RADT-23. MODALITY-SPECIFIC CNS INJURY FOLLOWING PROTON VS PHOTON BEAM RADIOTHERAPY IN GLIOMA Free

CNS injury following brain-directed radiotherapy (RT) is common and may mimic disease progression. Dosimetric advantages of protons (PRT) over photons (XRT) minimize radiation to healthy brain, potentially limiting radiotoxic sequelae. We characterized CNS radiotoxicity i.e., radiation-induced leukoencephalopathy (RIL), brain tissue necrosis (TN), and cerebral microbleeds (CMB), during progression-free survival (PFS) periods in glioma patients irradiated with PRT or XRT.

34 patients (19 male; mean age = 40.10y) with grade 2/3 gliomas treated by partial cranial RT were stratified by RT modality [XRT(n = 17) vs PRT(n = 17)] and matched on 11 criteria [age, sex, tumor type/location/laterality, mutational status (IDH; 1p19q deletion), concurrent/adjuvant chemotherapy, radiation dose/fractions] for retrospective analysis. Radiotoxicity was characterized longitudinally until 3 years post-RT via analysis of serial MRI T2/FLAIR- (RIL), T1+Contrast- (TN), and Susceptibility (CMB)-weighted sequences. RIL was rated using a novel scoring system with embedded Fazekas scale (intraclass correlation coefficient > 0.9), at global (whole-brain) and hemispheric levels.

Analysis of delayed radiotoxicity at 3 years post-RT identified significant modality-specific differences. While both groups developed moderate-to-severe RIL [62% (XRT) and 72% (PRT)], XRT resulted in greater RIL injury dynamics (i.e., average % change between 1 and 3 years post-RT) in the contralesional hemisphere [F(1, 31) = 4.32, p < .05]. Conversely, PRT was associated with higher TN incidence [6%(XRT) vs 18%(PRT) z = - 2.22, p < 0.03, two-tailed]. Finally, while CMB incidence [76%(XRT) vs 71%(PRT)] and burden [mean #CMB: 4.3(XRT) vs 4.2(PRT)] were comparable, lesion-to-radiation field (RF)-correlation identified preferential CMB clustering at RF margins with PRT [X2(2, N =200)= 8.8, p < .02].

CNS radiotoxicity is common and progressive in glioma patients. Injury patterns suggest radiation modality specificity as RIL, TN, and CMB exhibit unique spatiotemporal differences following XRT vs PRT, likely reflecting dosimetric and biological differences between protons and photons. The impact of such sequelae on cognition is subject of current investigation.