Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer

Rationale: To evaluate the response to a concomitant boost given during sta ndard chemoradiation for locally advanced rectal cancer. Methods and Materials: Concomitant boost radiotherapy was administered preo peratively to 45 patients with locally advanced rectal cancer in a prospect ive trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infu sion 5FU chemotherapy (300mg/n(2)) 5 days per week. The boost was given dur ing the last week of therapy with a 6-hour inter-fraction interval to the t umor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 G y/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor . Pretreatment tumor stage, determined by endorectal ultrasound and CT scan , included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the and verge was 5 cm (range 0-13 cm). Me dian age was 55 years (range 33-77 years). The population consisted of 34 m ales and 11 females. Median time of follow-up is 8 months (range 1-24 month s). Results: Sphincter preservation (SP) has been accomplished in 33 of 42 (79% ) patients resected to date. Three patients did not undergo resection becau se of the development of metastatic disease in the interim between the comp letion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgica l procedures included proctectomy and coloanal anastomosis (n = 16), low an terior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 1 3 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm f rom the anal verge, SP was accomplished in 21 cases (75%). Although periope rative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/ XRT (45Gy; 1.8 Gy per fraction), improvem ents were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.0 03). Conclusion: The SP rate with concomitant boost radiation has been highly fa vorable with rates of response which are higher than those previously repor ted for chemoradiation without administration of a boost. Further evaluatio n of this radiotherapeutic strategy appears warranted. (C) 2000 Elsevier Sc ience Inc.