Selectively recommend 18F-FDG PET/CT for patients with de novo nasopharyngeal carcinoma in endemic areas.

INTRODUCTION: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [18F] fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas. MATERIALS AND METHODS: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed. RESULTS: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group. CONCLUSIONS: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

Importance: Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. Objective: To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. Design, Setting, and Participants: This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Exposures: Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. Main Outcomes and Measures: The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. Results: A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. Conclusions and Relevance: An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

Comparison of Epstein-Barr Virus Serological Tools for the Screening and Risk Assessment of Nasopharyngeal Carcinoma: a Large Population-based Study.

Epstein-Barr virus (EBV)-based serologic antibody testing has been found to be a feasible alternative for nasopharyngeal carcinoma (NPC) screening in endemic areas. The purpose of this study was to evaluate the performance of ELISA based on VCA IgA antibody, EA-IgA and Rta-IgG antibody specific to EBV in the diagnosis of NPC. A total of 2155 untreated NPC patients and 6957 healthy volunteers without nasopharyngeal disorder were recruited, and all subjects received EBV VCA-IgA, EA-IgA and Rta-IgG antibody tests simultaneously. The diagnostic efficiency of three testing alone or in combination for the diagnosis of NPC was evaluated. The prevalence of IgA antibody against EBV-VCA, IgA antibody against EBV-EA and IgG antibody against EBV-Rta was 89.9%, 46.6% and 63.2%. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 89.88%, 89.65%, 73.18%, 96.63% and 0.79 for the EBV VCA-IgA antibody test, 46.59%, 96.89%, 82.5%, 85.42% and 0.43 for the EA-IgA antibody test, and 63.25%, 94.87%, 79.48%, 89.29% and 0.58 for the Rta-IgG antibody test in the diagnosis of NPC, and ROC curve analysis revealed the greatest diagnostic efficiency for EBV VCA-IgA antibody test and the lowest efficiency for EBV EA-IgA antibody test in the diagnosis of NPC. In addition, the simultaneous triple positivity of VCA-IgA, EA-IgA and Rta-IgG antibodies specific to EBV indicated the highest risk of NPC, and the simultaneous triple negativity of the three types of anti-EBV antibodies suggested the lowest risk of NPC. Our data demonstrate that EBV VCA-IgA antibody test shows a higher diagnostic efficiency than EA-IgA and Rta-IgG antibody tests for the screening of NPC, and triple positivity of is a better biomarker for the diagnosis of NPC.

Hopkins criteria for residual disease assessment after definitive radiotherapy in nasopharyngeal carcinoma.

OBJECTIVES: Assessment of viable tumor residue after definitive radiotherapy is essential in patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the use of Hopkins criteria on positron emission tomography/computed tomography (PET/CT) for posttreatment response evaluation and whether plasma Epstein-Barr virus (EBV) DNA could bring additional value. MATERIALS AND METHODS: NPC patients who underwent FDG-PET/CT scan within 26 weeks after definitive radiotherapy were retrospectively reviewed. Residual disease was evaluated by Hopkins 5-point score. Accuracy of Hopkins criteria before and after incorporating EBV DNA was calculated. Prognostic value for locoregional failure-free survival (LRFFS) and disease-free survival (DFS) was analyzed. RESULTS: One hundred and sixteen patients were evaluated. Median follow-up time was 28.3 months (range 3.3-92.0 months). Residual disease was found in 19 (16.4%) patients. Overall, Hopkins criteria had high specificity (86.6%; 95% CI, 78.2%-92.7%) and negative prognostic value (NPV) (94.4%; 95% CI, 88.7%-97.3%), while sensitivity and positive prognostic value (PPV) was 73.7% (95% CI, 48.8%-90.9%), 51.9% (95% CI, 37.8%-65.6%), respectively. Posttreatment plasma EBV DNA was not predictive of residual tumor (P = .272). PPV and accuracy were 50.0% (95% CI, 32.1%-67.9%) and 83.0% (95% CI, 73.8%-90.0%) after incorporating detectable EBV DNA into the scoring system. Positive PET/CT results were significantly correlated with inferior 3-year LRFFS (95.7% vs 79.5%, P = .043) and 3-year DFS (84.6% vs 54.4%, P = .028). CONCLUSIONS: The Hopkins criteria demonstrated high NPV and specificity in posttreatment assessment, with the potential to be a reliable prognostic indicator for locoregional failure. Combining EBV DNA with PET/CT did not improve diagnostic accuracies. PET/CT should not be performed less than 12 weeks after treatment.