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Lymph-node Epstein–Barr virus concentration in diagnosing cervical lymph-node metastasis in nasopharyngeal carcinoma

September 2020
European Archives of Oto-Rhino-Laryngology 277(6)

September 2020
277(6)

Authors:

PurposeCervical lymph-node (CLN) metastasis commonly occurs in patients with nasopharyngeal carcinoma (NPC) metastasis. The presence of Epstein–Barr virus (EBV) genomes in neck lymph nodes may diagnose CLN. This research was designed to appraise the diagnostic value of EBV concentration for cervical lymph nodes in NPC.Methods Two hundred and fifty-three NPC patients with 276 CLNs were enrolled. MRI was performed to detect CLN metastasis, and plasma EBV concentration was measured by quantitative PCR before treatment. Ultrasonography (US) and US-FNA were subsequently performed in the suspicious lymph nodes. Fifteen patients (22 lymph nodes) underwent fine-needle aspiration cytology (FNAC), and the remaining 242 patients (254 lymph nodes) underwent core needle biopsy (CNB) for CLNs at the clinician’s demand. The aspiration needle was rinsed with 1 ml of normal saline for EBV detection. The method of lymph-node EBV measurement was consistent with that for plasma. The MRI results and EBV concentrations in plasma and lymph nodes were recorded and analyzed. Plasma EBV concentrations ≥ 4000 copies/ml were regarded as positive.ResultsCLN-EBV concentrations ≥ 787.5 copies/ml were regarded as positive according to receiver-operating characteristic curve analysis. The AUC of the EBV (0.925) concentration in CLN metastasis was significantly larger than the AUC of MRI (0.714) (P < 0.001). The sensitivity and specificity were 94.09% and 48.72% for MRI in lymph-node metastasis and 95.36% (P > 0.05) and 84.62% (P < 0.01) for EBV DNA in CLN metastasis, respectively. The sensitivity and specificity of EBV in plasma were 77.2% and 71.8%, respectively. The diagnostic specificity and AUC of EBV in CLNs were higher than those of MRI and plasma EBV (P < 0.005).Conclusions Ultrasound-guided CLN FNA to obtain EBV concentrations may provide a new method to diagnose CLN metastasis with high sensitivity and specificity.

ROC curve analysis of different methods for the diagnosis of CLN metastasis in patients with NPC

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Vol.:(0123456789)

1 3

European Archives of Oto-Rhino-Laryngology (2020) 277:2513–2520

https://doi.org/10.1007/s00405-020-05937-5

HEAD ANDNECK

Lymph‑node Epstein–Barr virus concentration indiagnosing cervical

lymph‑node metastasis innasopharyngeal carcinoma

HuiFangLi1· CanHuang1,2· QiuyanChen3· ChuanPeng1· RongZhang4· JingxianShen4· MingyuanChen3·

HaiqiangMai3· RuhaiZou1

Received: 1 December 2019 / Accepted: 18 March 2020 / Published online: 2 April 2020

Abstract

Purpose Cervical lymph-node (CLN) metastasis commonly occurs in patients with nasopharyngeal carcinoma (NPC) metas-

tasis. The presence of Epstein–Barr virus (EBV) genomes in neck lymph nodes may diagnose CLN. This research was

designed to appraise the diagnostic value of EBV concentration for cervical lymph nodes in NPC.

Methods Two hundred and ﬁfty-three NPC patients with 276 CLNs were enrolled. MRI was performed to detect CLN metas-

tasis, and plasma EBV concentration was measured by quantitative PCR before treatment. Ultrasonography (US) and US-

FNA were subsequently performed in the suspicious lymph nodes. Fifteen patients (22 lymph nodes) underwent ﬁne-needle

aspiration cytology (FNAC), and the remaining 242 patients (254 lymph nodes) underwent core needle biopsy (CNB) for

CLNs at the clinician’s demand. The aspiration needle was rinsed with 1ml of normal saline for EBV detection. The method

of lymph-node EBV measurement was consistent with that for plasma. The MRI results and EBV concentrations in plasma

and lymph nodes were recorded and analyzed. Plasma EBV concentrations ≥ 4000 copies/ml were regarded as positive.

Results CLN-EBV concentrations ≥ 787.5 copies/ml were regarded as positive according to receiver-operating characteristic

curve analysis. The AUC of the EBV (0.925) concentration in CLN metastasis was signiﬁcantly larger than the AUC of MRI

(0.714) (P < 0.001). The sensitivity and speciﬁcity were 94.09% and 48.72% for MRI in lymph-node metastasis and 95.36%

(P > 0.05) and 84.62% (P < 0.01) for EBV DNA in CLN metastasis, respectively. The sensitivity and speciﬁcity of EBV in

plasma were 77.2% and 71.8%, respectively. The diagnostic speciﬁcity and AUC of EBV in CLNs were higher than those

of MRI and plasma EBV (P < 0.005).

Conclusions Ultrasound-guided CLN FNA to obtain EBV concentrations may provide a new method to diagnose CLN

metastasis with high sensitivity and speciﬁcity.

Keywords Lymph-node metastasis· Epstein–Barr virus· Nasopharyngeal carcinoma· Cervical lymph-node metastasis·

Fine-needle aspiration

Abbreviations

CLN Cervical lymph node

NPC Nasopharyngeal carcinoma

EBV Epstein-Barr virus

FNAC Fine-needle aspiration cytology

FNA Fine-needle aspiration

PCR Polymerase chain reaction

IMRT Intensity-modulated radiotherapy

* Haiqiang Mai

maihq@sysucc.org.cn

* Ruhai Zou

zourh@sysucc.org.cn

1 State Key Laboratory ofOncology inSouth China,

Department ofUltrasound, Collaborative Innovation Center

ofCancer Medicine, Sun Yat-Sen University Cancer Center,

Guangzhou510060, Guangdong, People’sRepublicofChina

2 Kanghua Hospital, Dongguan523039, Guangdong,

People’sRepublicofChina

3 State Key Laboratory ofOncology inSouth China,

Department ofNasopharyngeal Carcinoma, Collaborative

Innovation Center ofCancer Medicine, Sun Yat-Sen

University Cancer Center, Guangzhou510060, Guangdong,

People’sRepublicofChina

4 State Key Laboratory ofOncology inSouth China,

Department ofRadiology, Collaborative Innovation Center

ofCancer Medicine, Sun Yat-Sen University Cancer Center,

Guangzhou510060, Guangdong, People’sRepublicofChina

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Recurrence risk stratification based on Epstein–Barr virus DNA to identify enlarged retropharyngeal lymph nodes of nasopharyngeal carcinoma: A model-histopathologic correlation study

Article

Full-text available

Dec 2022

Background Accurate assessment of the nature of enlarged retropharyngeal lymph nodes (RLN) of nasopharyngeal carcinoma (NPC) patients after radiotherapy is related to selecting appropriate treatments and avoiding unnecessary therapy. This study aimed to develop a non-invasive and effective model for predicting the recurrence of RLN (RRLN) in NPC. Materials and methods The data of post-radiotherapy NPC patients ( N = 76) with abnormal enlargement of RLN who underwent endonasopharyngeal ultrasound-guided fine-needle aspirations (EPUS-FNA) were examined. They were randomly divided into a discovery ( n = 53) and validation ( n = 23) cohort. Univariate logistic regression was used to assess the association between variables (magnetic resonance imaging characteristics, EBV DNA) and RRLN. Multiple logistic regression was used to construct a prediction model. The accuracy of the model was assessed by discrimination and calibration, and decision curves were used to assess the clinical reliability of the model for the identification of high risk RLNs for possible recurrence. Results Abnormal enhancement, minimum axis diameter (MAD) and EBV-DNA were identified as independent risk factors for RRLN and could stratify NPC patients into three risk groups. The probability of RRLN in the low-, medium-, and high-risk groups were 37.5, 82.4, and 100%, respectively. The AUC of the final predictive model was 0.882 (95% CI: 0.782–0.982) in the discovery cohort and 0.926 (95% CI, 0.827–1.000) in the validation cohort, demonstrating good clinical accuracy for predicting the RRLN of NPC patients. The favorable performance of the model was confirmed by the calibration plot and decision curve analysis. Conclusion The nomogram model constructed in the study could be reliable in predicting the risk of RRLN after radiotherapy for NPC patients.

Recurrence risk stratification using radiologic-EBV DNA to identify enlarged retropharyngeal lymph nodes of nasopharyngeal carcinoma: a model-histopathologic correlation study

Preprint

Full-text available

Apr 2022

Background Accurate assessment of the nature of enlarged retropharyngeal lymph nodes (RLN) of nasopharyngeal carcinoma (NPC) patients after radiotherapy is essential for planning the treatment. This study aimed to develop a non-invasive and effective model for predicting the recurrence of RLN (RRLN) in NPC. Methods The data of post-radiotherapy NPC patients (N = 76) with abnormal enlargement of RLN who underwent endonasopharyngeal ultrasound-guided fine-needle aspirations (EPUS-FNA) were examined. They were randomly divided into a discovery (n = 53) and validation (n = 23) cohort. Univariate logistic regression was used to assess the association between variables (magnetic resonance imaging characteristics, EBV DNA) and RRLN. Multiple logistic regression was used to construct a prediction model. The accuracy of the model was assessed by discrimination and calibration, and decision curves were used to assess the clinical reliability of the model to assist decision-making. Results Abnormal enhancement, minimum axis diameter (MAD) and EBV-DNA were identified as independent risk factors for RRLN and could stratify NPC patients into three risk groups. The probability of RRLN in the low-, medium- and high-risk groups were 37.5%, 82.4%, and 100%, respectively. The AUC of the final predictive model was 0.882 (95% CI:0.782–0.982) in the discovery cohort and 0.926 (95% CI,0.827–1.000) in the validation cohort, demonstrating good clinical accuracy for predicting the RRLN of NPC patients. The favorable performance of the model was confirmed by the calibration plot and decision curve analysis. Conclusions The proposed radiologic and EBV DNA model to predict the RRLN of NPC patients after radiotherapy could be a valuable tool for clinical decision-making.

Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma

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Determining the suitability of definitive radiation therapy in patients with metastatic nasopharyngeal carcinoma based on PET/CT: a large cohort study

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EUR RADIOL

Objectives To determine patients with de novo metastatic nasopharyngeal carcinoma (mNPC) who would benefit from receiving definitive radiation therapy (DRT) along with their pre-existing palliative chemotherapy (PCT) by evaluating their post-PCT Deauville scores and EBV DNA.MethodsA total of 570 mNPC patients, treated with PCT or PCT+DRT, were studied. EBV DNA levels, along with post-PCT Deauville scores, were used to stratify risk based on the recursive partitioning analysis (RPA).ResultsSignificant differences were observed in the survival rates of patients with Deauville scores of 1–3 and 4–5 (2-year progression-free survival (PFS): 23.4% versus 8.5%, p < 0.001; 2-year overall survival (OS): 56.8% versus 18.8%, p < 0.001). RPA yielded three distinct groups in the increasing order of risk (Deauville scores of all RPA I-II were within the range of 1–3): (1) RPA I: EBV DNA levels at a pretreatment concentration ≤ 4000 copies/mL and undetectable post-PCT; (2) RPA II: EBV DNA levels either at a pretreatment concentration > 4000 copies/mL or at a pretreatment concentration ≤ 4000 copies/mL and detectable post-PCT; (3) RPA III: Deauville scores 4–5. While patients in RPA I and RPA II had significantly PFS rates when treated with PCT+DRT than when treated with PCT alone (RPA I: 72.7% versus 13.4%, RPA II: 37.8% versus 6.3%), those in RPA III did not experience such PFS benefits (6.5% versus 9.7%).ConclusionPCT+DRT might improve the survival rates in mNPC patients in the low- and mid-risk strata but not those of patients in the high-risk strata.Key Points We use the Deauville scores and the concentrations of the Epstein-Barr virus (EBV) DNA to determine those patients with de novo metastatic NPC who would benefit from radiation therapy.

Management of first‐line palliative chemotherapy for post‐treatment metastasis after gemcitabine plus cisplatin induction chemotherapy: Gemcitabine plus cisplatin and non‐gemcitabine plus cisplatin chemotherapy

Article

Oct 2021

Background To evaluate whether patients with post-treatment metastasis are suitable for GP first-line palliative chemotherapy (PCT) after undergoing GP IC. Methods Seven hundred and forty-six patients with post-treatment metastasis after undergoing GP IC were eligible. Survival outcomes were compared. Results Significant differences in survival rates were observed between patients treated with GP and non-GP chemotherapy (2-year progression-free survival [PFS]: 0.7% vs. 9.7%). We investigated survival outcomes of patients treated with GP PCT within 2 years after undergoing GP IC, treated with GP PCT 2 years after undergoing GP IC, and those of non-GP PCT patients (2-year PFS: 0.0%, 2.3%, 9.7%). However, there was no difference in the 2-year PFS between the patients that received GP PCT 2 years after undergoing GP IC and the non-GP PCT treated patients. Conclusions GP is not recommended for patients that have received GP IC within 2 years. Two years after undergoing GP IC, GP can be considered.

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

Article

Full-text available

Oct 2018
CANCER-AM CANCER SOC

Background 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. Methods 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. Results 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. Conclusions 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.

The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification

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Full-text available

Dec 2018
INT J CANCER

The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity‐modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein–Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five‐year progression‐free survival (PFS), overall survival (OS) and cancer‐specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA‐I (T1–T4 N0–N2 & EBV DNA <500 copies per mL; PFS 94%, OS 89%, CSS 96%), RPA‐II (T1–T4 N0–N2 & EBV DNA ≥500 copies per mL; PFS 80%, OS 83%, CSS 89%), RPA‐III (T1–T2 N3; PFS 64%, OS 83%, CSS 83%) and RPA‐IVA (T3–T4 N3; PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1–T2 N0–N2; II: T3–T4 N0–N2 or T1–T2 N3 and III: T3–T4 N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA‐based stage groups revealed better survival prediction compared to the eighth edition TNM and the AHR stage groups.

The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels

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Aug 2017
Radiat Oncol

Background: Level IB metastasis is rare in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the high-risk factors for level IB metastasis and evaluate the feasibility of omission of elective irradiation to level IB in the low-risk subgroups in NPC. Methods: This retrospective study identified 532 patients with NPC treated by definitive radiation in our institution from 2009 to 2010. Level IB nodes were electively irradiated based on the physician’s decision. Diagnostic head and neck MRIs were reviewed. The involvements of nodal levels were evaluated according to 2013 updated guidelines of RTOG. The correlation of level IB metastasis and other factors were studied using Chi-square test and logistic regression model. Log-rank test was used to compare survival rates. Cox proportional-hazards models were used to evaluate the effect of various factors. Patient-reported xerostomia was recoded in every follow-up and the delayed xerostomia at one year post-radiation were compared between those with/without elective level IB irradiation. Results: N stage, bilateral nodal metastasis, level II involvement, level IIA involvement, level IIA with multiple levels involvement, maximal axial diameter (MAD) of level IIA nodes >20mm, MAD of neck lymph nodes >30mm, necrosis of level IIA nodes, extracapsular spread of level IIA correlated with level IB metastasis by univariate analysis. In multivariate analysis (MVA), bilateral nodal involvement, MAD of level IIA nodes >20mm or extracapsular spread of level IIA nodes, were independent predictive factors for level IB metastasis. Patients without either these factors were denoted low-risk group and the rest high-risk group. Of the low-risk group, there was no significant difference of regional control and overall survival (OS) between those with or without elective irradiation. The percentage of level IB recurrence of those without elective irradiation was 0.46%. Elective level IB irradiation was not significant upon MVA both for regional control and OS. Of the high-risk group, elective level IB irradiation was marginal significant for regional control, but not for OS upon MVA. No regional recurrence located at level IB. Overall, omission of elective irradiation to level IB reduced the mean doses of submandibular glands, but did not improve patient-reported xerostomia. Conclusion: For patients without high-risk factors of level IB metastasis, omission of elective level IB irradiation did not impair regional control and OS in NPC.

Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer

Article

Full-text available

Aug 2017

Background Circulating cell-free Epstein–Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. Methods We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). Results A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively. Conclusions Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399.)

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries: Global Cancer Statistics 2018

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Sep 2018
CA-CANCER J CLIN

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high‐quality cancer registry data, the basis for planning and implementing evidence‐based cancer control programs, are not available in most low‐ and middle‐income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1‐31. © 2018 American Cancer Society

Outlooks on Epstein-Barr Virus Associated Gastric Cancer

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Mar 2018
CANCER TREAT REV

Epstein-Barr virus associated gastric cancer (EBVaGC) comprises approximately 10% of gastric carcinomas. Multiple factors contribute to tumorigenesis, including EBV driven hypermethylation of tumor suppressor genes, inflammatory changes in gastric mucosa, host immune evasion by EBV and changes in cell cycle pathways. The unique molecular characteristics of EBVaGC, such as programmed death ligand 1 (PD-L1) overexpression, highlight the potential for using EBV as a biomarker for response to immunotherapy. Few studies have reported benefit from immunotherapy in EBV positive cancers, and clinical trials investigating the impact of checkpoint inhibitors in EBVaGC are currently underway. This review provides the most recent updates on molecular pathophysiology, epidemiology, clinical features and treatment advances pertaining to EBVaGC.

International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma

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Nov 2017
RADIOTHER ONCOL

Purpose: Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome. Method: A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies. Results: Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration. Conclusion: Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients' factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery).

Current State of PCR-Based Epstein-Barr Virus DNA Testing for Nasopharyngeal Cancer

Article

Apr 2017
J NATL CANCER I

Clinical studies have shown plasma Epstein-Barr virus (EBV) DNA level to be an independent prognostic biomarker for nasopharyngeal carcinoma (NPC). However, the proportion of NPC patients whose tumors are associated with EBV vary with geographic location, and there are a variety of assays for plasma EBV. To develop the level of evidence needed to demonstrate the clinical utility of plasma EBV DNA detection for NPC patients and encourage widespread adoption of this biomarker test in clinical laboratories, validated harmonized assays are needed. In 2015, the National Cancer Institute (NCI) convened a Workshop on Harmonization of EBV Testing for Nasopharyngeal Cancer, where experts in head and neck oncology and laboratory medicine addressed the limitations of currently available polymerase chain reaction-based EBV DNA quantitation assays and discussed strategies for advancing the development of harmonized EBV DNA assays and their appropriate clinical use. This article presents the key recommendations to direct future efforts in assay harmonization and validation.

Clinical Utility of Epstein-Barr Virus DNA Testing in the Treatment of Nasopharyngeal Carcinoma Patients

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Mar 2017

Epstein-Barr virus (EBV) DNA analysis has been shown to be useful for early detection, prognostication and monitoring of treatment response of nasopharyngeal carcinoma (NPC), and the recent literature provides accumulating evidence of the clinical utility of EBV DNA testing, particularly to inform treatment decisions for NPC patients. Despite the fact that NPC is a rare disease, the XXX cooperative group has successfully activated a phase II/III randomized clinical trial for NPC with international partners, and in that process discovered that the development of a harmonized EBV DNA test was absolutely critical for integration into clinical trials as well as for future deployment in clinical and central laboratories. XXX institution convened a workshop of international experts in the treatment of NPC and EBV testing to provide a forum for discussing the state of EBV DNA testing and its clinical utility, as well as to stimulate consideration of future studies and clinical practice guidelines for EBV DNA. This review provides a summary of that discussion.

The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging: The Eighth Edition AJCC Cancer Staging Manual

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The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017. © 2017 American Cancer Society.

Lymph-node Epstein–Barr virus concentration in diagnosing cervical lymph-node metastasis in nasopharyngeal carcinoma

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