Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma
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NOBRE, L., M. ZAPOTOCKY, S. KHAN, K. FUKUOKA, A. FONSECA, T. MCKEOWN, D. SUMERAUER, A. VICHA, W. A. GRAJKOWSKA, J. TRUBICKA, K. K. W. LI, H. K. NG, L. MASSIMI, J. Y. LEE, S. K. KIM, S. ZELCER, A. VASILJEVIC, C. FAURE-CONTER, P. HAUSER, B. LACH, M. L. VAN VEELEN-VINCENT, PJ FRENCH, Meir EG VAN, W. A. WEISS, N. GUPTA, I. F. POLLACK, R. L. HAMILTON, A. A. N. RAO, C. GIANNINI, J. B. RUBIN, A. S. MOORE, L. B. CHAMBLESS, R. VIBHAKAR, Y. S. RA, M. MASSIMINO, R. E. MCLENDON, H. WHEELER, M. ZOLLO, V. FERRUCI, T. KUMABE, C. C. FARIA, Jaroslav ŠTĚRBA (203 Česká republika, domácí), S. JUNG, E. LOPEZ-AGUILAR, J. MORA, C. G. CARLOTTI, J. M. OLSON, S. LEARY, J. CAIN, L. KRSKOVA, J. ZAMECNIK, C. E. HAWKINS, U. TABORI, A. N. HUANG, U. BARTELS, P. A. NORTHCOTT, M. D. TAYLOR, S. YIP, J. R. HANSFORD, E. BOUFFET a V. RAMASWAMY (garant)
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.
NOBRE, L., M. ZAPOTOCKY, S. KHAN, K. FUKUOKA, A. FONSECA, T. MCKEOWN, D. SUMERAUER, A. VICHA, W. A. GRAJKOWSKA, J. TRUBICKA, K. K. W. LI, H. K. NG, L. MASSIMI, J. Y. LEE, S. K. KIM, S. ZELCER, A. VASILJEVIC, C. FAURE-CONTER, P. HAUSER, B. LACH, M. L. VAN VEELEN-VINCENT, PJ FRENCH, Meir EG VAN, W. A. WEISS, N. GUPTA, I. F. POLLACK, R. L. HAMILTON, A. A. N. RAO, C. GIANNINI, J. B. RUBIN, A. S. MOORE, L. B. CHAMBLESS, R. VIBHAKAR, Y. S. RA, M. MASSIMINO, R. E. MCLENDON, H. WHEELER, M. ZOLLO, V. FERRUCI, T. KUMABE, C. C. FARIA, Jaroslav ŠTĚRBA, S. JUNG, E. LOPEZ-AGUILAR, J. MORA, C. G. CARLOTTI, J. M. OLSON, S. LEARY, J. CAIN, L. KRSKOVA, J. ZAMECNIK, C. E. HAWKINS, U. TABORI, A. N. HUANG, U. BARTELS, P. A. NORTHCOTT, M. D. TAYLOR, S. YIP, J. R. HANSFORD, E. BOUFFET a V. RAMASWAMY. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma. CELL REPORTS MEDICINE. AMSTERDAM: ELSEVIER, 2020, roč. 1, č. 3, s. 1-11. ISSN 2666-3791. Dostupné z: https://dx.doi.org/10.1016/j.xcrm.2020.100038.
@article{1766037, author = {Nobre, L. and Zapotocky, M. and Khan, S. and Fukuoka, K. and Fonseca, A. and McKeown, T. and Sumerauer, D. and Vicha, A. and Grajkowska, W. A. and Trubicka, J. and Li, K. K. W. and Ng, H. K. and Massimi, L. and Lee, J. Y. and Kim, S. K. and Zelcer, S. and Vasiljevic, A. and FaureandConter, C. and Hauser, P. and Lach, B. and Van VeelenandVincent, M. L. and French, PJ and Van, Meir EG and Weiss, W. A. and Gupta, N. and Pollack, I. F. and Hamilton, R. L. and Rao, A. A. N. and Giannini, C. and Rubin, J. B. and Moore, A. S. and Chambless, L. B. and Vibhakar, R. and Ra, Y. S. and Massimino, M. and McLendon, R. E. and Wheeler, H. and Zollo, M. and Ferruci, V. and Kumabe, T. and Faria, C. C. and Štěrba, Jaroslav and Jung, S. and LopezandAguilar, E. and Mora, J. and Carlotti, C. G. and Olson, J. M. and Leary, S. and Cain, J. and Krskova, L. and Zamecnik, J. and Hawkins, C. E. and Tabori, U. and Huang, A. N. and Bartels, U. and Northcott, P. A. and Taylor, M. D. and Yip, S. and Hansford, J. R. and Bouffet, E. and Ramaswamy, V.}, article_location = {AMSTERDAM}, article_number = {3}, doi = {http://dx.doi.org/10.1016/j.xcrm.2020.100038}, keywords = {WNT-Activated Medulloblastoma}, language = {eng}, issn = {2666-3791}, journal = {CELL REPORTS MEDICINE}, title = {Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma}, url = {https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(20)30050-1.pdf}, volume = {1}, year = {2020} }
TY - JOUR ID - 1766037 AU - 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. - Lach, B. - Van Veelen-Vincent, M. L. - French, PJ - Van, Meir EG - Weiss, W. A. - Gupta, N. - Pollack, I. F. - Hamilton, R. L. - Rao, A. A. N. - Giannini, C. - Rubin, J. B. - Moore, A. S. - Chambless, L. B. - Vibhakar, R. - Ra, Y. S. - Massimino, M. - McLendon, R. E. - Wheeler, H. - Zollo, M. - Ferruci, V. - Kumabe, T. - Faria, C. C. - Štěrba, Jaroslav - Jung, S. - Lopez-Aguilar, E. - Mora, J. - Carlotti, C. G. - Olson, J. M. - Leary, S. - Cain, J. - Krskova, L. - Zamecnik, J. - Hawkins, C. E. - Tabori, U. - Huang, A. N. - Bartels, U. - Northcott, P. A. - Taylor, M. D. - Yip, S. - Hansford, J. R. - Bouffet, E. - Ramaswamy, V. PY - 2020 TI - Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma JF - CELL REPORTS MEDICINE VL - 1 IS - 3 SP - 1-11 EP - 1-11 PB - ELSEVIER SN - 26663791 KW - WNT-Activated Medulloblastoma UR - https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(20)30050-1.pdf 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. ER -
NOBRE, L., M. ZAPOTOCKY, S. KHAN, K. FUKUOKA, A. FONSECA, T. MCKEOWN, D. SUMERAUER, A. VICHA, W. A. GRAJKOWSKA, J. TRUBICKA, K. K. W. LI, H. K. NG, L. MASSIMI, J. Y. LEE, S. K. KIM, S. ZELCER, A. VASILJEVIC, C. FAURE-CONTER, P. HAUSER, B. LACH, M. L. VAN VEELEN-VINCENT, PJ FRENCH, Meir EG VAN, W. A. WEISS, N. GUPTA, I. F. POLLACK, R. L. HAMILTON, A. A. N. RAO, C. GIANNINI, J. B. RUBIN, A. S. MOORE, L. B. CHAMBLESS, R. VIBHAKAR, Y. S. RA, M. MASSIMINO, R. E. MCLENDON, H. WHEELER, M. ZOLLO, V. FERRUCI, T. KUMABE, C. C. FARIA, Jaroslav ŠTĚRBA, S. JUNG, E. LOPEZ-AGUILAR, J. MORA, C. G. CARLOTTI, J. M. OLSON, S. LEARY, J. CAIN, L. KRSKOVA, J. ZAMECNIK, C. E. HAWKINS, U. TABORI, A. N. HUANG, U. BARTELS, P. A. NORTHCOTT, M. D. TAYLOR, S. YIP, J. R. HANSFORD, E. BOUFFET a V. RAMASWAMY. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma. \textit{CELL REPORTS MEDICINE}. AMSTERDAM: ELSEVIER, 2020, roč.~1, č.~3, s.~1-11. ISSN~2666-3791. Dostupné z: https://dx.doi.org/10.1016/j.xcrm.2020.100038.