Development and validation of a gene expression-based signature predicting efficacy of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A multicenter cohort study.

Abstract

6522 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene expression signature that can identify patients who will benefit from IC. Methods: We screened chemoresistance-related genes by comparing gene expression profiles of patients with short-term tumor response or non-response to IC (n = 95) using microarray analysis. Chemoresistance-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Results: We identified 43 chemoresistance-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] 0.87, sensitivity = 87.5%, specificity = 75.6%). We then apply the 6-gene signature to classify patients into the benefit group and the no-benefit group. In the benefit group, patients could benefit from IC in terms of failure-free survival (hazard ratio [HR] 0.54 [95% confidence interval 0.34-0.87]; p = 0.01), while patients in the no-benefit group could not (HR 1.25 [95%CI 0.62-2.51]; p = 0.53). In the clinical trial cohort, the developed 6-gene signature was also highly accurate at predicting the response to IC (AUC = 0.82; sensitivity = 87.5%; specificity = 71.8%). Additionally, IC conferred failure-free survival benefits only on patients in the benefit group (HR 0.37 [95%CI 0.18-0.75], p = 0.004) and not on those in the no-benefit group (HR 0.70 [95%CI 0.27-1.82]; p = 0.46). In the external independent cohort, similar results were observed. Conclusions: The 6-gene signature can help select patients who will benefit from IC and thus lay a foundation for a more individualized therapeutic strategy for LA-NPC patients.