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.
Pattern of Relapse and Treatment Response in WNT- Activated Medulloblastoma / Nobre, Liana; Zapotocky, Michal; Khan, Sara; Fukuoka, Kohei; Fonseca, Adriana; Mckeown, Tara; Sumerauer, David; Vicha, Ales; Grajkowska, Wieslawa A.; Trubicka, Joanna; Ka Wai Li, Kay; Ng, Ho-Keung; Massimi, Luca; Yeoun Lee, Ji; Kim, Seung-Ki; Zelcer, Shayna; Vasiljevic, Alexandre; ́ cile Faure-Conter, Ce; Hauser, Peter; Lach, Boleslaw; van Veelen-Vincent, Marie-Lise; French, Pim J.; Van Meir, Erwin G.; Weiss, William A.; Pollack, Nalin Gupta Ian F.; Hamilton, Ronald L.; Nageswara Rao, Amulya A.; Giannini, Caterina; Rubin, Joshua B.; Moore, Andrew S.; Chambless, Lola B.; Vibhakar, Rajeev; Shin Ra, Young; Massimino, Maura; Mclendon, Roger E.; Wheeler, Helen; Zollo, Massimo; Ferrucci, Veronica; Kumabe, Toshihiro; Faria, Claudia C.; Sterba, Jaroslav; Jung, Shin; ́ pez-Aguilar, Enrique Lo; 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; Vijay Ramaswamy, And. - In: CELL REPORTS MEDICINE. - ISSN 2666-3791. - 1:3(2020), pp. 1-9. [10.1016/j.xcrm.2020.100038]
Pattern of Relapse and Treatment Response in WNT- Activated Medulloblastoma
Massimo Zollo;Veronica Ferrucci;
2020
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.| File | Dimensione | Formato | |
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