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

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).

Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC)

“…LRF was the predominant pattern of relapse, with a 5-year LRF rate in accordance with recent trials [28][29][30]. Shorter OTTs were significantly associated with less LRF, as were small tumor sizes for tumors of the anal canal and female gender.…”

“…With regards to survival rates, PFS at 5 years was similar to a recent phase II study evaluating the addition of Cetuximab to 5-FU-Cisplatin concurrent chemoradiotherapy, and approximately 10% lower than in two other recent studies [28][29][30]. Five-year OS (76.7%) was also similar to the results of the Cetuximab association trial, and 4-7% lower than the other two recent studies [28][29][30].…”

Evolving Concepts toward Individualized Treatment of Squamous Cell Carcinoma of the Anus

“…The difference in toxicity between 3D-CRT and IMRT or VMAT has never been compared in a prospective randomized trial, but several retrospective studies and one recent prospective study have reported an improved toxicity profile with the newer techniques [12][13][14][15][16][17]. A recent national audit in the UK comparing these techniques confirmed the reduced toxicity with IMRT ( Table 1) [18].…”

Intensification of Radiation Therapy with Control of the Amount of Radiation Using MRI in Patients with Squamous Cell Carcinoma of the Anal Canal

“…Очевидно, что улучшение результатов лечения в значительной степени связано с разработкой и внедрением современных технологий лучевой терапии (ЛТ), что делает необходимым изучение ее роли в лечении пациентов с недавно диагностированным плоскоклеточным раком анального канала (ПРАК) [5,6,7,9].…”

“…За последние 40 лет заболеваемость плоскоклеточным раком анального канала в России, как и в США, увеличивалась примерно на 2 % в год [1,5,7]. Большинство пациентов имеют локализованное заболевание, отдаленные метастазы, часто вовлекающие печень, легкие, обнаруживаются толь-ко у 5-8 % пациентов на начальном этапе лечения.…”