Feasibility Trial of IMPT to Reduce Toxicity in Anal Cancer Patients

Abstract

<h3>Purpose/Objective(s)</h3> The purpose of this prospective trial was to assess patient and physician reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity modulated proton therapy (IMPT). <h3>Materials/Methods</h3> Patients with AJCC v8 Stage II-III disease were treated with IMPT using a multi-field, split-target technique using robust optimization with dose prescribed as per RTOG 0529 (50.4-54 Gy). All patients received two cycles of 5-fluorouracil and Mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation and in follow-up using physician graded CTCAE v 4.0 and PRO-CTCAE for relevant domains (17 items). The primary endpoint was to define point estimates and 95% CI for ≥ grade 2/3 GI, GU, Dermatologic, and Hematologic toxicity within 90 days from treatment. The proportion of PRO-CTCAE questions scored ≥ 3 for each domain was compared to baseline. Survival outcomes were assessed using the Kaplan-Meier method. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared to historic IMRT patients treated on RTOG 0529 using Fisher's exact test. <h3>Results</h3> Fourteen patients were enrolled from 2017-2020. The median age was 56 (range 31-85) with 50% female participants. Eleven patients (79%) had Stage III disease. The respective T/N stages are T2 (n=5, 36%), T3 (n=7, 50%), T4 (n=1,7%), N0 (n=2,14%), N1 (n=9,64%), and N2 (n=3,21%). All patients completed prescribed treatment with 1 patient requiring a treatment break. <b>Table 1</b> shows rates of ≥ grade 2/3 CTCAE events for IMPT. Rates of patient reported Derm and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high grade PRO-CTCAE GI scores was 40% at baseline which persisted through 1 year post treatment. A complete clinical response at 6 months was observed in 11 patients (79%). The median overall survival was not reached with a median follow-up is 32.5 months. The 2 years overall, progression-free, and colostomy free survival was 92%, 64%, and 85%, respectively. Median time to progression was 9 months with local only (n=2,14%), local and distant (n=2,14%) and distant (n=1,7%) recurrence patterns. <h3>Conclusion</h3> In this single arm trial, rates of clinician reported toxicity with IMPT were similar to IMRT. High grade PRO-CTCAE events were common during IMPT. GU and Derm events normalized at 3 months from treatment but high-grade GI symptoms persisted to12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related chemoradiation.