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Background: The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA.Methods: In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT.Results: The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA >2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance.Conclusions: The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC. [ABSTRACT FROM AUTHOR]

Objective: This study focused on developing an effective nomogram for improving prognostication for patients with primary nasopharyngeal carcinoma (NPC) restaged according to the eighth edition of the AJCC/UICC TNM staging system. Methods: Based on data of 5,903 patients with non-metastatic NPC (primary cohort), we used Cox regression analysis to identify survival risk factors and created a nomogram. We used the nomogram to predict overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the primary and independent validation (3,437 patients) cohorts. Moreover, we compared the prognostic accuracy between the 8th TNM system and the nomogram. Results: The nomogram included gender, age, T stage, N stage, Epstein–Barr virus DNA, hemoglobin, C-reactive protein, lactate dehydrogenase, and radiotherapy with/without induction or concurrent chemotherapy. In the prediction of OS, DMFS and DFS, the nomogram had significantly higher concordance index (C-index) and area under ROC curve (AUC) than the TNM system alone. Calibration curves demonstrated satisfactory agreements between nomogram-predicted and observed survival. The stratification in different groups permitted remarkable differentiation among Kaplan–Meier curves for OS, DMFS, and DFS. Conclusion: The nomogram led to a more precise prognostic prediction for NPC patients in comparison with the 8th TNM system. Therefore, it could facilitate individualized and personalized patients' counseling and care. [ABSTRACT FROM AUTHOR]

Dear Editor, The anatomic extent or stage of cancer provides the critical benchmarks and standards for defining prognosis and for determining the best treatment approach, and it also presents stratification criteria for clinical trials and consistent nomenclature for exchanging experience.1,2 The AJCC/UICC TNM staging system is widely used in tumor staging worldwide due to its periodic revision supported by high-quality evidence.1,2 In response to the better delineation of tumor extent resulting from advances in imaging techniques, the latest released 8th edition staging system of nasopharyngeal carcinoma (NPC) empirically introduces cervical vertebrae invasion (CVI) into T3 and parotid gland invasion (PGI) into T4. The 5-year OS of patients in T2'-3' group with CVI and/or PGI ranged from 67% to 75%, which was worse than that of patients in T2'-3' group without CVI/PGI (86%), and comparable to that of patients in T4' (77%). The presence of CVI/PGI was associated with advanced disease and poor prognosis, which served as evidence for the introduction of CVI and PGI into the 8th edition T category. [Extracted from the article]

Objectives: To investigate the prognostic value of magnetic resonance imaging (MRI)‐determined cervical lymph node (CLN) size in nasopharyngeal carcinoma (NPC). Methods: We retrospectively reviewed 2066 patients with NPC treated with intensity‐modulated radiotherapy, and randomly divided them into two groups, in a 1:1 ratio. One group was used for training (the training group), and the other one was for internal validation (the validation group). All patients had undergone MRI examination and the maximal axial diameters (MAD) of the axial plane of all positive nodes had been measured and recorded. Results: Of 683 patients with CLN metastases in the training group (n = 1033), MAD = 4 cm was associated with worse OS (64.7% vs 84.6%, P <.001), DFS (55.9% vs 76.3%, P =.001), and DMFS (67.6% vs 86.1%, P =.001). Multivariate analysis showed that MAD = 4 cm was a significant negative prognostic factor for OS (HR = 2.058; P =.025), DFS (HR = 1.727; P =.049), and DMFS (HR = 2.034; P =.036). When MRI‐determined MAD = 4 cm was classified as N3 in the N classification, the OS, DFS, DMFS, and RRFS survival curves were well separated. The OS, DFS, DMFS, and RRFS concordance indexes were not statistically different between the proposed N staging system and the UICC/AJCC staging system in the training group, or between the training group and the validation group (all P =.05). Conclusion: MAD = 4 cm on axial MRI slices can be recommended as a prognostic factor in future versions of the UICC/AJCC NPC staging system. [ABSTRACT FROM AUTHOR]

Background: The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) have independently developed their own frameworks to assess the benefits of different cancer treatment options, which have significant implications in health science and policy. We aimed to compare these frameworks in nasopharyngeal carcinoma. Methods: We identified all randomized controlled trials of systemic chemotherapies for nasopharyngeal carcinoma until April 5th, 2020. Trials were eligible if significant differences favoring the experimental group in a prespecified primary or secondary outcome were reported. Two assessors independently scored the trials and the final scores were determined by consensus. Results: Fifteen trials were included in the analysis. Five different toxicity grading criteria were applied to the 15 trials. Ten (66.7%) trials did not report grade 1–2 toxicities and eight (53.3%) did not report late toxicities. The number of acute toxicities reported was strikingly different (17 vs. 8) in two trials using the same regimen. All trials met the ESMO criteria for a high level of benefit. However, significant variations in ASCO scores between trials were observed (mean [standard deviation]: 38.9 [20.0]). Conclusions: The underreporting and inconsistent reporting of toxicities would significantly impair the assessment of value using any framework. Moreover, there is a concern that the ASCO framework generated highly inconsistent scoring for treatments that met the ESMO criteria for a high level of benefit. The anomalies identified in the frameworks function would be helpful in their future improvement. [ABSTRACT FROM AUTHOR]

Background: The treatment effects of cumulative cisplatin dose (CCD) during radiotherapy (RT) following induction chemotherapy (IC) have not been determined for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 3460 patients with locoregionally advanced NPC who were treated with IC plus cisplatin-based concurrent chemoradiotherapy or RT alone were included in this retrospective study. Three CCD groups (0 mg/m2 ⩽ CCD <100 mg/m2, 100 mg/m2 ⩽ CCD <200 mg/m2, CCD ⩾200 mg/m2) were balanced through the inverse probability of treatment weighting based on propensity scores estimated by a general boosted model. The primary endpoint was overall survival (OS); the secondary endpoints were distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). Results: CCD ⩾200 mg/m2 and <200 mg/m2 exhibited similar treatment effects for OS and DMFS, and were both superior to CCD <100 mg/m2 for OS and DMFS in patients with stage IVa NPC. The three CCD groups achieved similar treatment effects for patients with stage II–III NPC. After IC, CCD during RT appeared to exert little treatment effect on LRFS. Conclusion: The CCD during RT exerts treatment effects and improves OS by reducing the risk of distant metastasis for patients with stage IVa NPC following IC, and CCD <200 mg/m2 (mainly 160 mg/m2 in this group) is recommended. However, RT alone may be sufficient after IC in patients with stage II–III NPC. [ABSTRACT FROM AUTHOR]

Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC. [ABSTRACT FROM AUTHOR]

Purpose: The National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) provide surveillance guidelines for nasopharyngeal carcinoma (NPC). We evaluated the ability of these guidelines to capture disease recurrence. Materials and methods: All 749 NPC patients were stratified for analysis by T and N stage. We evaluated the guidelines by calculating the percentage of relapses detected when following the 2018 NCCN, 2015 NCCN, and 2012 ESMO surveillance guidelines, and related surveillance costs were compared. Results: At a median follow-up of 100.8 months, 168 patients (22.4%) had experienced recurrence. Nineteen recurrences (11.3%) were detected using the 2018 NCCN, 53 (31.5%) using the 2015 NCCN and 46 (27.4%) using the ESMO guidelines. To capture 95% recurrences, surveillance would be required for 85.57 months for T1/2, 67.45 months for T3/4, 83.57 months for N0/1, and 55.80 months for N2/3 disease. In T1/2 disease, Medicare surveillance costs per patient were US$1642.66 using 2018 NCCN or ESMO and US$2179.81 using 2015 NCCN. Costs per recurrence detected were US$42,578.64, 62,088.70, and 73,329.76 using 2018 NCCN, 2015 NCCN, and ESMO, respectively. Conclusions: If strictly followed, the NCCN and ESMO guidelines will miss more than two-thirds recurrences. Improved surveillance algorithms to balance patient benefit against costs are needed. [ABSTRACT FROM AUTHOR]

Objectives: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC) merged T4N0-2 and T1-4N3 to create stage IVa. In the present study, we aimed to assess the difference in clinical outcomes and patterns of failure between 8th AJCC T4N0-2 and T1-4N3 NPC patients treated with intensity-modulated radiotherapy (IMRT).Methods: We included 3107 patients with stage IVa NPC disease (1871 with T4N0-2 and 1236 with T1-4N3) according to the 8th AJCC staging system. Overall survival (OS) was the primary endpoint. The clinical outcomes between T4N0-2 and T1-4N3 patients were compared.Results: T1-4N3 patients had significantly worse 3-year OS (84.1% vs. 89.2%; p < 0.001) and distant metastasis-free survival (DMFS; 78.3% vs. 85.9%; p < 0.001), but better local relapse-free survival (LRFS; 94.9% vs. 92.2%; p = 0.003), as compared with T4N0-2 patients. Multivariate analysis showed that T1-4N3 was still an independent adverse prognostic factor for both DMFS (hazard ratio [HR] = 1.517, 95% confidence interval [CI] = 1.274-1.806, p < 0.001) and OS (HR = 1.315, 95% CI = 1.100-1.572, p = 0.003), whereas T4N0-2 was an independent adverse prognostic factor for LRFS (HR = 1.581, 95% CI = 1.158-2.158, p = 0.004).Conclusions: In terms of the OS, T4N0-2 patients had better prognosis compared with T1-4N3 patients, and the patterns of failure differed between T4N0-2 and T1-4N3 patients. We believe that future modifications of the AJCC/UICC staging system should separate T4N0-2 from T1-4N3.Key Points: • In nasopharyngeal carcinoma, T4N0-2 patients tended to develop local relapse, whereas T1-4N3 patients were more likely to develop distant metastasis. • In terms of overall survival, T4N0-2 patients had better prognosis than T1-4N3 patients. • T4N0-2 should be separated from T1-4N3 in the UICC/AJCC staging system. [ABSTRACT FROM AUTHOR]

Background and Purpose: Evidence for induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) in nasopharyngeal carcinoma (NPC) was derived from landmark clinical trials excluding the T3N0, T3N1, T4N0 subgroups. This study used Epstein-Barr virus (EBV) DNA to select IC beneficiaries from the three subgroups. Materials and Methods: Significant predictors of overall survival (OS) were identified using multivariate Cox analyses. Risk stratification was generated using recursive partitioning analysis (RPA). IC+CCRT was compared with CCRT in each risk stratification and in different subgroups. Individual-level data from a clinical trial (NCT01245959) was used for validation. Results: Gender and EBV DNA were included in RPA-generated risk stratification, categorizing patients into low-risk (EBV DNA <2,000 copies/mL; female and EBV DNA ≥2,000 copies/mL) and high-risk groups (male and EBV DNA ≥2,000 copies/mL). The OS superiority of IC+CCRT over CCRT was only observed in the high-risk group (HR = 0.64, 95% CI = 0.43–0.97; P = 0.032). Subgroup analysis indicated the OS benefit was exclusively from the docetaxel–cisplatin−5-fluorouracil regimen (HR = 0.41, 95% CI = 0.22–0.78; P = 0.005). The status of the T3N1 subgroup as an IC beneficiary is more explicit than the T3N0 and T4N0 subgroups. IC+CCRT showed improved OS in the validation cohort combining high-risk cases of real-world data with clinical trial data (HR = 0.62, 95% CI = 0.42–0.94; P = 0.023). Conclusion: Patients with high-risk T3N1 NPC is the definite target population for receiving IC+CCRT in real-world practice. T3N0 and T4N0 subgroups need further investigations in future IC-related studies. [ABSTRACT FROM AUTHOR]

Background: To identify thyroid dose‐volume thresholds for radiotherapy (RT)‐related hypothyroidism (HT) in patients with nasopharyngeal carcinoma (NPC) treated with intensity‐modulated RT (IMRT). In this way, we desired to guide the design of treatment plans and, finally, lower HT prevalence. Methods: In total, 345 NPC patients treated with IMRT were evaluated retrospectively during a median follow‐up of 45.2 (range, 11.3‐64.9) months. Serum‐based assessments of thyroid function before and after IMRT were monitored periodically. Thyroid dose‐volume parameters were analyzed for their association with HT risk. Results: In total, 44.1% of patients (152/345) developed primary HT. Analyses of thyroid dose‐volume parameters identified a stringent dose‐volume histogram (DVH) threshold defined by V25Gy (the percentage thyroid volume that receives >25 Gy, not the absolute volume) ≤60%, V35Gy ≤ 55%, and V45Gy ≤ 45%. Patients whose thyroid DVHs satisfied these constraints had a lower prevalence of 2‐year HT compared with the overall prevalence (13.2% vs 25.8%, P < .001). Another DVH was defined by V25Gy > 95%, V35Gy > 90%, and V45Gy > 75%, and patients whose thyroid DVHs satisfied with these constraints had a higher prevalence of 2‐year HT than the overall incidence (36.0% vs 25.8%, P < .001). Conclusion: We recommend V25Gy ≤ 60%, V35Gy ≤ 55%, and V45Gy ≤ 45% as the "stringent" DVH line, and V25Gy > 95%, V35Gy > 90%, and V45Gy > 75% as the "inhibition" DVH line, under the precondition of not compromising the target coverage. These findings could help in the design of individual treatment plans and, eventually, to lowering of HT prevalence. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated the prognostic value of the integrated model consisting of gross tumor volume of lymph nodes (GTVnd) and pretreatment plasma Epstein–Barr virus DNA (pre-EBV DNA) in nasopharyngeal carcinoma (NPC) patients. Methods: A well-established big-data intelligence platform with 10,126 NPC patients was used for a retrospective review. A total of 1500 cases with cervical nodal metastases but without distant metastases were randomly assigned to a training (n = 503) or test condition (n = 997) for analyses. The cut-off point for the GTVnd derived from the receiver operating characteristic (ROC) curve was combined with the published cut-off point for pre-EBV DNA to develop an integrated model by which patients were classified into four groups. Results: Both GTVnd and pre-EBV DNA were independent prognostic factors. Regardless of whether patients received induction chemotherapy (IC), the 5-year distant metastasis-free survival (DMFS) (69.5%) and overall survival (OS) (68.4%) were significantly worse in those with both a GTVnd >20 ml and pre-EBV DNA >2000 copies/ml (all p- values < 0.001). In patients with IC, all others had better 5-year DMFS and OS; in patients without IC, those with either a GTVnd >20 ml or pre-EBV DNA >2000 copies/ml had the medium 5-year DMFS and OS, while patients with neither of them had the best. Conclusions: The integrated GTVnd and pre-EBV DNA model not only predicted DMFS and OS in NPC patients effectively, but was an indicator of timely adjustment of therapeutic strategies for NPC patients, especially those completing IC. [ABSTRACT FROM AUTHOR]

Background: Intensity‐modulated radiotherapy (IMRT) provides excellent local control in nasopharyngeal carcinoma (NPC). We investigated whether simplifying 8th American Joint Committee on Cancer staging system T categories improves prognostic value. Methods: We used 2191 NPC patients as a training set and 414 patients separately as an independent, external validation cohort. Results: In the training set, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS) were not significantly different between the 8th edition T2/T3 (P = 0.610, 0.380 and 0.353, respectively). Merging T2 and T3 to proposed T2 (proT2) provided significant differences in LRFS, DFS, and OS between proposed T categories. Proposed T categories had similar c‐indices for LRFS, DFS, and OS (vs the 8th edition), which was validated in the external cohorts. Moreover, for DFS, the adjusted HRs of the proT2N0 (3.8), proT1N1 (3.8), and proT2N1 (6.0) subsets were similar; the adjusted HRs of the proT3N0 (7.0), proT3N1 (11.4), proT1N2 (11.0), proT2N2 (11.6), and proT3N2 (13.3) subsets were similar; the adjusted HRs of the proT1N3 (17.8), proT2N3 (15.3), and proT3N3 (26.4) subsets were similar; the results of the adjusted HRs for OS had the same rule. Defining proT1N0 as stage I; proT1N1/proT2N0‐1 as stage II; proT3N0‐2/proT1‐2N2 as stage III; and proT1‐3N3 as stage IVa generated orderly, significant differences in DFS and OS between stages in the training set and external validation cohort. Conclusions: In the IMRT era, three T categories are more reasonable (merging T2/T3 into T2) and proT3N0‐2 (the 8th edition T4N0‐2) should be down‐staged to stage III.Survival outcomes cannot be discriminated between the 8th edition of AJCC T2/T3 NPC. The simplified T category had similar prognostic value to the 8th edition of AJCC. The proposed staging system provided superior prognostic value than the 8th edition. [ABSTRACT FROM AUTHOR]

Detectable post‐therapy plasma Epstein–Barr virus (EBV) DNA predicts poor survival in non‐metastatic nasopharyngeal carcinoma (NPC). However, some patients subsequently experience spontaneous remission of residual EBV DNA during follow‐up and it was unclear whether these patients were still at high risk of disease failure. Using the NPC database from an established big‐data intelligence platform, 3269 NPC patients who had the plasma EBV DNA load measured at the end of therapy (± 1 week) were identified. In total, 93.0% (3031/3269) and 7.0% (238/3269) of patients had undetectable and detectable (> 0 copy/ml) plasma EBV DNA at the end of therapy (EBV DNAend), respectively. Detectable EBV DNAend was a prognostic factor for poorer 3‐year disease‐free survival (DFS), overall survival (OS), distant metastasis‐free survival (DMFS), and loco‐regional recurrence‐free survival (LRRFS) in both univariate and multivariate analyses. Of 238 patients with residual EBV DNAend, 192 underwent EBV DNA assay 3 months after and spontaneous remission occurred in 72.4% (139/192). However, these patients still had poorer 3‐year DFS (55.1% vs. 89.8%), OS (79.1% vs. 96.2%), DMFS (68.4% vs. 94.1%) and LRRFS (84.5% vs. 95.0%) than patients with undetectable EBV DNAend (all p < 0.001). And patients with persistent detectable post‐therapy EBV DNA had the worst outcomes. These results were confirmed in multivariate analysis. In conclusion, residual EBV DNA post therapy was a robust biomarker for NPC prognosis. Although residual post‐therapy EBV DNA could spontaneous remit during follow‐up, these patients were still at high risk of disease failure and such patients may benefit from adjuvant therapy. What's new?: Maintenance of circulating Epstein‐Barr virus (EBV) DNA after treatment is associated with poor disease outcome in patients with nasopharyngeal carcinoma. Here the authors focused on the small percentage of patients who initially maintain EBV DNA after therapy but eventually clear this marker from their blood. These patients maintain a high risk of disease failure when compared to patients with no detectable post‐therapy EBV DNA, underscoring the prognostic value of nuanced EBV DNA measurements after nasopharyngeal cancer treatment. [ABSTRACT FROM AUTHOR]

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Background: Pretreatment plasma Epstein‐Barr virus (EBV) DNA is an important tumor marker and prognostic factor in nasopharyngeal carcinoma (NPC). This study aimed to clarify the relationship between plasma EBV DNA level and tumor burden. Materials and Methods: Pretreatment tumor burden was measured by radiologically delineated volumes, including nasopharynx tumor volume (GTVnx) and malignant nodes volume (GTVnd); pretreatment level of plasma EBV DNA was quantified by quantitative polymerase chain reaction. The relationship between natural logarithm of EBV DNA (ln‐DNA) and square root of tumor volume (sq‐GTV) was analyzed by Pearson correlation coefficient and partial correlation coefficient. Correlations in subgroups of tumor and nodal stages were also analyzed. A linear regression model was constructed to evaluate the contribution of tumor volumes to plasma EBV DNA. The prognostic effects of EBV DNA independent of tumor burden were evaluated. Results: Two thousand two hundred and forty nine nonmetastatic NPC patients with detectable plasma EBV DNA were included in correlation analyses. Ln‐DNA showed significant correlation with sq‐GTVnx (r = 0.171) and sq‐GTVnd (r = 0.339) separately. Together, sq‐GTVnx and sq‐GTVnd could only explain 12.9% of the ln‐DNA. Tumor and nodal stages of disease could clearly influence the strength of relationship in subgroup analysis. After excluding confounding volume information, EBV DNA still can predict death and distant metastasis, but not locoregional relapse. Conclusion: This study suggests that plasma EBV DNA is not only an index of tumor burden, but may also reflect other tumor features, such as accessibility to circulation, angiogenesis, tumor cell kinetics, metabolic activity, and metastatic potential, among others. Tumor volume can only explain about 13% of pretreatment plasma Epstein‐Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma. Plasma EBV DNA may reflect more tumor features besides tumor burden. Comprehensive understanding allows for appropriate clinical application of EBV DNA. [ABSTRACT FROM AUTHOR]

Little is known about the value of the nutritional risk screening 2002 (NRS2002) scale in nasopharyngeal carcinoma (NPC). We conducted a large‐scale study to address this issue. We employed a big‐data intelligence database platform at our center and identified 3232 eligible patients treated between 2009 and 2013. Of the 3232 (12.9% of 24 986) eligible patients, 469 (14.5%), 13 (0.4%), 953 (29.5%), 1762 (54.5%) and 35 (1.1%) had NRS2002 scores of 1, 2, 3, 4 and 5, respectively. Survival outcomes were comparable between patients with NRS2002 <3 and ≥3 (original scale). However, patients with NRS2002 ≤3 vs >3 (regrouping scale) had significantly different 5‐year disease‐free survival (DFS; 82.7% vs 75.0%, P < .001), overall survival (OS; 88.8% vs 84.1%, P = .001), distant metastasis‐free survival (DMFS; 90.2% vs 85.9%, P = .001) and locoregional relapse‐free survival (LRRFS; 91.6% vs 87.2%, P = .001). Therefore, we proposed a revised NRS2002 scale, and found that it provides a better risk stratification than the original or regrouping scales for predicting DFS (area under the curve [AUC] = 0.530 vs 0.554 vs 0.577; P < .05), OS (AUC = 0.534 vs 0.563 vs 0.582; P < .05), DMFS (AUC = 0.531 vs 0.567 vs 0.590; P < .05) and LRRFS (AUC = 0.529 vs 0.542 vs 0.564; P < .05 except scale A vs B). Our proposed NRS2002 scale represents a simple, clinically useful tool for nutritional risk screening in NPC. [ABSTRACT FROM AUTHOR]

Purpose: Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database. Patients and methods: We used the keyword “nasopharyngeal carcinoma” to search the ClinicalTrials.gov database and assessed the characteristics of these trials. Results: Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001). Conclusions: The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease. [ABSTRACT FROM AUTHOR]

Little is known about the efficacy and toxicity of anti-epidermal growth factor receptor therapy concurrently with induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The present study aimed to address this question. We identified 2848 patients with newly diagnosed LA-NPC receiving IC between January 2012 and May 2015. The propensity score matching (PSM) method was used to balance various factors and to match patients. Survival outcomes and toxicities between different groups were compared. In total, 596 patients were selected at a 1:3 ratio, with 149 in the IC + CTX/NTZ group and 447 in the IC alone group. The 3-year disease-free survival, overall survival, distant metastasis- free survival and locoregional relapse-free survival rates for IC + CTX/NTZ vs IC alone were 84.3% vs 75.2% (P = .059), 94.0% vs 87.9% (P = .053), 88.0% vs 84.9% (P = .412) and 93.3% vs 88.2% (P = .242). Multivariate analysis established a treatment group (IC vs IC + CTX/NTZ) as a prognostic predictor for DFS (hazard ratio [HR], 1.497; 95% confidence interval [CI], 1.016-2.206; P = .041) and OS (HR, 1.984; 95%, CI, 1.023-3.848; P = .043). Grade 3-4 skin reaction (15.4% vs 0.4%, P < .001) and mucositis (10.1% vs 2.7%, P < .001) were more common in the IC + CTX/NTZ group than that in the IC alone group. Our findings suggested that CTX/NTZ in combination with IC may be a more effective and promising strategy for patients with LA-NPC treated with intensity-modulated radiotherapy. [ABSTRACT FROM AUTHOR]

To clarify the optimal cumulative cisplatin dose (CCD) in locoregionally‐advanced nasopharyngel carcinoma (NPC) patients receiving induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Using the NPC‐specific database from the established big‐data intelligence platform at Sun Yat‐Sen University Cancer Center, 583 non‐disseminated, locoregionally‐advanced NPC patients receiving IC plus CCRT were enrolled. Propensity score matching (PSM) analysis was conducted to control for confounding factors. The median CCD was 160 mg/m2 after IC (range, 40‐300 mg/m2); only 74 patients (12.7%) achieved CCD >200 mg/m2. Patients receiving >200 mg/m2 CCD did not show significantly improved 5‐year overall survival (OS) (HR = 1.19; 95% confidence intervals [CI] 0.69‐2.06, P = .53) and progression‐free survival (PFS) (HR = 1.03; 95% CI: 0.63‐1.68, P = .92) compared with patients receiving <200 mg/m2 CCD. Further investigations of the potential of median CCD (160 mg/m2) to yield survival benefits revealed that there were no significant differences in survival endpoints between patients receiving CCD >160 mg/m2 and CCD < 160 mg/m2 in both the original and PSM cohorts. In addition, subgroup analysis indicated a favorable PFS, but not OS, with higher cisplatin administration in patients with pretreatment Epstein–Barr virus deoxyribonucleic acid (EBV DNA) <1000 copies/mL (HR = 0.26, 95% CI: 0.07‐0.93, P = .03) and receiving <3 IC cycles (HR = 0.59, 95% CI 0.33‐1.07, P = .08). Our analysis of real world data provided references for the optimal CCD in locoregionally‐advanced NPC receiving additional IC. The causal relationship between 200 mg/m2 CCD and improved survival was not defined; 160 mg/m2 CCD might be enough. However, for patients with EBV DNA <1000 copy/mL and receiving <3 IC cycles, a higher dose might be necessary. [ABSTRACT FROM AUTHOR]

The impact of marital status at diagnosis on survival outcomes and its change over time in patients with nasopharyngeal carcinoma ( NPC) are unclear. The Surveillance, Epidemiology, and End Results ( SEER) database was used to identify patients diagnosed with NPC in the United States from 1973 to 2012. A primary comparison (married vs. unmarried) was implemented with 1:1 propensity score matching. Secondary comparisons were performed individually between three unmarried subgroups (single, separated/divorced, widowed) and married group. The effect of marital status on cause-specific survival ( CSS) and overall survival ( OS) were evaluated using univariate/multivariate analysis. Moreover, we investigated the change over time (1973-2012) in the effect of marital status on NPC survival. Married patients had better 5-year CSS/ OS than unmarried patients (61.1% vs. 52.6%, P < 0.001; 55.6% vs. 45.3%, P < 0.001, respectively). In multivariate analysis, unmarried patients had significantly poorer CSS/ OS than married patients (adjusted hazard ratio [ aHR] = 1.35, P < 0.001; aHR = 1.40, P < 0.001, respectively). The survival benefit of being married was only detected in non-Hispanic white and Chinese American patients. Single, separated/divorced, and widowed patients had significantly poorer CSS/ OS than married patients ( aHR = 1.37 and 1.37; 1.46 and 1.42; 1.43 and 1.48, respectively; all P < 0.001). The change over time in the effect of marital status on survival was more stable in male than female. The strength of the negative effect of separated/divorced and widowed status showed a downward and upward trend, respectively. Gender difference in the adverse effect of single status on NPC survival became smaller over time. Only non-Hispanic white and Chinese American patients with NPC obtain survival benefits from married status. Single and widowed patients are regarded as high-risk population [ABSTRACT FROM AUTHOR]

This study investigated the combined prognostic value of pretreatment anemia and cervical node necrosis ( CNN) in patients with nasopharyngeal carcinoma ( NPC). Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC treated with intensity-modulated radiotherapy ( IMRT) ± chemotherapy. Patients were classified into four groups according to anemia and CNN status. Survival was compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. The primary end-point was overall survival ( OS); secondary end-points were disease-free survival ( DFS), locoregional relapse-free survival ( LRRFS), and distant metastasis-free survival ( DMFS). Pretreatment anemia was an independent, adverse prognostic factor for DMFS; pretreatment CNN was an independent adverse prognostic factor for all end-points. Five-year survival for non-anemia and non- CNN, anemia, CNN, and anemia and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P < 0.001), DFS (87.0%, 84.0%, 73.9%, 64.6%, P < 0.001), DMFS (94.1%, 92.1%, 82.4%, 72.5%, P < 0.001), and LRRFS (92.8%, 92.4%, 88.7%, 84.0%, P = 0.012). The non-anemia and non- CNN group had best survival outcomes; anemia and CNN group, the poorest. Multivariate analysis demonstrated combined anemia and CNN was an independent prognostic factor for OS, DFS, DMFS, and LRRFS ( P < 0.05). The combination of anemia and CNN is an independent adverse prognostic factor in patients with NPC treated using IMRT ± chemotherapy. Assessment of pretreatment anemia and CNN improved risk stratification, especially for patients with anemia and CNN who have poorest prognosis. This study may aid the design of individualized treatment plans to improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: To evaluate the incidence of neck muscle spasm in nasopharyngeal carcinoma (NPC) patients that received intensity-modulated radiotherapy (IMRT), and to analyse the patient- and treatment-related risk factors associated with neck muscle spasm.Methods: A sample of 152 IMRT-treated, biopsy-proven, nondisseminated NPC patients were retrospectively analysed. All had documented IMRT treatment plans and had returned for follow-up review at 4 years post-radiotherapy. Spasm of the sternocleidomastoid (SCM) muscle was graded from 0 to 3 (absent to severe) and this grade served as the clinical endpoint. Risk factors were identified using logistic regression analysis.Results: Within 4 years of radiotherapy, neck muscle spasm developed in 23.68% of the patients; Grades 0, 1, 2 and 3 were respectively assigned to 83.55, 7.57, 6.58 and 2.30% of assessed SCMs. Multivariate analysis indicated that gender, N stage, V60 (percentage of SCM volume that received >60 Gy) were independent prognostic variables, and that the optimal threshold for using V60 to predict neck muscle spasm was 61.92% (sensitivity = 0.900, specificity = 0.953).Conclusions: Gender, N stage and V60 were independent predictive factors for post-radiotherapy neck muscle spasm, and a V60 of ≤61.92% in the SCM was relatively safe. [ABSTRACT FROM AUTHOR]

The effect of socioeconomic factors on receipt of definitive treatment and survival outcomes in non-metastatic head and neck squamous cell carcinoma ( HNSCC) remains unclear. Eligible patients ( n = 37 995) were identified from the United States Surveillance, Epidemiology and End Results ( SEER) database between 2007 and 2012. Socioeconomic factors (i.e., median household income, education level, unemployment rate, insurance status, marital status and residence) were included in univariate/multivariate Cox regression analysis; validated factors were used to generate nomograms for cause-specific survival ( CSS) and overall survival ( OS), and a prognostic score model for risk stratification. Low- and high-risk groups were compared for all cancer subsites. Impact of race/ethnicity on survival was investigated in each risk group. Marital status, median household income and insurance status were included in the nomograms for CSS and OS, which had higher c-indexes than the 6th edition TNM staging system (all P < 0.001). Based on three disadvantageous socioeconomic factors (i.e., unmarried status, uninsured status, median household income < US $65 394), the prognostic score model generated four risk subgroups with scores of 0, 1, 2 or 3, which had significantly separated CSS/ OS curves (all P < 0.001). Low-risk patients (score 0-1) were more likely to receive definitive treatment and obtain better CSS/ OS than high-risk patients (score 2-3). Chinese and non-Hispanic black patients with high-risk socioeconomic status had best and poorest CSS/ OS, respectively. Therefore, marital status, median household income and insurance status have significance for predicting survival outcomes. Low-risk socioeconomic status and Chinese race/ethnicity confer protective effects in HNSCC. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcomes of patients with ascending type (T4&N0-1) and descending type (T1-2&N3) of nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT), neoadjuvant chemotherapy (NACT) + intensity-modulated radiotherapy (RT) or NACT + CCRT. Methods: Retrospective analysis of 839 patients with ascending or descending types of NPC treated at a single institution between October 2009 to February 2012. CCRT was delivered to 236 patients, NACT + RT to 302 patients, and NACT + CCRT to 301 patients. Results: The 4-year overall survival rate, distant metastasis-free survival rate, local relapse-free survival rate, nodal relapse-free survival rate, loco-regional relapse-free survival rate, and progression free survival rate were 75.2% and 73.4% (P = 0.114), 85.7% and 74.1% (P = 0.008), 88.8% and 97.1% (P = 0.013), 96.9% and 94.1% (P = 0.122), 86.9% and 91.2% (P = 0.384), 73.7% and 66.2% (P = 0.063) in ascending type and descending type. Subgroup analyses indicated that NACT + RT significantly improved distant metastasis-free survival rate and progression-free survival rate when compared with CCRT in the ascending type, and there were no significant differences between the survival curves of NACT +RT and NACT + CCRT. For descending type, there were no significant differences among the survival curves of NACT +RT, CCRT, and NACT + CCRT groups, and the survival benefit mainly came from CCRT. Conclusions: Compared with NACT + CCRT or CCRT, NACT + RT may be a reasonable approach for ascending type. Although concurrent chemotherapy was effective in descending type, NACT + CCRT may be a more appropriate strategy for descending type. [ABSTRACT FROM AUTHOR]

Background: In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects.Methods: We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient.Results: No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest.Conclusions: 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate. [ABSTRACT FROM AUTHOR]

Background: To evaluate the influence of the progonistic nutritional index (PNI) and weight loss on metastasis and long-term mortality in nasopharyngeal carcinoma (NPC).Methods: We retrospectively reviewed 694 newly diagnosed patients with non-disseminated, biopsy-proven NPC. Survival analysis was used to evaluate the predictive value of PNI and weight loss.Results: Multivariate analysis demonstrated that a low pre-therapy PNI (< 55.0) was an independent predictor of poor overall survival (OS) (P = 0.012), distant metastasis-free survival (DMFS) (P = 0.011) and progression-free survival (P = 0.012). High weight loss (HWL, weight loss during treatment ≥10 %) was an independent predictor of poor OS (P = 0.001) and DMFS (P = 0.014). Advanced stage disease, female gender, chemotherapy, high white blood cell count, high serum globulin concentration and pre-therapy body-mass index were predictors of HWL.Conclusion: Pre-therapy PNI and weight loss have significant predictive value for metastasis and mortality in patients with NPC. [ABSTRACT FROM AUTHOR]

Background and purpose This study investigated the contribution of intensity-modulated radiotherapy (IMRT) to improved treatment outcome in patients with nasopharyngeal carcinoma (NPC) and parapharyngeal space (PPS) extension. Material and methods A total of 1052 cases with PPS extension were retrospectively reviewed, including 512 (48.7%) patients treated with two-dimensional conventional radiotherapy (2D-CRT) and 540 (51.3%) patients treated with IMRT. Results Significant differences in local relapse-free survival (LRFS) and overall survival (OS) ( P < 0.001, P < 0.001, respectively), but not distant metastasis-free survival (DMFS; P = 0.383), were observed between the 2D-CRT and IMRT groups in univariate analysis. The radiotherapy technique was found to be an independent prognostic factor for death (HR = 0.674, 95% CI: 0.537–0.846, P = 0.001) and local recurrence (HR = 0.486, 95% CI: 0.324–0.727, P < 0.001), but not for DMFS. IMRT improved local control in patients with carotid space (CS) involvement compared to 2D-CRT ( P < 0.001). LRFS was significantly different between patients with and without CS extension in the 2D-CRT group ( P < 0.001), but not in the IMRT group ( P = 0.215). Conclusions Compared to 2D-CRT, IMRT improved LRFS in patients with PPS extension, especially patients with CS extension, but did not improve DMFS. CS extension was not statistically prognostic for local control in NPC patients with PPS extension. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). Material and Methods: 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68–70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. Results: The median follow-up period was 37.3 months (range, 6.3–45.1 months). The 3-year estimated local failure–free survival, regional failure–free survival, locoregional failure–free survival, distant metastasis–free survival, disease–free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2–3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. Conclusions: VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To report the incidence of and risk factors for mastoiditis after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Patients and Methods: Retrospective analysis of pretreatment and follow-up magnetic resonance imaging (MRI) data for 451 patients with NPC treated with IMRT at a single institution. The diagnosis of mastoiditis was based on MRI; otomastoid opacification was rated as Grade 0 (none), 1 (mild), 2 (moderate) or 3 (severe) by radiologists blinded to clinical outcome. This study mainly focused on severe mastoiditis; patients were divided into three groups: the G0M (Grade 0 mastoiditis before treatment) group, G1-2M (Grade 1 to 2 mastoiditis before treatment) group and G3M (Grade 3 mastoiditis before treatment) group. The software SAS9.3 program was used to analyze the data. Results: For the entire cohort, the incidence of Grade 3 mastoiditis was 20% before treatment and 31%, 19% and 17% at 3, 12 and 24 months after radiotherapy, respectively. In the G0M group, the incidence of severe mastoiditis was 0% before treatment and 23%, 15% and 13% at 3, 12 and 24 months after radiotherapy, respectively. Multivariate analysis revealed T category (OR=0.68, 95% CI = 0.469 to 0.984), time (OR=0.668, 95% CI = 0.59 to 0.757) and chemotherapy (OR=0.598, 95% CI = 0.343 to 0.934) were independent factors associated with severe mastoiditis in the G0M group after treatment. Conclusions: Mastoiditis, as diagnosed by MRI, occurs as a progressive process that regresses and resolves over time in patients with NPC treated using IMRT. [ABSTRACT FROM AUTHOR]

Background: The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era. Material and Methods: We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease. Results: The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994). Conclusions: In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the long-term survival outcomes and acute toxicity of cisplatin administered weekly versus every three weeks concurrently with intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). Methods: This was a retrospective review of 154 patients with histologically proven, non-disseminated NPC who were treated using IMRT between January 2003 and December 2007. Seventy-three patients (47.4%) received 5–7 weeks of 30–40 mg/m2 cisplatin weekly; 81 patients (52.6%) received two or three cycles of 80 mg/m2 cisplatin every three weeks. IMRT was delivered at 68 Gy/30 fractions to the nasopharyngeal gross target volume and 60–66 Gy to the involved neck area. Results: The clinical characteristics and treatment factors of the two groups were well-balanced. The median follow-up was 74 months (range, 6–123 months), and the 5-year overall survival, disease-free survival, locoregional relapse-free survival, and distant metastasis–free survival rates were 85.2% vs. 78.9% (P = 0.318), 71.6% vs. 71.0% (P = 0.847), 93.5% vs. 92.6% (P = 0.904), and 80.9% vs. 80.1% (P = 0.925) for the group treated every three weeks and weekly, respectively. Subgroup analyses indicated no significant differences in the survival rates of the two groups among patients with early- or advanced-stage disease. The incidence of acute toxicities was similar between groups. Conclusion: IMRT with concurrent cisplatin administered weekly or every three weeks leads to similar long-term survival outcomes and acute toxicity in NPC regardless of whether patients have early- or advanced-stage disease. [ABSTRACT FROM AUTHOR]

Background: Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC. Methods: This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR. Results: Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P  = 0.029) and DMFS (P  = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P  = 0.033), high neutrophil count (P  = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001). Conclusion: The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma and to search for ways to improve the system. Methods and Materials: We performed a retrospective review of data from 749 biopsy-proven nonmetastatic nasopharyngeal carcinoma patients. All patients had undergone contrast-enhanced computed tomography and had received radiotherapy as their primary treatment. Results: The T stage, N stage, and stage group were significant, independent predictors for disease-specific death. No significant differences were found between Stage T2a and T1 in local failure-free survival or between Stage N3a and N2 in distant failure-free survival. Survival curves of the different T/N subsets showed a better segregation when T2a and N3a were downstaged to T1 and N2, respectively. The hazard ratio of disease-specific deaths for patients with T2N0 disease was similar to that of patients with T1N0 disease; the same result was found for the T3N0 and T4N0 subsets. Downstaging the T2N0 subset to Stage I, T3N0 to Stage II, and T4N0 to Stage III resulted in a more balanced patient distribution, better hazard consistency among subgroups, and improved hazard discrimination between overall stages. Conclusion: Using the 6th edition of the American Joint Committee on Cancer staging system produced an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorization of the T, N, and group stage criteria. [Copyright &y& Elsevier]

Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment. [ABSTRACT FROM AUTHOR]

The prevalence of nasopharyngeal carcinoma is characterized by an unbalanced distribution: the disease is particularly prevalent in East and Southeast Asia. In this article, we review the evolution of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. With the increasing using of newer imaging methods, more advanced radiotherapy techniques and systemic chemotherapy, we also discuss newer clinical features that might affect staging. Finally, we propose the future direction of staging and potential prognostic factors that have a major influence on the treatment outcomes of this disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2-3 disease, plasma Epstein-Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0-1 risk factors; and 2) high-risk group: 2-4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. [ABSTRACT FROM AUTHOR]

This study is to identify significant dosimetric parameters for ear disorders in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated therapy only. Ninety-seven patients with NPC were retrospectively reviewed. Organs at risk (OARs) in the auditory apparatus were contoured. Dose-volume histogram parameters were generated for the Eustachian tube (ET), tympanic cavity (TC), mastoid air cells, vestibular apparatus, cochlea and internal auditory canal (IAC). Ear disorders were rated 0 (none), 1 (mild) or 2 (severe) by a clinician blinded to radiation doses; Grade 2 ear disorders was the study end-point. Multivariate analysis revealed ET.D30 (dose to 30% of ET volume) >52.75 Gy and M.D0.5CC (dose to 0.5 ml of mastoid volume) >41.04 Gy (OR = 3.77, P = 0.012 and OR = 1.27, P = 0.033, respectively) were associated with Grade 2 ear disorders. Our results demonstrated that post-irradiation ear disorders remain a common late toxicity in NPC after IMRT. ET.D30 and M.D0.5CC should be considered during IMRT treatment plan optimization, review and approval. [ABSTRACT FROM AUTHOR]