A systematic review including 10 studies with a total of 2458 subjects was abstracted in DARE. The pooled hazard ratio (HR) of death for all studies was 0.82 (95% CI 0.71 to 0.95; P =0.01) corresponding to an absolute survival benefit of 4% after 5 years. Three categories of trials were defined according to the sequence of chemotherapy, including neoadjuvant chemotherapy, at least concomitant chemoradiotherapy, and adjuvant chemotherapy. A significant interaction term (P = 0.02) was found among these three categories. The largest effect was found for concomitant chemotherapy (2 studies), with a pooled HR of 0.48 (95% CI 0.32 to 0.72), which corresponds to a survival benefit of 20% after 5 years. Comparable results were found for the incidence of local-regional recurrences and distant metastases.