Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making

objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but not evidence-confirmed.This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy,toxicity and cost-effectiveness.Methods:This real-world study from two epidemic centers used propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses.The enrolled patients were divided into three groups based on treatment modality:Group A(2IC+2CCRT),Group B(3IC+2CCRT or 2IC+3CCRT)and Group C(3IC+3CCRT).Long-term survival,acute toxicities and cost-effectiveness were compared among the groups.We developed a prognostic model dividing the population into high-and low-risk cohorts,and survivals including overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS)and locoregional relapse-free survival(LRRFS)were compared among the three groups according to certain risk stratifications.Results:Of 4,042 patients,1,175 were enrolled,with 660,419,and 96 included in Groups A,B and C,respectively.Five-year survivals were similar among the three groups after PSM and confirmed by IPTW.Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A(52.1%vs.41.5%vs.25.2%;41.7%vs.32.7%vs.25.0%)as were grade 3-4 nausea/vomiting and oral mucositis(29.2%vs.15.0%vs.6.1%;32.3%vs.25.3%vs.18.0%).Cost-effective analysis suggested that 2IC+2CCRT was the least expensive,while the health benefits were similar to those of the other groups.Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients,while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals,mainly reflected by LRRFS.Conclusions:In LA-NPC patients,2IC+2CCRT was the optimal choice regarding efficacy,toxicity and costeffectiveness;however,2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high-and low-risk populations,respectively.

KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.

SIRT2 interacts with DDX24 to promote nasopharyngeal carcinoma growth

Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.Sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerous biological processes.However,Its function in NPC remains uncertain.The primary aim of this study is to clarify the role of SIRT2 in NPC.Methods:In this research,we examined the effect of SIRT2 silencing on NPC cell proliferation and colony formation using vitro NPC cell lines.Co-immunoprecipitation and mass spectrometry was applied to identify SIRT2-interacting proteins in NPC cells.Results:In comparison to nasopharyngeal epithelial NP69 cells,SIRT2 was up-regulated in multiple NPC cell lines,particularly in CNE2 cells.SIRT2 knockdown abrogated CNE2 cell proliferation and colony formation,whereas SIRT2 overexpression promoted HNE1 cell proliferation and colony formation.The SIRT2-interacting proteins were gathered in gene expression and regulation processes including RNA processing and translation.Among the SIRT2-interacting proteins,there were multiple DEAD-box(DDX)family members.Of note,silencing of DDX24 phenocopied the effect of SIRT2 knockdown on NPC growth.Overexpression of DDX24 restored SIRT2-depleted CNE2 cells to proliferative and colony formation.Conclusions:Our study indicates that SIRT2 can interact with DDX24 to enhance NPC growth.The clinical relevance of SIRT2 and DDX24 in NPC warrants further investigation.

Nasopharyngeal carcinoma with synchronous breast metastasis:A case report

BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking.Therefore,additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies.CASE SUMMARY We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom.The first pathological biopsy report suggested triple-negative breast invasive carcinoma.Subsequent imaging revealed a nasopharyngeal mass.Further puncture biopsy of the nasopharyngeal mass,molecular pathological Epstein–Barr virus in situ hybridization,and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis.The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy.She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period.CONCLUSION This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses.Furthermore,clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.

Effects of Cisplatin and Metformin on Proliferation of Nasopharyngeal Carcinoma SUNE-1 Cells

[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.

Comparative Study between Patients Treated with Conventional Radiotherapy and IMRT with Chemotherapy for Stage III - IVA Nasopharyngeal Carcinoma: A Single Institution Retrospective Report

Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ2 = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.

Three-Dimensional Conformal and Intensity Modulated Dynamic Radiotherapy in Juvenile Nasopharyngeal Angiofibroma

Objective: Juvenile Nasopharyngeal Angiofibroma (JNA) is a benign neoplasm with a high vascularity component, greater craniofacial involvement in adolescent patients, and aggressive local behaviour. In unresectable patients, radiotherapy is a therapeutic option for local control. Our aim in this study was to analyze the clinical benefit and local control provided by two modalities of radiotherapy: the Three-Dimensional Conformal (3DC) technique and volumetric modulated arc therapy (VMAT), applied to pediatric patients with JNA considered unresectable and non-recurrent. Methods: In retrospective study, the information was recorded from pediatric patients with a diagnosis of non-recurrent and unresectable JNA treated with radiotherapy at the Oncology Hospital of the National Medical Center SXXI of Mexico City, from March 2010 to March 2021. Radiotherapy management and its association with clinical outcomes of tumour control, and symptoms were assessed. In addition, an evaluation of acute and chronic toxicity was performed. Results: It was found that the median age was 14 years. 9 patients (37.5%) underwent 3DC and 15 (62.5%) VMAT. In terms of local control, and progression-free survival, we did not find significant difference between radiotherapy modalities (p ≤ 0.57). Acute toxicity for both modalities presented statistical differences for radio epithelitis (p = 0.03). Only Grade I and II radiation-induced acute toxicity was observed. Regarding chronic toxicity, statistical significance was observed for craniofacial hypoplasia, in relation to its absence in the VMAT group (p = 0.001). Conclusion: The VMAT presents improvements in dosimetry parameters that improve patient toxicity. In both techniques adequate tumour control was observed, however, the rarity of the disease is a limitation to establish the most appropriate therapeutic technique.

Massive Rhinorrhea as a Complication of COVID-19 Nasopharyngeal Swab

The nasopharyngeal swab for COVID-19 testing is generally considered safe;however, it is primarily performed by staff that may not completely understand the anatomy of the nasal cavity and nasopharynx. We report the treatment of a 48-year-old man who developed unilateral left rhinorrhea after a nasopharyngeal swab sample. It is aimed to draw attention to this complication that can be prevented with the appropriate technique during nasopharyngeal swab sampling.

A Prospective Study on Therapeutic Gain by Concurrent Chemoradiotherapy for Stage Ⅱ-Ⅳa Nasopharyngeal Carcinoma

The benefit achieved by concurrent chemoradiotherapy（CCR） and sequential chemoradiotherapy（SCR） vs radiotherapy（RT） alone for patients with stage Ⅱ-Ⅳa nasopharyngeal carcinoma（NPC） was compared.A total of 113 patients with stage Ⅱ-Ⅳa NPC were allotted into CCR group（n=38）,SCR group（n=36） and RT alone group（n=39）.All patients were irradiated with the same RT technique to ≥66 Gy at 2 Gy per fraction,conventional 5 fractions/week in all groups.The CCR group received concurrent chemotherapy of weekly cisplatin for 7 weeks,and the SCR group received neoadjuvant and（or） adjuvant chemotherapy.The results showed that the 3-and 5-year overall survival rate was significantly higher in CCR group than in RT alone group（92.16% vs 61.54%,81.58% vs 51.28%,P〈0.005）.The median survival time was significantly longer in CCR group than in RT alone group（67.8 months vs 52.7 months,P〈0.005）.It was concluded that CCR could significantly improve overall survival rate,progression-free survival rate,and median survival time when compared with RT alone.

Stereotactic radiotherapy for the treatment of nasopharyngeal carcinoma: a Meta-analysis of 1371 cases in China

Objective The aim of this study was to clarify the outcomes of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma and to promote scientific clinical treatment and research on it in China and other countries by creating a large data resource.Methods This Meta-analysis conducted a literature search using the China National Knowledge Infrastructure database for all clinical research articles on stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma in China.Data on patient cohort numbers and other research factors were recorded for every relevant clinical research article.Calculated and analyzed these fact sheets to pave the way for the objective of this project.Results A total of 40 clinical research articles including 1,371 patients in China from 1998 to 2012 were identified.The average cohort size was 34 patients(range 9-98 patients).The average total radiation dose range was 16-33.6 Gy.The average study or treatment duration was 3.51 years.The calculated average follow-up time was 31.59 months.Conclusion The study provided the largest resource for further research and Meta-analyses to determine the clinical pathway of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma.The results indicated that variability in the total radiation dose,treatment or research time,and follow-up duration may have contributed to the complications and side effects of stereotactic radiotherapy for local residual and(or) local recurrent nasopharyngeal carcinoma in China.The calculated average total radiation dose,follow-up time,and treatment and research durations may be referenced for future treatment and research.This study also proposed worldwide cooperation for the metaanalysis of research articles on stereotactic radiotherapy for treating local residual and(or) local recurrent nasopharyngeal carcinoma.

CLINICOPATHOLOGIC ANALYSIS ON 121 CASES OF NASAL AND NASOPHARYNGEAL LYMPHOMA (NPL)

One handled twenty- one cases of nasal and naso-pharyngeal lymphoma were analyzed in this paper. These cases were divided macroscopically Into 4 main types Including giant mass type, nodular type, thickbulgy type and ulcerating type. Microscopic histologic varieties were classified to non-Hodgkin' s lymphoma (NHL) and Hodg-Kin' s disease (HD).Differential diagnosis between NPL and nasopharyngeal carcinoma (NPC) and the problem how to ascertain the primary and secondary tumors were discussed.

Nasopharyngeal carcinoma incidence and mortality in China,2013

Background: We estimated the incidence and mortality of nasopharyngeal carcinoma(NPC) in China in 2010 according to the data of 145 domestic population-based cancer registries in 2014, and no such reports since then.Hence, to further and better understand its epidemiology in China and to provide more precise scientific information for its control and prevention in China, we analyzed the NPC incidence and mortality of 255 domestic populationbased cancer registries, and estimated the national rates in 2013 again.Methods: NPC incidence and mortality data of 255 domestic cancer registries in 2013, accepted by the 2016 National Cancer Registry Annual Report, were collected and collated, and the indices of NPC such as the numbers of new cases and deaths, crude rates, age-standardized rates, and truncated rates of incidence and mortality were calculated and analyzed. The incidence and mortality in China and its constituent areas were estimated according to the national population in 2013.Results: An estimated 42,100 new cases and 21,320 deaths were attributed to NPC in China in 2013, accounting for1.14% of all new cancer cases and 0.96% of all cancer-related deaths that year in China. Crude incidence and mortality of NPC were 3.09/100,000 and 1.57/100,000, respectively. World age-standardized incidence and mortality were2.17/100,000 and 1.08/100,000, respectively. The incidence and mortality of males were obviously higher than those of females and slightly higher in urban areas than in rural areas. Among seven Chinese administrative regions, NPC incidence and mortality were obviously higher in South China than in other regions and lowest in North China. Top3 incidence and mortality provinces and registering areas all located in South China. The age-specific incidence and mortality rose quickly from age 25-29 and 35 to 39 years, respectively, peaked at different ages and varied by location.Conclusions: These results demonstrated that NPC incidence and mortality in China in 2013 were also at high levels worldwide, which suggested that its control and prevention should be enhanced.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Magnetic resonance imaging staging of nasopharyngeal carcinoma in the head and neck

Magnetic resonance imaging (MRI) is the modality of choice for staging nasopharyngeal carcinoma in the head and neck. This article will review the patterns of primary and nodal spread on MRI with reference to the latest 7th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system.

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas

AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.

Significant value of 18F-FDG-PET/CT in diagnosing small cervical lymph node metastases in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.

Prognostic value of plasma Epstein-Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.

Locally advanced nasopharyngeal carcinoma:Current and emerging treatment strategies

Although nasopharyngeal carcinoma(NPC)is a widespread malignant tumor,it is particularly frequent in Southeast Asia.Although T1 tumors can be effectively controlled with exclusive radiotherapy,this treatment modality is insufficient for most NPC patients,who present with locally advanced disease at diagnosis.In fact,for stages ranging from T2b N0 to T4 N3,definitive scientific evidence supports the use of concurrent platinum-based chemotherapy with standard external beam radiotherapy.This treatment approach has shown a statistically significant advantage in terms of overall survival,with respect to radiotherapy alone.Several trials have also investigated the use of neoadjuvant and adjuvant chemotherapy in combination with radiotherapy or chemo-radiotherapy.Platinum compounds,anthracyclines and taxanes are among the chemotherapy agents employed.This review focuses on the clinical results obtained in the field of adjuvant/concurrent/neoadjuvant chemotherapy for locally advanced NPC,for which exclusive concurrent chemo-radiotherapy currently represents the standard treatment approach.

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

Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.