Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma.

BACKGROUND: Since Immune response, nutritional status and Epstein-Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis. METHODS: A total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan-Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms' predictive value. RESULTS: Patients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65-0.73) and 0.77 (95% CI: 0.71-0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power. CONCLUSIONS: LA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.

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).

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA.

BACKGROUND: Inflammatory parameters and Epstein-Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA. METHODS: A total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher's exact test. RESULTS: The optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters. CONCLUSIONS: The SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.

Combination of smoking and Epstein-Barr virus DNA is a predictor of poor prognosis for nasopharyngeal carcinoma: a long-term follow-up retrospective study.

BACKGROUND: This retrospective study was performed to determine the prognostic potential of smoking and its combination with pre-treatment plasma Epstein-Barr virus (EBV) DNA levels in patients with nasopharyngeal carcinoma (NPC). METHODS: Medical records of 1080 non-metastatic NPC patients who received intensity-modulated radiotherapy were reviewed. Male patients were categorized as never and ever smokers, and the smoking amount, duration, and cumulative consumption were used to evaluate dose-dependent effects. Survival outcomes were assessed using Kaplan-Meier survival analysis and the multivariate Cox regression analysis. Propensity score matching (PSM) was constructed. RESULTS: The 5-year overall survival (OS) was worse for ever smokers than never smokers, and significantly decreased with the increase of smoking amount, duration, and cumulative consumption. Compared with never smokers, the multivariate-adjusted hazard ratio (HR) of death was higher in ever smokers (HR = 1.361, P = 0.049), those smoked ≥20 cigarettes/day (HR = 1.473, P = 0.017), those smoked for ≥30 years (HR = 1.523, P = 0.023), and those cumulative smoked for ≥30 pack-years (HR = 1.649, P = 0.005). The poor prognostic effects of smoking was also confirmed in the PSM analysis. The combination of cumulative smoking consumption and pre-treatment EBV DNA levels was proven to be an independent poor prognostic factor for male NPC, and the risk of death, progression, and distant metastases gradually increased with both factors (P < 0.001). CONCLUSIONS: Combination of smoking and pre-treatment EBV DNA levels as a predictor of poor prognosis could further improve the risk stratification and prognostication for NPC.

Effects of writers, erasers and readers within miRNA-related m6A modification in cancers.

BACKGROUND: As one of the most abundant post-transcriptional mRNA modifications, N6-methyladenosine (m6A) has attracted extensive attention from scientists. Emerging evidence indicates that m6A modification plays a significant role in cancer-related signalling pathways. Existing research demonstrates that m6A modifications were also identified in miRNAs and contribute to cancer-related signalling pathways. METHODS: A literature retrieval has been performed to collect m6A-miRNA-related original articles published in recent years. Later, a systematic analysis has been conducted to abstract and classify the relationships between m6A modification and miRNAs, and their contributions to tumorigenesis and cancer development. RESULTS: Accumulating literature provides important insights into multiple relationships between m6A modifications and miRNAs. Mechanically, m6A writer and eraser alter pri-miRNAs m6A levels, and m6A readers could dually modulate pri-miRNAs processing and pri-miRNAs degradation. It is also been demonstrated that miRNAs impair m6A regulators' translation to influence m6A medication function in return. Aberrant expressions of m6A regulators and miRNAs could dysregulate proliferative, apoptosis, cell adhesion-related, and malignant transformation signalling pathways, and contribute to tumour occurrence and development. CONCLUSION: This review summarizes the interrelationship between m6A modification and miRNAs; highlights the combined effects of each type of m6A regulator and miRNAs in cancers. These findings enhance our understanding of m6A-miRNAs' multiple interactions and significant modulatory role in tumorigenesis and progression.

Systemic immune-inflammation index during treatment predicts prognosis and guides clinical treatment in patients with nasopharyngeal carcinoma.

PURPOSE: Systemic immune-inflammation index (SII) has been demonstrated to be closely associated with the poor prognosis of nasopharyngeal carcinoma (NPC). However, the role of SII during treatment of NPC has not been reported. This study aimed to determine the prognostic value of SII during treatment for NPC patients. METHODS: A total of 759 patients diagnosed with NPC were included in this retrospective study (393 in training cohort and 366 in validation cohort). The correlation between variables was analyzed by the chi-squared test, the Fisher's exact test or the likelihood test. Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The independent prognostic factors were determined by multivariate analysis of Cox proportional hazards regression model. The uncontrolled risk was analyzed by Logistic regression. Receiver operating characteristic (ROC) curves were used to assess prognostic value. RESULTS: The optimal cut-off point for the SII during treatment was 937.32. High SII during treatment group had higher uncontrolled risk than low SII during treatment group (p = 0.008). In multivariate Cox proportional hazard models analysis, SII during treatment was an independent prognostic factor for 5-year PFS (p < 0.001) and 5-year OS (p < 0.001). All results were found in the training cohort and confirmed in the validation cohort. CONCLUSIONS: The SII during treatment is a promising indicator of predicting the survival in NPC patients, especially the risk of uncontrolled occurrence. By monitoring the SII during treatment, it is possible to better evaluate the treatment effect and formulate personalized treatment.

Integrating pre- and post-treatment Plasma Epstein-Barr Virus DNA levels for better prognostic prediction of Nasopharyngeal Carcinoma.

Background: Pre- and post-treatment plasma Epstein-Barr virus (EBV) DNA are important biomarkers for the prognosis of nasopharyngeal carcinoma (NPC). This study was performed to determine the prognostic potential of integrating EBV DNA levels in plasma measured pre-treatment (pre-EBV) and 3 months post-treatment (3 m-EBV). Materials and methods: A total of 543 incident non-metastatic NPC patients treated with intensity-modulated radiotherapy, with or without chemotherapy, were reviewed. Patients were divided into four subgroups based on pre-EBV and 3 m-EBV status. The data for pre-EBV and 3 m-EBV samples were integrated, and the predictability of the survival of patients with NPC was analyzed. Results: There were significant differences in the 5-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival among the four patient subgroups (P<0.001). Patients who tested negative for both pre-EBV and 3 m-EBV had the best prognosis, followed by patients who tested positive for pre-EBV and negative for 3 m-EBV, and those who tested negative for pre-EBV and positive for 3 m-EBV; however, patients who tested positive for both pre-EBV and 3 m-EBV had the poorest chances of survival. Multivariate analyses demonstrated that integration of pre-EBV and 3 m-EBV data was an independent predictor of NPC progression in patients. Receiver operating characteristic curve analysis further confirmed that the combination of pre-EBV and 3 m-EBV had a greater prognostic value than pre-EBV or 3 m-EBV alone. Conclusions: Integrating pre-EBV and 3 m-EBV data could provide more accurate risk stratification and better prognostic prediction in NPC.