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Objectives: Current guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM., Methods and Materials: 18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance., Results: Pre-treatment Epstein-Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels., Conclusion: The PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC., Methods: This retrospective study reviewed the results of EGFR expression and pretreatment 18 F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan-Meier., Results: The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS., Conclusion: The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy., (© 2023. The Author(s).)

Introduction: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [ 18 F] fluorodeoxyglucose positron emission tomography and computed tomography ( 18 F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas., Materials and Methods: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed., Results: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group., Conclusions: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18 F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis., (© 2021. The Author(s).)

Background: Previous studies showed poorer survival in T4 disease with residual lesion. To evaluate the efficacy and toxicity of a boost dose for T4 nasopharyngeal carcinoma (NPC), patients with a residual primary lesion after intensity-modulated radiotherapy (IMRT)., Methods: 398 T4 NPC patients with residual primary lesions after radical IMRT were retrospectively reviewed. An IMRT boost dose of 4-6.75 Gy was delivered to the residual lesions in 2-3 fractions. Propensity score matching (PSM) was applied to balance potential confounders between groups (ratio, 1:2). The presence of Epstein-Barr virus (EBV) DNA in plasma after IMRT was used for risk stratification., Results: Patients who received boost radiation had significantly improved overall survival (OS) and local recurrence-free survival (LRFS) compared with those who did not (all P < 0.05). In the matched cohort, 3-year OS was 86.6% in the boost radiation group and 72.7% in the non-boost group (P = 0.022). Three-year LRFS was 93.4% in the boost radiation group and 83.5% in the non-boost group (P = 0.022). In the subgroup analysis, boost dose was shown to significantly improve 3-year OS (88.0% vs. 74.1%, P = 0.021) in the low-risk group (with undetectable plasma EBV DNA after IMRT). The administration of a boost dose also improved 3-year OS in the high-risk group (with detectable plasma EBV DNA after IMRT) (66.7% vs. 60.0%, P = 0.375). Multivariate analysis demonstrated that boost dose was the only protective prognostic factor., Conclusion: The addition of a boost dose for T4 NPC patients with residual primary lesion after radical IMRT provides satisfactory tumor control and clinical benefit. Additional timely and effective strengthening treatments are recommended for patients with detectable levels of plasma EBV DNA after radiotherapy.

Background: This study aimed to assess the effectiveness and cost-effectiveness of nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC)., Methods: LA-NPC patients treated between October 2013 and December 2016 were retrospectively reviewed. A well-balanced cohort of patients who received nimotuzumab in addition to standard treatment (n = 50) and patients who did not receive nimotuzumab (n = 100) was selected using propensity score-matching method (1:2 ratio) for the cost-effectiveness analysis., Results: Compared with concurrent chemoradiotherapy (CCRT) alone, addition of nimotuzumab to CCRT significantly improved the 3-year overall survival (OS) (98.00% vs. 91.00%, P = 0.032). On multivariate analysis, nimotuzumab (hazard ratio = 0.124, 95% confidence interval: 0.017-0.902, P = 0.039) showed prognostic significance for OS. No serious treatment-related adverse events were observed in the nimotuzumab group (P > 0.05). Cost-effectiveness analysis revealed that addition of nimotuzumab increased the average treatment costs by $14,364.63. The additional cost for every one percent increase in OS rate was $ 2,052.09., Conclusion: Addition of nimotuzumab to CCRT for LA-NPC confers significant survival benefits; however, it is not cost-effective.

Nasopharyngeal carcinoma (NPC) is the most common cancer with high metastatic potential that occurs in the epithelial cells of the nasopharynx. Distant metastases are the primary cause for treatment failure and mortality of NPC patients. However, the underlying mechanism responsible for the initiation of tumour cell dissemination and tumour metastasis in NPC is not well understood. Here, we demonstrated that epidermal growth factor receptor (EGFR) was highly expressed in tumour tissues of NPC patients with distant metastases and was associated with a decrease in reactive oxygen species (ROS). We also revealed that extracellular vesicles (EVs) transfer occurred from highly to poorly metastatic NPC cells, mediating cell-cell communication and enhancing the metastatic potential of poorly metastatic NPC cells. Further experiments indicated that EVs derived from highly metastatic NPC cells induced the up-regulation of EGFR and down-regulation of ROS in low metastatic NPC cells. Mechanistically, EGFR-rich EVs-mediated EGFR overexpression down-regulated intracellular ROS levels through the PI3K/AKT pathway, thus promoting the metastatic potential of poorly metastatic NPC cells. Strikingly, treatment with EVs secreted from highly metastatic NPC cells was significantly associated with rapid NPC progression and shorter survival in xenografted mice. These findings not only improve our understanding of EVs-mediated NPC metastatic mechanism but also have important implications for the detection and treatment of NPC patients accompanied by aberrant EGFR-rich EVs transmission., Competing Interests: The authors report no conflict of interest., (© 2020 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background and Purpose: We evaluated the relationship between patient-, tumor-, and treatment-related features and radiation-induced lymphopenia (RIL) and evaluated the correlation between RIL and survival outcome in NPC patients to help improve the treatment strategy., Methods: This retrospective study included 374 patients with stage II-IVa NPC who had been treated with definitive RT and were enrolled from 2004 to 2015; The associations between the G3-4 RIL (absolute lymphocyte count, ALC <  0.5 × 10 9 cells/L) during RT and patient-, tumor-, and treatment-related factors were assessed using Cox regression analyses. The correlation between ALC nadir and survival was examined using a Kaplan-Meier analysis, compared with the log-rank test, and confirmed by a Cox proportional hazards analysis., Results: In the multivariate analysis, lower baseline ALC and intensity modulated radiation therapy (IMRT) (vs. 2 dimensional-conformal radiation therapy,2D-CRT) were identified as 2 independent factors that were associated with G3-4 RIL. In the multivariate survival analysis, patients with G3-4 ALC nadir had longer local recurrence-free survival durations (LRFS) (vs. G0-2 nadir, HR = 0.548, P = 0.005) and longer progression-free survival durations (PFS) (vs. G0-2 nadir, HR = 0.676, P = 0.022), while patients with G4 ALC nadir had a shorter distant-metastasis-free survival duration (DMFS) (vs. G0-2 nadir, hazard ratio [HR] = 2.567, P = 0.037)., Conclusions: In the study, lymphopenia during RT were affected by baseline ALC and RT modality independently. Moreover, G3-4 ALC nadir was independently linked with longer PFS and LRFS durations, while G4 ALC nadir was independently linked with a shorter DMFS duration.

Purpose: A randomized phase III trial demonstrated that gemcitabine plus cisplatin (GP) prolonged progression-free survival and overall survival compared with fluorouracil plus cisplatin (FP) as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). The cost-effectiveness analysis was designed to identify the economic option for metastatic NPC from a Chinese societal perspective., Methods: We established a Markov model that involved three health states representing the stages of disease to simulate therapy. Survival data of clinical outcomes were derived from the trial and adjusted to quality-adjusted life years (QALYs). Transition probabilities and health utilities were obtained from the clinical trial and published literatures. The cost-effective strategy was estimated for these treatments using a willing-to-pay (WTP) threshold. A one-way sensitivity analysis was conducted to study the influences of parameters., Results: GP treatment group produced a gain of 0.37 QALYs with an incremental cost of $2520.80, yielding an incremental cost-effectiveness ratio (ICER) of $6812.97 per QALY, compared with FP treatment ($15,530.96 versus $13,010.16). The ICER was lower than the accepted WTP threshold, which was 3 times gross domestic product per capita of China ($25,749 per QALY)., Conclusion: GP regimen is more cost-effective compared with FP regimen as the first-line treatment for Chinese patients with metastatic NPC.

Gambogenic acid (GNA) is one of the main components of Gamboge, and its anti-cancer effects have been well confirmed by previous researches. Nasopharyngeal carcinoma (NPC) has not been thoroughly studied, and the pathogenesis of NPC is unclear. Scientists have neither discovered effective therapies nor achieved a desirable prognosis. Some studies have found that the regulation of intra- and extracellular ion channels hinges directly on cell apoptosis, and treatment with GNA brings changes to the volume-sensitive outwardly rectifying chloride (VSOR Cl - ) current of CNE-2Z cells recorded by the patch clamp method. Nevertheless, rarely have any researchers probed into the relevance between this variation and the anti-tumor mechanism of GNA. This paper is suggested that 2.0 μmol/L GNA activates VSOR Cl - currents on CNE-2Z cell membranes and that the activation of VSOR Cl - currents by GNA in CNE-2Z cells is blocked by the chloride channel blockers DIDS (400 μmol/L) and DCPIB (20 μmol/L). MQAE experiment further proves that GNA leads to the opening of chloride ion channel, which in turn results in the efflux of VSOR Cl - current; GNA induces the downregulation of GRP78 and the upregulation of ATF4 and CHOP proteins. These effects are correlated with endoplasmic reticulum (ER) stress. GNA can activate VSOR Cl - channels, leading to ER stress, inducing apoptosis and inhibiting proliferation in CNE-2Z cells., (Copyright © 2019. Published by Elsevier B.V.)

Background: To identify patients at low risk of synchronous bone metastasis who should not receive bone scans when initially diagnosed with nasopharyngeal carcinoma (NPC). Methods: In total, 6652 patients were enrolled in the training cohort and 1919 patients in the multicenter external validation cohort. Logistic regression analyses were performed to assess independent predictors of synchronous bone metastasis for the nomogram model. Results: After risk stratification, 46.3% (3081/6652) patients were separated into the low‐risk group with an incidence of 0.71% for synchronous bone metastasis. The odds ratio of the intermediate and high‐risk groups was 5.61 and 23.82 times that of the low‐risk group, respectively. For patients with high EBV DNA, we recommend routine screening for N2‐3 female patients, but that all male subgroups are screened. Conclusions: Bone scans should not be routine. Patients in the low‐risk group should not be screened, which would avoid excessive radiation and economize iatrical resource. [ABSTRACT FROM AUTHOR]

Background: To develop a common follow‐up strategy for appropriate imaging examination at an appropriate time for nasopharyngeal carcinoma (NPC). Methods: Independent prognostic factors were identified by Cox regression analysis, and a nomogram model was developed. Random survival forest (RSF) model was constructed to depict probability of disease failure during a 5‐year follow‐up and establish a reasonable risk‐based follow‐up strategy. Results: The nomogram model finally categorized the patients into three risk groups. RSF model demonstrated distribution trends for local and regional recurrences, bone metastasis, liver metastasis, and lung metastasis of NPC. Adequate imaging at follow‐up should be considered between 10 and 21 months for patients at moderate‐risk of recurrence or metastasis and 7–36 months for those at high‐risk. Conclusions: The temporal distribution of incidence rates of recurrence or metastasis varied among different risk groups. We recommend implementing a focused and targeted imaging surveillance intervention at appropriate times to improve its efficiency and reduce costs. [ABSTRACT FROM AUTHOR]

Background: To rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET).Methods: We retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan-Meier and Cox regression analyses were used to assess survival.Results: The optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039-3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021-2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214-5.325, P = 0.013).Conclusion: High SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential. [ABSTRACT FROM AUTHOR]

Introduction: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [18F] fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas.Materials and Methods: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed.Results: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group.Conclusions: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between absolute neutrophils count (ANC) in different periods of treatment and the outcomes of patients and assess effect of longitudinal neutrophils variation during radiotherapy (RT) on prognosis in patients with nasopharyngeal carcinoma (NPC). Methods: A total of 1753 patients with newly diagnosed NPC were retrospectively analyzed. Complete blood counts of patients were obtained before treatment, before, during, and end of RT. The survival rate was calculated by Kaplan‐Meier method and the result was compared by the log‐rank test. The univariate and multivariate COX regression analyses were performed to investigate the association between the variation of ANC and survival for patients in different periods. Results: Higher ANC pretreatment (>4 × 109/L) and pre‐RT (>7 × 109/L) were correlated with poor OS (89.7% vs 85.6%, P =.009; 88.3% vs 77.3%, P =.002, respectively). An increase >5 × 109/L of ANC during RT was associated with adverse OS (87.9% vs 73.6%, P =.042). The multivariate Cox regression analysis showed that high ANC of pre‐RT (>7 × 109/L) and a high increase (>5 × 109/L) of ANC during RT were independent prognostic factors of patients with NPC (P =.002,.044, respectively). Conclusion: Our results demonstrated that ANC was an independent prognostic factor for survival in patients with NPC who received RT. Neutrophils may promote tumor resistance to radiotherapy in NPC. Level of Evidence: 2a. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the survival and prognosis of older patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy using propensity score matching (PSM). We enrolled 841 older patients with NPC aged 60 years and above without metastasis receiving IMRT alone or chemoradiotherapy from 2012 to 2019. The comorbidity was assessed by adult comorbidity evaluation (ACE-27). PSM (1:3 ratio) was conducted between the two treatment groups based on four clinical factors including age, T-stage, N-stage, and ACE-27. Differences in overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method and Cox proportional hazard model. A total of 841 patients with NPC were included in the study, there were 94 patients in the IMRT alone group and 747 patients in the chemoradiotherapy (CRT) group. After a 1:3 ratio PSM, 89 patients underwent IMRT alone and 223 patients underwent CRT. The baseline analysis showed an insignificant difference after PSM (P > 0.05). In multivariate analysis, we found that ACE-27 (≥2) was associated with worse five-year OS and CSS (HR = 1.994, 95%CI: 1.276–3.116, P = 0.002; HR = 1.849, 95%CI: 1164–2.935, P = 0.009, respectively). Chemotherapy was an independent prognosticator of better five-year OS and CSS (HR = 0.333, 95%CI: 0.213–0.552, P < 0.001; HR = 0.327, 95%CI: 0.204–0.524, P < 0.001, respectively). In terms of subgroup analysis, chemotherapy was a statistically beneficial predictor for stage III-IV patients (P < 0.05), but no significant difference in stage II patients (P > 0.05). About the adverse events, the incidence of hepatotoxicity (P = 0.002), neutropenia (P < 0.001), anemia (P < 0.001), and thrombocytopenia (P < 0.001) were significantly higher in the CRT group. Combined modality therapy was associated with improved five-year OS and CSS in older adults with stage III-IV NPC, but was not associated with improved survival over IMRT alone in patients with stage II disease. Risk factors including T3–4 disease, positive lymph nodes, ACE-27 score ≥ 2, and IMRT alone were were associated with worse OS and CSS. There was a significantly higher incidence of hepatotoxicity and blood toxicity in the CRT group. [ABSTRACT FROM AUTHOR]

Purpose: Nasopharyngeal carcinoma (NPC) is more common among women in Southeast Asia. An important issue is whether it is safe for them to bear children after treatment and when it is safe to do so. We conducted this study to explore the relation between fertility and prognosis in child-bearing women with NPC. Patients and Methods: Child-bearing women were defined as young women between the ages of 18 and 30. A total of 127 eligible child-bearing NPC patients were identified from December 2003 to December 2014. The patients were divided into two groups, depending on whether or not they had post-therapeutic births. The Kaplan–Meier method was used for survival analyses. The Log rank test was used to compare two survival curves and the independent significances of different prognostic factors were assessed by Cox proportional hazards regression analysis. Results: The 5-year overall survival (OS) and disease-free survival (DFS) in the Childbirth group were significantly higher than those in the Non-Childbirth group (100% vs 88.8%, P = 0.026 and 100% vs 77.5%, P = 0.007, respectively). In the Childbirth group, no difference was found in the 5-year DFS between different birth interval times, from 1 to 5 years after treatment. The clinical stage was identified as the risk factor of OS (HR = 101.725, 95% CI: 2.160– 4790.910, P = 0.019), and consequent childbirth after treatment was associated with favorable DFS (HR = 0.148, 95% CI: 0.034– 0.643, P = 0.011). Conclusion: Post-therapeutic birth did not increase the mortality risk of child-bearing women with NPC. There was no significant correlation between the subsequent birth time window after treatment and the prognosis. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma, Radiotherapy, Artificial intelligence, Psychosocial support. [Extracted from the article]

• Systematically evaluated seven N stage schemes using a quantification system. • Big retropharyngeal lymph node is an independent prognostic factor for NPC. • Radiological extranodal extension infiltrating surrounding structures (ENEmax) is a strong prognostic factor but simply upgrading ENEmax to N3 should be considered with caution. To identify the prognostic value of the nodal features, propose a nomogram-based N stage system and evaluate the performance of seven N stage schemes of nasopharyngeal carcinoma (NPC) patients. Data from 1638 non-distant metastatic NPC patients were used to develop nomograms predicting 3-year and 5-year overall survival (OS) and distant metastasis-free survival (DMFS). Based on nomogram and multivariate analyses, a new N-stage scheme was proposed. The performance of the nomogram-based N staging system was assessed against five newly proposed N staging systems and the current 8th N staging system using a quantitative model to compare hazard consistency, discrimination, outcome prediction, and sample size balance. The Kaplan-Meier method with log-rank tests was used to compare survival differences. Nomograms to predict OS and DMFS were constructed using extranodal extension infiltrating the surrounding structures (ENEmax), maximal axial diameter (MAD), large retropharyngeal lymph nodes (RLN, minimal axial diameter > 1.5 cm), multiple central nodal necrosis (CNN), and total lymph node (LN) number and level. Multivariate analysis showed the independent prognostic value of ENEmax and MAD > 3 cm for all selected survival endpoints (p < 0.05). Large RLN and lower neck involvement were independently associated with OS (p < 0.05). We proposed using a large RLN and MAD > 3 cm as N2 factors, and ENEmax and lower neck involvement as N3 factors. Among the seven N-stage schemes, our nomogram-based N scheme and ENEmax to N3 scheme (ENE3) ranked in the top two in the overall comparison with the elevated outcome predicting value (highest c-index). However, between the N0, N1, N1, and N2 subgroups, the ENE3 scheme showed no difference in OS or DMFS (p > 0.05). The predictive model highlighted the independent prognostic value of ENEmax, cervical lymph node, MAD, and large RLN, which can be used as criteria for future N staging. [ABSTRACT FROM AUTHOR]

Aim of the study Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). Methods Patients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m 2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m 2 and fluorouracil 800 mg/m 2 /d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. Results Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14). Conclusion Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. Registration number NCT00677118 . [ABSTRACT FROM AUTHOR]