Can Patients With Recurrent or Primary Squamous Cell Carcinoma of the Anus in a Previously Irradiated Pelvis Receive Definitive Reirradiation?

Purpose: Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients. Methods and Materials: Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously irradiated field were included. The reRT regimen consisted of 1.5 Gy in twice daily fractions separated by 6 hours to a median (range) of 39 (30-51) Gy. Complete clinical response rates, recurrence rates, and toxicities were reported. Results: The median (IQR) follow-up was 13.4 (7.5-42.2) months. Twenty-six (74.3%) patients were treated with reRT for recurrent anal cancer, and 9 (25.7%) patients were treated with reRT for a new squamous cell carcinoma of the anus (SCCA) primary after prior pelvic radiation. The complete clinical response rate was 46.2% among patients with recurrent anal cancer and 77.8% among patients with a new SCCA primary after prior pelvic radiation. Two-year locoregional recurrence rate was 64.0% among patients with recurrent anal cancer and 22.0% among patients treated with reRT for a new SCCA primary after prior pelvic radiation. Eight patients (22.9%) developed acute grade 3 toxicity and 10 (28.6%) developed late grade 3-4 toxicity. Conclusions: Hyperfractionated accelerated reRT results in promising complete clinical response rates that appear to translate into durable pelvic control for patients with recurrent anal cancer or a new SCCA primary after prior pelvic radiation. Acute toxicity appears similar to initial standard chemoradiation, but limiting reRT doses to 39 Gy may reduce the risk of serious late toxicity.