title: Cigarette smoking complements the prognostic value of baseline plasma Epstein-Barr virus deoxyribonucleic acid in patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy: a large-scale retrospective cohort study.
abstract: We evaluated the combined prognostic value of cigarette smoking and baseline plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Of consecutive patients, 1501 with complete data were eligible for retrospective analysis. Smoking index (SI; cigarette packs per day times smoking duration [years]), was used to evaluate the cumulative effect of smoking. Primary end-point was overall survival (OS); progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were secondary end-points. Both cigarette smoking and baseline plasma EBV DNA load were associated with poorer survival (P <0.001). Patients were divided into four groups: low EBV DNA and light smoker (LL), low EBV DNA and heavy smoker (LH), high EBV DNA and light smoker (HL), and high EBV DNA and heavy smoker (HH). The respective 5-year survival rates were: OS (93.1%, 87.2%, 82.9%, and 76.3%, P<0.001), PFS (87.0%, 84.0%, 73.9%, and 64.6%, P<0.001), DMFS (94.1%, 92.1%, 82.4%, and72.5%, P<0.001), and LRFS (92.8%, 92.4%, 88.7%, and 84.0%, P=0.012).OS and PFS were significantly different between the LH and HL groups and HL and HH groups, but not LL and LH groups (pairwise comparisons). The combined risk stratification remained an independent prognostic factor for all endpoints (all Ptrend<0.001; multivariate analysis). Both cigarette smoking and baseline plasma EBV DNA were independent prognostic factors for survival outcomes. Combined interpretation of EBV DNA with smoking led to the refinement of the risks stratification for patient subsets, especially with improved risk discrimination in patients with high baseline plasma EBV DNA.
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Lv
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Guan-Qun
authors.initials: GQ
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Mao
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000209:etiology* / Q000401:mortality / Q000532:radiotherapy*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000209:etiology* / Q000401:mortality / Q000532:radiotherapy*; D016016:Proportional Hazards Models; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*
chemical_list: D004279:DNA, Viral
keywords: baseline plasma EBV DNA; cigarette smoking; intensity-modulated radiation therapy; nasopharyngeal carcinoma; prognostication