Abstract

ABSTRACT Introduction Anal canal squamous cell carcinoma is an uncommon malignancy, accounting for a small percentage (4%) of all cancers of the lower intestinal tract. Concurrent chemoradiation with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care. Due to acute and long term treatment related toxicities, a split radiotherapy course was the norm. Developments in radiation technique with three-dimensional planning and conformal treatment decreased toxicity, allowing for a shortened 6 weeks treatment time with no planned treatment break. The concurrent use of chemotherapy is also responsible for treatment toxicity. The best way to combine chemotherapy with the shortened radiotherapy is still subject to debate. Along with MMC, a continuous infusion of 5-FU for the hole duration of radiotherapy could reduce the toxicity, maintaining the effectiveness of the treatment. We aim to describe a single institution experience in advanced anal carcinoma combined treatment with radiation and MMC with continuous infusion of 5-FU. Methods Retrospective analysis of all anal cancer patients treated at our institution with the chemoradiation regimen of MMC (10mg/m2 in the beginning of the first and the last week of radiotherapy) and 5-FU (200mg/m2/day continuously for the whole duration). Radiotherapy doses were 45 Gy plus a 9 Gy boost. Endpoints were response, toxicity, colostomy-free rate, relapse and survival. Results From 2007-2011, 29 patients (pts) were included (20 women and 9 men), median age 67 years (35-82) and median follow-up time 25 months (1-58). Tumor location: canal – 28, margin – 1. Histology: squamous cell carcinoma – 25, basaloid carcinoma – 4. Stage groups: I – 4, II – 13, IIIA – 1, IIIB – 11. Median duration of chemoradiotherapy (CMT) was 57 days. Tumor response: complete response – 23, partial response – 1, progression – 5. Among 28 pts who completed CMT, 14 pts (50%) presented with recurrence (local – 5, distant – 9) at a median time of 7 months after CMT ending. Local relapse was treated with salvage surgery in 3 cases and palliative colostomy in 2. Distant metastasis locations were bone – 3, lung, liver and lymph node – 2 each, skin – 1. Four pts received chemotherapy and 1 had a local resection of a single lesion. 6 pts died (related to cancer – 5, AIDS – 1) at a median time of 15 months. Acute grade III/IV toxicities were present in 12 pts (perineal skin reaction – 10, haematological – 4, diarrhoea – 1, mucositis – 1) and 3 pts had severe late toxicity (vaginal and canal anal stenosis). Conclusion In our results continuous infusion of 5-FU during radiotherapy in the treatment of anal carcinoma was associated with complete remission in 82.1% of patients with acceptable toxicity (42.8% of acute and 10.7% of late severe events). The response data is comparable to our previous experience, but there is a high rate of early recurrence that warrants further analysis and suggests that continuous infusion might not be the best 5-FU regimen to combine with radiation in anal canal cancer.

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