Prognostic value of gross tumor regression and plasma Epstein Barr Virus DNA levels at the end of intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma

Abstract

a b s t r a c tPurpose: To assess gross tumor regression and plasma Epstein-Barr virus (EBV)-DNA levels at the end of intensity-modulated radiation therapy (IMRT) and its prognostic impact on patients with nasopharyngeal carcinoma (NPC). Participants and Methods: In total, 397 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients underwent magnetic resonance imaging of the nasopharynx and neck, and plasma EBV DNA assays before treatment and at the end of IMRT. Results: The estimated 5-year loco-regional, local and regional relapse-free survival rates for patients with complete response (CR) and non-CR of the total tumor, primary tumor and metastatic lymph nodes at the end of IMRT were 94.9% vs. 85.8%, 96.6% vs. 87.3%, and 98.7% vs. 89.8%, respectively (P < 0.05). The estimated 5-year loco-regional relapse-free survival (LRRFS) rates for patients with persistent tumor with and without boost irradiation were 95.3% vs. 83%, respectively (P = 0.034). The estimated 5-year overall survival (OS), failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates for patients with negative and positive plasma EBV DNA at the end of IMRT were 83.1% vs. 50.3%, 81.5% vs. 49.3%, and 87.6% vs. 61.5%, respectively (P < 0.001). Multivariate analyses indicated that regression of the total tumor and boost irradiation was an independent predictor of LRRFS, and plasma EBV DNA levels were independent predictors of OS, FFS and DMFS. Conclusions: Gross tumor regression and plasma EBV DNA levels at the end of IMRT served as predictors of poor prognosis for patients with NPC. The patients with persistent tumor and/or positive plasma EBV DNA might require timely strengthening treatment. Ó 2018 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 132 (2019) 223-229 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Radical radiotherapy (RT) is the first treatment option for nonmetastatic nasopharyngeal carcinoma (NPC). Intensity-modulated radiation therapy (IMRT) was a milestone development in RT technology, as IMRT can provide a high conformal radiation dose to the tumor target area while effectively decreasing the dose to the sur-rounding normal tissues. IMRT, instead of 2-dimensional RT (2-DRT) and 3-dimensional conformal RT (3-DCRT), is currently more commonly used to treat NPC, due to the associated better tumor control and lower RT-related toxicities [1][2][3][4][5]. The 5-year overall survival (OS), 5-year local relapse-free survival (LRFS), 5-year regional relapse-free survival (RRFS), and 5-year distant metastasis-free survival (DMFS) rates of patients with NPC treated with IMRT ranged from 74% to 84%, 83% to 95%, 91% to 97%, and 83.3% to 85.6%, respectively [6][7][8][9][10].Both loco-regional relapse and distant metastasis are the main reasons of treatment failure in patients with NPC [6-10]. Due to the poor survival of patients with loco-regional relapse and distant metastasis, some effective the...

Prognostic Value of Plasma Epstein-Barr Virus DNA Levels Pre- and Post-Neoadjuvant Chemotherapy in Patients With Nasopharyngeal Carcinoma

“…EBV infection is associated with an increased risk of NPC (9)(10)(11)(12). The relationship between the EBV DNA levels and the prognosis of patients at different stages of treatment has also been reported (13)(14)(15)(16). Pre-treatment and post-treatment EBV DNA levels are considered as an indicator of tumor load and tumor malignancy.…”

“…Additionally, post-radiotherapy EBV DNA levels in the plasma of patients with NPC predicted locoregional failure, distant metastasis, and death ( 20 ). Post-treatment plasma EBV DNA levels also predicted distant metastasis ( 21 ) and tumor recurrence ( 22 ); thus, additional treatment in patients with high post-treatment EBV DNA levels may prevent relapse ( 14 ). Many NPC prognostic models are based on the EBV characteristics and serological indicators ( 19 , 23 , 24 ).…”

Effects of oral maintenance chemotherapy and predictive value of circulating EBV DNA in metastatic nasopharyngeal carcinoma

“…Circulating EBV DNA derived from tumors could be regarded as an archetypal circulating tumor DNA . The prognostic value of EBV‐DNA at pretreatment and posttreatment time points is clearly established in NPC . Changes in EBV‐DNA can reflect dynamic changes in tumor burden in NPC and are more effective than imaging for monitoring .…”

Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy

“…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. Although 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).…”