Neoadjuvant chemoradiotherapy (NCRT) using concurrent S-1 and irinotecan in rectal cancer: Impact on long-term clinical outcomes and prognostic factors.

Abstract

3556 Background: To assess long-term clinical outcomes of neoadjuvant chemoradiotherapy (NCRT) of rectal cancer using concurrent irinotecan and S-1. Methods: One hundred and fifteen patients without distant metastases entered this phase II trial in cT3/T4 rectal cancer (n=104/11). Pelvic radiotherapy was given to 45 Gy in 25 fractions over 5 weeks with concurrent oral S-1 at 80 mg/m2 and intravenous irinotecan at 80 mg/m2 once weekly. Median follow-up term was 60 months (ranged from 20 to 96 months). Results: Adverse effect of Grade 3 was recognized in 7 patients (6%), and completion rate of this NCRT regimen was 87 %. All 115 patients (100%) could undergo R0 surgical resection. Twenty-eight patients (24%) demonstrated a pathologic complete response (ypCR). Local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. By the multivariate proportional hazard model for DFS and OS, ypN2 was only remnant independent prognostic factor (P=0.0019 and P=0.0064, respectively). ypN2 was recognized in 9 patients (8%), and prognosis was extremely dismal (8 patients were recurred within 2 years). We again performed the multivariate analysis for 106 cases restricted to ypN0/1, which exhibited 85% of DFS, and both ypT and tumor portion were independent predictors (P=0.0065 and P=0.003, respectively). Combination of them could greatly enrich high risk patients for recurrence (P<0.0001), and dominant recurrences were uniquely found in lung. Conclusions: Novel NCRT regimen using S1/irinotecan demonstrated high response rates and excellent long-term survival, with acceptable adverse effects. ypN2 is a definitive indicator of dismal prognosis, and combination of ypT and tumor portion can identify high risk patients among the ypN0/1 patients.