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