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Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma

Bibliographic Details
Main Author: Kumar, Rahul
Publication Date: 2021
Other Authors: Smith, Kyle S., Deng, Maximilian, Terhune, Colt, Robinson, Giles W, Orr, Brent A., Liu, Anthony P. Y., Lin, Tong, Billups, Catherine A., Chintagumpala, Murali, Bowers, Daniel C., Hassall, Timothy E., Hansford, Jordan R., Khuong-Quang, Dong Anh, Crawford, John R., Bendel, Anne E., Gururangan, Sridharan, Schroeder, Kristin, Bouffet, Eric, Bartels, Ute, Fisher, Michael J., Cohn, Richard, Partap, Sonia, Kellie, Stewart J., McCowage, Geoffrey, Paulino, Arnold C., Rutkowski, Stefan, Fleischhack, Gudrun, Dhall, Girish, Klesse, Laura J., Leary, Sarah, Nazarian, Javad, Kool, Marcel, Wesseling, Pieter, Ryzhova, Marina, Zheludkova, Olga, Golanov, Andrey V., McLendon, Roger E., Packer, Roger J., Dunham, Christopher, Hukin, Juliette, Fouladi, Maryam, Faria, Claudia, Pimentel, José, Walter, Andrew W., Jabado, Nada, Cho, Yoon-Jae, Perreault, Sebastien, Croul, Sidney E., Zapotocky, Michal, Hawkins, Cynthia, Tabori, Uri, Taylor, Michael D., Pfister, Stefan M., Klimo, Paul, Boop, Frederick A., Ellison, David W., Merchant, Thomas E., Onar-Thomas, Arzu, Korshunov, Andrey, Jones, David T. W., Gajjar, Amar, Ramaswamy, Vijay, Northcott, Paul A.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/46204
Summary: © 2021 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
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spelling Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma© 2021 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/Purpose: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. Methods: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. Results: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. Conclusion: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.American Society of Clinical OncologyRepositório da Universidade de LisboaKumar, RahulSmith, Kyle S.Deng, MaximilianTerhune, ColtRobinson, Giles WOrr, Brent A.Liu, Anthony P. Y.Lin, TongBillups, Catherine A.Chintagumpala, MuraliBowers, Daniel C.Hassall, Timothy E.Hansford, Jordan R.Khuong-Quang, Dong AnhCrawford, John R.Bendel, Anne E.Gururangan, SridharanSchroeder, KristinBouffet, EricBartels, UteFisher, Michael J.Cohn, RichardPartap, SoniaKellie, Stewart J.McCowage, GeoffreyPaulino, Arnold C.Rutkowski, StefanFleischhack, GudrunDhall, GirishKlesse, Laura J.Leary, SarahNazarian, JavadKool, MarcelWesseling, PieterRyzhova, MarinaZheludkova, OlgaGolanov, Andrey V.McLendon, Roger E.Packer, Roger J.Dunham, ChristopherHukin, JulietteFouladi, MaryamFaria, ClaudiaPimentel, JoséWalter, Andrew W.Jabado, NadaCho, Yoon-JaePerreault, SebastienCroul, Sidney E.Zapotocky, MichalHawkins, CynthiaTabori, UriTaylor, Michael D.Pfister, Stefan M.Klimo, PaulBoop, Frederick A.Ellison, David W.Merchant, Thomas E.Onar-Thomas, ArzuKorshunov, AndreyJones, David T. W.Gajjar, AmarRamaswamy, VijayNorthcott, Paul A.2021-02-05T13:14:57Z2021-01-272021-01-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46204engJ Clin Oncol. 2021 Jan 27:JCO20013590732-183X10.1200/JCO.20.013591527-7755info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:28:07Zoai:repositorio.ulisboa.pt:10451/46204Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:12:46.442435Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
title Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
spellingShingle Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
Kumar, Rahul
title_short Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
title_full Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
title_fullStr Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
title_full_unstemmed Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
title_sort Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma
author Kumar, Rahul
author_facet Kumar, Rahul
Smith, Kyle S.
Deng, Maximilian
Terhune, Colt
Robinson, Giles W
Orr, Brent A.
Liu, Anthony P. Y.
Lin, Tong
Billups, Catherine A.
Chintagumpala, Murali
Bowers, Daniel C.
Hassall, Timothy E.
Hansford, Jordan R.
Khuong-Quang, Dong Anh
Crawford, John R.
Bendel, Anne E.
Gururangan, Sridharan
Schroeder, Kristin
Bouffet, Eric
Bartels, Ute
Fisher, Michael J.
Cohn, Richard
Partap, Sonia
Kellie, Stewart J.
McCowage, Geoffrey
Paulino, Arnold C.
Rutkowski, Stefan
Fleischhack, Gudrun
Dhall, Girish
Klesse, Laura J.
Leary, Sarah
Nazarian, Javad
Kool, Marcel
Wesseling, Pieter
Ryzhova, Marina
Zheludkova, Olga
Golanov, Andrey V.
McLendon, Roger E.
Packer, Roger J.
Dunham, Christopher
Hukin, Juliette
Fouladi, Maryam
Faria, Claudia
Pimentel, José
Walter, Andrew W.
Jabado, Nada
Cho, Yoon-Jae
Perreault, Sebastien
Croul, Sidney E.
Zapotocky, Michal
Hawkins, Cynthia
Tabori, Uri
Taylor, Michael D.
Pfister, Stefan M.
Klimo, Paul
Boop, Frederick A.
Ellison, David W.
Merchant, Thomas E.
Onar-Thomas, Arzu
Korshunov, Andrey
Jones, David T. W.
Gajjar, Amar
Ramaswamy, Vijay
Northcott, Paul A.
author_role author
author2 Smith, Kyle S.
Deng, Maximilian
Terhune, Colt
Robinson, Giles W
Orr, Brent A.
Liu, Anthony P. Y.
Lin, Tong
Billups, Catherine A.
Chintagumpala, Murali
Bowers, Daniel C.
Hassall, Timothy E.
Hansford, Jordan R.
Khuong-Quang, Dong Anh
Crawford, John R.
Bendel, Anne E.
Gururangan, Sridharan
Schroeder, Kristin
Bouffet, Eric
Bartels, Ute
Fisher, Michael J.
Cohn, Richard
Partap, Sonia
Kellie, Stewart J.
McCowage, Geoffrey
Paulino, Arnold C.
Rutkowski, Stefan
Fleischhack, Gudrun
Dhall, Girish
Klesse, Laura J.
Leary, Sarah
Nazarian, Javad
Kool, Marcel
Wesseling, Pieter
Ryzhova, Marina
Zheludkova, Olga
Golanov, Andrey V.
McLendon, Roger E.
Packer, Roger J.
Dunham, Christopher
Hukin, Juliette
Fouladi, Maryam
Faria, Claudia
Pimentel, José
Walter, Andrew W.
Jabado, Nada
Cho, Yoon-Jae
Perreault, Sebastien
Croul, Sidney E.
Zapotocky, Michal
Hawkins, Cynthia
Tabori, Uri
Taylor, Michael D.
Pfister, Stefan M.
Klimo, Paul
Boop, Frederick A.
Ellison, David W.
Merchant, Thomas E.
Onar-Thomas, Arzu
Korshunov, Andrey
Jones, David T. W.
Gajjar, Amar
Ramaswamy, Vijay
Northcott, Paul A.
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dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Kumar, Rahul
Smith, Kyle S.
Deng, Maximilian
Terhune, Colt
Robinson, Giles W
Orr, Brent A.
Liu, Anthony P. Y.
Lin, Tong
Billups, Catherine A.
Chintagumpala, Murali
Bowers, Daniel C.
Hassall, Timothy E.
Hansford, Jordan R.
Khuong-Quang, Dong Anh
Crawford, John R.
Bendel, Anne E.
Gururangan, Sridharan
Schroeder, Kristin
Bouffet, Eric
Bartels, Ute
Fisher, Michael J.
Cohn, Richard
Partap, Sonia
Kellie, Stewart J.
McCowage, Geoffrey
Paulino, Arnold C.
Rutkowski, Stefan
Fleischhack, Gudrun
Dhall, Girish
Klesse, Laura J.
Leary, Sarah
Nazarian, Javad
Kool, Marcel
Wesseling, Pieter
Ryzhova, Marina
Zheludkova, Olga
Golanov, Andrey V.
McLendon, Roger E.
Packer, Roger J.
Dunham, Christopher
Hukin, Juliette
Fouladi, Maryam
Faria, Claudia
Pimentel, José
Walter, Andrew W.
Jabado, Nada
Cho, Yoon-Jae
Perreault, Sebastien
Croul, Sidney E.
Zapotocky, Michal
Hawkins, Cynthia
Tabori, Uri
Taylor, Michael D.
Pfister, Stefan M.
Klimo, Paul
Boop, Frederick A.
Ellison, David W.
Merchant, Thomas E.
Onar-Thomas, Arzu
Korshunov, Andrey
Jones, David T. W.
Gajjar, Amar
Ramaswamy, Vijay
Northcott, Paul A.
description © 2021 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
publishDate 2021
dc.date.none.fl_str_mv 2021-02-05T13:14:57Z
2021-01-27
2021-01-27T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/46204
url http://hdl.handle.net/10451/46204
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Clin Oncol. 2021 Jan 27:JCO2001359
0732-183X
10.1200/JCO.20.01359
1527-7755
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society of Clinical Oncology
publisher.none.fl_str_mv American Society of Clinical Oncology
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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