Locally advanced primary colorectal cancer: Intraoperative electron and external beam irradiation ± 5-FU

Abstract

Purpose : For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) ± 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT dose of 10–20 Gy, usually combined with 45–55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, ≤ microscopic in 39, and unresected in 1. Results : Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) amd ≤ microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), ≤ microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with ≤ microscopic residual after gross total resection ( p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free DR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (≤12.5 Gy—1 of 29 or 3%, ≤ 16 Gy—6 of 26 or 23%, p = 0.03). Conclusion : Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatemnt regimens because the incidence of distant metastases was ∼50% of patients at risk.