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Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.

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
Cell reports. Medicine | 2020

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.

Pubmed ID: 32743560 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA235162
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS096236
  • Agency: NCI NIH HHS, United States
    Id: R01 CA148699
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS106155
  • Agency: NCI NIH HHS, United States
    Id: R01 CA159859

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