Does phase I radiotherapy dose of 30.6Gy in 17 fractions provide adequate microscopic nodal disease control in squamous cell carcinoma of the anus?

Abstract

588 Background: Definitive chemoradiation has been established as the standard of care for patients with squamous cell carcinoma of the anus. The ACT II study recommends 30.6Gy in 17 fractions for Phase I to the lower pelvis with a superior border 2 cm above the inferior aspect of the sacro-illiac joints, then a Phase II boost of 19.8Gy in 11 fractions to the tumor and involved nodes. Our goal was to retrospectively evaluate patterns of failure in the volumes that received microscopic dose 30.6Gy. Methods: Between January 2002 and December 2008, 106 patients with non-metastatic squamous cell carcinoma of the anus were treated with definitive chemoradiation. 81 (76.45%) of these patients received Phase I dose of 30.6Gy.The tumor stage was Tx or T1 in 18 % , T2 in 36% , T3 in 29%, and T4 in 12% of patients. The nodal stage was N0 in 57%, N1 in 13%, N2 in 14% and N3 in 11% of patients. The median radiotherapy dose was 50.4 Gy (range 50.4Gy -60 Gy). Concurrent chemotherapy was given with 5-fluorouracil (5-FU) and cisplatin in 12%, 5-FU and mitomycin C in 34%, capecitabine and mitomycin C in 38% and other regimens in 8% of patients. The median follow-up interval was 43 months (range 3.2 - 112.9 months). Results: A total of 21 patients (19.8%) experienced persistent or progressive disease during follow up. Out of this total, 16 patients received 30.6Gy in Phase I. Of these, 5 patients (4.7%) had persistent disease at the end of chemo-radiation, 4 patients (3.7%) relapsed in the anal region, 2 patients (2.4%) relapsed in the 30.6Gy area and 5 patients (6.2%) developed metastases. 8 patients with local recurrence/persistent disease underwent salvage surgery. Estimated 3 year rates for locoregional control and overall survival were 78% and 82% respectively. Conclusions: The majority of locoregional failures involve the anus and mesorectum, while nodal recurrence occurs rarely supporting the use of 30.6Gy for microscopic nodal disease control. This makes the case for dose escalation of primary tumours in Phase II. Placing the superior border of the radiotherapy field at 2 cm above inferior sacroiliac joints for phase I could potentially spare bone marrow and small bowel toxicity with minimal risk of nodal relapse.