WNT pathway medulloblastomas have the best prognosis amongst all four subgroups with 5-year
      overall survival exceeding 90%. Overall medulloblastoma is more common in males. They can
      occur at all ages, but, are uncommon in infants. They are mostly uniform in their genetic
      aberrations, histological pattern, and clinical presentation. The WNT pathway is involved in
      regulating embryonal development in the brain. They are frequently described as having CTNNB1
      mutations, nuclear immunohistochemical staining for β-catenin, and monosomy six (deletion of
      one copy of chromosome 6 in the tumor). Thus monosomy 6 in conjunction with nuclear β-catenin
      accumulation is considered a sensitive and specific marker for WNT pathway medulloblastoma
      they are typically located in the midline vermian region filling up the fourth ventricle and
      infiltrating the brain stem consistent with their proposed cell of origin from the dorsal
      brainstem nuclei. The immediate impact of enhanced understanding of molecular biology has led
      to biologically driven next-generation clinical trials in newly diagnosed medulloblastoma.
      Given the excellent long-term survival outcomes in WNT-pathway medulloblastoma and potential
      for significant late toxicities with currently prevalent doses of CSI (23.4-36Gy), it has
      been hypothesized that further reduction of dose or in certain cases avoidance of CSI would
      translate into reduction in late morbidity of treatment.

      In our first generation FOR-WNT study, the investigators had avoided upfront CSI and treated
      the tumor-bed alone with focal conformal radiotherapy in low-risk WNT-pathway medulloblastoma
      followed by 6-cycles of adjuvant systemic chemotherapy. However, early experience from our
      own study and similar results from another study (primary chemotherapy approach completely
      avoiding radiotherapy) suggests an unduly increased risk of relapse - spinal leptomeningeal
      or supratentorial if CSI is avoided and local recurrence at primary site too if radiation is
      completely avoided. Given the excellent long-term survival outcomes in WNT-pathway
      medulloblastoma treated with currently prevalent doses of CSI (23.4-36Gy), presence of
      significant late toxicities with such doses, but the increased risk of relapse with avoidance
      of CSI and/or local irradiation, the investigators hypothesize that further moderate
      reduction of CSI dose to 18Gy/10fx keeping the primary-site dose to 54Gy/30fx would translate
      into a meaningful reduction in late morbidity of treatment without compromising disease
      control or survival. Thus, the investigators herewith propose the second-generation study
      (FOR-WNT 2) to include low-dose CSI (18Gy/10fx) plus tumor-bed boost (36Gy/20fx) for a total
      primary site dose of 54Gy/30fx without concurrent chemotherapy followed by standard 6-cycles
      of adjuvant systemic chemotherapy.