Yuan Lei1, Ying-Qin Li2, Wei Jiang3, Xiao-Hong Hong1, Wen-Xiu Ge4, Yuan Zhang1, Wei-Han Hu1, Ya-Qin Wang1, Ye-Lin Liang1, Jun-Yan Li1, William C S Cho5, Jing-Ping Yun6, Jing Zeng6, Jie-Wei Chen6, Li-Zhi Liu7, Li Li7, Lei Chen1, Fang-Yun Xie1, Wen-Fei Li1, Yan-Ping Mao1, Xu Liu1, Yu-Pei Chen1, Ling-Long Tang1, Ying Sun1, Na Liu2, Jun Ma1. 1. Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China. 2. Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China. 3. Department of Radiation Oncology, Affiliated Hospital of Guilin Medical University, Guilin, China. 4. Department of Probability and Statistics, School of Mathematical Sciences, South China Normal University, Guangzhou, China. 5. Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, Hong Kong, China. 6. Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China. 7. Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
Abstract
BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. 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 nonresponse 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 2-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 in 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 locoregionally advanced nasopharyngeal carcinoma patients.
BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. 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 nonresponse 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 2-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 in 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 locoregionally advanced nasopharyngeal carcinomapatients.
Authors: M Frikha; A Auperin; Y Tao; F Elloumi; N Toumi; P Blanchard; P Lang; S Sun; S Racadot; J Thariat; M Alfonsi; C Tuchais; A Cornely; A Moussa; J Guigay; J Daoud; J Bourhis Journal: Ann Oncol Date: 2018-03-01 Impact factor: 32.976
Authors: E A Eisenhauer; P Therasse; J Bogaerts; L H Schwartz; D Sargent; R Ford; J Dancey; S Arbuck; S Gwyther; M Mooney; L Rubinstein; L Shankar; L Dodd; R Kaplan; D Lacombe; J Verweij Journal: Eur J Cancer Date: 2009-01 Impact factor: 9.162
Authors: Joseph A Sparano; Robert J Gray; Della F Makower; Kathleen I Pritchard; Kathy S Albain; Daniel F Hayes; Charles E Geyer; Elizabeth C Dees; Matthew P Goetz; John A Olson; Tracy Lively; Sunil S Badve; Thomas J Saphner; Lynne I Wagner; Timothy J Whelan; Matthew J Ellis; Soonmyung Paik; William C Wood; Peter M Ravdin; Maccon M Keane; Henry L Gomez Moreno; Pavan S Reddy; Timothy F Goggins; Ingrid A Mayer; Adam M Brufsky; Deborah L Toppmeyer; Virginia G Kaklamani; Jeffrey L Berenberg; Jeffrey Abrams; George W Sledge Journal: N Engl J Med Date: 2018-06-03 Impact factor: 91.245