Abstract
Introduction: The prognostic role of plasma Epstein–Barr virus (EBV) DNA clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered. We investigated if its half-life clearance during radical treatment for non-metastatic nasopharyngeal carcinoma (NPC) was an early prognosticator.Patients and methods: Patients with previously untreated non-metastatic NPC were prospectively treated with radical IMRT and concurrent chemotherapy +/– induction/adjuvant chemotherapy from 2014 to 2018. Their plasma EBV DNA was measured immediately before treatment followed by weekly schedules until 0 copy/ml in two consecutive measurements. Cox regression models were employed to identify prognostic factors.Results: Forty-five patients were prospectively recruited and analyzed. After a median follow-up of 30.3 months, 2 (4.5%), 1 (2.3%), and 6 (13.6%) patients experienced local, regional, and distant relapses, respectively. The median half-life clearance of plasma EBV DNA was 7.92 days. Those with half-life clearance of >15 days had a worse 3-years progression-free survival (PFS) (79.5 vs. 25.0%, p = 0.005), distant metastasis-free survival (DMFS) (85.0 vs. 31.3%, p = 0.009), and overall survival (OS) (91.3 vs. 75.0%, p = 0.024) when compared to those with a shorter half-life. Multivariable analyses demonstrated that only half-life (>15 days) was prognostic of DMFS [HR (95% CI): 4.91 (1.31; 18.39), p = 0.01] and OS [HR (95% CI): 5.24 (1.06; 26.05)] while half-life (>15 days) [HR (95% CI): 5.14 (1.28; 22.73), p = 0.02] and sum of pretreatment gross tumor volumes of the primary nasopharyngeal tumor and the radiologically positive neck nodes (GTV_P+N) [HR (95% CI): 1.01 (1.00; 1.03), p = 0.02] were prognostic of PFS.Conclusion: The half-life clearance of plasma EBV DNA was prognostic in non-metastatic NPC staged and treated in the contemporary era. Earlier biomarker surveillance during treatment should be considered.Clinical Trial Registration: This study has been registered with ClinicalTrials.gov (Identifier: NCT03830996).
Highlights
The prognostic role of plasma Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA) clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered
One (2.2%) patient was excluded in subsequent statistical analysis due to the failure of complete clearance of plasma EBV DNA followed by subsequent elevation secondary to distant metastases as described further below
One patient (2.3%) presented with stage IVA T4N0M0 disease and clinically evident dysphagia due to palsies of the last four cranial nerves by tumor compression on the brainstem developed febrile neutropenia and succumbed to subsequent aspiration pneumonia 7 weeks after completion of induction chemotherapy and concurrent chemoradiation, despite feeding tube insertion, potent broad-spectrum antibiotics, and aggressive ventilation support. His plasma EBV DNA was normalized after completion of chemotherapy and start of concurrent chemoradiation
Summary
The prognostic role of plasma Epstein–Barr virus (EBV) DNA clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered. Its clearance and prognostic role after salvage surgery for recurrent NPC was investigated [16, 17] All of these studies were conducted long time ago when old radiation techniques and the earlier editions of AJCC/UICC staging classification were still used. The prognostic roles of plasma EBV DNA measured at the beginning, in the midcourse, and after treatment have been evaluated in IMRT era, there has been hitherto no publications with reference to the impact of its halftime clearance (which necessitates more frequent measurement) on survival in patients staged and treated in IMRT era and the current edition of AJCC/UICC staging classification [18,19,20,21,22,23]
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