The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy
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Ali Hosni1, Kathy Han1, Lisa W. Le2, Jolie Ringash1, James Brierley1, Rebecca Wong1, Robert Dinniwell1, Anthony Brade1, Laura A. Dawson1, Bernard J. Cummings1, Monika K. Krzyzanowska3, Eric X. Chen3, David Hedley3, Jennifer Knox3, Alexandra M. Easson4, Patricia Lindsay1, Tim Craig1 and John Kim1
1Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
2Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
3Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
4Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
John Kim, email: [email protected]
Keywords: anal cancer; chemoradiotherapy; IMRT; pattern of failure; outcomes
Received: November 11, 2017 Accepted: February 27, 2018 Published: April 17, 2018
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).
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