Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma.

Victor Ho-Fun Lee,Patty Pui-Ying Ho,Dennis Kwok-Chuen Leung,Lydia Ng,Chun-Kin Sze,Wing-Lok Chan,Dora Lai-Wan Kwong,Chi-Chung Tong,Cheuk-Wai Choi,Vincent Lai,Ka-On Lam,Lai-San Wong,Sherry Chor-Yi Ng,To-Wai Leung,Pek-Lan Khong,Sum-Yin Chan

doi:10.18632/oncotarget.14137

Victor Ho-Fun Lee, Patty Pui-Ying Ho + Show 14 more

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https://doi.org/10.18632/oncotarget.14137

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Abstract

Plasma Epstein-Barr virus (EBV) DNA titers have been used to monitor treatment response and provide prognostic information on survival for nasopharyngeal carcinoma (NPC). However, the long-term prognostic role of pretreatment and posttreatment titers after radical contemporaneous radiation therapy remains uncertain. We recruited 260 evaluable patients with non-metastatic NPC treated with radical intensity-modulated radiation therapy (IMRT) with or without adjunct chemotherapy. Plasma EBV DNA titers at baseline and then 8 weeks and 6 months after IMRT were measured. Cox regression models were employed to identify interaction between post-IMRT 8th week and 6th month undetectable titers and 3-year survival endpoints. Concordance indices (Ct) from time-dependent receiver-operating characteristics (TDROC) were compared between patients with post-IMRT undetectable and those with detectable titers. After a median follow-up duration of 3.4 years (range 1.4-4.6 years), patients with post-IMRT 8th week and 6th month undetectable plasma EBV DNA titers enjoyed longer 3-year survival endpoints than those who had detectable titers at the same time points. Post-IMRT 8th week, and more significantly, post-IMRT 6th month undetectable plasma EBV DNA were the only significant prognostic factors of 3-year survival endpoints. Ct values for all 3-year survival endpoints for both post-IMRT 8th week and 6th month undetectable plasma EBV DNA were significantly higher in those with stage IVA–IVB diseases compared to stage I-III counterparts. Early post-IMRT undetectable plasma EBV DNA titers were prognostic of 3-year survival endpoints in patients with non-metastatic NPC. Intensified treatment should be further explored for patients with persistently detectable titers after IMRT.

Highlights

Nasopharyngeal carcinoma (NPC) is unique in its geographical distribution with prevalence in Southern China, Hong Kong, Taiwan, Singapore and Malaysia as well as association with Epstein-Barr virus (EBV) [1, 2]
29 patients were excluded from subsequent analyses after written informed consent: 23 patients did not have blood taken for baseline or serial plasma EBV DNA, three patients suffered from stage IVC metastatic disease confirmed by PETCT scan and another three patients died during intensity-modulated radiation therapy (IMRT)
Five patients developed progressive disease with distant metastases between 8 weeks and 6 months after IMRT, and they were only included in the subsequent time-dependent receiver-operating characteristics (TDROC) and survival analysis using post-IMRT 8th week undetectable plasma EBV DNA as stratifying factor

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is unique in its geographical distribution with prevalence in Southern China, Hong Kong, Taiwan, Singapore and Malaysia as well as association with Epstein-Barr virus (EBV) [1, 2]. There is an unmet and urgent need for identifying its role at baseline and in posttreatment monitoring to improve risk stratification, leading to closer surveillance and intensified treatment in poor-risk groups in the modern era of radiation therapy. We initiated this prospective observational study on measuring baseline and serial plasma EBV DNA titers for all patients with newly diagnosed non-metastatic NPC to determine the prognostic value of early post-IMRT plasma EBV DNA on long-term survival outcomes. This study was registered with the National Cancer Trial Registry as NCT02476669 (ClinicalTrials.gov)

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