Prognostic Clinical and Biologic Features for Overall Survival after Relapse in Childhood Medulloblastoma

SIMPLE SUMMARY: Despite progress in the biology and upfront treatment of childhood medulloblastoma, relapse is almost universally fatal. No standardized treatment has so far been established for these patients. By determining which characteristics are prognostic after relapse, treatment strategies may be optimized for each of these children. We demonstrated that molecular subgroup at diagnosis is a relevant prognostic factor of outcome after relapse. Moreover, we showed that time to relapse and the use of salvage radiotherapy at relapse might have a potential impact on post-relapse survival. Our data suggest that ongoing efforts toward a better understanding of the biology, timing and type of relapse would be important to understand the determinants of tumor behavior at relapse. This could help us address more specific questions on the best surveillance strategies after completion of the treatment and the introduction of risk-stratified second-line treatment strategies. ABSTRACT: Given the very poor prognosis for children with recurrent medulloblastoma, we aimed to identify prognostic factors for survival post-relapse in children with childhood medulloblastoma. We retrospectively collected clinico-biological data at diagnosis and main clinical characteristics at relapse of children newly diagnosed with a medulloblastoma between 2007 and 2017 at Gustave Roussy and Necker Hospital. At a median follow-up of 6.6 years (range, 0.4–12.3 years), relapse occurred in 48 out 155 patients (31%). The median time from diagnosis to relapse was 14.3 months (range, 1.2–87.2 months). Relapse was local in 9, metastatic in 22 and combined (local and metastatic) in 17 patients. Second-line treatment consisted of chemotherapy in 31 cases, radiotherapy in 9, SHH-inhibitor in four and no treatment in the remaining four. The 1-year overall survival rate post-relapse was 44.8% (CI 95%, 31.5% to 59.0%). While molecular subgrouping at diagnosis was significantly associated with survival post-relapse, the use of radiotherapy at relapse and time to first relapse (>12 months) might also have a potential impact on post-relapse survival.