A gene-expression predictor for efficacy of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma
Menée sur 342 patients atteints d'un carcinome rhinopharyngé de stade locorégionalement avancé et validée sur 427 patients supplémentaires, cette étude identifie une signature, basée sur l'expression de 6 gènes, pour identifier les patients pouvant bénéficier d'une chimiothérapie d'induction
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 beneficiaries of IC.
Methods : We screened chemosensitivity-related genes by comparing gene expression profiles of patients with short-term tumor response or non-response to IC (n = 95) using microarray analysis. Chemosensitivity-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). Tests of statistical significance are two-sided.
Results : We identified 43 chemosensitivity-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 further found that IC conferred failure-free survival benefits only on patients in the benefit group (hazard ratio [HR]=0.54, 95% confidence interval [CI]=0.34 to 0.87, P=.01) and not on those in the no-benefit group (HR = 1.25, 95%CI=0.62 to 2.51, P=.53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC=0.82; sensitivity=87.5%; specificity=71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed.
Conclusions : The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for LA-NPC patients.
Journal of the National Cancer Institute , résumé, 2019