title: Intellectual Outcome in Molecular Subgroups of Medulloblastoma.
abstract: Purpose To evaluate intellectual functioning and the implications of limiting radiation exposure in the four biologically distinct subgroups of medulloblastoma: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. Patients and Methods A total of 121 patients with medulloblastoma (n = 51, Group 4; n = 25, Group 3; n = 28, SHH; and n = 17, WNT), who were treated between 1991 and 2013 at the Hospital for Sick Children (Toronto, Ontario, Canada), Children's National Health System (Washington, DC), or the Lucile Packard Children's Hospital (Palo Alto, CA), had intellectual assessments. First, we compared intellectual trajectories between subgroups. Next, we evaluated the effect of treatment with reduced-dose craniospinal irradiation (CSI) plus a tumor bed boost versus treatments that deliver higher CSI doses and/or larger boost volumes to the brain (all other treatments) within subgroups. Linear mixed modeling was used to determine the stability or change in intelligence scores over time. Results Intellectual outcomes declined comparably in each subgroup except for processing speed; SHH declined less than Group 3 ( P = .04). SHH had the lowest incidence of cerebellar mutism and motor deficits. Treatment with reduced-dose CSI plus a tumor bed boost was associated with preserved intellectual functioning in WNT and Group 4 patients considered together (ie, subgroups containing patients who are candidates for therapy de-escalation), and not in Group 3 or SHH. Across all subgroups, patients in the all other treatments group declined over time (all P < .05). Conclusion SHH patients appear to have the most distinct functional (ie, motor deficits and mutism) outcomes and a unique processing speed trajectory. Only WNT and Group 4 patients seem to benefit from limiting radiation exposure. Our findings highlight the value of conducting subgroup-specific analyses, and can be used to inform novel biologically based treatment protocols for patients with medulloblastoma.
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Iska
authors: I
authors: Moxon-Emre
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Michael D
authors: MD
authors: Taylor
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Eric
authors: E
authors: Bouffet
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Kristina
authors: K
authors: Hardy
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Cynthia J
authors: CJ
authors: Campen
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: David
authors: D
authors: Malkin
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Cynthia
authors: C
authors: Hawkins
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Normand
authors: N
authors: Laperriere
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Vijay
authors: V
authors: Ramaswamy
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Ute
authors: U
authors: Bartels
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Nadia
authors: N
authors: Scantlebury
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Laura
authors: L
authors: Janzen
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Nicole
authors: N
authors: Law
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Karin S
authors: KS
authors: Walsh
authors: Iska Moxon-Emre, Michael D. Taylor, Eric Bouffet, David Malkin, Cynthia Hawkins, Normand Laperriere, Vijay Ramaswamy, Ute Bartels, Nadia Scantlebury, Laura Janzen, Nicole Law, and Donald J. Mabbott, Hospital for Sick Children; Iska Moxon-Emre, Michael D. Taylor, David Malkin, Cynthia Hawkins, Normand Laperriere, Laura Janzen, Nicole Law, and Donald J. Mabbott, University of Toronto; Iska Moxon-Emre and David Malkin, Pediatric Oncology Group of Ontario; Normand Laperriere, Princess Margaret Hospital, Toronto, ON, Canada; Kristina Hardy and Karin S. Walsh, Children's National Health System, Washington, DC; and Cynthia J. Campen, Lucile Packard Children's Hospital, Palo Alto, CA.
authors: Donald J
authors: DJ
authors: Mabbott
mesh_terms: D000293:Adolescent; D002140:California; D002528:Cerebellar Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D061888:Craniospinal Irradiation; D004219:District of Columbia; D005260:Female; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000528:radiation effects*; D008137:Longitudinal Studies; D008297:Male; D008527:Medulloblastoma / Q000473:pathology / Q000532:radiotherapy*; D009864:Ontario; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome