Impact of sex on treatment-related adverse effects and prognosis in nasopharyngeal carcinoma.

BACKGROUND: In nasopharyngeal cancer (NPC), women have a lower incidence and mortality rate than men. Whether sex influences the prognosis of NPC patients remains debatable. We retrospectively examined the influence of sex on treatment-related side effects and prognosis in NPC. METHODS: Clinical data of 1,462 patients with NPC treated at the Southern Hospital of Southern Medical University from January 2004 to December 2015 were retrospectively examined. Statistical analysis was performed to assess differences in overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival(LRFS), and progression-free survival(PFS), as well as treatment-related adverse effects, including myelosuppression, gastrointestinal responses, and radiation pharyngitis and dermatitis, between men and women. RESULTS: Women had better 5-year OS (81.5% vs. 87.1%, P = 0.032) and DMFS (76.2% vs. 83.9%, P = 0.004) than men. Analysis by age showed that the prognoses of premenopausal and menopausal women were better than those of men, whereas prognoses of postmenopausal women and men were not significantly different. Additionally, women had a better prognosis when stratified by treatment regimen. Furthermore, chemotherapy-related adverse effects were more severe in women than in men; however, the incidences of radiation laryngitis and dermatitis were not significantly different between the sexes. Logistic regression analysis revealed that the female sex was an independent risk factor for severe myelosuppression and gastrointestinal reactions. CONCLUSIONS: Chemotherapy-related side effects are more severe but the overall prognosis is better in women with NPC than in men with NPC. Patients may benefit from a personalized treatment approach for NPC. TRIAL REGISTRATION: This study was approved by the Medical Ethics Committee of Nanfang Hospital of the Southern Medical University (NFEC-201,710-K3).

Survival benefit of induction chemotherapy for locally advanced nasopharyngeal carcinoma: prognosis based on a new risk estimation model.

BACKGROUND: Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. METHODS: This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18-70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the ß regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. RESULTS: The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. CONCLUSIONS: Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

Retrospective study comparing anti-EGFR monoclonal antibody plus cisplatin-based chemoradiotherapy versus chemoradiotherapy alone for stage II-IVb nasopharyngeal carcinoma and prognostic value of EGFR and VEGF expression.

OBJECTIVES: The benefits of adding anti-EGFR therapy to conventional chemoradiotherapy (CRT) for nasopharyngeal carcinoma (NPC) remain uncertain, possibly because only a subgroup of patients show better outcome. To address this issue, we compared the efficacy of CRT plus cetuximab (CTX) or nimotuzumab (NTZ) to CRT alone for stage II-IVb NPC and examined possible prognostic indicators, including tumour EGFR and VEGR expression levels. DESIGN, SETTING AND PARTICIPANTS: This retrospective study enrolled 1812 patients at initial NPC diagnosis at Nanfang Hospital Affiliated to Southern Medical University between January 2005 and December 2015. The cetuximab or nimotuzumab plus CRT group (CRT+NTZ/CTX) and the conventional chemoradiotherapy group (CRT) were matched by propensity scoring at 1:5, yielding 282 patients at clinical stage II-IVb with 47 in the CRT+NTZ/CTX group and 235 in the CRT group. MAIN OUTCOME MEASURES: The endpoints of the present study were locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS). Immunohistochemistry (IHC) was used to investigate EGFR and VEGF expression levels in 31 patients of the CRT+NTZ/CTX group. RESULTS: There were no significant differences in LRFS, DMFS and OS, haematologic toxicity reactions, and gastrointestinal reactions between CRT+NTZ/CTX and CRT groups. There was a positive correlation between EGFR and VEGF expression levels. Among CRT+NTZ/CTX patients, those with high EGFR and VEGF expression levels exhibited better DMFS. CONCLUSIONS: Addition of anti-EGFR to cisplatin-based CRT appears to benefit only a subset of stage II-IVb NPC patients, those with elevated EGFR and VEGF expression levels.

A Retrospective Study to Compare Five Induction Chemotherapy Regimens Prior to Radiotherapy in the Reduction of Regional Lymph Node Size in Patients with Nasopharyngeal Carcinoma.

BACKGROUND Combined chemotherapy and radiation therapy are used to treat nasopharyngeal carcinoma (NPC). Previous studies have shown that induction chemotherapy, given before radiotherapy, is beneficial in patients with local lymph node metastases. The aim of this study was to evaluate regional lymph node size in patients with NPC and the efficacy of five induction chemotherapy regimens given before radiotherapy. MATERIAL AND METHODS Between December 2007 and June 2011, 190 patients were included in this study, who had regionally advanced NPC (Stages II-IV). Five induction chemotherapy regimens were given prior to radiation: 98 patients (51.6%) received the TPF regimen (docetaxel, cisplatin, and fluorouracil); 56 patients (29.5%) received PF regimen (cisplatin and fluorouracil); 26 patients (13.7%) received the TP regimen (cisplatin and docetaxel); seven patients (3.7%) received combined nimotuzumab with TPF; three patients (1.6%) received a combination of the novel modified recombinant human endostatin (Endostar) with PF. The length and width of the regional lymph nodes were measured using neck B-mode (high-resolution grey scale) ultrasonography before chemotherapy and on the second day following completion of chemotherapy. Gastrointestinal tract and bone marrow suppression were also monitored during and after chemotherapy. RESULTS The TPF chemotherapy induction regimen resulted in an improved early response of lymph node size reduction, compared with the PF and TP chemotherapy induction regimens. The combined use of nimotuzumab with the TPF regimen improved efficacy by 15%. The combined use of Endostar improved the efficacy of the PF regimen by 56% (P<0.05). CONCLUSIONS In a retrospective study in patients with NPC, different induction chemotherapy regimens had different effects on lymph node size before radiation therapy.

Dynamic Changes in Plasma MicroRNAs Have Potential Predictive Values in Monitoring Recurrence and Metastasis of Nasopharyngeal Carcinoma.

Although circulating microRNAs (miRNAs) have already proven to be useful as diagnostic and prognostic biomarkers in nasopharyngeal carcinoma (NPC), the potential of these molecules to monitor patients over time has been less explored. This study aimed to analyze dynamic changes in plasma miRNAs before and after treatment and explore their clinical significance in monitoring recurrence and metastasis of NPC. Candidate miRNAs were screened by microarray analysis and validated by real-time quantitative polymerase chain reaction (RT-qPCR). In the follow-up cohort including 102 patients, blood samples (plasma) were collected before the treatment initiation, 3 months, 6 months, and 12 months after treatments, and at the time of any recurrence or metastasis. Among these plasma miRNAs, miR-9-3p, miR-124-3p, miR-892b, and miR-3676-3p were significantly upregulated (P = 0.018, P = 0.039, P = 0.001, and P = 0.01, resp.) after treatment compared with pretreatment, and the four plasma miRNAs were downregulated again at recurrence or metastasis (P < 0.001, P = 0.015, P = 0.003, and P = 0.026, resp.). The dynamic changes in plasma miRNAs after treatment reflect the outcome of the disease and have the potential to monitor recurrence and metastasis in patients with NPC.

[Clinical significance of plasma miR-24 dysregulation in nasopharyngeal carcinoma].

OBJECTIVE: To examine the expression level of miR-24 in the plasma of nasopharyngeal carcinoma (NPC) patients and investigate the clinical significance of miR-24 in NPC development. METHODS: Blood samples were from 217 NPC patients admitted in our Department between December, 2007 and June, 2011, with those from 73 patients with chronic purulent otitis media or chronic sinusitis as control. The follow-up data of all the patients were reviewed and the expression of miR-24 in the plasma was examined by qRT-PCR. The correlation of miR-24 expression with clinical staging of NPC was analyzed, and miR-24 levels before and after the treatment were compared. RESULTS: Compared with the control group, the NPC patients showed significantly up-regulated level of miR-24 in the plasma (P<0.001). Plasma miR-24 level differed significantly among patients with different T stages (P=0.007) and was negatively correlated with the N stages (P=0.028) and plasma EBV-DNA (P=0.048). The expression levels of miR-24 were significantly reduced after treatment in the NPC patients and were significantly lowered in patients without relapse or metastasis (P=0.001). CONCLUSION: Plasma miR-24 may serve as a novel molecular biomarker for early diagnosis and prognosis of NPC.

Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma.

The level of Epstein-Barr virus DNA (EBV-DNA) in the plasma prior and subsequent to treatment is a reliable biomarker for the screening, diagnosis, monitoring and prognosis of nasopharyngeal carcinoma (NPC). The present retrospective study aimed to determine whether pre- and post-treatment levels of plasma EBV-DNA were predictive of survival in a large sample of patients with NPC. The level of plasma EBV-DNA in 637 NPC patients prior and subsequent to treatment was determined by quantitative polymerase chain reaction. The value of pre- and post-treatment plasma EBV-DNA in predicting the survival of NPC patients was then analyzed. The results revealed that pre-treatment plasma EBV-DNA loads were significantly higher in patients with NPC than those in healthy controls (P<0.001). The percentage of patients with positive plasma EBV-DNA was markedly higher prior to treatment (70.64%; median, 1150 copies/ml; range, 0-9.75×106 copies/ml) than following treatment (25.99%; median, 0 copies/ml; range, 0-3.83×106 copies/ml) (P<0.001). Patients with a high plasma EBV-DNA load presented with a higher clinical tumor classification, lymph node status, metastatic status and overall cancer stage. The risk of NPC relapse and mortality was higher in patients with pre-treatment plasma EBV-DNA levels of ≥1,500 copies/ml than that in patients with <1,500 copies/ml. Furthermore, the risk of relapse and mortality was higher in patients with positive post-treatment plasma EBV-DNA than in patients with negative post-treatment plasma EBV-DNA. Detectable post-treatment plasma EBV-DNA was the most significant prognostic factor to affect relapse-free survival, whilst metastasis was the prognostic factor with the greatest effect on overall survival. These data indicated that pre- and post-treatment levels of plasma EBV-DNA were able to predict the prognosis of NPC. This finding may provide novel references for research and clinical practice.

MicroRNA-378 functions as an onco-miR in nasopharyngeal carcinoma by repressing TOB2 expression.

Increasing evidence indicates that microRNAs (miRNAs) has been implicated in the progression and metastasis of numerous cancers. In particular, abnormal expression of miR-378 has been observed in various cancers and is associated with cell survival, migration, invasion, angio-genesis and tumor growth. Our previous studies have shown that miR-378 was decreased in nasopharyngeal carcinoma (NPC) plasma and was negatively correlated with NPC progression. However, the tissue expression of miR-378 and its biological function remained unknown in NPC. In this study, we report for the first time that expression level of miR-378 was commonly upregulated in both NPC tissues and NPC cell lines compared to normal healthy nasopharyngeal epithelial samples and human nasopharyngeal epithelial cell lines (NP69), respectively, and was opposite to the reported results in plasma. Functional studies showed that upregulation of miR-378 dramatically promoted cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Bioinformatics analyses were performed to predict the target genes of miR-378, and the following mechanistic investigations revealed that miR-378 overexpression was able to downregulate the expression of transducer of ERBB2 (TOB2), a potential tumor suppressor, and miR-378 silencing enhanced TOB2 expression. In clinical specimens, TOB2 was widely repressed in tumor tissues accompanied by miR-378 overexpression. Taken together, this study indicates that miR-378 regulates TOB2 and may function as an onco-miR in NPC progression, providing a potential target for gene therapy of NPC.

Positivity of both plasma Epstein-Barr virus DNA and serum Epstein-Barr virus capsid specific immunoglobulin A is a better prognostic biomarker for nasopharyngeal carcinoma.

BACKGROUND: Positivity of plasma Epstein-Barr virus (EBV)-DNA or serum virus capsid antigen-specific IgA (VCA-IgA) is a biomarker for the prognosis of nasopharyngeal carcinoma (NPC). The objective of this study was to determine the value of positivity for plasma EBV-DNA and/or VCA-IgA in predicting the survival of patients with NPC. METHODS: Plasma EBV-DNA and serum VCA-IgA in 506 NPC patients in this retrospective study were detected by quantitative real time polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively. The value of positivity for EBV-DNA and/or VCA-IgA in predicting the survival of patients with NPC was analyzed. RESULTS: Patients with positivity for both EBV-DNA and VCA-IgA had significantly shorter periods of relapse free survival (RFS) and overall survival (OS) than those with positive single measure or negative for both measures, and patients with positive single measure had significantly shorter periods of RFS and OS than those with negative for both. Multivariate analysis indicated that the positivity for EBV-DNA and/or VCA-IgA were significant risk factors for shorter periods of RFS and OS. CONCLUSION: These data indicated that positivity for both EBV-DNA and VCA-IgA was a better biomarker for the prognosis of patients with NPC. Our findings may provide new references for clinical practice.