults with relapsed or refractory bone sarcomas compared outcomes between patients managed at a specialized high-volume sarcoma center from initial diagnosis ("internal" group) and those referred only at relapse ("external" group). Baseline characteristics, prior treatments, and trial exposure were assessed. Overall survival (OS) and event-free survival (EFS) were estimated from trial enrollment using Kaplan-Meier methods and compared between groups.

Results: Thirty patients were included (18 internal, 12 external). Baseline clinical features, including histologic subtype, metastatic status at diagnosis, and time from diagnosis to first relapse/progression, were broadly similar between groups. EFS from trial enrollment did not differ significantly between groups. However, 24-month OS was longer in patients managed at the specialized center from diagnosis (77% vs. 42%), suggesting a persistent influence of earlier phases of care despite equal access to protocol-based relapse therapy at study entry.

Conclusions: Early centralization of care at a specialized pediatric and AYA sarcoma center may confer a long-term survival advantage in relapsed or refractory bone sarcomas, even when investigational relapse therapy is standardized. These findings support timely referral to expert centers and may inform the organization of care and referral pathways for pediatric and AYA patients with bone sarcomas.