Contrast-enhancing Lesions Induced by Central Nervous System-directed Intensity Modulated Proton Therapy: Distribution Patterns, Kinetics, Risk Factors, and Outcomes.

Abstract

Patients treated with intensity modulated proton therapy (IMPT) may develop intracranial radiation-induced contrast enhancement (RICE). The incidence, distribution, kinetics, predisposing factors, linear energy of transfer (LET) associations, and clinical outcomes of RICE are inadequately defined. The incidence and characteristics of RICE were analyzed in brain tumor patients treated with at least 50 Gy IMPT, 1-year follow-up, and 3 posttreatment magnetic resonance imaging scans. RICE distribution was classified as overlapping with tumor/tumor bed (A), inside or marginal to high-dose region (≤5 mm from the 95% isodose line [IDL]) (B), or distant (>5 mm from 95% IDL) (C). Voxelized dose and LET were computed for each RICE lesion. Risk factors were assessed using binary logistic regression. With a median follow-up of 3 years, 73 RICE lesions were observed in 36 of 137 patients (26%), appearing at a median of 11 months post-IMPT. Group-wise distribution demonstrated 10 (28%), 24 (67%), and 2 (5%) lesions in groups A, B, and C, respectively. Ten (7% overall) patients were symptomatic. After a median of 5 months, most lesions (78%) improved or resolved. Median dose and LET in RICE lesions were 50.4 Gy and 3.1 keV/µm. RICE risk increased with age as a continuous variable (0.4%/year), age ≥18 years (odds ratio [OR], 5.4), tumor volume >30 cc (OR, 2.8), and 95% IDL overlapping the ventricles (OR, 3.8). RICE is a common radiographic finding after IMPT, primarily occurring in the periventricular and high-dose regions, but is infrequently symptomatic. Periventricular-sparing treatment may be considered to minimize the risk of RICE.