Induction chemotherapy plus chemoradiotherapy in esophageal cancer: long-term results and exploratory analyses of a randomized controlled trial

Background: Previous results of our trial demonstrated that the addition of induction chemotherapy (IC) prior to defnitive chemoradiotherapy (CRT) failed to signifcantly improve the response rate or 3-year survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Here, we report long-term results and exploratory analyses to further evaluate the therapeutic value of IC.<br /> Methods: Patients with previously untreated, unresectable, stage II-IVA ESCC were randomly assigned to receive IC followed by CRT or CRT alone. The relationship between tumor response to IC and long-term survival was analyzed. Baseline tumor biopsies were collected for RNA-Seq to identify patients who may beneft from IC.<br /> Results: Eligible patients were randomized to either the IC + CRT group (n = 55) or the CRT group (n = 55). With a median follow-up of 74.9 months, the 5-year overall survival rate was 31.8% in the IC + CRT group and 29.1% in the CRT group (P =.675; HR, 0.91; 95% CI, 0.58-1.43). Similarly, no signifcant differences were identifed in 5-year progression-free survival between groups (30.5% vs 25.5%, P =.508; HR, 0.86; 95% CI, 0.56-1.34). Patients who responded to IC had signifcantly better survival than nonresponders. A risk-score model incorporating 6 key genes to predict IC effcacy was also constructed.<br /> Conclusions: Compared with defnitive CRT alone, the addition of IC before CRT still failed to demonstrate superior survival in patients with unselected ESCC, based on long-term follow-up. However, because IC responders were associated with more favorable survival, potential molecular biomarkers were identifed for selection of beneft population from IC