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Cell Rep Med ; 1(3)2020 06 23.
Article in English | MEDLINE | ID: mdl-32743560

ABSTRACT

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cerebellar Neoplasms/drug therapy , Medulloblastoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adolescent , Biomarkers, Tumor/metabolism , Child , Cyclophosphamide/therapeutic use , Female , Humans , Ifosfamide/therapeutic use , Male , Medulloblastoma/metabolism , Middle Aged , Neoplasm Recurrence, Local/metabolism , Progression-Free Survival
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