MEDB-49. Relapsed SHH medulloblastomas in young children. Are there alternatives to full-dose craniospinal irradiation?

BACKGROUND/RATIONAL: Following initial irradiation sparing therapy, many young children with relapsed medulloblastoma can be salvaged with craniospinal irradiation (CSI). However, the interval to relapse is short and neurocognitive sequelae remain a major concern. The contribution of molecular subgrouping may help refine indications and modalities of salvage strategies in this population. METHOD: From a cohort of 151 young children with molecularly characterized relapsed medulloblastoma, subset analysis of the SHH medulloblastoma was conducted to describe the practice of salvage radiotherapy and associated post-relapse survival (PRS). RESULTS: Sixty-seven SHH medulloblastoma patients (46 M0; 54 GTR; 11 non-ND/MBEN) received salvage therapy with curative intent. Before relapse, 54 (80.6%) received conventional chemotherapy (CC), 13 (19.4%) high-dose chemotherapy (HDC), while seven had additional focal radiotherapy (fRT). Median time to relapse was 11.1 months (range 3.8-41.0) and 43.3% were localized. Thirty patients (16 localized relapse) underwent surgery. Forty-seven (71.2%) received salvage radiotherapy (20 with CC; 10 with HDC; 15 alone, two unknown). CSI and fRT accounted for 82% and 18% respectively. CSI median dose was 36Gy (range 18-39Gy). Ten patients (eight with localized relapse) received CSI doses ≤23.4Gy. Nineteen patients (28.8%) did not receive any radiotherapy (nine HDC; 10 CC only). Radiotherapy was associated with better 3-year PRS (73.0% versus 36.1%; p=0.001). All patients treated with CSI ≤ 23.4Gy were alive at median follow-up of 69 months(24-142). Six of nine patients treated with HDC without irradiation were alive at last follow-up. Sixty-three percent of patients received reduced dose CSI(≤23.4Gy), fRT, or no radiotherapy, and their PRS did not significantly differ from those who received CSI ≥ 30.6Gy (p = 0.54). CONCLUSION: While salvage CSI provided PRS benefit in this SHH medulloblastoma cohort, we report the use of reduced salvage radiotherapy and irradiation avoidance in 63% of the patients, with 60% alive at last follow-up.