Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients

The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT).

Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529.

Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic 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 posttreatment.

Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.