Outcomes and after Hyperfractionated, Accelerated Reirradiation for Recurrent Anal Squamous Cell Carcinoma

Abstract

Abdominoperineal resection (APR) is the standard salvage treatment for recurrent or persistent squamous cell carcinoma of the anus (SCCA). However, reirradiation (reRT) can be used preoperatively or for those who are not candidates for surgery. Using a single institutional database, patients were identified who underwent reRT for SCCA from 2003 to 2022. Response to reRT and outcomes after reRT were recorded. Variables analyzed included age at reRT, sex, reason for reRT (recurrent SCCA vs new SCCA after pelvic radiation for a different malignancy), interval between initial radiation and reRT, reRT dose, concurrent chemotherapy, receipt of APR and the presence of distant metastases at the time of reRT. Cox Proportional Hazard Model was used; multivariable analysis for all factors with a univariate P-value <0.1 on univariable analysis. A total of 42 patients received reRT, which consisted of 1.5 Gray (Gy) twice daily fractions with ≥6-hour interval to a total dose ranging 30Gy to 54Gy (median [IQR] 39Gy [39-42Gy]. Thirty-eight patients (90.5%) received concurrent chemotherapy; most often with weekly cisplatin and 5-fluorouracil (N = 23, 54.8%). Median [IQR] follow-up after reRT was 11.4 months [4.9-40.8 months]. Median [IQR] initial radiation dose was 54Gy [54-58Gy], and median [IQR] interval between initial radiation and reRT was 3.6 years [2.1-6.0 years]. For 8 patients (19.1%), the initial radiation was given for a different pelvic malignancy prior to being diagnosed with SCCA. Four of these patients received brachytherapy alone or in conjunction with external beam. For the remaining 34 patients, the initial radiation was for SCCA and the reRT was for recurrent SCCA either in the anal canal (N = 23, 67.6%) or regional nodes (N = 11, 32.3%). Four patients (9.5%) had distant disease at the time of reRT. Eleven patients (26.2%) had planned APR after preoperative reRT; 1 patient had a pathologic complete response (pCR), 2 patients had a near pCR (<5% viable cancer). Twenty-nine patients (69.0%) were treated with reRT alone; 15 (51.7%) attained a clinical CR. Two patients (4.8%) were treated with palliative intent and response was not assessed. Median local recurrence free survival (LRFS) was 9.9 months; 2- and 3-year LRFS were both 41%. Median distant metastasis free survival (DMFS) was 11.8 months; 2- and 3-year DMFS were 38% and 34%, respectively. Median overall survival (OS) was 40.5 months; 2- and 3-year OS were 54% and 51%, respectively. On multivariable analysis, only the presence of distant disease at the time of reRT was significantly associated with worse LRFS (HR (95% CI) 4.14 (1.34-12.81); P = .014), worse DMFS (4.06 (1.37-12.06); P = .012) and worse OS (5.73 (1.57-20.9); P = .008). ReRT is an option for patients presenting with either recurrent SCCA or new SCCA after prior pelvic radiation for a different malignancy. ReRT can be given prior to planned salvage APR or alone for patients who are not surgical candidates with an approximate 50% cCR rate.