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Recurrence patterns across medulloblastoma subgroups

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Recurrence patterns across medulloblastoma subgroups : an integrated clinical and molecular analysis. / Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Faria, Claudia C; Perreault, Sebastien; Cho, Yoon-Jae; Shih, David J H; Luu, Betty; Dubuc, Adrian M; Northcott, Paul A; Schüller, Ulrich; Gururangan, Sridharan; McLendon, Roger E; Bigner, Darell D; Fouladi, Maryam; Ligon, Keith L; Pomeroy, Scott L; Dunn, Sandra E; Triscott, Joanna; Jabado, Nada; Fontebasso, Adam; Jones, David T W; Kool, Marcel; Karajannis, Matthias A; Gardner, Sharon L; Zagzag, David; Nunes, Sofia; Pimentel, José; Mora, Jaume; Lipp, Eric S; Walter, Andrew W; Ryzhova, Marina; Zheludkova, Olga; Kumirova, Ella; Alshami, Jad; Croul, Sidney E; Rutka, James T; Hawkins, Cynthia; Tabori, Uri; Codispoti, Kari-Elise T; Packer, Roger J; Pfister, Stefan M; Korshunov, Andrey; Taylor, Michael D.

in: LANCET ONCOL, Jahrgang 14, Nr. 12, 11.2013, S. 1200-7.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Ramaswamy, V, Remke, M, Bouffet, E, Faria, CC, Perreault, S, Cho, Y-J, Shih, DJH, Luu, B, Dubuc, AM, Northcott, PA, Schüller, U, Gururangan, S, McLendon, RE, Bigner, DD, Fouladi, M, Ligon, KL, Pomeroy, SL, Dunn, SE, Triscott, J, Jabado, N, Fontebasso, A, Jones, DTW, Kool, M, Karajannis, MA, Gardner, SL, Zagzag, D, Nunes, S, Pimentel, J, Mora, J, Lipp, ES, Walter, AW, Ryzhova, M, Zheludkova, O, Kumirova, E, Alshami, J, Croul, SE, Rutka, JT, Hawkins, C, Tabori, U, Codispoti, K-ET, Packer, RJ, Pfister, SM, Korshunov, A & Taylor, MD 2013, 'Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis', LANCET ONCOL, Jg. 14, Nr. 12, S. 1200-7. https://doi.org/10.1016/S1470-2045(13)70449-2

APA

Ramaswamy, V., Remke, M., Bouffet, E., Faria, C. C., Perreault, S., Cho, Y-J., Shih, D. J. H., Luu, B., Dubuc, A. M., Northcott, P. A., Schüller, U., Gururangan, S., McLendon, R. E., Bigner, D. D., Fouladi, M., Ligon, K. L., Pomeroy, S. L., Dunn, S. E., Triscott, J., ... Taylor, M. D. (2013). Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. LANCET ONCOL, 14(12), 1200-7. https://doi.org/10.1016/S1470-2045(13)70449-2

Vancouver

Ramaswamy V, Remke M, Bouffet E, Faria CC, Perreault S, Cho Y-J et al. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. LANCET ONCOL. 2013 Nov;14(12):1200-7. https://doi.org/10.1016/S1470-2045(13)70449-2

Bibtex

@article{06af33d5ba4b45d484ddb4a9672649d5,
title = "Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis",
abstract = "BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns.METHODS: We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and established molecular subgroups using a nanoString-based assay on formalin-fixed paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival after recurrence were assessed in a subgroup-specific manner. Two independent, non-overlapping cohorts (cohort 2: samples from patients with recurrent medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012; cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were analysed to confirm and validate observations. When possible, molecular subgrouping was done on tissue obtained from both the initial surgery and at recurrence.RESULTS: Cohort 1 consisted of 30 patients with recurrent medulloblastomas; nine with local recurrences, and 21 with metastatic recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs (five pairs from cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This finding was validated in 17 pairs from cohort 3. When analysed in a subgroup-specific manner, local recurrences in cohort 1 were more frequent in SHH tumours (eight of nine [89%]) and metastatic recurrences were more common in group 3 and group 4 tumours (17 of 20 [85%] with one WNT, p=0·0014, local vs metastatic recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of recurrence was confirmed in cohort 2 (p=0·0013 for local vs metastatic recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0·0001). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival after recurrence was significantly longer in patients with group 4 tumours in cohort 1 (p=0·013) than with other subgroups, which was confirmed in cohort 2 (p=0·0075), but not cohort 3 (p=0·70).INTERPRETATION: Medulloblastoma does not change subgroup at the time of recurrence, reinforcing the stability of the four main medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours. Refinement of therapy for patients with group 3 or group 4 tumours should focus on metastases.",
keywords = "Adolescent, Canada, Cerebellar Neoplasms, Child, Child, Preschool, Europe, Female, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Male, Medulloblastoma, Neoplasm Recurrence, Local, Phenotype, Principal Component Analysis, Prognosis, Retrospective Studies, Risk Factors, Time Factors, United States, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Vijay Ramaswamy and Marc Remke and Eric Bouffet and Faria, {Claudia C} and Sebastien Perreault and Yoon-Jae Cho and Shih, {David J H} and Betty Luu and Dubuc, {Adrian M} and Northcott, {Paul A} and Ulrich Sch{\"u}ller and Sridharan Gururangan and McLendon, {Roger E} and Bigner, {Darell D} and Maryam Fouladi and Ligon, {Keith L} and Pomeroy, {Scott L} and Dunn, {Sandra E} and Joanna Triscott and Nada Jabado and Adam Fontebasso and Jones, {David T W} and Marcel Kool and Karajannis, {Matthias A} and Gardner, {Sharon L} and David Zagzag and Sofia Nunes and Jos{\'e} Pimentel and Jaume Mora and Lipp, {Eric S} and Walter, {Andrew W} and Marina Ryzhova and Olga Zheludkova and Ella Kumirova and Jad Alshami and Croul, {Sidney E} and Rutka, {James T} and Cynthia Hawkins and Uri Tabori and Codispoti, {Kari-Elise T} and Packer, {Roger J} and Pfister, {Stefan M} and Andrey Korshunov and Taylor, {Michael D}",
note = "Copyright {\textcopyright} 2013 Elsevier Ltd. All rights reserved.",
year = "2013",
month = nov,
doi = "10.1016/S1470-2045(13)70449-2",
language = "English",
volume = "14",
pages = "1200--7",
journal = "LANCET ONCOL",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "12",

}

RIS

TY - JOUR

T1 - Recurrence patterns across medulloblastoma subgroups

T2 - an integrated clinical and molecular analysis

AU - Ramaswamy, Vijay

AU - Remke, Marc

AU - Bouffet, Eric

AU - Faria, Claudia C

AU - Perreault, Sebastien

AU - Cho, Yoon-Jae

AU - Shih, David J H

AU - Luu, Betty

AU - Dubuc, Adrian M

AU - Northcott, Paul A

AU - Schüller, Ulrich

AU - Gururangan, Sridharan

AU - McLendon, Roger E

AU - Bigner, Darell D

AU - Fouladi, Maryam

AU - Ligon, Keith L

AU - Pomeroy, Scott L

AU - Dunn, Sandra E

AU - Triscott, Joanna

AU - Jabado, Nada

AU - Fontebasso, Adam

AU - Jones, David T W

AU - Kool, Marcel

AU - Karajannis, Matthias A

AU - Gardner, Sharon L

AU - Zagzag, David

AU - Nunes, Sofia

AU - Pimentel, José

AU - Mora, Jaume

AU - Lipp, Eric S

AU - Walter, Andrew W

AU - Ryzhova, Marina

AU - Zheludkova, Olga

AU - Kumirova, Ella

AU - Alshami, Jad

AU - Croul, Sidney E

AU - Rutka, James T

AU - Hawkins, Cynthia

AU - Tabori, Uri

AU - Codispoti, Kari-Elise T

AU - Packer, Roger J

AU - Pfister, Stefan M

AU - Korshunov, Andrey

AU - Taylor, Michael D

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/11

Y1 - 2013/11

N2 - BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns.METHODS: We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and established molecular subgroups using a nanoString-based assay on formalin-fixed paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival after recurrence were assessed in a subgroup-specific manner. Two independent, non-overlapping cohorts (cohort 2: samples from patients with recurrent medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012; cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were analysed to confirm and validate observations. When possible, molecular subgrouping was done on tissue obtained from both the initial surgery and at recurrence.RESULTS: Cohort 1 consisted of 30 patients with recurrent medulloblastomas; nine with local recurrences, and 21 with metastatic recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs (five pairs from cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This finding was validated in 17 pairs from cohort 3. When analysed in a subgroup-specific manner, local recurrences in cohort 1 were more frequent in SHH tumours (eight of nine [89%]) and metastatic recurrences were more common in group 3 and group 4 tumours (17 of 20 [85%] with one WNT, p=0·0014, local vs metastatic recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of recurrence was confirmed in cohort 2 (p=0·0013 for local vs metastatic recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0·0001). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival after recurrence was significantly longer in patients with group 4 tumours in cohort 1 (p=0·013) than with other subgroups, which was confirmed in cohort 2 (p=0·0075), but not cohort 3 (p=0·70).INTERPRETATION: Medulloblastoma does not change subgroup at the time of recurrence, reinforcing the stability of the four main medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours. Refinement of therapy for patients with group 3 or group 4 tumours should focus on metastases.

AB - BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns.METHODS: We retrospectively identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children (Toronto, ON, Canada) from 1994 to 2012 (cohort 1), and established molecular subgroups using a nanoString-based assay on formalin-fixed paraffin-embedded tissues or frozen tissue. The anatomical site of recurrence (local tumour bed or leptomeningeal metastasis), time to recurrence, and survival after recurrence were assessed in a subgroup-specific manner. Two independent, non-overlapping cohorts (cohort 2: samples from patients with recurrent medulloblastomas from 13 centres worldwide, obtained between 1991 and 2012; cohort 3: samples from patients with recurrent medulloblastoma obtained at the NN Burdenko Neurosurgical Institute [Moscow, Russia] between 1994 and 2011) were analysed to confirm and validate observations. When possible, molecular subgrouping was done on tissue obtained from both the initial surgery and at recurrence.RESULTS: Cohort 1 consisted of 30 patients with recurrent medulloblastomas; nine with local recurrences, and 21 with metastatic recurrences. Cohort 2 consisted of 77 patients and cohort 3 of 96 patients with recurrent medulloblastoma. Subgroup affiliation remained stable at recurrence in all 34 cases with available matched primary and recurrent pairs (five pairs from cohort 1 and 29 pairs from cohort 2 [15 SHH, five group 3, 14 group 4]). This finding was validated in 17 pairs from cohort 3. When analysed in a subgroup-specific manner, local recurrences in cohort 1 were more frequent in SHH tumours (eight of nine [89%]) and metastatic recurrences were more common in group 3 and group 4 tumours (17 of 20 [85%] with one WNT, p=0·0014, local vs metastatic recurrence, SHH vs group 3 vs group 4). The subgroup-specific location of recurrence was confirmed in cohort 2 (p=0·0013 for local vs metastatic recurrence, SHH vs group 3 vs group 4,), and cohort 3 (p<0·0001). Treatment with craniospinal irradiation at diagnosis was not significantly associated with the anatomical pattern of recurrence. Survival after recurrence was significantly longer in patients with group 4 tumours in cohort 1 (p=0·013) than with other subgroups, which was confirmed in cohort 2 (p=0·0075), but not cohort 3 (p=0·70).INTERPRETATION: Medulloblastoma does not change subgroup at the time of recurrence, reinforcing the stability of the four main medulloblastoma subgroups. Significant differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications. Specifically, intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours. Refinement of therapy for patients with group 3 or group 4 tumours should focus on metastases.

KW - Adolescent

KW - Canada

KW - Cerebellar Neoplasms

KW - Child

KW - Child, Preschool

KW - Europe

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Medulloblastoma

KW - Neoplasm Recurrence, Local

KW - Phenotype

KW - Principal Component Analysis

KW - Prognosis

KW - Retrospective Studies

KW - Risk Factors

KW - Time Factors

KW - United States

KW - Journal Article

KW - Multicenter Study

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/S1470-2045(13)70449-2

DO - 10.1016/S1470-2045(13)70449-2

M3 - SCORING: Journal article

C2 - 24140199

VL - 14

SP - 1200

EP - 1207

JO - LANCET ONCOL

JF - LANCET ONCOL

SN - 1470-2045

IS - 12

ER -