Publication details

Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

Authors

NOBRE L. ZAPOTOCKY M. KHAN S. FUKUOKA K. FONSECA A. MCKEOWN T. SUMERAUER D. VICHA A. GRAJKOWSKA W. A. TRUBICKA J. LI K. K. W. NG H. K. MASSIMI L. LEE J. Y. KIM S. K. ZELCER S. VASILJEVIC A. FAURE-CONTER C. HAUSER P. LACH B. VAN VEELEN-VINCENT M. L. FRENCH PJ VAN Meir EG WEISS W. A. GUPTA N. POLLACK I. F. HAMILTON R. L. RAO A. A. N. GIANNINI C. RUBIN J. B. MOORE A. S. CHAMBLESS L. B. VIBHAKAR R. RA Y. S. MASSIMINO M. MCLENDON R. E. WHEELER H. ZOLLO M. FERRUCI V. KUMABE T. FARIA C. C. ŠTĚRBA Jaroslav JUNG S. LOPEZ-AGUILAR E. MORA J. CARLOTTI C. G. OLSON J. M. LEARY S. CAIN J. KRSKOVA L. ZAMECNIK J. HAWKINS C. E. TABORI U. HUANG A. N. BARTELS U. NORTHCOTT P. A. TAYLOR M. D. YIP S. HANSFORD J. R. BOUFFET E. RAMASWAMY V.

Year of publication 2020
Type Article in Periodical
Magazine / Source CELL REPORTS MEDICINE
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(20)30050-1.pdf
Doi http://dx.doi.org/10.1016/j.xcrm.2020.100038
Keywords WNT-Activated Medulloblastoma
Description 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.

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