NCOG-23. Relapse is not the end: Post-relapse survival in young children with medulloblastoma treated with HeadStart-Like regimens. A retrospective institutional review

Abstract In young children with medulloblastoma, treatment strategies often aim to delay or avoid craniospinal irradiation (CSI) to minimize long-term neurotoxicity. Despite these efforts, relapse remains a major clinical challenge. This study examines relapse patterns, salvage therapies, and survival outcomes in a uniformly young cohort, regardless of initial treatment regimen. We conducted a retrospective review of 20 patients diagnosed with medulloblastoma before age 5, all treated at a single institution. Patients received treatment with HeadStart, ACNS 0334, or Protocol 99703, without upfront radiation. Data collected included demographics, initial therapy, relapse timing and pattern, salvage approaches, and outcomes. Primary endpoints were post-relapse survival (PRS), overall survival (OS), and event-free survival (EFS). All patients received intensive multi-agent chemotherapy followed by autologous stem cell transplantation (58% single, 42% tandem). Relapse occurred in 50% (10/20) of patients, with 80% presenting with disseminated and 20% with localized recurrence. Salvage regimens included combinations of irinotecan, temozolomide, ICE, intrathecal chemotherapy, and radiation. PRS was 60% (6/10). Across the entire cohort, OS was 65% and EFS was 45%. Durable survival after relapse was associated with localized recurrence and the use of salvage CSI. Survivors frequently experienced late effects, including learning difficulties, growth hormone deficiency, and global developmental delay. In this single-center cohort of young children with medulloblastoma, relapse was common despite intensive frontline treatment. However, post-relapse survival was encouraging, with 60% of relapsed patients achieving long-term survival following aggressive multimodal salvage therapy. These findings highlight the potential for disease control even after recurrence and underscore the importance of individualized salvage strategies. Continued refinement of both frontline and relapse therapies is essential to optimize outcomes while minimizing long-term toxicity in this high-risk pediatric population.