Integrating postradiotherapy plasma Epstein–Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy
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AbstractBackground: After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein-Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor-lymph node-metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy.

Patients and methods: The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n= 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II-IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death.

Results: Combining post-RT EBV DNA level (0, 1-49, 50-499, and >= 500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage 0 (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts.

Conclusion: Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.
All Author(s) ListHui EP, Li WF, Ma BB, Lam WKJ, Chan KCA, Mo F, Ai QYH, King AD, Wong CH, Guo R, Poon DMC, Tong M, Li L, Lau TKH, Wong KCW, Lam DCM, Lo YMD, Ma J, Chan ATC
Journal nameAnnals of Oncology
Year2020
Month6
Volume Number31
Issue Number6
Pages769 - 779
ISSN0923-7534
eISSN1569-8041
LanguagesEnglish-United States
Keywordsnasopharyngeal carcinoma, plasma Epstein–Barr virus DNA, recursive-partitioning analysis, risk stratification, TNM stage

Last updated on 2020-12-09 at 00:04