A controlled comparison of cerebral volume loss after brain irradiation with proton versus photon radiotherapy.

Abstract

2017 Background: Previous work has demonstrated cerebral volume loss after glioma treatment with concurrent photon radiotherapy (PHT) and chemotherapy. Proton radiotherapy (PRT) minimizes exposure of normal brain tissue compared with PHT. The objective of this study was to compare neurotoxic effects of PRT vs PHT in a retrospective case-matched control series of WHO grade 2 and 3 gliomas. Methods: PRT subjects were selected from ongoing longitudinal single-arm outcome studies being conducted at our institution (NCT01358058, NCT03286335). PHT subjects were identified via medical record search and were individually matched to PRT subjects 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). When individual matching was not possible on all 11 variables, efforts were made to identify the closest possible match. Only those subjects with at least two years of progression free survival and available T1 and T2/FLAIR MRI at baseline, one year, and two years following RT were included. The resulting sample included 17 PRT and 17 PHT patients with grade 2 and 3 gliomas (19 male; mean age = 40.10y; SD = 11.27). Non-parametric analyses were used to compare groups on demographic and tumor/treatment-related variables. Diffuse cerebral volume loss was estimated by manually measuring lateral ventricular volume in the tumor-free hemisphere. Results: Mann-Whitney tests of independence showed no significant differences between groups on any of the demographic variables or clinical characteristics. One-way ANOVA demonstrated that ventricular volume increase after two years was significantly greater in patients treated with PHT than with PRT, (F(1, 32.00) = 5.90, p <.021, η2 =.156). Change in ventricular volume in the PHT group was 24.85% (SD = 14.45%) and in the PRT group was 12.03% (SD = 16.3%). Conclusions: The findings of this study suggest that 2 years post treatment for glioma, PRT is associated with less brain volume loss and ventricular expansion than PHT. The findings support the hypothesis that PRT can reduce neurotoxicity within the tumor-free hemisphere. This study is limited by the retrospective design and lack of randomization to treatment arms, though cohorts were well-matched following a rigorous set of criteria. The effects of PRT beyond 2 years after treatment remain unknown. Preservation of brain structure may be critically important for maintenance of brain function in this population of patients who have prolonged survival. Longitudinal cognitive assessment in brain tumor patients undergoing PHT vs PRT is needed and is currently being collected in NRG BN-005 (NCT03180502), which may provide important data regarding functional impact of the brain changes we have demonstrated.