scholarly journals Subdivision of de novo metastatic nasopharyngeal carcinoma based on tumor burden and pretreatment Epstein-Barr virus DNA for therapeutic guidance of primary tumor radiotherapy

Author(s):  
Jin-Hao Yang ◽  
Xue-Song Sun ◽  
Bei-Bei Xiao ◽  
Li-Ting Liu ◽  
Shan-Shan Guo ◽  
...  

Abstract Purpose: To improve individualized treatment of de novo metastatic nasopharyngeal carcinoma (dmNPC) patients by investigating prognostic factors and identifying patients who achieved better survival outcomes after locoregional radiotherapy (LRRT).Materials and methods: Our study included a cohort of 498 dmNPC patients. Overall survival (OS) was the primary endpoint. We analyzed the correlation of all potential prognostic factors and survival outcomes by Kaplan-Meier survival curves using log-rank test and Cox proportional hazards regression model.Results: Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, we successfully divided all patients into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-RT groups, we found statistical differences in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT was a protective factor only for the low- and intermediate-risk subgroups.Conclusions: The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin-Hao Yang ◽  
Xue-Song Sun ◽  
Bei-Bei Xiao ◽  
Li-Ting Liu ◽  
Shan-Shan Guo ◽  
...  

Abstract Background Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80–90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified. Results Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups. Conclusions The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xue-Song Sun ◽  
Yu-Jing Liang ◽  
Sai-Lan Liu ◽  
Qiu-Yan Chen ◽  
Shan-Shan Guo ◽  
...  

Abstract Background This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. Methods From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. Result Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. Conclusion In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.


2020 ◽  
Vol 10 ◽  
Author(s):  
Joo Young Ha ◽  
Hyungwoo Cho ◽  
Heungsup Sung ◽  
Ah Ra Jung ◽  
Yoon Sei Lee ◽  
...  

BackgroundExtranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes.MethodsWe analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion.ResultsEBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79–9.97; P=0.001) and OS (HR, 8.38; 95% CI, 3.03–23.19; P&lt;0.001) in the multivariate analysis. After treatment completion, positivity of plasma-EBV was independently associated with poor PFS (HR, 9.41; 95% CI, 2.27–39.02; P=0.002) and OS (HR, 32.38; 95% CI, 3.25–322.56; P=0.003), whereas no significant association was observed between WB-EBV status and survival outcomes.ConclusionsOur results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL.


Head & Neck ◽  
2011 ◽  
Vol 34 (8) ◽  
pp. 1064-1070 ◽  
Author(s):  
Cheng-Lung Hsu ◽  
Kai-Ping Chang ◽  
Chien-Yu Lin ◽  
Hsien-Kun Chang ◽  
Cheng-Hsu Wang ◽  
...  

2000 ◽  
Vol 111 (1) ◽  
pp. 239-246 ◽  
Author(s):  
Kenny I. K. Lei ◽  
Lisa Y.S. Chan ◽  
Wing Y. Chan ◽  
Philip J. Johnson ◽  
Y. M. Dennis Lo

Author(s):  
S.I. Kutukova ◽  
A.B. Chukhlovin ◽  
A.I. Yaremenko ◽  
Yu.V. Ivaskova ◽  
A.Ya. Razumova ◽  
...  

The aim of the study was to assess the prevalence of DNA viruses (HSV I and II, CMV, EBV, HPV6.11, HPV16 and HPV18) in the native oral mucosa of healthy volunteers (n=50; 30 men (60.0%), 20 women (40.0%); 25—74 years, median age — 55.0 years (95% CI 47.60-56.76)). All samples of the normal oral mucosa were detected by real-time PCR to detect viral DNA. The majority of the examined — 76% (33/50) — revealed the DNA: one type of viral DNA in 17 (38.00%) of the examined, a combination of the two types in 14 (28.00%). In the normal oral mucosa, DNA of Epstein-Barr virus was significantly more often detected: 15 (30.00%) (p = 0.0276) and human papilloma viruses 27 (54.00%) (p <0.0001), especially HPV-18 (24 (48.00%)): mono-association in 9 (18.00%) examined and in 7 (14.00%) in combination with EBV DNA (p = 0.0253).


2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-Jie Chen ◽  
Wen-Na Xu ◽  
Hai-Yun Wang ◽  
Xiao-Xia Chen ◽  
Xue-Qi Li ◽  
...  

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.


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