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

doi:10.1016/j.xcrm.2020.100038

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 LachMarie 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	100038
Journal	Cell Reports Medicine
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/j.xcrm.2020.100038
Publication status	Published - 23 Jun 2020

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© 2020 The Author(s)

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Pattern of Relapse and Treatment Response in WNT-Activated MedulloblastomaFinal published version, 2.16 MBLicence: CC BY-NC-ND

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Nobre, L., Zapotocky, M., Khan, S., Fukuoka, K., Fonseca, A., McKeown, T., Sumerauer, D., Vicha, A., Grajkowska, W. A., Trubicka, J., Li, K. K. W., Ng, H. K., Massimi, L., Lee, J. Y., Kim, S. K., Zelcer, S., Vasiljevic, A., Faure-Conter, C., Hauser, P., ... Ramaswamy, V. (2020). Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma. Cell Reports Medicine, 1(3), Article 100038. https://doi.org/10.1016/j.xcrm.2020.100038

@article{a65bb43a9c424f059295f32f2847687e,

title = "Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma",

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.",

author = "Liana Nobre and Michal Zapotocky and Sara Khan and Kohei Fukuoka and Adriana Fonseca and Tara McKeown and David Sumerauer and Ales Vicha and Grajkowska, {Wieslawa A.} and Joanna Trubicka and Li, {Kay Ka Wai} and Ng, {Ho Keung} and Luca Massimi and Lee, {Ji Yeoun} and Kim, {Seung Ki} and Shayna Zelcer and Alexandre Vasiljevic and C{\'e}cile Faure-Conter and Peter Hauser and Boleslaw Lach and {van Veelen-Vincent}, {Marie Lise} and French, {Pim J.} and {Van Meir}, {Erwin G.} and Weiss, {William A.} and Nalin Gupta and Pollack, {Ian F.} and Hamilton, {Ronald L.} and {Nageswara Rao}, {Amulya A.} and Caterina Giannini and Rubin, {Joshua B.} and Moore, {Andrew S.} and Chambless, {Lola B.} and Rajeev Vibhakar and Ra, {Young Shin} and Maura Massimino and McLendon, {Roger E.} and Helen Wheeler and Massimo Zollo and Veronica Ferruci and Toshihiro Kumabe and Faria, {Claudia C.} and Jaroslav Sterba and Shin Jung and Enrique L{\'o}pez-Aguilar and Jaume Mora and Carlotti, {Carlos G.} and Olson, {James M.} and Sarah Leary and Jason Cain and Lenka Krskova and Josef Zamecnik and Hawkins, {Cynthia E.} and Uri Tabori and Annie Huang and Ute Bartels and Northcott, {Paul A.} and Taylor, {Michael D.} and Stephen Yip and Hansford, {Jordan R.} and Eric Bouffet and Vijay Ramaswamy",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = jun,

day = "23",

doi = "10.1016/j.xcrm.2020.100038",

language = "English",

volume = "1",

journal = "Cell Reports Medicine",

publisher = "Cell Press",

number = "3",

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Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, HK, Massimi, L, Lee, JY, Kim, SK, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, van Veelen-Vincent, ML , French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Nageswara Rao, AA, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, López-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E & Ramaswamy, V 2020, 'Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma', Cell Reports Medicine, vol. 1, no. 3, 100038. https://doi.org/10.1016/j.xcrm.2020.100038

TY - JOUR

T1 - Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

AU - Nobre, Liana

AU - Zapotocky, Michal

AU - Khan, Sara

AU - Fukuoka, Kohei

AU - Fonseca, Adriana

AU - McKeown, Tara

AU - Sumerauer, David

AU - Vicha, Ales

AU - Grajkowska, Wieslawa A.

AU - Trubicka, Joanna

AU - Li, Kay Ka Wai

AU - Ng, Ho Keung

AU - Massimi, Luca

AU - Lee, Ji Yeoun

AU - Kim, Seung Ki

AU - Zelcer, Shayna

AU - Vasiljevic, Alexandre

AU - Faure-Conter, Cécile

AU - Hauser, Peter

AU - Lach, Boleslaw

AU - van Veelen-Vincent, Marie Lise

AU - French, Pim J.

AU - Van Meir, Erwin G.

AU - Weiss, William A.

AU - Gupta, Nalin

AU - Pollack, Ian F.

AU - Hamilton, Ronald L.

AU - Nageswara Rao, Amulya A.

AU - Giannini, Caterina

AU - Rubin, Joshua B.

AU - Moore, Andrew S.

AU - Chambless, Lola B.

AU - Vibhakar, Rajeev

AU - Ra, Young Shin

AU - Massimino, Maura

AU - McLendon, Roger E.

AU - Wheeler, Helen

AU - Zollo, Massimo

AU - Ferruci, Veronica

AU - Kumabe, Toshihiro

AU - Faria, Claudia C.

AU - Sterba, Jaroslav

AU - Jung, Shin

AU - López-Aguilar, Enrique

AU - Mora, Jaume

AU - Carlotti, Carlos G.

AU - Olson, James M.

AU - Leary, Sarah

AU - Cain, Jason

AU - Krskova, Lenka

AU - Zamecnik, Josef

AU - Hawkins, Cynthia E.

AU - Tabori, Uri

AU - Huang, Annie

AU - Bartels, Ute

AU - Northcott, Paul A.

AU - Taylor, Michael D.

AU - Yip, Stephen

AU - Hansford, Jordan R.

AU - Bouffet, Eric

AU - Ramaswamy, Vijay

PY - 2020/6/23

Y1 - 2020/6/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85095781132&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2020.100038

DO - 10.1016/j.xcrm.2020.100038

M3 - Article

C2 - 32743560

AN - SCOPUS:85095781132

VL - 1

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 3

M1 - 100038

ER -

Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

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