The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy

Ali Hosni, Kathy Han, Lisa W Le, Jolie Ringash, James Brierley, Rebecca Wong, Robert Dinniwell, Anthony Brade, Laura A Dawson, Bernard J Cummings, Monika K Krzyzanowska, Eric X Chen, David Hedley, Jennifer Knox, Alexandra M Easson, Patricia Lindsay, Tim Craig, John Kim, Ali Hosni, Kathy Han, Lisa W Le, Jolie Ringash, James Brierley, Rebecca Wong, Robert Dinniwell, Anthony Brade, Laura A Dawson, Bernard J Cummings, Monika K Krzyzanowska, Eric X Chen, David Hedley, Jennifer Knox, Alexandra M Easson, Patricia Lindsay, Tim Craig, John Kim

Abstract

Purpose: Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer.

Methods: Between 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.

Results: Overall, 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%]).

Conclusions: Individualized 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).

Keywords: IMRT; anal cancer; chemoradiotherapy; outcomes; pattern of failure.

Conflict of interest statement

CONFLICTS OF INTEREST No related potential conflict of interest

Figures

Figure 1. Long-term outcomes of chemoradiation with…
Figure 1. Long-term outcomes of chemoradiation with risk-stratified radiation dose selection
Figure 2. Distribution and pattern of failure…
Figure 2. Distribution and pattern of failure in anal/perianal cancer

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