QOL-01. Curing Sonic Hedgehog (SHH) Medulloblastoma without Irradiation: Investigating Late Effects in Survivorship

Abstract Introduction Cranial irradiation, a mainstay in medulloblastoma treatment, can be associated with neurocognitive late effects: lowered attention, working memory, processing speed, executive functioning, and learning, with young age at diagnosis a risk factor. By eliminating cranial irradiation for young, low-risk patients, will neurocognitive and quality of life morbidities decrease? Methods Patients with newly diagnosed SHH medulloblastoma enrolled on the Head Start 4 trial between 2016-2021 at 25 participating institutions in the US, Canada and New Zealand underwent baseline assessment prior to consolidation and autologous hematopoietic progenitor cell rescue and again at two-year-follow-up. Serial standardized test scores were compared using a linear mixed model with restricted maximum likelihood estimates and a random intercept for each patient. Results Thirty-two patients (median age 2.3 years, 68.6% male) completed baseline evaluation, and 21 (91% compliance rate) survivors on study were reassessed at 2-year follow-up. IQ and working memory remained stable over time (WPPSI-IV/WISC-V p = 0.71; p = 0.99, respectively). Similarly, overall quality of life (PedsQL p = 0.31), overall executive functioning (BRIEF GEC p = 0.08), overall adaptive functioning (ABAS-III GEC p = 0.10), adaptive skills (BASC-3 p = 0.65) and internalizing problems (BASC-3 p = 0.36) did not significantly change over time. In contrast, participants displayed increased attention difficulties (BASC-3 p = 0.02), decreased social quality of life (PedsQL p = 0.04), and lower practical skills at home (ABAS-3 p = 0.04). Discussion These novel results provide encouraging follow-up data for young patients treated for SHH Medulloblastoma without cranial irradiation. At the same time, areas such as attention, socialization, and practical skills at home appear to be impacted. These findings need to be further substantiated with continued monitoring through biannual assessments and additional trials, such as an upcoming phase III international randomized study. Specifically, two effective irradiation-sparing treatment regimens will be compared - Head Start 4 and HIT-SKK - across Europe and North America, to harmonize diagnostic and therapeutic standards for medulloblastoma.