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

PURPOSE: 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.

METHODS AND MATERIALS: 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.

RESULTS

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).

CONCLUSIONS

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.