Abstract Background WNT medulloblastoma accounts for ∼10%of all pediatric medulloblastoma cases and is associated with excellent survival using contemporary treatment, namely craniospinal radiation and multiagent chemotherapy. Outcomes for patients with high-risk (HR) disease are based on small numbers though generally felt to also be favourable. In COG ACNS0332, outcomes were reported on 14 HR patients with 5-yr EFS and OS 93% and 100%, respectively1. SJMB03 reported outcomes of 7 HR patients with 5-yr EFS and OS both at 100%2. Other retrospective series have suggested that metastatic disease and extent of resection in WNT medulloblastoma does not impact relapse risk or survival345. Rationale Despite generally favourable outcomes of HR WNT patients, it is not definitively known whether therapy reduction in this population maintains the same excellent survival. We hope to investigate this further by gathering real-world data on treatment and outcomes of patients with HR WNT medulloblastoma, including those who may have received therapy reduction. Aims We will describe EFS and OS in a larger cohort of patients with HR WNT medulloblastoma, determine prognostic factors associated with outcomes, and describe treatments prescribed and their impact on survival. Methods In collaboration with 20 participating institutions (estimated 30 patients), we will conduct a multicentre retrospective review of pediatric patients diagnosed with HR WNT medulloblastoma. HR features will include metastatic disease, subtotal resection (post-operative residual 1.5cm2), large cell/anaplastic histology, or adverse molecular features (MYC/MYCN amplification, TP53 mutation, OTX2 gain). Descriptive statistics will be used to summarize patient and treatment characteristics and EFS and OS will be assessed using the Kaplan-Meier estimator. Statistical significance will be defined by a p-value of 0.05. Hypothesis: We hypothesise that patients with HR WNT medulloblastoma have an excellent EFS and OS despite “high risk” features, and that there may be a trend for reduction of therapy in this population. 1. Leary, Sarah E S et al. “Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children’s Oncology Group.” JAMA oncology vol. 7,9 (2021): 1313-1321. doi:10.1001/jamaoncol.2021.2224 2. Gajjar, Amar et al. “Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03).” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 39,7 (2021): 822-835. doi:10.1200/JCO.20.01372 3. Nobre, Liana et al. “Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.” Cell reports. Medicine vol. 1,3 (2020): 100038. 4. Korshunov, Andrey et al. “DNA methylation profiling is a method of choice for molecular verification of pediatric WNT-activated medulloblastomas.” Neuro-oncology vol. 21,2 (2019): 214-221. 5. Thompson, Eric M et al. “Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.” The Lancet. Oncology vol. 17,4 (2016): 484-495.
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