Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy
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 unde...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.01417/full |
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| author | Sik-Kwan Chan Sum-Yin Chan Horace Cheuk-Wai Choi Chi-Chung Tong Ka-On Lam Ka-On Lam Dora Lai-Wan Kwong Dora Lai-Wan Kwong Varut Vardhanabhuti To-Wai Leung To-Wai Leung Mai-Yee Luk Anne Wing-Mui Lee Anne Wing-Mui Lee Victor Ho-Fun Lee Victor Ho-Fun Lee |
| author_facet | Sik-Kwan Chan Sum-Yin Chan Horace Cheuk-Wai Choi Chi-Chung Tong Ka-On Lam Ka-On Lam Dora Lai-Wan Kwong Dora Lai-Wan Kwong Varut Vardhanabhuti To-Wai Leung To-Wai Leung Mai-Yee Luk Anne Wing-Mui Lee Anne Wing-Mui Lee Victor Ho-Fun Lee Victor Ho-Fun Lee |
| author_sort | Sik-Kwan Chan |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-12-21T17:46:16Z |
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| id | doaj.art-c3724f004dbb446880ac0f107ba4e9f3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T17:46:16Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c3724f004dbb446880ac0f107ba4e9f32022-12-21T18:55:30ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-08-011010.3389/fonc.2020.01417560590Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation TherapySik-Kwan Chan0Sum-Yin Chan1Horace Cheuk-Wai Choi2Chi-Chung Tong3Ka-On Lam4Ka-On Lam5Dora Lai-Wan Kwong6Dora Lai-Wan Kwong7Varut Vardhanabhuti8To-Wai Leung9To-Wai Leung10Mai-Yee Luk11Anne Wing-Mui Lee12Anne Wing-Mui Lee13Victor Ho-Fun Lee14Victor Ho-Fun Lee15Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaClinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaClinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaDepartment of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaClinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaClinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaClinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaIntroduction: 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).https://www.frontiersin.org/article/10.3389/fonc.2020.01417/fullnasopharyngeal carcinomaintensity-modulated radiation therapyplasma Epstein–Barr virus deoxyribonucleic acidhalf-life clearanceprognostication |
| spellingShingle | Sik-Kwan Chan Sum-Yin Chan Horace Cheuk-Wai Choi Chi-Chung Tong Ka-On Lam Ka-On Lam Dora Lai-Wan Kwong Dora Lai-Wan Kwong Varut Vardhanabhuti To-Wai Leung To-Wai Leung Mai-Yee Luk Anne Wing-Mui Lee Anne Wing-Mui Lee Victor Ho-Fun Lee Victor Ho-Fun Lee Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy Frontiers in Oncology nasopharyngeal carcinoma intensity-modulated radiation therapy plasma Epstein–Barr virus deoxyribonucleic acid half-life clearance prognostication |
| title | Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy |
| title_full | Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy |
| title_fullStr | Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy |
| title_full_unstemmed | Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy |
| title_short | Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy |
| title_sort | prognostication of half life clearance of plasma ebv dna in previously untreated non metastatic nasopharyngeal carcinoma treated with radical intensity modulated radiation therapy |
| topic | nasopharyngeal carcinoma intensity-modulated radiation therapy plasma Epstein–Barr virus deoxyribonucleic acid half-life clearance prognostication |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.01417/full |
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