Nasopharyngeal Carcinoma Disease Research Articles

Use of transoral nasopharyngeal brush biopsy for Epstein-Barr virus DNA detection of local recurrence of nasopharyngeal carcinoma after radiotherapy.

The purpose of this study was to evaluate the use of transoral nasopharyngeal brush biopsies and quantitative polymerase chain reaction (qPCR) Epstein-Barr virus (EBV) DNA detection system in surveillance of local recurrence of nasopharyngeal carcinoma (NPC). A prospective cohort study was performed to compare the nasopharyngeal epithelial EBV DNA levels of patients with recurrent NPC and the control group of postirradiated patients with NPC disease in remission. Fourteen patients with recurrent NPC and 15 postirradiated patients in disease remission were recruited for transoral brush biopsies. There was a statistically significant difference between the mean EBV detection level (EDL) of the recurrence group (EDL = 2.38) and the control group (EDL = 0.17; p < .0001). There was no significant correlation between the EDL and the recurrence of T classification disease. The transoral brush biopsy and qPCR EBV DNA detection system may provide an additional surveillance strategy for recurrence of NPC. Further study is required to validate its sensitivity, specificity, and cost-effectiveness. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1301-E1304, 2016.

Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value.

Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (≥2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (P = 0.01). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment.

Using computational strategies to predict potential drugs for nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a unique cancer. Refinement of current therapy by discovering potential drugs may be approached by several computational strategies. We collected NPC genes from published microarray data and the literature. The NPC disease network was constructed via a protein-protein interaction (PPI) network. The Connectivity Map (CMap) was used to predict potential chemicals, and support vector machines (SVMs) were further utilized to classify the effectiveness of tested drugs against NPC using their gene expression from CMap. A highly interconnected network was obtained. Several chemically sensitive genes were identified and 87 drugs were predicted with the potential for treating NPC by SVM, in which nearly half of them have anticancer effects according to the literature. The 2 top-ranked drugs, thioridazine and vorinostat, were demonstrated to be effective in inhibiting NPC cells. This in silico approach provides a promising strategy for screening potential therapeutic drugs for NPC treatment.

Preliminary assessment of nasopharyngeal carcinoma incidence in the Philippines: a second look at published data from four centers

In endemic regions such as southern China and Southeast Asia, the annual incidence of nasopharyngeal carcinoma (NPC) ranges from 3 to 30 per 100,000. In the Philippines, the estimated incidence in 2010 was 1.2 per 100,000. However, this rate is based on data collected from registries covering only two regions in the country. Here, we report the findings from our study to better approximate the incidence of NPC in the Philippines. Between September 1, 2011 and August 31, 2012, data were collected from 49 patients from 4 different institutions—University of Santo Tomas, Makati Medical Center, Philippine Oncology Center Corporation, and Cardinal Santos Memorial Medical Center—using a NPC screening questionnaire. Crude incidence was 0.09 per 100,000. Age-standardized incidences using Segi and WHO standards were 2.08 and 1.79 per 100,000, respectively. Of the 49 patients, 31 were males and 18 were females, and 71% of patients were between 30 and 59 years old. WHO types II and III represented 22% and 78% of the subjects, respectively, and 75.5% of cases were locally advanced (stages III–IVB). Although the age-standardized incidence from the 4 institutions was numerically higher than the published age-standardized incidence (2.07 per 100,000 vs. 1.2 per 100,000), two-proportion z-test showed no significant difference between them (P = 0.68). A more concerted effort is needed for a better approximation of the country's NPC disease burden.

Ergebnisse beim Nasopharynxkarzinom im Erwachsenenalter

Nasopharyngeal carcinoma (NPC) is a rare tumor entity in Germany in contrast to endemic countries in Asia or Africa. This retrospective study investigated patient characteristics and prognostic factors with respect to different NPC treatment strategies. A total of 63 NPC patients treated during the period 1990-2009 at the University Hospital Bonn, Germany, were included. The median age of the patients was 56.4 years, the male:female ratio was 3.2:1, 23.8% were in Union Internationale Contre le Cancer (UICC) stage I/II and 76.2% were in stage III/IV. Most of the carcinomas were WHO type III (57.1%), followed by World Health Organization (WHO) type II (33.3%) and at last WHO type I (9.6%). The 5-year overall survival rate after concomitant chemoradiotherapy (RCT) was 75% and after radiotherapy (RT) 60%. The mortality rate increased by 3.5 times with each increase in T-stage (p ≤ 0.047). The recurrence rate (RR) after RCT was 34% and after RT alone 68% (p ≤ 0.04). Tumor ablation increased the RR significantly (p ≤ 0.047). Combined chemotherapy and RT is an effective treatment of NPC disease and clearly superior to RT alone. Tumor ablation before RCT/RT worsens the prognosis and is now obsolete.

Nasopharyngeal carcinoma: differences in presentation between different ethnicities in the New Zealand setting

There is an elevated incidence of nasopharyngeal carcinoma (NPC) in the Maori and Pacific Island (MPI) population as well as the Asian population in New Zealand; however, no studies have been conducted to evaluate how the two populations differ in their clinical presentation according to the TNM stage. A retrospective review was conducted of all patients presenting to the Auckland City Hospital ENT department with a newly diagnosed NPC between the years 1995 and 2007 inclusive. The patient's radiological and biopsy results were reviewed, and each patient was staged according to the TNM stage at presentation as per the revised 2002 American Joint Committee on Cancer staging criteria. The Fisher's exact test was used to compare the differences between ethnicities in the T and N stages of the disease at presentation; the Cochran-Armitage Trend test was used to look for statistically significant trends. There was a statistically significant difference in T stage at presentation between MPIs and Asians (P < 0.0001), with a positive, statistically significant (P < 0.0001) trend indicating that MPIs present with greater T stage. A statistically significant difference in the N stage at diagnosis between MPIs and Asians, independent of the T stage, was found at stages T2 (P = 0.046) and T4 (P = 0.0083), with a statistically significant trend (T2 -P = 0.009; T4 -P = 0.026). These results show that MPIs have a more advanced local NPC disease than Asians at presentation, and that for specific T stages, the nodal disease is also more advanced than that found in Asians.

Extension of Local Disease in Nasopharyngeal Carcinoma Detected by Magnetic Resonance Imaging: Improvement of Clinical Target Volume Delineation

To define by MRI the local extension patterns in patients presenting with nasopharyngeal carcinoma (NPC) and to improve clinical target volume delineation. Consecutive patients (N = 943) with newly diagnosed and untreated NPC were included in this study. All patients underwent MRI of the nasopharynx and neck, which was reviewed by two radiologists. According to the incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were initially classified into three risk grades: high risk (> or = 35%), medium risk (> or = 5-35%), and low risk (< 5%). Incidence rates of tumor invasion into anatomic sites at medium risk were increased, reaching 55.2%, when adjacent high-risk anatomic sites were involved. However, the rates were substantially lower, mostly < 10%, when adjacent high-risk sites were not involved. The incidence rates of concurrent tumor invasion into bilateral sites were < 10%, except in the case of prevertebral muscle involvement (13.1%). Among the 178 incidences of cavernous sinus invasion, there were often two or more simultaneous infiltration routes (60.6%); when only one route was involved, the foramen ovale was the most common (26.4%). In patients presenting with NPC, local disease spreads stepwise from proximal sites to more distal sites. Tumors extend quickly through privileged pathways such as neural foramina. The anatomic sites surrounding the nasopharynx are at low risk of concurrent bilateral tumor invasion. Selective radiotherapy of the local disease in NPC may be feasible.

Nasopharyngeal carcinoma in adolescents: a retrospective review of 42 patients

The aim of the present study was to evaluate the characteristics and outcome of adolescent patients with nasopharyngeal carcinoma (NPC) disease. The study concerned 46 pediatric NPC patients treated during the period 1999-2002 at the National Institute of Oncology, Rabat. The median age of the patients was 16 years. The male/female ratio was 2.8/1. Histologically, all patients had undifferentiated carcinoma. A total of 93% presented nodal metastasis. Four (9%) had distant metastasis. All patients received neoadjuvant multiagent chemotherapy containing cisplatin, followed by radiotherapy. Kaplan-Meier curves were used to evaluate prognostic factors. The log-rank test was used to evaluate the differences between the groups. While none of the patients had locoregional failure, nine patients (29%) developed distant metastasis. The disease-free survival and overall survival (OS) rate for the entire group were 73 and 41%, respectively. Responders to chemotherapy had superior OS (P < 0.001). We suggest that combined modality management using multi-agent chemotherapy and RT as an effective treatment of NPC disease which will achieve satisfactory locoregional control and OS of NPC pediatric patients. Response to chemotherapy was an important prognostic factor.

Functional IL-18 promoter gene polymorphisms in Tunisian nasopharyngeal carcinoma patients

Objectives: There is growing evidence suggesting that IL-18 levels may affect individual to virus-associated neoplasia and that single nucleotide polymorphisms (SNPs) within the gene may influence its production. In this study we wanted to know whether IL-18 polymorphisms at positions −607 C/A and −137 G/A are associated with susceptibility and/or are markers of nasopharyngeal carcinoma (NPC) prognosis. Methods: Using the restriction fragment length polymerase chain reaction (RFLP-PCR), 163 Tunisian patients and 164 healthy controls were genotyped. Results: No significant association was found between each studied polymorphism and NPC. However, we noted that the −607 A allele, which is associated with lower IL-18 production, increased the risk of advanced tumor stages (OR=3.59; P=0.017) and that this risk was more pronounced among the older patient’s age at onset (OR=3.85; P=0.012). Moreover, the significant difference in CA/GG haplotype frequency distribution between young and older patients supported the idea that NPC disease has biologically different features between age sub-groups. Conclusion: Functional IL-18 gene polymorphisms do not influence the susceptibility to NPC in Tunisians but may contribute to disease onset and aggressiveness.

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

Purpose: To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC. Methods and Materials: Between November 1994 and March 1999, 157 patients with Stage IV, M 0 (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35–40 fractions, 1.8–2.0 Gy/fraction/day, 5 days/week, to a total dose 70–72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m 2 cisplatin, 2,200 mg/m 2 5-fluorouracil, and 120 mg/m 2 leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis. Results: With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% ( p = 0.5) and 49.5% vs. 54.4% ( p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 ( p value = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3). Conclusions: We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.

The 30-bp deletion variant: a polymorphism of latent membrane protein 1 prevalent in endemic and non-endemic areas of nasopharyngeal carcinomas in China

Development of nasopharyngeal carcinoma (NPC) is closely associated with Epstein–Barr virus (EBV) infection. However, NPC occurs with a marked geographic and racial distribution, whereas EBV infection is ubiquitous in the world. This leads to a question whether certain subtypes of EBV have a greater potential to induce cell transformation. Latent membrane protein 1 (LMP1) is an EBV-encoded oncogenic protein and its 30-bp deleted variant (del-LMP1) has been reported to be predominant in biopsies of NPC. We have assessed the polymorphism of LMP1 in 47 biopsies of NPC, 107 cases of throat washings (TWs) from NPC patients, and 106 cases of TWs from non-NPC patients in Guangzhou, an endemic area of NPC in southern China, as well as 103 cases of TWs from healthy donors in Haerbin, a non-endemic area of NPC in northern China. Our results found a similar extent of the LMP1 polymorphism between NPC patients and non-NPC patients in Guangzhou, with the del-LMP1 being predominant in both Guangzhou and Haerbin. Sequence analyses showed identical substitutions in other coding regions of the del-LMP1 isolated from Guangzhou and Haerbin. These results indicate that del-LMP1 represents a geographic or race-associated polymorphism rather than an NPC disease phenotype-associated polymorphism.

Management of extensive cervical nodal metastasis in nasopharyngeal carcinoma after radiotherapy: a clinicopathological study.

To evaluate the efficacy of afterloading brachytherapy following radical neck dissection (RND) in the management of extensive cervical lymph node disease in nasopharyngeal carcinoma after radiotherapy; and to examine prospectively prognostic factors and the pathologic behavior of neck disease. Twenty-seven patients with nasopharyngeal carcinoma who had extensive cervical lymph node metastasis following external radiotherapy were treated with RND. Thirteen of them also underwent afterloading brachytherapy with iridium wire (Ir 192). The RND specimens of the 27 patients were also examined with step serial whole-specimen sectioning. All patients survived and their wounds healed primarily. Pathologic examination revealed 183 tumor-bearing lymph nodes that contained tumors in the neck: level I, 4% (8/183); level II, 53% (96/183); level III, 34% (62/183); level IV, 5% (9/183); and level V, 4% (8/183). Extracapsular tumor extension was seen in 84% of patients. Multivariate analysis identified the number of tumor-bearing lymph nodes detected in the specimens to be the only significant factor that affected control of disease. Although the neck disease in the group of patients who had afterloading brachytherapy was more extensive, the 3-year actuarial tumor control for the groups with and without brachytherapy were 60% and 61%, respectively. Recurrent cervical lymph nodes after radiotherapy in nasopharyngeal carcinoma are extensive and RND is mandatory for a successful salvage. When the nodal metastasis infiltrate or adhere to surrounding tissue, afterloading brachytherapy with iridium wire can provide satisfactory local tumor control.

The pattern of nodal recurrence following definitive radiotherapy for nasopharyngeal carcinoma.

The pattern of nodal metastasis in previously untreated nasopharyngeal carcinoma (NPC) has been studied and reported. In order to analyse the pattern of recurrent nodal disease in previously treated NPC, a retrospective study on 68 patients who underwent radical neck dissection for regionally recurrent NPC was conducted. Seventy-four neck dissections were performed on 68 patients who developed nodal recurrence after a mean disease-free interval of 39.2 months. None of the patients had evidence of local or systemic disease at the time of surgery. Histopathological reports of the 74 neck dissections were analysed with regard to the number of positive nodes as well as the number of involved nodal levels. Of the 65 neck dissection specimens with analysable data, 31 showed metastatic disease at a single nodal level with a mean number of positive nodes of 1.2, while 34 showed metastatic disease at multiple levels with a mean number of positive nodes of 6.6. Nodal recurrence occurred at level II with the greatest frequency (78.5%). Of the 31 specimens with single level nodal involvement, 21 (67.7%) occurred at level II. Isolated involvement at the other levels did occur, but was uncommon (range 3-16%). Of the 34 specimens with multiple level nodal involvement, 30 (88.2%) showed involvement at level II. Once more than one level was involved, the frequency of involvement at any given level was at least 30%. The predominant involvement at level II and the high frequencies of involvement at all levels support the use of a classical radical neck dissection in treating recurrent nodal disease in NPC.

Strong association between hyperferritinaemia and metastatic disease in nasopharyngeal carcinoma

We have investigated the role of serum ferritin, in relation to disease stages, in patients with nasopharyngeal carcinoma. Patients with localised disease (Ho's stage I-IV) had levels which were not significantly different from age, sex matched normal subjects and there was no relationship between mean serum ferritin levels and stage. However, in patients with metastatic disease levels were grossly elevated with mean levels increased more than 6-fold compared to normal subjects and patients with localised disease. Furthermore, among the small group of patients with localised disease but hyperferritinaemia, the subsequent development of metastatic disease within 1 year was significantly much higher (32.4%) than in those with levels falling within the reference range (10.3%). Hyperferritinaemia is strongly associated with, and may predict, metastatic disease in patients with nasopharyngeal carcinoma.

9 Radioresponsiveness of nodal disease in nasopharyngeal carcinoma

9 Radioresponsiveness of nodal disease in nasopharyngeal carcinoma

Fiberoptic endoscopic examination and biopsy in determining the extent of nasopharyngeal carcinoma.

This is a prospective study on the use of flexible endoscope and multiple biopsies in the assessment of nasopharyngeal carcinoma in 72 patients. This study confirmed the presence of submucosal growth pattern in nasopharyngeal carcinoma in 72 patients. This study confirmed the presence of submucosal growth pattern in nasopharyngeal carcinoma and this occurred in 13.8% of patients. Occult microscopic extension of tumor not detectable by fiberoptic endoscopy occurred in another 51.4% of patients. It has also been shown that multiple biopsy is superior to clinical examination in evaluating the extent of disease in nasopharyngeal carcinoma. Multiple biopsies are suggested for the early detection of nasopharyngeal carcinoma in high-risk cases. Although the better-defined tumor extent do not currently influence the treatment policy of nasopharyngeal carcinoma, and it is too early to assess its prognostic significance, it betters our understanding of the behavior of this tumor. Future analysis in correlation with long-term follow-up data may help to improve the stage classification systems and treatment strategy.

Immunoglobulin allotypes in patients with nasopharyngeal carcinoma.

Gm phenotypes and the Km(1) allotype were studied in Tunisian patients with nasopharyngeal carcinoma (NPC). A highly significant association was found between the Km(1) allotype and the NPC disease. Two rare Gm haplotypes, Gm(1, 17; 11, 15, 21) and Gm(1, 3, 5, 11), were found to be significantly increased among the NPC patients.