Impact of preoperative radiation dose escalation on pathologic outcomes and radiation toxicity in locally advanced rectal cancer (LARC): A matched-pair analysis.

Abstract

e14036 Background: Compared with postoperative chemoradiotherapy (CRT), preoperative CRT has been shown to improve local control and reduce toxicity for LARC patients. However, the dose of preoperative RT in such regimens is empirically chosen based on experience with postoperative CRT regimens. We hypothesized that higher RT dose improves tumor downstaging without increasing toxicity. Methods: Between 1995 and 2003, LARC patients were treated with preoperative RT and concurrent protracted venous infusion 5-fluorouracil (5FU). 76 patients in the high dose (boost) CRT group (5FU + 52.5 Gy in five weeks, 1.8 Gy/morning and an additional 1.5 Gy/afternoon in the fifth week) were matched (based on type of surgery and clinical T/N stage) with 76 patients in the low dose CRT group (5FU + 45 Gy in five weeks, 1.8 Gy/day). Radiation toxicity, pathological complete response (pCR), and T downstaging were tabulated. Discrete and categorical variables were compared using McNemar’s chi-square test. Results: Both groups were balanced for patient gender, age, and matched parameters. There was a trend in increased grade I/II skin toxicity in the boost group (Table) but no difference in grade III toxicity. Rate of pCR did not differ between the boost and no boost groups (17.1% vs. 15.8%, p=0.83) but T downstaging was greater with RT boost (76.3% vs. 51.3%, p<0.001). Conclusions: CRT with radiation dose escalation in LARC improves T downstaging without significantly increasing toxicity. This approach could improve resectability of more advanced tumors, particularly within the distal rectum. Parameter Boost (n=76) No boost (n=76) P value Gender (M) 49 (64.5%) 50 (65.8%) 0.87 Age (years) 57.1 ± 13.0 55.9 ± 11.7 0.54 Procedure LAR: 19 (25.0%) Same N/A CAA: 36 (47.4%) APR: 21 (27.6%) Initial T stage T2: 2 (2.6%) Same N/A T3: 71 (93.4%) T4: 3 (4.0%) Same N/A Initial N stage N+: 34 (44.7%) Same N/A Grade I/II Skin 53/76 (69.7%) 34/63 (54.0%) 0.06 Radiation toxicity Nausea 21/76 (27.6%) 12/63 (19.0%) 0.24 Diarrhea 44/76 (57.9%) 41/63 (65.1%) 0.39 Pain 14/76 (18.4%) 8/63 (12.7%) 0.36 Abbreviations: APR, abdominoperineal resection; CAA, proctectomy with coloanal anastomosis; LAR, low anterior resection.