Abstract

BACKGROUNDImpact of isolated spread into the cerebrospinal fluid (CSF) is still not investigated comprehensively for childhood medulloblastoma and the best therapeutic strategy is currently unclear. MATERIAL ANDMETHODSSixty-six patients with isolated M1-MB registered to the HIT-MED-database from 2000–2018 were identified. CSF and MRI were centrally reviewed for all patients. Patients were stratified by age and either treated with upfront craniospinal irradiation (CSI) followed by maintenance chemotherapy (CT) or with postoperative CT and delayed CSI.RESULTSForty-nine patients were non-infants ≥4 years and seventeen were infants <4 years. Median age was 7.3y (1.1–18.0). 83.3% were histologically classified as CMB, 12.1% as LCA-MB and 4.6% as DMB. Molecular subgroup was Gr.3 in 25.8%, Gr.4 in 28.8%, SHH in 4.5%, WNT in 1.5% and not evaluated for 39.4%. Lumbar puncture was performed on median postoperative day 19 (range: 14–77). Median follow-up for survivors was 7.6y (range: 1.2–15.9). The whole cohort showed a 3y- and 5y-PFS of 68.0(±6.0) and 60.0(±6.5)%, while OS was 79.1(±5.2) and 72.9(± 5.9)%. 10y-OS was 54.4(±7.5). Patients with upfront CSI had more favourable outcomes (5y-PFS 66.1 vs. 55.8% [p=0.119]; 5y-OS 90.6 vs. 64.5% [p=0.035]). The trend towards improved survival in patients with postoperative CSI was retained when only non-infants were considered (pPFS=0.176, pOS=0.055). M1-persistence occurred exclusively in patients with postoperative CT.CONCLUSIONIsolated M1-MB is rare. Patients without contraindication for CSI appear to benefit from treatment by upfront CSI followed by maintenance CT, while cumulative CT-doses would be reduced compared to sandwich strategies.

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