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
• 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.