ABSTRACT
BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18â237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.
Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Antibodies, Viral , DNA , DNA, Viral , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/genetics , Humans , Immunoglobulin A , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Neoplasms/diagnosis , Nasopharynx , Reflex , TriageABSTRACT
Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.
ABSTRACT
BACKGROUND 18Fluoro-fluorodeoxyglucose (FDG)- based positron-emission computed tomography (PET) has less specificity for noncalcified nodules (NNs). Somatostatin receptors affect the expression of normal and malignant cells. The purpose of the study was to compare the sensitivity, specificity, and accuracy of 68Gallium-tagged DOTA-octreotate (Ga-tDO) with that of FDG PET for diagnosis of newly detected and/or untreated NNs in lung cancer patients. MATERIAL AND METHODS A total of 45 patients with lung cancer were included in the cross-sectional study and underwent Ga-tDO and FDG PET. We further confirmed observed outcomes by testing immune histochemical staining for subtype 2A of somatostatin receptor in a granuloma tissue array. The chi-square test was performed for sensitivity and specificity of predictive values among the 3 diagnostic modalities. McNemar's test was performed to compare accuracy between Ga-tDO and FDG PET. Results were considered significant at 95% confidence level. RESULTS Ga-tDO had less sensitivity (69% vs. 89%) but more specificity (91% vs. 78%) than FDG PET. Ga-tDO and FDG PET were characterized as 36 and 6 and in 36 and 3 lesions as accurate and inaccurate, respectively. There was an insignificant difference between Ga-tDO and FDG PET regarding diagnostic accuracy (p=0.7). Dosimetry results showed that the lungs were one of the least critically affected organs. CONCLUSIONS Ga-tDO was more specific but less sensitive than FDG PET scanning and imaging.
Subject(s)
Contrast Media/chemistry , Lung Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Fluorodeoxyglucose F18/chemistry , Gallium , Heterocyclic Compounds, 1-Ring , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Multimodal Imaging , Organometallic Compounds , Positron-Emission Tomography , Receptors, Somatostatin , Sensitivity and Specificity , Somatostatin , Tomography, X-Ray Computed/methodsABSTRACT
Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.
ABSTRACT
In this article, a new distributed filtering problem is studied for a class of state-saturated time-varying systems over sensor networks under measurement censoring, where the censored measurements are described by the Tobit measurement model. To curb the data collision and ease communication burden, a random access protocol (RAP) is implemented onto the sensor-to-filter channels to orchestrate the transmission sequence of multiple sensor nodes. The purpose of the addressed problem is to construct a state-saturated distributed filter such that upper bounds (on filtering error covariances) are guaranteed and filter parameters are determined to accommodate both measurement censoring and state saturation under the RAP. By means of matrix difference equations, the desired upper bounds are first acquired and later minimized through appropriately designing filter parameters. Particularly, the sparsity issue with respect to the network topology is tackled via the employing certain matrix simplification technique. A simulation example is finally presented to showcase the applicability of the proposed state-saturated distributed filtering algorithm.
ABSTRACT
BACKGROUND: The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long-term based on a prospective cohort design. METHODS: A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA-IgA, EBNA1-IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non-NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE). RESULTS: With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46-6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07-6.23) for male and 3.75 (95%CI: 1.25-11.20) for female, respectively. Among the non-NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3-5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29-2.18) for VCA-IgA and 1.92 (95%CI: 1.42-2.59) for EBNA1-IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE. CONCLUSION: Smoking could significantly increase the long-term risk of NPC in southern China, partly by persistently reactivating EBV.