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.

Jia-Wei Lv,Rui Guo,Ai-Hua Lin,Ying Sun,Ling-Long Tang,Wen-Fei Li,Jun Ma,Yan-Ping Mao,Guan-Qun Zhou,Yu-Pei Chen

doi:10.18632/oncotarget.7609

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 endpoint was overall survival (OS); progression-free survival (PFS), distant metastasisfree 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.

Highlights

Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that originates from the epithelial lining of the nasopharynx and is endemic in southern China and Southeast Asia, where the prevalence is approximately 50 cases per 100,000 individuals. [1, 2] Radiotherapy (RT) is the primary treatment modality for nasopharyngeal carcinoma (NPC). [3] The introduction of intensity-modulated radiation therapy (IMRT) in recent years has greatly enhanced the locoregional control rate and leads to superior outcomes in NPC
Baseline plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA) is widely assessed in clinical use for its proven ability to assist with diagnosis, risk stratification, prognostication and relapse supervision in patients with NPC. [6,7,8] even patients with the same baseline plasma EBV DNA load exhibit different treatment outcomes, which reflects the heterogeneity of NPC
Having witnessed the revolutionary changes that IMRT has provided in the treatment of NPC in recent decades, we consider it necessary to reevaluate the value and significance of existing prognostic factors

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that originates from the epithelial lining of the nasopharynx and is endemic in southern China and Southeast Asia, where the prevalence is approximately 50 cases per 100,000 individuals. [1, 2] Radiotherapy (RT) is the primary treatment modality for NPC. [3] The introduction of intensity-modulated radiation therapy (IMRT) in recent years has greatly enhanced the locoregional control rate and leads to superior outcomes in NPC. Baseline plasma EBV DNA is widely assessed in clinical use for its proven ability to assist with diagnosis, risk stratification, prognostication and relapse supervision in patients with NPC. [6,7,8] even patients with the same baseline plasma EBV DNA load exhibit different treatment outcomes, which reflects the heterogeneity of NPC. [9] additional efforts should be made to explore other markers that may correlate with and complement baseline plasma EBV DNA in order to improve risk stratification and prognostication in NPC. Among the various prognostic factors that have already been reported, cigarette smoking attracts attention due to its demonstrated relationships with NPC etiology, prognostication and EBV seropositivity. According to a 20-year follow-up study in Taiwan, heavy smokers maintained a higher EBV seropositivity rate than never smokers and light smokers and were proned to higher risk of nasopharyngeal carcinoma. [10]

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