paediatrics Brussels 17

VOLUME 32 NUMBER 17 JUNE 10 2014

J OURNAL OF C LINICAL O NCOLOGY

O R I G I N A L R E P O R T

Impact of Craniospinal Dose, Boost Volume, and Neurologic Complications on Intellectual Outcome in Patients With Medulloblastoma Iska Moxon-Emre, Eric Bouffet, Michael D. Taylor, Normand Laperriere, Nadia Scantlebury, Nicole Law, Brenda J. Spiegler, David Malkin, Laura Janzen, and Donald Mabbott See accompanying editorial on page 1749; listen to the podcast by Dr Armstrong at www.jco.org/podcasts Purpose To examine the impact of radiation (ie, craniospinal irradiation [CSR] dose and boost volume) and complications (ie, hydrocephalus and other neurologic complications, including mutism) on patterns of change in intellectual functioning in medulloblastoma survivors. Patients and Methods We conducted a retrospective review of 113 patients treated for medulloblastoma between 1983 and 2011 who were seen for neuropsychological assessment, including longitudinal follow-up of intellec- tual function. Patients were treated with either standard-dose CSR with a posterior fossa (PF) boost (n 51), standard-dose CSR plus tumor bed (TB) boost (n 9), reduced-dose CSR plus PF boost (n 28), or reduced-dose CSR plus TB boost (n 23), with or without chemotherapy. A subset of patients developed hydrocephalus that required cerebrospinal fluid (CSF) diversion (n 54) and/or other neurologic complications (n 40), more than half of which were postoperative mutism (n 25). Growth curve analysis was used to determine stability or change in intelligence scores over time. Results Patients treated with reduced-dose CSR plus TB boost showed stable intellectual trajectories, whereas patients treated with higher doses and larger boost volumes experienced intellectual declines. Presence of complications was associated with worse intellectual outcome; however, hydrocephalus requiring CSF diversion and mutism differed in their pattern of decline. Conclusion These results improve our understanding of factors that impair intellectual outcome in patients treated for medulloblastoma. Lower doses of CSR and smaller boost volumes seem to mitigate intellectual decline. Our findings validate the use of TB boost and suggest PF boost should be reconsidered. A B S T R A C T

Iska Moxon-Emre, Eric Bouffet, Michael D. Taylor, Nadia Scantlebury, Nicole Law, Brenda J. Spiegler, David Malkin, Laura Janzen, and Donald Mabbott, Hospital for Sick Children; Iska Moxon- Emre, Michael D. Taylor, Normand Laperriere, Brenda J. Spiegler, David Malkin, and Laura Janzen, University of Toronto; and Normand Laperriere, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada. Published online ahead of print at www.jco.org on February 10, 2014. Processed as a Rapid Communication manuscript. Supported by Canadian Institute of Health Research, Pediatric Oncology Group of Ontario, and MAGIC (Medullablastoma Advanced Genomics International Consortium) project, which is funded by Genome Canada, Genome British Columbia, Terry Fox Research Institute, Ontario Institute for Cancer Research, Pediatric Oncology Group Ontario, the family of Kathleen Lorette, Clark H. Smith Brain Tumour Centre, Montreal Children’s Hospital Founda- tion, Hospital for Sick Children, Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, and B.R.A.I.N. Child (Brain Tumour Research Assis- tance and Information Network). Presented in part at the 15th Interna- tional Symposium on Pediatric Neuro- Oncology, Toronto, Ontario, Canada, June 24-27, 2012. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Donald Mabbott, PhD, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; e-mail: donald .mabbott@sickkids.ca. © 2014 by American Society of Clinical Oncology 0732-183X/14/3217w-1760w/$20.00 DOI: 10.1200/JCO.2013.52.3290

J Clin Oncol 32:1760-1768. © 2014 by American Society of Clinical Oncology

results in a decline in neuropsychological function- ing over time. 4-7 However, much less is known about the mediating impact of specific radiation doses and boost volumes on changes in intellectual outcome. Neurologic complications can also have deleterious effects on cognitive function. 8 It is cru- cial to understand the relationship between radia- tion dose/exposure and complications on the time course of intellectual change after treatment, be- cause this will help to inform current protocol selection as well as the nature and design of future treatment protocols and may identify time win- dows for the delivery of protective or rehabilita- tive interventions. To address these critical issues, we examined patterns of change in intellectual

INTRODUCTION Medulloblastomas are the most common ma- lignant CNS tumors in childhood, accounting for 50% of all posterior fossa (PF) tumors. 1 Current treatment protocols include surgery, craniospinal irradiation (CSR) with a boost to the tumor site, and chemotherapy—a lifesaving combination that unfortunately contributes to long-term physical, endocrine, and neuropsycho- logical impairments in survivors 2 ; 90% percent of survivors require long-term special education services and have reduced rates of high school graduation and employment. 3 Treatment with CSR after surgical resection of medulloblastoma

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© 2014 by American Society of Clinical Oncology

2015 from 139.18.235.208 Information downloaded from jco.ascopubs.org and provided by at UNIVERSITAETSKLINIKUM LEIPZIG on February 17, Copyright © 2014 American Society of Clinical Oncology. All rights reserved.