We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiotherapy (RT).
Methods and Materials
27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. Patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, Ktrans, and the fraction of blood plasma volume, Vp. The temporal changes in the means of hippocampal Ktrans and Vp after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampi was correlated with neurocognitive dysfunction 6 and 18-months post-RT.
The Ktrans mean increased significantly from pre-RT to 1-month post-RT (p<0.0004), which significantly depended on sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r = −0.95, p<0.0006) and 18-months (r = −0.88, p<0.02) post-RT.
The early hippocampal vascular dose-response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.