Radiation induced cerebral volume loss and cerebrovascular disease risk in survivors of grade 2 and 3 gliomas

Abstract INTRODUCTION Cranial irradiation with protons (PRT) as compared with photons (PHT) reduces radiation exposure to healthy brain tissue and may mitigate early- and late-delayed complications. Prior work in our group has demonstrated that PRT results in less brain atrophy over 2 years post-treatment as compared with PHT. It is unknown whether individual factors, such as cerebrovascular disease risk (CVDR; known to be important in post-RT brain changes), interacts with treatment type to affect brain volume change. METHODS Patients treated with PRT for grade 2 or 3 gliomas were meticulously matched to patients treated with PHT using an eleven-tiered criterion (i.e., age, sex, tumor type, tumor location, laterality, IDH mutation status, 1p19q deletion status, concurrent chemotherapy, adjuvant chemotherapy, total Gy dose, and number of fractions). Brain volume changes were evaluated by measuring changes in ventricular size in the contralesional hemisphere (to reduce impact of tumor-related changes on volumetric measurements). A CVDR score was created, incorporating history of hypertension, hyperlipidemia, smoking, and diabetes. Correlation and multiple regression analyses examined the relationship between CVDR and brain volume loss over 2 years. RESULTS Mann-Whitney tests of independence showed no significant differences in CDVR between PHT and PRT treatment groups. Cerebral volume loss correlated significantly with CVDR (r =.404, p =0.02) and treatment type (r=-.366, p =0.036). Age and gender were unrelated to volume loss. A multiple regression analysis that included treatment type (PHT, PRT) and CVDR accounted for 23% of the variance in volume loss, F(2, 32) = 4.383, p < .021. CONCLUSION The current study demonstrates that neurotoxicity of radiation therapy is related to both CVDR and radiation treatment type. Longitudinal data, including a larger sample size, are warranted to confirm these preliminary findings. Inclusion of routine neuropsychological outcome data will be critical to understand the functional significance of these results.