Tumori, 89: 157-163, 2003 PREOPERATIVE CONCOMITANT RADIOCHEMOTHERAPY WITH A 5-FLUOROURACIL PLUS FOLINIC ACID BOLUS IN THE COMBINED TREATMENT OF LOCALLY ADVANCED EXTRAPERITONEAL RECTAL CANCER: A LONG-TERM ANALYSIS ON 27 PATIENTS Antonella Ciabattoni1, Antonio Cavallaro 2 , Angelo Eugenio Potenza 2 , Rosa Colli 2 , Francesca Maurizi1, Francesco Micciche\ and Vincenzo Valentini1 1 Cattedra di Radioterapia, lstituto di Radiologia, 2 Istituto di Semeiotica Chirurgica, Universitii Cattolica del Sacra Cuore, Rome, Italy Aims and background: Many studies of preoperative chemoradi- ation in resectable rectal cancer have focused on down-stag- ing and sphincter-saving procedures. The aim of this study was to evaluate long-term outcome in resectable rectal cancer treated with preoperative chemoradiation and surgery by only one surgical team irrespective of the tumor downstaging. Material and methods: From 1992 to 2001, in a cooperative study between the Institute of Semeiotica Chirurgica and the Division of Radiotherapy of the Catholic University of the Sacred Heart, 27 patients with locally advanced rectal cancer were treated with preoperative chemoradiation, followed by surgery after 4-6 weeks, and, just for 6 of them, by adjuvant chemotherapy. Seven- teen patients were staged T3 N1 (63%), 4 patients T3NO (15%), 4 patients T3N2 (15%) and 2 T4N2 (7.5%). Twenty-three patients (85.1%) had signs of nodal involvement at combined imaging. Radiation therapy was delivered to the posterior pelvis at a dose of 45 Gy to the tumor (clinical target volume) and the whole pelvis (planning target volume). Fractionation was conventional: 1.8 Gy/day, 5 fractions a week. Radiotherapy was started on Monday for all patients and was delivered with a linear accelera- tor. Concomitant chemotherapy consisted of 5-fluorouracil (350 mg/m 2 /day, as an intravenous bolus on days 1-5 and 29-33 of ra- diotherapy) and folinic acid (L-isomer) (10 mg/m 2 as an intra- venous bolus on days 1-5 and 29-33). This chemotherapy was generally administered about 1 hr before radiotherapy. Data were analyzed on July 2002; median follow-up was 59 months (range, 20-116 months). No patient was lost during the follow-up. Results: All patients completed the treatment. Grade >3 acute toxicity occurred in 11 % of the patients and late toxicity was 15%. A pathologic complete response was recorded in 22% of patients; sphincter-preserving surgery was feasible in 44%. Seven patients died: 2 of them perioperatively, 1 patient died with local recurrence, and 1 died with distant metastases; 3 patients died during the follow-up for other causes. Five-year local control was 95% and overall survival was 84%. Conclusions: Our study, although limited in number, demon- strated good results in local control and disease-free survival with a limited toxicity. Key words: infusional chemotherapy, local control, prognostic factors, sphincter saving procedure, survival. Introduction Chemoradiation consists in the concurrent adminis- tration of chemotherapeutic agents and radiation thera- py. This combination has as a main goal the enhance- ment of the effects of radiotherapy, with a possible im- provement of local control compared to radiotherapy alone, and secondly, spatial cooperation, which results in a better local control afforded by radiotherapy while chemotherapy controls micrometastases. Preoperative chemoradiation has all the theoretical advantages of preoperative radiotherapy in rectal cancer such as re- duction of the probability of residual microscopic dis- ease after surgery and of viable cell dissemination. Pre- operative radiation also acts on a better oxygenated and therefore more sensitive tumor and may require smaller tissue volumes, particularly compared to postoperative radiation following an abdominoperineal resection, where the perinea! scar must be included in the treated volume. Furthermore, preoperatively, the bowel is more likely to be mobile than postoperatively, with a lesser chance of radiation-induced injury and morbidity. With preoperative radiation, a significant shrinkage of initial- ly fixed and marginally resectable lesions is achievable, allowing subsequent complete resection and/or a higher rate of sphincter-saving procedures 1 • Many studies of preoperative chemoradiation in re- sectable rectal cancer have focused on down-staging and sphincter-saving procedures 2 . The aim of this study was to evaluate long-term outcome in resectable rectal cancer treated with preoperative chemoradiation and surgery by only one surgical team irrespective of tumor down-staging. Material and methods From 1992 to 2001, in a cooperative study between the Institute of Semeiotica Chirurgica and the Institute of Radioterapia of the Catholic University of the Sacred Heart, 27 patients with locally advanced rectal cancer were treated with preoperative chemoradiation, fol- lowed by surgery after 4-6 weeks, and, just for some of them, by adjuvant chemotherapy. Eight of the patients were women and 19 were men; median age was 63.7 years (range, 38-77). Correspondence to: Prof Antonio Cavallaro, Istituto di Semeiotica Chirurgica, Universita Cattolica de! Sacro Cuore, Policlinico "A Gemelli", Largo A Gemelli 8, 00168 Roma, Italy. Tel +39-06-30154199; fax +39-06-3051343; e-mail aepotenza@yahoo.it Received September 23, 2002; accepted December 4, 2002.