Top Line: Can craniospinal irradiation (CSI) dose and posterior fossa (PF) boost volume be de-intensified for children with average-risk medulloblastoma (MB)?
The Study: The standard radiation approach for average-risk medulloblastoma has been 23.4 Gy of craniospinal irradiation and a 32.4 Gy boost (55.8 Gy total) to the entire posterior fossa. Average risk MB includes kids ages > 2 who have gross total resection (≤ 1.5 cm2 residual), no CNS dissemination, and non-anaplastic histology. ACNS0331 was a randomized phase 3 trial that sought to determine if radiation could be de-intensified by: 1) reducing CSI dose to 18 Gy for kids under 8, and 2) reducing the boost volume from the entire PF to an involved field. In total, 464 patients were randomized to either PF boost or involved field boost and 226 patients ages 3-7 were also randomized to either 18 Gy or 23.4 Gy CSI. At 5-years, event-free survival and overall survival for involved-field boost were non-inferior to standard PF boost (83% vs 81% and 85% vs 85%, respectively). No PF failures in the involved field arm occurred outside the boost volume. In contrast, low-dose CSI resulted in a decrease in 5-year EFS from 83 → 71% and in OS from 86 → 78%. When results were analyzed by WHO molecular subgroup, the inferior outcomes for low-dose CSI were primarily driven by group 4 patients. Interestingly, the SHH subgroup actually had worse EFS with whole PF boost, which may have been due to excess secondary malignancies with larger boost volume. To make things more conflicting, it was low-dose CSI (not reduced boost volume) that was associated with reduced cognitive toxicity (mainly in younger patients).
TBL: Involved-field boost is non-inferior to whole posterior fossa boost for average risk MB. However, reduced-dose CSI is associated with worse EFS and OS, which is mainly driven by inferior outcomes for patients with WHO molecular group 4 disease. | Michalski, J Clin Oncol 2021