1. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma
- Author
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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, and Vijay Ramaswamy
- Subjects
medulloblastoma ,WNT ,subgroup ,chemotherapy ,radiation ,wingless ,Medicine (General) ,R5-920 - 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.
- Published
- 2020
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