Li-Ting Liu1, Lin-Quan Tang1, Qiu-Yan Chen1, Lu Zhang1, Shan-Shan Guo1, Ling Guo1, Hao-Yuan Mo1, Chong Zhao1, Xiang Guo1, Ka-Jia Cao1, Chao-Nan Qian1, Mu-Sheng Zeng2, Jin-Xin Bei2, Ming-Huang Hong3, Jian-Yong Shao4, Ying Sun5, Jun Ma5, Hai-Qiang Mai6. 1. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China. 2. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. 3. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Good Clinical Practice Center, Sun Yat-sen University Cancer Center, Guangzhou, China. 4. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China. 5. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. 6. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: maihq@sysucc.org.cn.
Abstract
PURPOSE: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). CONCLUSION: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.
PURPOSE: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). CONCLUSION: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.