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Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis
EM. Thompson, T. Hielscher, E. Bouffet, M. Remke, B. Luu, S. Gururangan, RE. McLendon, DD. Bigner, ES. Lipp, S. Perreault, YJ. Cho, G. Grant, SK. Kim, JY. Lee, AA. Rao, C. Giannini, KK. Li, HK. Ng, Y. Yao, T. Kumabe, T. Tominaga, WA. Grajkowska,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
NLK
ProQuest Central
od 2000-09-01 do Před 2 měsíci
Nursing & Allied Health Database (ProQuest)
od 2000-09-01 do Před 2 měsíci
Health & Medicine (ProQuest)
od 2000-09-01 do Před 2 měsíci
Public Health Database (ProQuest)
od 2000-09-01 do Před 2 měsíci
- MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- meduloblastom klasifikace genetika patologie chirurgie MeSH
- nádory mozku klasifikace genetika patologie chirurgie MeSH
- předškolní dítě MeSH
- přežití bez známek nemoci MeSH
- prognóza * MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Kanada MeSH
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.
2nd Department of Pediatrics Semmelweis University Budapest Hungary
Cancer and Blood Disorders Center Seattle Children's Hospital Seattle WA USA
Center for Neuropathology Ludwig Maximilians Universität Munich Germany
Centre de Pathologie EST Groupement Hospitalier EST Université de Lyon Lyon France
Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany
Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA
Department of Neurological Surgery University of California San Francisco San Francisco CA USA
Department of Neurological Surgery University of Pittsburgh School of Medicine Pittsburgh PA USA
Department of Neurological Surgery Vanderbilt Medical Center Nashville TN USA
Department of Neurology Children's National Medical Center Washington DC USA
Department of Neurology University of California San Francisco San Francisco CA USA
Department of Neurology Vanderbilt Medical Center Nashville TN USA
Department of Neurosurgery Duke University Durham NC USA
Department of Neurosurgery Erasmus University Medical Center Rotterdam Netherlands
Department of Neurosurgery Hua Shan Hospital Fudan University Shanghai China
Department of Neurosurgery Kitasato University School of Medicine Sagamihara Kanagawa Japan
Department of Neurosurgery Lucille Packard Children's Hospital Stanford CA USA
Department of Neurosurgery Osaka University Graduate School of Medicine Osaka Japan
Department of Neurosurgery Stanford University School of Medicine Stanford CA USA
Department of Neurosurgery Tohoku University Graduate School of Medicine Sendai Japan
Department of Neurosurgery University of Michigan Medical School Ann Arbor MI USA
Department of Oncology The Children's Memorial Health Institute Warsaw Poland
Department of Pathology and Laboratory Medicine University of Calgary Calgary AB Canada
Department of Pathology Duke University Durham NC USA
Department of Pathology Erasmus University Medical Center Rotterdam Netherlands
Department of Pathology The Children's Memorial Health Institute Warsaw Poland
Department of Pathology University Hospital Brno Brno Czech Republic
Department of Pathology University of Pittsburgh School of Medicine Pittsburgh PA USA
Department of Pediatric Neurosurgery Shizuoka Children's Hospital Shizuoka Japan
Department of Pediatric Oncology School of Medicine Masaryk University Brno Czech Republic
Department of Pediatric Oncology University Hospital Heidelberg Heidelberg Germany
Department of Pediatrics University of California San Francisco San Francisco CA USA
Department of Pediatrics University of Colorado Denver Aurora CO USA
Departments of Pediatrics and Human Genetics McGill University Montreal QC Canada
Developmental and Stem Cell Biology Program The Hospital for Sick Children Toronto ON Canada
Division of Biostatistics German Cancer Research Center Heidelberg Germany
Division of Child Neurology CHU Sainte Justine Montreal QC Canada
Division of Haematology Oncology The Hospital for Sick Children Toronto ON Canada
Division of Hematology Oncology McGill University Montreal QC Canada
Division of Neuropathology University of Debrecen Medical and Health Science Centre Debrecen Hungary
Division of Neurosurgery Centro Hospitalar Lisboa Norte Hospital de Santa Maria Lisbon Portugal
Division of Neurosurgery The Hospital for Sick Children Toronto ON Canada
Division of Pathology The Hospital for Sick Children Toronto ON Canada
Division of Pediatric Hematology Oncology Mayo Clinic Rochester MN USA
Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany
Division of Stem Cell Research Institute for Clinical Research Osaka National Hospital Osaka Japan
Divison of Pathology Centro Hospitalar Lisboa Norte Hospital de Santa Maria Lisbon Portugal
INSERM U1028 CNRS UMR5292 Centre de Recherche en Neurosciences Université de Lyon Lyon France
Institute of Pediatric Hematology and Oncology Lyon France
Neurosurgical Service KK Women's and Children's Hospital Singapore Singapore
Pediatric Neurosurgery Catholic University Medical School Rome Italy
The Preston Robert Tisch Brain Tumor Center Duke University Durham NC USA
UO Neurochirurgia Istituto Giannina Gaslini Genova Italy
UQ Child Health Research Centre University of Queensland Brisbane QLD Australia
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- $a Thompson, Eric M $u Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; Department of Neurosurgery, Duke University, Durham, NC, USA.
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- $a Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis / $c EM. Thompson, T. Hielscher, E. Bouffet, M. Remke, B. Luu, S. Gururangan, RE. McLendon, DD. Bigner, ES. Lipp, S. Perreault, YJ. Cho, G. Grant, SK. Kim, JY. Lee, AA. Rao, C. Giannini, KK. Li, HK. Ng, Y. Yao, T. Kumabe, T. Tominaga, WA. Grajkowska, M. Perek-Polnik, DC. Low, WT. Seow, KT. Chang, J. Mora, IF. Pollack, RL. Hamilton, S. Leary, AS. Moore, WJ. Ingram, AR. Hallahan, A. Jouvet, M. Fèvre-Montange, A. Vasiljevic, C. Faure-Conter, T. Shofuda, N. Kagawa, N. Hashimoto, N. Jabado, AG. Weil, T. Gayden, T. Wataya, T. Shalaby, M. Grotzer, K. Zitterbart, J. Sterba, L. Kren, T. Hortobágyi, A. Klekner, B. László, T. Pócza, P. Hauser, U. Schüller, S. Jung, WY. Jang, PJ. French, JM. Kros, ML. van Veelen, L. Massimi, JR. Leonard, JB. Rubin, R. Vibhakar, LB. Chambless, MK. Cooper, RC. Thompson, CC. Faria, A. Carvalho, S. Nunes, J. Pimentel, X. Fan, KM. Muraszko, E. López-Aguilar, D. Lyden, L. Garzia, DJ. Shih, N. Kijima, C. Schneider, J. Adamski, PA. Northcott, M. Kool, DT. Jones, JA. Chan, A. Nikolic, ML. Garre, EG. Van Meir, S. Osuka, JJ. Olson, A. Jahangiri, BA. Castro, N. Gupta, WA. Weiss, I. Moxon-Emre, DJ. Mabbott, A. Lassaletta, CE. Hawkins, U. Tabori, J. Drake, A. Kulkarni, P. Dirks, JT. Rutka, A. Korshunov, SM. Pfister, RJ. Packer, V. Ramaswamy, MD. Taylor,
- 520 9_
- $a 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.
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- $a Hielscher, Thomas $u Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 700 1_
- $a Bouffet, Eric $u 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.
- 700 1_
- $a Remke, Marc $u Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
- 700 1_
- $a Luu, Betty $u Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Gururangan, Sridharan $u The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
- 700 1_
- $a McLendon, Roger E $u Department of Pathology, Duke University, Durham, NC, USA.
- 700 1_
- $a Bigner, Darell D $u Department of Pathology, Duke University, Durham, NC, USA; The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
- 700 1_
- $a Lipp, Eric S $u Department of Pathology, Duke University, Durham, NC, USA.
- 700 1_
- $a Perreault, Sebastien $u Division of Child Neurology, CHU Sainte-Justine, Montreal, QC, Canada.
- 700 1_
- $a Cho, Yoon-Jae $u 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.
- 700 1_
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- 700 1_
- $a Kim, Seung-Ki $u Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea.
- 700 1_
- $a Lee, Ji Yeoun $u Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea.
- 700 1_
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- 700 1_
- $a Giannini, Caterina $u Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
- 700 1_
- $a Li, Kay Ka Wai $u Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
- 700 1_
- $a Ng, Ho-Keung $u Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China.
- 700 1_
- $a Yao, Yu $u Department of Neurosurgery, Hua Shan Hospital, Fudan University, Shanghai, China.
- 700 1_
- $a Kumabe, Toshihiro $u Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
- 700 1_
- $a Tominaga, Teiji $u Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
- 700 1_
- $a Grajkowska, Wieslawa A $u Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.
- 700 1_
- $a Perek-Polnik, Marta $u Department of Oncology, The Children's Memorial Health Institute, Warsaw, Poland.
- 700 1_
- $a Low, David C Y $u Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore.
- 700 1_
- $a Seow, Wan Tew $u Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore.
- 700 1_
- $a Chang, Kenneth T E $u Department of Pathology & Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
- 700 1_
- $a Mora, Jaume $u Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Jabado, Nada $u Division of Hematology/Oncology, McGill University, Montreal, QC, Canada.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Schneider, Christian $u Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Adamski, Jennifer $u Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Northcott, Paul A $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 700 1_
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- 700 1_
- $a Jones, David T W $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 700 1_
- $a Chan, Jennifer A $u Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
- 700 1_
- $a Nikolic, Ana $u Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
- 700 1_
- $a Garre, Maria Luisa $u UO Neurochirurgia, Istituto Giannina Gaslini, Genova, Italy.
- 700 1_
- $a Van Meir, Erwin G $u Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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- $a Osuka, Satoru $u Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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- $a Jahangiri, Arman $u Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
- 700 1_
- $a Castro, Brandyn A $u Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
- 700 1_
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- 700 1_
- $a Weiss, William A $u 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.
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- $a Moxon-Emre, Iska $u Program in Neuroscience and Mental Health and Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Mabbott, Donald J $u Program in Neuroscience and Mental Health and Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Lassaletta, Alvaro $u Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Hawkins, Cynthia E $u Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
- 700 1_
- $a Tabori, Uri $u 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.
- 700 1_
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- 700 1_
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- 700 1_
- $a Rutka, James T $u 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.
- 700 1_
- $a Korshunov, Andrey $u Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 700 1_
- $a Pfister, Stefan M $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, University Hospital Heidelberg, Heidelberg, Germany.
- 700 1_
- $a Packer, Roger J $u Department of Neurology, Children's National Medical Center, Washington, DC, USA.
- 700 1_
- $a Ramaswamy, Vijay $u 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.
- 700 1_
- $a Taylor, Michael D $u 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.
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