Clinical investigation
Anal canal
Radiochemotherapy in the conservative treatment of anal canal carcinoma: Retrospective analysis of results and radiation dose effectiveness

https://doi.org/10.1016/j.ijrobp.2004.07.687Get rights and content

Purpose

This retrospective analysis reports the results on patients with anal canal carcinoma treated by combined radiotherapy and chemotherapy.

Methods and materials

Between March 1993 and December 2001, 43 patients with anal canal carcinoma were treated with radiochemotherapy at the Hospital do Câncer A.C. Camargo. Stage distribution was as follows: I, 3 (7%); II, 23 (53.5%); IIIA, 8 (18.6%); and IIIB, 9 (21%). The median age was 56 years (range, 36–77 years) with most patients being women (4:1). External radiotherapy (RT) was delivered at the whole pelvis followed by a boost at the primary tumor. The median dose of RT at the whole pelvis and at the primary tumor was 45 Gy and 55 Gy, respectively. Chemotherapy was carried out during the first and last 4 days of RT with continuous infusion of 5-fluorouracil (1000 mg/m2) and bolus mitomycin C (10 mg/m2). Median overall treatment time was 51 days (range, 30–129 days). Thirty-four patients (79%) did not receive elective RT at the inguinal region. Patient's age, tumor stage, overall treatment time, and RT dose at primary tumor were variables analyzed for survival and local control.

Results

Median follow-up time was 42 months (range, 4–116 months). Overall survival and colostomy-free survival at 5 years was 68% and 52%, respectively. Overall survival according to clinical stage was as follows: I, 100%; II, 82%; IIIA, 73%; and IIIB, 18% (p = 0.0049). Complete response was observed in 40 patients (93%). Local recurrence occurred in 9 (21%) patients, and of these, 6 were rescued by surgery. Local control with a preserved sphincter was observed in 34 patients (79%). According to the RT dose, local control was higher among patients who received more than 50 Gy at primary tumor (86.5% vs. 34%, p = 0.012). Inguinal failure was observed in 5 patients (15%) who did not receive inguinal elective RT. Distant metastasis was observed in 11 patients (25.6%). Temporary interruption of the treatment as a result of acute toxicity was necessary in 12 patients (28%). Four patients developed mild chronic complications.

Conclusions

This analysis suggests that the treatment scheme employed was effective for anal sphincter preservation and local control; however, the incidence of distant metastases was relatively high. The clinical stage was the main prognostic factor for overall survival. Local control was higher in patients treated with doses of more than 50 Gy at primary tumor. The high incidence of inguinal failure implies the need for elective RT in this region.

Introduction

Cancer of the anal canal is uncommon, accounting for approximately 1–2% of all large-bowel cancers and 4% of all anorectal cancers (1, 2). However, because of higher spreading of human papilloma virus and human immunodeficiency virus (HIV) through sexual transmission, there has been a marked incidence of this disease over the last two decades (2). Before 1974, the conventional treatment for anal canal cancer was abdominoperineal resection (APR). This therapeutic approach has undergone dramatic changes since the publication by Nigro et al. (3). Their preliminary report stated that 3 patients who had been submitted to a combination of preoperative radiation therapy with 30 Gy, 5-fluorouracil (5-FU), and mitomycin C (MMC) had a complete response at the time of APR. Based upon this experience, several trials were developed with combined radiochemotherapy alone, keeping surgery for salvage.

A number of trials have demonstrated that this combined modality treatment yields a complete response rate of approximately 80–90%, associated with a high rate of sphincter preservation, local control, and survival. Nevertheless, its acute toxicity is relatively high, and the ideal dose of radiation has yet to be defined. This retrospective analysis intends to report results on patients with anal canal carcinoma treated with radiotherapy (RT) combined with chemotherapy (CT) based on 5-FU and MMC, as well as the analysis of some prognostic factors and effectiveness of the radiation dose.

Section snippets

Patients

Between March 1993 and December 2001, 43 patients with squamous cell carcinoma of the anal canal were treated at the Hospital do Câncer A.C. Camargo with associated radiotherapy and chemotherapy. Clinical stage distribution of patients according to the American Joint Committee on Cancer (4) was as follows: I, 3 (7%); II, 23 (53.5%); IIIA, 8 (18.6%); and IIIB, 9 (21%). Staging was determined in all patients by means of physical examination, chest radiograph, computerized tomography (CT) of the

Results

Median follow-up time for all patients was 42 months (range, 4–116 months). Because of some treatment interruptions, overall treatment time ranged from 30 to 129 days with a median of 51 days. The rate of treatment response, evaluated 30 days after the end of RT, was considered complete in 40 patients (93%) and partial in 3 (7%). No patients developed tumor progression during or up to 30 days after treatment. At the time of this analysis, 24 patients (55.8%) were alive with no evidence of

Discussion

Until the late 1970s, the conventional treatment for anal canal cancer was APR (8). This practice was challenged after the article by Nigro et al. was published in 1974 (3). They reported on 3 patients with squamous cell cancer of the anal canal who, after preoperative treatment with radiation plus concurrent chemotherapy, achieved a pathologic complete remission of the primary tumor at the time of surgery. The radiation dose used was 30 Gy, and chemotherapy was based on 5-FU and MMC. Since

Conclusions

This retrospective analysis suggests that the treatment strategy used was effective in terms of local control and sphincter preservation. However, incidence of acute toxicity and distant metastasis was relatively high. The clinical stage was the main prognostic factor for overall survival and colostomy-free survival. Local control was significantly higher in patients treated at primary tumor with a higher than 50 Gy radiation dose. Patients treated with more than 55 Gy did not have higher local

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