There are 4 molecular subgroups of medulloblastoma: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. Treatment for medulloblastoma that follows the WNT route is being weakened because of its excellent long-term outcomes. Children with low-risk WNT-pathway medulloblastoma were evaluated for the safety of delaying craniospinal irradiation (CSI) in the initial stages of treatment. Low-risk WNT-pathway medulloblastoma in children was treated with postoperative targeted conformal radiation and 6 cycles of adjuvant systemic chemotherapy. To protect the well-being of trial participants, a group-sequential design (triangular test) was implemented, with preset ending rules if the relapse rate after 2 years was greater than 15%. Following the acquisition of written informed consent/assent, 7 children with low-risk WNT-pathway medulloblastoma were enrolled and treated according to the established protocol. Sadly, 1 youngster died due to chemotherapy-induced neutropenic sepsis and multiorgan failure. Within 2 years of the index diagnosis, surveillance neuro-imaging revealed neuraxial failure (supratentorial brain and/or spine) in 3 children, prompting the early discontinuation of the trial. Children with a recurrence were given second-line chemotherapy after a salvage CSI and boost irradiation of metastatic deposits. Although 2 of the children have remained in remission for over a year (32 and 26 months, respectively), the third kid experienced a second relapse, requiring further systemic chemotherapy and craniospinal reirradiation, which led to a good clinico-radiologic response. Kaplan-Meier estimates of 2-year event-free survival, recurrence-free survival, and overall survival were 42.9%, 50%, and 85.7%, respectively, based on a median follow-up of 42 months. The probability of neuraxial failure is unacceptably high when the first CSI is not performed in low-risk WNT-pathway medulloblastoma.
