1074 - Long-Term Outcomes of Definitive Chemoradiation with Proton Therapy for Treatment of Carcinoma of the Anal Canal: Combined Analysis of Two Prospective Trials

Purpose/Objective(s): While definitive chemoradiation (CRT) with 5FU/MMC remains the standard of care for localized anal cancer, treatment is associated with significant acute and long term toxicity. Proton radiotherapy (RT) may potentially reduce such toxicity. Here, we assess the long term outcomes of anal cancer patients treated with CRT using proton RT in two prospective pilot studies.

Materials/Methods: Patients with stage I-III anal cancer treated with proton RT (pencil beam scanning or intensity modulated proton therapy) per RTOG 0529 dose schema with concurrent 5FU/MMC (2 cycles) in two prospective, single arm trials were followed. Loco-regional failure (LRF) and distant metastases (DM) were estimated by the cumulative incidence method. Colostomy-free survival (CFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Physician graded late toxicity (>90 days from CRT) was assessed per CTCAE v4.0. Rates of G2+ and G3+ late toxicities were compared with RTOG 0529 via Fisher exact test. Patient-reported outcome measures (PROMs) were analyzed.

Results: Between 2013-2020, 39 patients were treated. 37 (95%) patients completed treatment per protocol; two patients died on treatment. Median follow up was 63 months. Clinical stage was I in 8%, II in 41%, and III in 51%. 5-year LRF, DM, CFS, DFS, and OS were 21% (95% CI 10-35), 19% (95% CI 8-34), 72% (95% CI 55-83), 69% (95% CI 51-81), and 75% (95% CI 57-86), respectively. Five (13%) patients had colostomy failure: 2 due to local progression, 2 due to failure of colostomy reversal <1 year of enrollment, and 1 due to treatment related rectal stricture. Nine (23%) patients had disease progression: 6 with both LRF and DM, 2 LRF only, and 1 DM only. Worst late treatment toxicities were G1 in 38%, G2 in 24%, G3 in 19%, G4 in 3%, and no G5. Rates of overall and dermatologic G2+ late toxicities were significantly lower in comparison to RTOG 0529 (Table). Among 25 (64%) cases with available dosimetric data, no dosimetric correlations were found with late toxicities. PROMs available for a subset of patients (up to 64%) demonstrated no significant difference in gastrointestinal and sexual function or symptom scores at long term compared to baseline.

Conclusion: Definitive CRT with proton RT with concurrent 5FU/MMC for the treatment of anal cancer resulted in comparable long term disease control outcomes and lower rate of G2+ late toxicities, specifically dermatologic, compared to RTOG 0529. Future studies are needed to evaluate additional measures to minimizing treatment toxicity and subsets of patients who are most likely to benefit from proton RT.