MDB-08. Pattern of relapse and outcome of early childhood medulloblastoma treated with upfront adjuvant focal radiotherapy

Abstract Background Infant MB (iMB) treatment strategies may include adjuvant focal RT (fRT) for local control, to minimize neurocognitive side-effect of craniospinal irradiation (CSI). From a large international cohort of 380 relapsed iMB, we previously described fRT was associated with worse post relapse survival (PRS) compared to chemotherapy alone, in univariate analysis. Methods We performed a sub-analysis of patients initially treated with adjuvant fRT, to describe their pattern of relapse and salvage practices. Results The cohort included 51 patients who relapsed after initial fRT (median dose: 54 Gy) along with conventional in 47 patients or high-dose chemotherapy (HDC) in 4 patients. Median age at diagnosis was 34.2 months (range 11-55). At initial diagnosis, 42(85.7%) achieved gross total resection and 46(90.2%) were localized. Maintenance therapy or intrathecal/intraventricular chemotherapy were added in 14 patients. Molecular subgrouping was available in 31 patients (8 SHH, 17 group 3, 6 group 4). Median time of relapse was 13 months from diagnosis (5-51.9). Relapse was disseminated or combined (local and distant) in 96% of the cases. Twelve patients (24%) underwent palliative management. Thirty-nine (76%) patients received curative intent salvage therapy, of which 31 (79%) received CSI (median dose of 36 Gy, range 18-39.6). CSI was administered alone in 22% or with conventional chemotherapy or HDC in 65% and 13% . The 5 years PRS was 20.8% (±9%). Female sex, age 24 months at diagnosis, late relapse ≥12 months from diagnosis, asymptomatic relapse, salvage CSI, CR post-salvage therapy were associated with better PRS. Patients salvaged with CSI had a 5-year PRS of 26.5% vs 0% without. Conclusion Following adjuvant fRT, almost all patients who relapsed presented with dissemination, despite initial localized disease, and dismal PRS. Focal RT in combination with upfront therapy is ineffective to prevent leptomeningeal relapses and the success of salvage CSI is limited.