학술논문
Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma
Document Type
article
Author
Liana Nobre; Michal Zapotocky; Sara Khan; Kohei Fukuoka; Adriana Fonseca; Tara McKeown; David Sumerauer; Ales Vicha; Wieslawa A. Grajkowska; Joanna Trubicka; Kay Ka Wai Li; Ho-Keung Ng; Luca Massimi; Ji Yeoun Lee; Seung-Ki Kim; Shayna Zelcer; Alexandre Vasiljevic; Cécile Faure-Conter; Peter Hauser; Boleslaw Lach; Marie-Lise van Veelen-Vincent; Pim J. French; Erwin G. Van Meir; William A. Weiss; Nalin Gupta; Ian F. Pollack; Ronald L. Hamilton; Amulya A. Nageswara Rao; Caterina Giannini; Joshua B. Rubin; Andrew S. Moore; Lola B. Chambless; Rajeev Vibhakar; Young Shin Ra; Maura Massimino; Roger E. McLendon; Helen Wheeler; Massimo Zollo; Veronica Ferruci; Toshihiro Kumabe; Claudia C. Faria; Jaroslav Sterba; Shin Jung; Enrique López-Aguilar; Jaume Mora; Carlos G. Carlotti; James M. Olson; Sarah Leary; Jason Cain; Lenka Krskova; Josef Zamecnik; Cynthia E. Hawkins; Uri Tabori; Annie Huang; Ute Bartels; Paul A. Northcott; Michael D. Taylor; Stephen Yip; Jordan R. Hansford; Eric Bouffet; Vijay Ramaswamy
Source
Cell Reports Medicine, Vol 1, Iss 3, Pp 100038- (2020)
Subject
Language
English
ISSN
2666-3791
Abstract
Summary: 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.