Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis
Vijay Ramaswamy,Marc Remke,Eric Bouffet,Claudia C. Faria,Sébastien Perreault,Yoon Jae Cho,David Shih,Betty Luu,Adrian M. Dubuc,Paul A. Northcott,Ulrich Schüller,Sridharan Gururangan,Roger E. McLendon,Darell D. Bigner,Maryam Fouladi,Keith L. Ligon,Keith L. Ligon,Keith L. Ligon,Scott L. Pomeroy,Scott L. Pomeroy,Sandra E. Dunn,Joanna Triscott,Nada Jabado,Adam M. Fontebasso,David T.W. Jones,Marcel Kool,Matthias A. Karajannis,Sharon Gardner,David Zagzag,Sofia Nunes,José Pimentel,Jaume Mora,Eric S. Lipp,Andrew W. Walter,Marina Ryzhova,Olga Zheludkova,Ella Kumirova,Jad Alshami,Sidney Croul,James T. Rutka,Cynthia Hawkins,Uri Tabori,Kari Elise T. Codispoti,Roger J. Packer,Stefan M. Pfister,Stefan M. Pfister,Andrey Korshunov,Andrey Korshunov,Michael D. Taylor +48 more
TLDR
Subgroup-specific differences in the location and timing of recurrence across medulloblastoma subgroups have potential treatment ramifications and intensified local (posterior fossa) therapy should be tested in the initial treatment of patients with SHH tumours.Abstract:
Summary 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 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. Funding Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children and The University of Toronto.read more
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Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups
Kristian W. Pajtler,Kristian W. Pajtler,Hendrik Witt,Martin Sill,David T.W. Jones,Volker Hovestadt,Fabian Kratochwil,Khalida Wani,Ruth G. Tatevossian,Chandanamali Punchihewa,Pascal Johann,Jüri Reimand,Hans-Jörg Warnatz,Marina Ryzhova,Steve Mack,Vijay Ramaswamy,David Capper,David Capper,Leonille Schweizer,Leonille Schweizer,Laura Sieber,Andrea Wittmann,Zhiqin Huang,Peter van Sluis,Richard Volckmann,Jan Koster,Rogier Versteeg,Daniel W. Fults,Helen Toledano,Smadar Avigad,Lindsey M. Hoffman,Andrew M. Donson,Nicholas K. Foreman,Ekkehard Hewer,Karel Zitterbart,Mark R. Gilbert,Terri S. Armstrong,Terri S. Armstrong,Nalin Gupta,Jeffrey C. Allen,Matthias A. Karajannis,David Zagzag,Martin Hasselblatt,Andreas E. Kulozik,Olaf Witt,V. Peter Collins,Katja von Hoff,Stefan Rutkowski,Torsten Pietsch,Gary D. Bader,Marie-Laure Yaspo,Andreas von Deimling,Andreas von Deimling,Peter Lichter,Michael D. Taylor,Richard J. Gilbertson,David W. Ellison,Kenneth Aldape,Andrey Korshunov,Andrey Korshunov,Marcel Kool,Stefan M. Pfister +61 more
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Intertumoral Heterogeneity within Medulloblastoma Subgroups
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Risk stratification of childhood medulloblastoma in the molecular era: the current consensus
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Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors
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Divergent clonal selection dominates medulloblastoma at recurrence
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