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

  • Author(s): 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
  • Nageswara Rao, Amulya A
  • 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
  • et al.

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.

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