Chemoradiation for anal canal carcinoma in a comprehensive cancer center: Retrospective cohort study

Abstract

Introduction: Squamous cell carcinoma of the anal region is a rare tumor largely caused by HPV. Radiotherapy concurrent with chemotherapy is the standard of care for localized disease, aiming to avoid abdominopelvic amputation and preserve quality of life. Methods: We conducted a retrospective chart review of patients with squamous cell carcinoma of the anal canal treated at our institution with definitive chemoradiotherapy, between January 1st 2012 and December 31st 2017. Baseline clinical and demographic variables were obtained, as well as treatment details and early and late toxicities. Results: 34 patients met inclusion criteria, of which 29(85,7%) were female, with a median age at diagnosis of 62 y (min-max: 39-79 y). The median time from the first symptom to diagnosis was 14,5 weeks (min-max: 3-48 weeks). The most common presenting symptom was local pain (n=13; 41,9%), followed by hemorrhage (n=11; 35,5%). Only 1(7,7%) patient was HIV-positive. Median SCC levels at diagnosis was 1.9 ng/mL, with 16(64%) cases with SCC levels above the institutional reference level. Tumor stage according to the 7th edition of the AJCC manual was distributed as follows: Stage I: 2 cases (5,7%); Stage II: 10 cases (29,4%); Stage IIIA: 8 cases (23,5%), stage IIIB: 14 cases (41,2%). Median tumor dimension was 43mm, and 4(12,5%) cases were cT4 tumors. Most patients were treated with a dose of 45Gy to nodal basins and a total dose between 50 and 60Gy to the tumor volume, usingVMAT in all but 4(11,8%) cases, in which IMRT was used. Median treatment duration was 44 days (min-max: 32-90). Radiotherapy delays due to toxicity - that was mostly hematologic - occurred in 22 (62,9%) cases. The chemotherapy regimen used was mitomycin combined with 5-fluorouracil, that was substituted for capecitabine in one patient. Grade 3 or greater acute treatment toxicities occurred in 27(79,4%) cases and there was one death during treatment due to neutropenia and mesenteric ischemia. In 8(23,5%) cases, only one cycle of chemotherapy was administered due to toxicity, and 7(20,6%) of patients underwent dose reductions. Febrile neutropenia occurred in 6(17,6%) cases. Persistent disease after therapy was seen in 3(8,8%) patients, that underwent abdominopelvic amputation with clear margins. Median follow up was 24 months. Relapse occurred in 9(26,5%) cases, of which most were local relapses (n=7; 77,8%). Distant relapse occurred in 4(11,8%) cases. Most relapses were treated with surgery (n=6; 66,7%) and palliative chemotherapy was done in 2 cases. The three year overall survival rate was 57,9%. All but one deaths were due to relapse or persistent disease. Late complications occurred in 5 cases (14,7%) - mostly radiation proctitis, followed by chronic lymphedema. One case of radiation proctitis lead to diverting colostomy. Conclusion: In our experience, combined modality treatment with chemotherapy and radiation showed to have a similar efficacy to other published studies, despite a high rate of acute toxicities. Due to the rarity of the disease and its complex management, treatment should be done at experienced centers. Strict adherence to treatment guidelines and careful follow-up is mandatory to optimize outcomes.