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Published on: September 1, 2010
Intellectual Outcome in Molecular Subgroups of Medulloblastoma
Iska Moxon-Emre1, Michael D Taylor1, Eric Bouffet1
1Iska 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.
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.
Insights
Intellectual functioning in medulloblastoma subgroups varies. Limiting radiation benefits wingless (WNT) and Group 4 patients, while sonic hedgehog (SHH) shows distinct outcomes.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Radiation Oncology
Background:
- Medulloblastoma comprises four distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4.
- Intellectual functioning is a critical outcome for pediatric cancer survivors, particularly those treated with craniospinal irradiation (CSI).
- Understanding subgroup-specific intellectual trajectories is essential for optimizing treatment strategies and minimizing long-term deficits.
Purpose of the Study:
- To evaluate intellectual functioning across the four main medulloblastoma subgroups.
- To assess the impact of reduced radiation exposure on intellectual outcomes within each subgroup.
- To identify subgroups that may benefit from de-escalated therapy.
Main Methods:
- Intellectual assessments were conducted on 121 medulloblastoma patients treated between 1991 and 2013.
- Linear mixed modeling was used to analyze intellectual trajectories over time.
- Comparisons were made between subgroups and treatment arms (reduced-dose CSI vs. higher-dose CSI/boosts).
Main Results:
- Intellectual outcomes declined comparably across subgroups, except for processing speed, which declined less in SHH than Group 3.
- SHH patients exhibited the lowest rates of cerebellar mutism and motor deficits.
- Reduced-dose CSI plus a tumor bed boost preserved intellectual functioning in WNT and Group 4 patients, but not in Group 3 or SHH.
Conclusions:
- SHH medulloblastoma patients have distinct functional outcomes and processing speed trajectories.
- Only WNT and Group 4 patients appear to benefit from reduced radiation exposure, suggesting therapy de-escalation is subgroup-specific.
- Subgroup-specific analyses are crucial for developing targeted, biologically-based treatment protocols for medulloblastoma.
