Long-term anorectal function after postoperative chemoradiotherapy in high-risk rectal cancer patients.

AIMS AND BACKGROUND: After sphincter-preserving surgery for rectal cancer and postoperative radiochemotherapy, many patients have unsatisfactory anorectal functional results which are not considered by the most common toxicity scales. The aim of the present study was to retrospectively assess the long-term incidence of impaired anorectal function in rectal cancer patients who underwent anterior resection and postoperative radiochemotherapy. METHODS: Ninety-nine patients who underwent sphincter-saving surgery and postoperative radiochemotherapy for stage II-III rectal cancer from July 1991 to January 2002 were given a questionnaire on anorectal function. Postoperative incontinence was evaluated according to a scale proposed by Jorge and Wexner. Factors influencing anorectal function were examined. RESULTS: The median follow-up from surgery was 10 years. Ten (10.1%) patients reported >or= 5 bowel movements per day and 26 (26.3%) experienced clustering. The median frequency of bowel movements per 24 h was 2 (range, 1-10). Stool fragmentation was recorded in 56 (56.6%) cases, and 36 (36.4%) patients experienced urgency to defecate with inability to delay defecation for more than 15 min. The mean continence score was 4.91 (median 1, range 0-18). Incontinence to flatus, liquid and solid stools was reported at least once a week in 24 (24.2%), 11 (11.1%) and 5 (5.1%) patients, respectively. According to the study criteria, 61% of patients had good functional results. None of the variables analyzed showed a significant correlation with functional outcome. CONCLUSIONS: Although retrospective, the present study included a large selected series that had undergone uniform adjuvant treatment and was followed for a median of 10 years. Our data demonstrated that 39% of patients did not have good functional results and suffered some degree of urgency, increased frequency and occasional incontinence even many years after the surgery. Anorectal function assessment should enter routinely in clinical practice and should have importance in the therapeutic decisions.

Raltitrexed and radiotherapy as adjuvant treatment for stage II-III rectal cancer: a feasibility study.

AIMS AND BACKGROUND: Adjuvant 5-FU chemotherapy plus radiotherapy represents the standard treatment for radically resected rectal cancer at high risk of relapse according to the NIH Consensus Conference. The therapeutic gain was obtained with a high rate of severe treatment-related toxicity and a suboptimal patient compliance with this regimen. Raltitrexed is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable toxicity and radiosensitizing properties, as the published phase I trials in combination with radiotherapy have shown. The aim of this prospective multicenter phase II study was to evaluate the feasibility, gastrointestinal and hematological acute toxicity of raltitrexed in combination with radiotherapy in rectal cancer patients. METHODS: From September 2000 to June 2004, 50 patients with radically resected stage II-III rectal adenocarcinoma were treated. All patients were evaluable for compliance and acute toxicity. Within 45-60 days of surgery, each patient underwent concomitant adjuvant radiochemotherapy. Radiotherapy was administered to the pelvis (plus perineum after abdominoperineal resection) with photon beam energy exceeding 5 MV, 3-4 fields, 45 Gy/25 fractions/5 weeks plus a boost delivered to the site of resected disease with 3-4 fields, 9 Gy/5 fractions/1 week to a total dose of 54 Gy. The boost dose was administered after complete exclusion of the small bowel from the treatment volumes; if this was not possible a total dose of 50.4 Gy was given. Raltitrexed was administered intravenously at a dose of 3 mg/m2 as a bolus injection on days 1 and 22 of radiotherapy one hour before treatment, for a total of two cycles. Each patient underwent weekly clinical evaluation and laboratory tests. Toxicity was assessed by the WHO scale. RESULTS: Forty-five (90%) patients completed the established treatment. Acute severe toxicity included grade III proctitis in 4/50 (8%), grade III-IV diarrhea in 4/50 (8%), grade III perineal dermatitis in 4/50 (8%) and grade III leukopenia in 2/50 (4%) patients; five patients (10%) experienced a transient grade Ill increase in their liver biochemistry values. CONCLUSIONS: Our data related to acute toxicity and patient compliance proved the feasibility of this adjuvant radiochemotherapy treatment. A longer follow-up is necessary to evaluate the effectiveness of this new regimen in terms of disease-free and overall survival.

T1-T2 breast cancer with four or more positive axillary lymph nodes: adjuvant locoregional radiotherapy with high-dose or standard-dose chemotherapy. Results of an observational study.

AIM AND BACKGROUND: The aim of this study was to investigate the efficacy of postoperative locoregional radiotherapy in patients with T1-T2 breast cancer and four or more positive axillary lymph nodes submitted to mastectomy or breast-conserving surgery followed by standard-dose or high-dose adjuvant chemotherapy. The incidence of locoregional relapses and the survival correlated with the number of positive nodes were recorded for each treatment arm. PATIENTS AND METHODS: From August 1992 to August 1999 86 breast cancer patients (median age, 54 years, T1-T2, N+ > or = 4) submitted to surgery were treated. Sixty-three patients received standard-dose chemotherapy while 23 patients with 10 or more positive nodes received high-dose chemotherapy. After four courses of standard-dose anthracycline-based chemotherapy peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (10-16 microg/kg/day/sc). High-dose chemotherapy consisted of etoposide 1000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2. Hormone receptor-positive patients underwent hormone therapy. Following chemotherapy all 86 patients were given conventional radiotherapy to the breast or the chest wall and the supraclavicular fossa. The high-dose subgroup received radiotherapy to the internal mammary nodes +/- axilla. RESULTS: The median follow-up from the start of radiotherapy was 36.5 months. Locoregional relapses occurred in nine patients (10.4%); in four of them they were isolated (4.6%). Local relapses were four (4.6%) and regional relapses six (6.9%). Twenty-five patients (29%) had distant metastases. The five-year and eight-year overall actuarial survival rates were 82.6% +/- 4.8 and 60.1% +/- 8.8, respectively. No statistical differences were found when the number of positive nodes or the type of treatment of N+ 10 patients was included in the analysis. CONCLUSIONS: Breast cancer patients with four or more positive axillary lymph nodes are at high risk of developing locoregional and distant relapses. The results reported here demonstrate the efficacy of radiotherapy in the reduction of locoregional failure; no differences in survival and locoregional control in relation to treatment arm and number of positive nodes were found.