Region-specific radiotherapy and neuropsychological outcomes in adult survivors of childhood CNS malignancies

Abstract

Childhood cancer survivors exposed to CNS irradiation are at increased risk for neurocognitive deficits; however, limited data exist linking outcomes with region-specific exposure to CNS irradiation. We report associations between region-specific radiation dose and self-reported neurocognitive and health-related quality of life (HRQOL) outcomes in 818 adult survivors of childhood central nervous system (CNS) malignancies from the Childhood Cancer Survivor Study. Survivors were compared with a sibling group and national normative samples to calculate standardized scores. Cumulative radiation dose was calculated for 4 specific brain regions. Logistic regression was used to estimate the association between radiation dose to specific brain regions and outcome measures of functional impairment adjusted for clinical and demographic factors, including sex and age at diagnosis. High radiation dose levels to temporal regions were associated with a higher risk for memory impairment (radiation doses ≥30 to <50 Gy: OR, 1.95; 95% CI, 1.01-3.78; dose ≥50 Gy: OR, 2.34; 95% CI, 1.25-4.39) compared with those with no radiation exposure. No such association was seen with radiation exposure to other regions. Exposure to temporal regions was associated with more social and general health problems, whereas exposure to frontal regions was associated with general health problems and physical performance limitations. Adult survivors of childhood CNS malignancies report higher rates of neuropsychological and HRQOL outcomes, which vary as a function of dose to specific neuroanatomical regions. Survivors with a history of radiation exposure to temporal brain regions are at increased risk for impairment in memory and social functioning.

Fig. 1.

Survivors of CNS malignancies in the Childhood Cancer Survivors Study eligible for the evaluation of region-specific neuropsychologic and quality of life outcomes. *CRT, cranial radiation therapy.

Fig. 2.

Division of the brain for regional dose estimation. 1, posterior fossa; 2, temporal; 3, frontal; 4, parieto-occipital. Reprinted with permission. ©2008 American Society of Clinical Oncology. All Rights Reserved. Packer et al.

Fig. 3.

(A) Odds ratios of working memory impairment by temporal region radiation dose (open boxes: mean observed odds ratios with 95% CI for memory impairment; solid line: fitted line for working memory impairment adjusted for RT dose to all other regions, age at diagnosis and sex). (B) Odds ratios of task efficiency impairment by temporal region radiation dose (open boxes: mean observed odds ratios with 95% CI for task efficiency impairment; solid line: fitted line for task efficiency impairment adjusted for RT dose to all other regions, age at diagnosis and sex). (C) Odds ratios of social function impairment by temporal region radiation dose (open boxes: mean observed odds ratios with 95% CI for social function impairment; solid line: fitted line for social function impairment adjusted for RT dose to all other regions, age at diagnosis and sex).