Current medulloblastoma subgroup specific clinical trials.

Medulloblastoma is a heterogeneous disease with at least four distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. Recently there has been considerable progress defining the molecular drivers and prognostic factors of each subgroup. However, this information has only rarely been used to stratify risk or impact treatment. The purpose of this work is to provide an update on current clinical trials that provide molecularly stratified treatment paradigms. A search was conducted on ClinicalTrials.gov using the following search terms: "medulloblastoma and subgroup", "medulloblastoma and SHH", "medulloblastoma and WNT", and "medulloblastoma and Non-WNT/Non-SHH". This search resulted in nine distinct clinical trials, five for newly diagnosed medulloblastoma and four for recurrent medulloblastoma. Four trials for newly diagnosed medulloblastoma had a component of craniospinal irradiation reduction for patients with WNT medulloblastoma. Molecularly stratified trials for recurrent medulloblastoma largely focus on SHH. As these trials are ongoing, there are limited data available. A trial in which newly-diagnosed WNT patients received modest chemotherapy without radiation has been closed to accrual due to several early failures. Phase II trials evaluating vismodegib for SHH medulloblastoma in children and adults have been disappointing. In conclusion, although there is an expanding array of clinical trials which incorporate molecular data in prescribing treatment for newly-diagnosed and recurrent medulloblastoma, treatments for these diseases are fairly uniform, with craniospinal radiation dose being the main variable. As the drivers of the distinct subgroups and their associated prognoses are better elucidated, future clinical trials and novel targeted agents are needed to improve outcomes and reduce toxicity where feasible.

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2020 Translational Pediatrics. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp.2020.03.03). EMT serves as the unpaid editorial board member of Translational Pediatrics from Jul 2019 to Jun 2021. DA reports personal fees from ISTARI ONCOLOGY, INC., personal fees from JACKSON LABORATORY, during the conduct of the study; other from DIVERSE BIOTECH, outside the submitted work. The other author has nothing to disclose.