. 2016 Apr;17(4):484-495.

doi: 10.1016/S1470-2045(15)00581-1. Epub 2016 Mar 12.

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Eric M Thompson¹, Thomas Hielscher², Eric Bouffet³, Marc Remke⁴, Betty Luu⁵, Sridharan Gururangan⁶, Roger E McLendon⁷, Darell D Bigner⁸, Eric S Lipp⁷, Sebastien Perreault⁹, Yoon-Jae Cho¹⁰, Gerald Grant¹¹, Seung-Ki Kim¹², Ji Yeoun Lee¹², Amulya A Nageswara Rao¹³, Caterina Giannini¹⁴, Kay Ka Wai Li¹⁵, Ho-Keung Ng¹⁵, Yu Yao¹⁶, Toshihiro Kumabe¹⁷, Teiji Tominaga¹⁸, Wieslawa A Grajkowska¹⁹, Marta Perek-Polnik²⁰, David C Y Low²¹, Wan Tew Seow²¹, Kenneth T E Chang²², Jaume Mora²³, Ian F Pollack²⁴, Ronald L Hamilton²⁵, Sarah Leary²⁶, Andrew S Moore²⁷, Wendy J Ingram²⁸, Andrew R Hallahan²⁷, Anne Jouvet²⁹, Michelle Fèvre-Montange³⁰, Alexandre Vasiljevic³¹, Cecile Faure-Conter³², Tomoko Shofuda³³, Naoki Kagawa³⁴, Naoya Hashimoto³⁴, Nada Jabado³⁵, Alexander G Weil³⁶, Tenzin Gayden³⁶, Takafumi Wataya³⁷, Tarek Shalaby³⁸, Michael Grotzer³⁸, Karel Zitterbart³⁹, Jaroslav Sterba³⁹, Leos Kren⁴⁰, Tibor Hortobágyi⁴¹, Almos Klekner⁴¹, Bognár László⁴¹, Tímea Pócza⁴², Peter Hauser⁴², Ulrich Schüller⁴³, Shin Jung⁴⁴, Woo-Youl Jang⁴⁴, Pim J French⁴⁵, Johan M Kros⁴⁶, Marie-Lise C van Veelen⁴⁵, Luca Massimi⁴⁷, Jeffrey R Leonard⁴⁸, Joshua B Rubin⁴⁹, Rajeev Vibhakar⁵⁰, Lola B Chambless⁵¹, Michael K Cooper⁵², Reid C Thompson⁵¹, Claudia C Faria⁵³, Alice Carvalho⁵⁴, Sofia Nunes⁵⁵, José Pimentel⁵⁶, Xing Fan⁵⁷, Karin M Muraszko⁵⁸, Enrique López-Aguilar⁵⁹, David Lyden⁶⁰, Livia Garzia⁵, David J H Shih⁶¹, Noriyuki Kijima⁵, Christian Schneider⁶², Jennifer Adamski⁶³, Paul A Northcott⁶⁴, Marcel Kool⁶⁴, David T W Jones⁶⁴, Jennifer A Chan⁶⁵, Ana Nikolic⁶⁵, Maria Luisa Garre⁶⁶, Erwin G Van Meir⁶⁷, Satoru Osuka⁶⁷, Jeffrey J Olson⁶⁸, Arman Jahangiri⁶⁹, Brandyn A Castro⁶⁹, Nalin Gupta⁷⁰, William A Weiss⁷¹, Iska Moxon-Emre⁷², Donald J Mabbott⁷², Alvaro Lassaletta⁶³, Cynthia E Hawkins⁷³, Uri Tabori³, James Drake⁶², Abhaya Kulkarni⁶², Peter Dirks⁷⁴, James T Rutka⁷⁵, Andrey Korshunov⁷⁶, Stefan M Pfister⁷⁷, Roger J Packer⁷⁸, Vijay Ramaswamy⁷⁹, Michael D Taylor⁸⁰

Affiliations

¹ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; Department of Neurosurgery, Duke University, Durham, NC, USA.
² Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁴ Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
⁵ Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁶ The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
⁷ Department of Pathology, Duke University, Durham, NC, USA.
⁸ Department of Pathology, Duke University, Durham, NC, USA; The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
⁹ Division of Child Neurology, CHU Sainte-Justine, Montreal, QC, Canada.
¹⁰ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Lucille Packard Children's Hospital, Stanford, CA, USA.
¹² Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea.
¹³ Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN, USA.
¹⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
¹⁵ Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
¹⁶ Department of Neurosurgery, Hua Shan Hospital, Fudan University, Shanghai, China.
¹⁷ Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
¹⁸ Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹⁹ Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.
²⁰ Department of Oncology, The Children's Memorial Health Institute, Warsaw, Poland.
²¹ Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore.
²² Department of Pathology & Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
²³ Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.
²⁴ Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁵ Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁶ Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, WA, USA.
²⁷ UQ Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia; Oncology Service, Lady Cilento Children's Hospital, Children's Health Queensland, Brisbane, QLD, Australia.
²⁸ UQ Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia.
²⁹ Centre de Pathologie EST, Groupement Hospitalier EST, Université de Lyon, Lyon, France.
³⁰ INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences, Université de Lyon, Lyon, France.
³¹ Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron; ONCOFLAM, Neuro-Oncologie et Neuro-Inflammation Centre de Recherche en Neurosciences de Lyon, Lyon, France.
³² Institute of Pediatric Hematology and Oncology, Lyon, France.
³³ Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, Osaka, Japan.
³⁴ Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
³⁵ Division of Hematology/Oncology, McGill University, Montreal, QC, Canada.
³⁶ Departments of Pediatrics and Human Genetics, McGill University, Montreal, QC, Canada.
³⁷ Department of Pediatric Neurosurgery, Shizuoka Children's Hospital, Shizuoka, Japan.
³⁸ Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich, Switzerland.
³⁹ Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno, Czech Republic.
⁴⁰ Department of Pathology, University Hospital Brno, Brno, Czech Republic.
⁴¹ Division of Neuropathology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
⁴² 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
⁴³ Center for Neuropathology, Ludwig-Maximilians-Universität, Munich, Germany.
⁴⁴ Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam South Korea.
⁴⁵ Department of Neurosurgery, Erasmus University Medical Center, Rotterdam, Netherlands.
⁴⁶ Department of Pathology, Erasmus University Medical Center, Rotterdam, Netherlands.
⁴⁷ Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy.
⁴⁸ Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO, USA.
⁴⁹ Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO, USA.
⁵⁰ Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
⁵¹ Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA.
⁵² Department of Neurology, Vanderbilt Medical Center, Nashville, TN, USA.
⁵³ Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.
⁵⁴ Departamento de Oncologia Pediátrica, Hospital Pediátrico de Coimbra, Centro Hospitalar de Coimbra, Coimbra, Portugal.
⁵⁵ Unidade de Neuro-Oncologia Pediátrica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal.
⁵⁶ Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.
⁵⁷ Department of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵⁸ Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵⁹ Division of Pediatric Hematology/Oncology, Hospital Pediatría Centro Médico Nacional Century XXI, Mexico City, Mexico.
⁶⁰ Department of Pediatrics and Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
⁶¹ Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁶² Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
⁶³ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
⁶⁴ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁵ Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
⁶⁶ UO Neurochirurgia, Istituto Giannina Gaslini, Genova, Italy.
⁶⁷ Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁶⁸ Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁶⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
⁷⁰ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
⁷¹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁷² Program in Neuroscience and Mental Health and Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada.
⁷³ Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
⁷⁴ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁷⁵ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁷⁶ Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷⁷ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg, Germany.
⁷⁸ Department of Neurology, Children's National Medical Center, Washington, DC, USA.
⁷⁹ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁸⁰ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address: mdtaylor@sickkids.ca.

PMID: 26976201
PMCID: PMC4907853
DOI: 10.1016/S1470-2045(15)00581-1

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Eric M Thompson et al. Lancet Oncol. 2016 Apr.

. 2016 Apr;17(4):484-495.

doi: 10.1016/S1470-2045(15)00581-1. Epub 2016 Mar 12.

Authors

Affiliations

¹ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; Department of Neurosurgery, Duke University, Durham, NC, USA.
² Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁴ Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
⁵ Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁶ The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
⁷ Department of Pathology, Duke University, Durham, NC, USA.
⁸ Department of Pathology, Duke University, Durham, NC, USA; The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
⁹ Division of Child Neurology, CHU Sainte-Justine, Montreal, QC, Canada.
¹⁰ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Lucille Packard Children's Hospital, Stanford, CA, USA.
¹² Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea.
¹³ Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN, USA.
¹⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
¹⁵ Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
¹⁶ Department of Neurosurgery, Hua Shan Hospital, Fudan University, Shanghai, China.
¹⁷ Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
¹⁸ Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹⁹ Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.
²⁰ Department of Oncology, The Children's Memorial Health Institute, Warsaw, Poland.
²¹ Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore.
²² Department of Pathology & Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
²³ Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.
²⁴ Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁵ Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁶ Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, WA, USA.
²⁷ UQ Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia; Oncology Service, Lady Cilento Children's Hospital, Children's Health Queensland, Brisbane, QLD, Australia.
²⁸ UQ Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia.
²⁹ Centre de Pathologie EST, Groupement Hospitalier EST, Université de Lyon, Lyon, France.
³⁰ INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences, Université de Lyon, Lyon, France.
³¹ Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron; ONCOFLAM, Neuro-Oncologie et Neuro-Inflammation Centre de Recherche en Neurosciences de Lyon, Lyon, France.
³² Institute of Pediatric Hematology and Oncology, Lyon, France.
³³ Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, Osaka, Japan.
³⁴ Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
³⁵ Division of Hematology/Oncology, McGill University, Montreal, QC, Canada.
³⁶ Departments of Pediatrics and Human Genetics, McGill University, Montreal, QC, Canada.
³⁷ Department of Pediatric Neurosurgery, Shizuoka Children's Hospital, Shizuoka, Japan.
³⁸ Departments of Oncology and Neuro-Oncology, University Children's Hospital of Zurich, Zurich, Switzerland.
³⁹ Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno, Czech Republic.
⁴⁰ Department of Pathology, University Hospital Brno, Brno, Czech Republic.
⁴¹ Division of Neuropathology, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
⁴² 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
⁴³ Center for Neuropathology, Ludwig-Maximilians-Universität, Munich, Germany.
⁴⁴ Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam South Korea.
⁴⁵ Department of Neurosurgery, Erasmus University Medical Center, Rotterdam, Netherlands.
⁴⁶ Department of Pathology, Erasmus University Medical Center, Rotterdam, Netherlands.
⁴⁷ Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy.
⁴⁸ Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO, USA.
⁴⁹ Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO, USA.
⁵⁰ Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
⁵¹ Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA.
⁵² Department of Neurology, Vanderbilt Medical Center, Nashville, TN, USA.
⁵³ Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.
⁵⁴ Departamento de Oncologia Pediátrica, Hospital Pediátrico de Coimbra, Centro Hospitalar de Coimbra, Coimbra, Portugal.
⁵⁵ Unidade de Neuro-Oncologia Pediátrica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal.
⁵⁶ Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.
⁵⁷ Department of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵⁸ Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵⁹ Division of Pediatric Hematology/Oncology, Hospital Pediatría Centro Médico Nacional Century XXI, Mexico City, Mexico.
⁶⁰ Department of Pediatrics and Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
⁶¹ Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁶² Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
⁶³ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
⁶⁴ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁵ Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
⁶⁶ UO Neurochirurgia, Istituto Giannina Gaslini, Genova, Italy.
⁶⁷ Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁶⁸ Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁶⁹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
⁷⁰ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
⁷¹ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁷² Program in Neuroscience and Mental Health and Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada.
⁷³ Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
⁷⁴ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁷⁵ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁷⁶ Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷⁷ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg, Germany.
⁷⁸ Department of Neurology, Children's National Medical Center, Washington, DC, USA.
⁷⁹ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁸⁰ Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address: mdtaylor@sickkids.ca.

PMID: 26976201
PMCID: PMC4907853
DOI: 10.1016/S1470-2045(15)00581-1

Erratum in

Correction to Lancet Oncol 2016; 17: 484-95.
[No authors listed] [No authors listed] Lancet Oncol. 2022 Feb;23(2):e59. doi: 10.1016/S1470-2045(22)00006-7. Lancet Oncol. 2022. PMID: 35114132 No abstract available.

Abstract

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.

Methods: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm(2) tumour remaining), or sub-total resection (≥1·5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.

Findings: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084).

Interpretation: The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.

Funding: Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

PubMed Disclaimer

Conflict of interest statement

Declaration of Interests

XF reports grants from the National Institute of Health. WJI reports grans from Children s Hospital Foundation Queensland and The BrainChild Foundation. JO reports personal fees from American Cancer Society, non-financial support from Merck, grants from Genetech, grants from Millenium/Takeda, and grants from the National Institute of Health.

Figures

**Fig 1**
Five-year PFS and OS survival curves for the entire cohort by extent of resection (A and C) and by molecular subgroup (B and D).

**Fig 2**
Five-year PFS and OS survival curves for EOR by subgroup. There was not a significant PFS or OS advantage of those patients that had NTR or STR compared to GTR for the WNT group (A and B), the SHH group (C and D), or Group 3 (E and F). There was an association of increased EOR and both PFS and OS for Group 4 (G and H).

**Fig 3**
Nomograms for the multivariable Cox model. The presence or absence of each variable is scored (top row). The cumulative score from each variable is used to determine 3 and 5-year PFS (A) and OS (B) probabilities.

**Fig 4**
Multivariable Forest Plots directly comparing EOR for PFS (A) and OS (B). Circles to the right of the grey vertical line indicate increased risk while those to the left of the grey vertical line indicated decreased risk.

See this image and copyright information in PMC

Comment in

Extent of resection in medulloblastoma: time to reconsider?
Hargrave D. Hargrave D. Lancet Oncol. 2016 Apr;17(4):409-410. doi: 10.1016/S1470-2045(16)00143-1. Epub 2016 Mar 12. Lancet Oncol. 2016. PMID: 26976202 No abstract available.

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Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

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Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

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