Intra-operative radiotherapy of rectal cancer: results of the French multi-institutional randomized study.

PURPOSE To assess efficacy and tolerance of intra-operative radiation therapy (IORT) in patients suffering from locally advanced rectal cancer, treated with preoperative radiotherapy followed by surgical resection. METHODS AND MATERIALS In this French, multicenter, comparative, phase III study, 142 patients with locally advanced rectal cancer (T3 or T4 or N+, and M0), treated with a 4-week preoperative radiotherapy (40 grays) were randomly assigned to either surgical resection alone ( CONTROL GROUP n=69) or combined to 18-gray intra-operative radiation therapy (IORT group: n=73) between 1993 and 2001. RESULTS The 5-year cumulative incidence of local control was 91.8% with IORT and 92.8% with surgery alone (p=0.6018); the mean duration without local relapse (Kaplan-Meier method) was 107 versus 126 months, respectively. No statistically significant difference was demonstrated for overall survival (p=0.2578) disease-free survival (p=0.7808) and probability of metastatic relapse (p=0.6037) with 5-year cumulative incidences of 69.8% versus 74.8%, 63.7% versus 63.1%, and 26.1% versus 30.2%, respectively. 48 patients of the IORT group and 53 patients of the control group were alive with a median follow-up of 60.1 and 61.2 months, respectively. Post-operative complications were observed in the IORT group in 21 patients (29.6%) and in the control group in 13 patients (19.1%) (p=0.15), with an acceptable tolerance profile. CONCLUSIONS Although this randomized study did not demonstrate any significant improvement in local control and disease-free survival in rectal cancer patients treated with preoperative radiation therapy receiving IORT or not, it confirmed the technical feasibility and the necessity for evaluating IORT for rectal carcinoma in further clinical studies.