Integrating Postradiotherapy MRI-Detected Lymph Node Necrosis and Pre- and Posttreatment Epstein-Barr Virus-DNA for Risk Stratification in Nasopharyngeal Carcinoma.

Residual lymphadenopathy and detectable Epstein-Barr virus (EBV) DNA after radiotherapy (RT) are known negative prognostic factors for nasopharyngeal carcinoma (NPC). However, there is a need to distinguish between patients with residual disease that will metastasize and those who will not. To develop a prognostic model to improve the risk stratification of NPC patients after RT. Retrospective. Three hundred eighty-seven NPC patients treated with RT between January 2010 and January 2013. T1-, T2-weighted and enhanced T1-weighted imaging at 1.5 or 3.0 T pretreatment and 3-4 months post-RT. Post-RT central nodal necrosis (CNN) and other nodal characteristics on MRI were assessed by three radiologists independently. EBV DNA was measured by quantitative polymerase chain reaction. The association between these variables and the primary endpoint (5-year distant metastasis-free survival [DMFS], time from the day of diagnosis to any distant metastasis) was analyzed. Nomograms A (pre-/posttreatment EBV-DNA + N stage + post-RT retropharyngeal lymph node [RLN] CNN), B (tumor-node-metastasis [TNM] stage + pretreatment EBV-DNA), and C (TNM stage + post-RT EBV-DNA) were developed. Univariate and multivariate analyses were performed with the Cox regression model. Nomograms were developed based on the Cox regression model and two prognostic models. The concordance index (C-index) and calibration curve were used to evaluate the discriminative ability of the nomograms and TNM stage. P-values < 0.05 were considered statistically significant. Post-RT RLN CNN was an independent prognostic factor for 5-year DMFS (hazard ratio, 2.88 [1.48-5.62]). Nomogram A (C-index 0.728 [0.660-0.797]) demonstrated better risk discrimination than nomogram B (0.638 [0.571-0.705]), nomogram C (0.707 [0.636-0.778]), and the TNM stage (0.587 [0.515-0.659]) for 5-year DMFS in NPC. Nomogram A combining pretreatment EBV-DNA and N stage with post-RT EBV-DNA and RLN CNN improved the prognostic risk stratification for DMFS in NPC. 4 TECHNICAL EFFICACY: Stage 2.

Cao D ，Li S ，Li H ，Liu L ，Wang X ，Quan T ... -  《-》

Integrating pretreatment MRI-detected nodal features and Epstein-Barr virus DNA to identify optimal candidates for intensity-modulated radiotherapy alone in patients with stage II nasopharyngeal carcinoma.

To develop and validate a prognostic nomogram based on MRI-detected features of retropharyngeal and cervical lymph nodes and Epstein-Barr virus (EBV) DNA in patients with stage II nasopharyngeal carcinoma (NPC) to distinguish low-risk patients for whom intensity-modulated radiotherapy (IMRT) alone is sufficient. This retrospective study enrolled 894 patients with stage II NPC (596 and 298 in the training and validation cohorts, respectively) with pretreatment MRI between August 2010 and May 2019. All patients received IMRT with or without additional chemotherapy. We identified independent risk factors using univariate and multivariate Cox regression analyses. Survival was compared using Kaplan-Meier curves with the log-rank test. Independent factors derived from the multivariate analysis include cervical nodal necrosis (CNN), the extracapsular spread (ECS) of cervical and retropharyngeal lymph nodes, and gamma-glutamyl transferase (γ-GGT). Nomograms A, B, and C were established based on the clinical [tumor-node-metastasis (TNM) stage + Epstein-Barr virus (EBV) DNA], the clinical-radiological [all independent predictors] and the combined models [the clinical-radiological model + EBV DNA], respectively. Nomogram C (C-index 0.769 [0.718-0.820]) demonstrated better risk discrimination than nomogram B (0.762 [0.715-0.809]), nomogram A (0.619 [0.564-0.674]), and the TNM stage (0.560 [0.509-0.611]). In the low-risk group divided by nomogram C, no significant survival differences were observed between patients treated with radiotherapy (RT) alone and other regimens including additional chemotherapy. The nomogram combining MRI-detected retropharyngeal and cervical lymph node features with pretreatment EBV-DNA improved the prognostic risk stratification for stage II NPC.

Guo J ，He Y ，Lin C ，Jiang Q ，Xing HW ，Zhang YC ，Shen GZ ，Lin HX ，Guo L ，Yang Q ... -  《-》

Integrating postradiotherapy plasma Epstein-Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy.

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. 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. 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 II (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. Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.

Hui 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 ... -  《-》

Proposed modifications and incorporation of plasma Epstein-Barr virus DNA improve the TNM staging system for Epstein-Barr virus-related nasopharyngeal carcinoma.

The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA >2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance. The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

Guo R ，Tang LL ，Mao YP ，Du XJ ，Chen L ，Zhang ZC ，Liu LZ ，Tian L ，Luo XT ，Xie YB ，Ren J ，Sun Y ，Ma J ... -  《-》

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma.

Yao JJ ，Zhou GQ ，Wang YQ ，Wang SY ，Zhang WJ ，Jin YN ，Zhang F ，Li L ，Liu LZ ，Cheng ZB ，Ma J ，Qi ZY ，Sun Y ... -  《-》