Abstract

PurposePatterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer.MethodsBetween 2008–2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27–36 Gy for elective target, and 45–63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed.ResultsOverall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF (n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF (n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%]).ConclusionsIndividualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).

Highlights

  • Anal cancer is a relatively rare disease, its incidence is increasing [1, 2]

  • Phase III randomized controlled trials (RCTs) evaluated treatment intensification to improve the outcomes of anal cancer using induction chemotherapy [8,9,10], maintenance chemotherapy [11] and split-course higher dose (>60 Gy) radiation [10]

  • We prospectively evaluated the long term outcomes, pattern of failure and late toxicities of tumor clinico-pathologic features-based dose selection in anal/perianal cancer patients treated with image-guided intensity-modulated radiation therapy (IG-IMRT) and concurrent chemotherapy without a planned treatment break

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Summary

Introduction

Anal cancer is a relatively rare disease, its incidence is increasing [1, 2]. Phase III randomized controlled trials (RCTs) evaluated treatment intensification to improve the outcomes of anal cancer using induction chemotherapy [8,9,10], maintenance chemotherapy [11] and split-course higher dose (>60 Gy) radiation [10]. None of these strategies improved the outcomes. Patients with larger tumors had worse outcomes [8, 9], suggesting that a “one-size-fits-all” approach may not be appropriate

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