Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study

Background. Neurocognitive toxicity from radiation therapy (RT) for brain tumors may be related to damage to neural progenitor cells that reside in the subventricular zone and hippocampus. This prospective study examines the relationship between RT dose to neural progenitor cell niches, temporal lobes, and cerebrum and neurocognitive dysfunction following cranial irradiation. Methods. Standardized assessments of motor speed/dexterity, verbal memory, visual perception, vocabulary, and visuospatial working memory were conducted in 19 pediatric patients receiving cranial RT and 55 controls at baseline and 6, 15, and 27 months following completion of RT. Prescription doses ranged from 12 Gy to 59.4 Gy. Linear mixed effects regression model analyses were used to examine the relationships among neuropsychological performance, age, and radiation dose to the subventricular zone, hippocampus, temporal lobes, and cerebrum. Results. Performance on all neuropsychological tests, except vocabulary, was significantly reduced in patients relative to controls, particularly among younger children. Performance on motor speed/dexterity decreased with increasing dose to hippocampus (P < .05) and temporal lobes (P < .035). There was also a significant relationship between (i) reduced performance on verbal learning and increasing dose to the cerebrum (P = .022) and (ii) reduced performance on visual perception and increasing dose to the left temporal lobe (P = .038). There was no association between radiation dose to evaluated structures and performance on vocabulary or visuospatial working memory. Conclusions. These prospective data demonstrate a significant association between increasing RT dose to hippocampus and temporal lobes and decline in neurocognitive skills following cranial irradiation. These findings have important implications for trials, including RTOG 0933 (hippocampal-sparing whole brain radiation therapy for brain metastases).