Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning.

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  • Additional Information
    • Source:
      Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE
    • Publication Information:
      Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology
      Original Publication: New York, N.Y. : Grune & Stratton, c1983-
    • Subject Terms:
      Cranial Irradiation*/adverse effects ; Dose Fractionation, Radiation* ; Radiation Dosage*; Brain/*radiation effects ; Cerebellar Neoplasms/*radiotherapy ; Cognition/*radiation effects ; Medulloblastoma/*radiotherapy; Adolescent ; Adolescent Behavior/radiation effects ; Adolescent Development/radiation effects ; Age Factors ; Brain/diagnostic imaging ; Brain/growth & development ; Cerebellar Neoplasms/diagnostic imaging ; Cerebellar Neoplasms/physiopathology ; Child ; Child Behavior/radiation effects ; Child Development/radiation effects ; Child, Preschool ; Clinical Trials, Phase III as Topic ; Female ; Humans ; Male ; Medulloblastoma/diagnostic imaging ; Medulloblastoma/physiopathology ; Memory/radiation effects ; Neuropsychological Tests ; Radiotherapy Planning, Computer-Assisted ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Young Adult
    • Abstract:
      Purpose: To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03.
      Patients and Methods: Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.4 Gy for average-risk patients and 36-39.6 Gy for high-risk patients. The boost dose was 55.8 Gy to the tumor bed. Patients underwent cognitive testing at baseline and once yearly for 5 years. Performance on tests of memory (associative memory and working memory) and processing speed (composite processing speed and perceptual speed) was analyzed. Mixed-effects models were used to estimate longitudinal trends in neurocognitive outcomes. Reliable change index and logistic regression were used to define clinically meaningful neurocognitive decline and identify variables associated with decline.
      Results: One hundred and twenty-four patients were eligible for inclusion, with a median neurocognitive follow-up of 5 years. Mean right and left hippocampal doses were significantly associated with decline in associative memory in patients without posterior fossa syndrome (all P < .05). Mean CC and frontal WM doses were significantly associated with decline in both measures of processing speed (all P < .05). Median brain substructure dose-volume histograms were shifted to the right for patients with a decline in associative memory or processing speed. The odds of decline in associative memory and composite processing speed increased by 23%-26% and by 10%-15% for every 1-Gy increase in mean hippocampal dose and mean CC or frontal WM dose, respectively.
      Conclusion: Increasing RT dose to the CC or frontal WM and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure-informed RT planning may mitigate neurocognitive impairment.
      Competing Interests: Lydia WilsonHonoraria: Elekta Amar GajjarConsulting or Advisory Role: Roche/Genentech, QED Therapeutics, Day One TherapeuticsResearch Funding: Genentech (Inst), Kazia Therapeutics (Inst) Thomas E. MerchantHonoraria: Varian Medical SystemsTravel, Accommodations, Expenses: Philips HealthcareNo other potential conflicts of interest were reported.
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    • Grant Information:
      P30 CA021765 United States CA NCI NIH HHS
    • Molecular Sequence:
      ClinicalTrials.gov NCT00085202
    • Publication Date:
      Date Created: 20211029 Date Completed: 20220221 Latest Revision: 20240923
    • Publication Date:
      20240923
    • Accession Number:
      PMC8683226
    • Accession Number:
      10.1200/JCO.21.01480
    • Accession Number:
      34714708