We conducted a phase II study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer. The apprent diffusion coefficient (ADC) of tumor was measured by diffusion-weighted magnetic resonance imaging (DW-MRI) and was evaluated as a predictive biomarker for pathologic responses.Methods
The total radiotherapy dose was 50.4 Gy. Chemotherapy, as determined in our previous phase I study, consisted of oxaliplatin 50 mg/m2 on days 1, 8, 22 and 29 and S-1 80 mg/m2/day on days 1–14 and 22–35. Total mesorectal excision was carried out within 6 ± 2 weeks. The primary end point was the pathologic complete response (pCR) rate. Tumor ADCs were measured by DW-MRI before and after CRT and were correlated with pathologic responses after surgery.Results
A total of 38 patients was enrolled; 22 (57.9%) were men and the median age was 54 years (range, 28–67 years). Of the 35 patients who underwent curative surgery, 28 received sphincter-saving operations. No grade 4 toxicity was evident, and grade 3 toxicities included leukopenia (5.4%), diarrhea (5.4%), anorexia (2.7%) and nausea (2.7%). The pCR rate was 25.7% (8/35, 95% CI: 10.9–42.1), with additional 10 patients (28.6%) showing near total regressions of tumor. Tumor ADCs, as measured by DW-MRI, were calculated in 38 patients (including those who participated in the phase I study). The post-CRT ADC (1.52 × 10−3 mm2/s ± 0.46 in the pCR group versus 1.07 × 10−3 mm2/s ± 0.58 in the non-pCR group, P = 0.037) and the percentage change in ADC (44.5% in the pCR group versus −7.6% in the non-pCR group, P = 0.026) were significantly correlated with the pCR rate.Conclusions
Preoperative CRT with S-1–oxaliplatin showed promising results in pathologic responses and favorable toxicity profiles. Tumor ADC, as measured by DW-MRI, seems to be useful in predicting responses.