Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma
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Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. / 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 C; Pimentel, Jose; 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.
in: J CLIN ONCOL, Jahrgang 39, Nr. 7, 01.03.2021, S. 807-821.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma
AU - Kumar, Rahul
AU - Smith, Kyle S
AU - Deng, Maximilian
AU - Terhune, Colt
AU - Robinson, Giles W
AU - Orr, Brent A
AU - Liu, Anthony P Y
AU - Lin, Tong
AU - Billups, Catherine A
AU - Chintagumpala, Murali
AU - Bowers, Daniel C
AU - Hassall, Timothy E
AU - Hansford, Jordan R
AU - Khuong-Quang, Dong Anh
AU - Crawford, John R
AU - Bendel, Anne E
AU - Gururangan, Sridharan
AU - Schroeder, Kristin
AU - Bouffet, Eric
AU - Bartels, Ute
AU - Fisher, Michael J
AU - Cohn, Richard
AU - Partap, Sonia
AU - Kellie, Stewart J
AU - McCowage, Geoffrey
AU - Paulino, Arnold C
AU - Rutkowski, Stefan
AU - Fleischhack, Gudrun
AU - Dhall, Girish
AU - Klesse, Laura J
AU - Leary, Sarah
AU - Nazarian, Javad
AU - Kool, Marcel
AU - Wesseling, Pieter
AU - Ryzhova, Marina
AU - Zheludkova, Olga
AU - Golanov, Andrey V
AU - McLendon, Roger E
AU - Packer, Roger J
AU - Dunham, Christopher
AU - Hukin, Juliette
AU - Fouladi, Maryam
AU - Faria, Claudia C
AU - Pimentel, Jose
AU - Walter, Andrew W
AU - Jabado, Nada
AU - Cho, Yoon-Jae
AU - Perreault, Sebastien
AU - Croul, Sidney E
AU - Zapotocky, Michal
AU - Hawkins, Cynthia
AU - Tabori, Uri
AU - Taylor, Michael D
AU - Pfister, Stefan M
AU - Klimo, Paul
AU - Boop, Frederick A
AU - Ellison, David W
AU - Merchant, Thomas E
AU - Onar-Thomas, Arzu
AU - Korshunov, Andrey
AU - Jones, David T W
AU - Gajjar, Amar
AU - Ramaswamy, Vijay
AU - Northcott, Paul A
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
U2 - 10.1200/JCO.20.01359
DO - 10.1200/JCO.20.01359
M3 - SCORING: Journal article
C2 - 33502920
VL - 39
SP - 807
EP - 821
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 7
ER -