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Abstract Background Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P P Conclusions Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.

Abstract Background Metastasis-associated protein 1 (MTA1) has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC). Methods MTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR), 95% confidence interval (CI) and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree. Results Nuclear overexpression of MTA1 was observed in 48.6% (101/208) of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P = 0.02), clinical stage (P = 0.04), distant metastasis (P < 0.01) and death (P = 0.01). Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS; P P < 0.01). MTA1 had prognostic significance in NPC patients with stage II disease, but not stage III or IV disease. Multivariate analysis demonstrated that nuclear overexpression of MTA1 was independently associated with poorer DMFS (HR, 2.05; 95% CI, 1.13–3.72; P = 0.02) and poorer OS (HR, 1.98; 95% CI, 1.09–3.59; P = 0.03). Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression. Conclusion The results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.

Objective: We analyzed the patterns of lymph node (LN) failure and prognosis in patients with regional recurrent nasopharyngeal carcinoma (rNPC) alone after primary intensity‐modulated radiotherapy (IMRT). Methods: A total of 175 patients who were treated with IMRT between 2010 and 2015 and who experienced regional recurrence alone were included. Recurrent LNs were re‐located in the initial pretreatment imaging and IMRT plan and failures were classified as in‐field or out‐field based on target volume delineation. All patients underwent curative salvage treatment. Independent prognostic factors for overall survival (OS) were selected by multivariate Cox analysis. Results: Level IIb (49.1%, 86/175) was the most frequent recurrence site, followed by level IIa (36%), level III (18.9%), level IVa (12%), the retropharyngeal region (8%), level Va (6.9%), and the parotid region (6.9%). A total of 264 recurrent LNs were recorded: 149 (56.4%) were classified as in‐field failure with a prescribed dose ≥66 Gy, 60 (22.7%) with 60 to <66 Gy, 32 (12.1%) with 50 to <60 Gy, and 23 (8.7%) as an out‐field failure, which mainly occurred in the parotid region and level Ib. After a median follow‐up of 52.8 months, the estimated 5‐year OS rate was 66.9%. Multivariate analysis showed that age, plasma Epstein–Barr virus DNA level, extranodal extension, lower neck involvement, and parotid LN recurrence were independent prognostic factors of OS. Conclusions: In‐field failure represented the main pattern of regional recurrence and out‐field failure mainly occurred in the parotid gland and level Ib. Patients with regional rNPC alone had a good prognosis after salvage treatment. [ABSTRACT FROM AUTHOR]

Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets. [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]

Objective: Twelve weeks after radiotherapy is the recommended time-point for assessing tumor response in nasopharyngeal carcinoma (NPC); however, regression after 12 weeks remains unclear. We explored NPC regression and the prognosis of patients with delayed clinical complete response (cCR).Materials and Methods: MRI images of 556 NPC patients treated with intensity-modulated radiotherapy (IMRT) between 2009 and 2012 were retrospectively reviewed. Clinical tumor response was assessed at 3-4 (assessment 1) and 6-9 months (assessment 2) after IMRT, and survival rates were compared.Results: Of the 556 patients, 463 (83.3%) had cCR at assessment 1 (early cCR). Of the 93 patients with partial response at assessment 1, 45 (48.4%) achieved cCR at assessment 2 (delayed cCR), and 48 did not have cCR at assessment 2 (non-cCR). Locoregional failure rate was lower in patients with a cCR than those without a cCR at assessment 1 (7.1% vs. 26.9%, P < .001) and assessment 2 (7.1% vs. 45.8%, P < .001). Multivariate analysis showed cCR was a favorable prognostic factor for locoregional failure-free survival (LRFFS), failure-free survival (FFS), and overall survival (OS). Early and delayed cCR groups had better 5-year LRFFS (92.6% vs. 93.3% vs. 54.2%), FFS (83.8% vs. 84.4% vs. 48.5%) and OS (92.1% vs. 90.6% vs. 65.4%) than the non-cCR group (all P < .001).Conclusions: Nearly half of the patients with partial response at 3-4 months achieve cCR by 6-9 months; delayed cCR is not a poor prognosticator. We suggest later assessment of cCR at 6-9 months after IMRT is acceptable in responding NPC. [ABSTRACT FROM AUTHOR]

Background: Tumor response to neoadjuvant chemotherapy using the regimen of cisplatin and 5-fluorouracil could define high-risk patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, the regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) appears to be more effective than the regimen of cisplatin and 5-fluorouracil. Therefore, one needs to redefine the high-risk subpopulation of patients receiving neoadjuvant chemotherapy with TPF.Methods: A total of 231 patients from a randomized phase 3 trial with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC (except T3-T4N0 disease) who were receiving treatment with the TPF regimen were enrolled. Patient survival rates between different groups were compared.Results: Of the 231 patients, the overall response to neoadjuvant chemotherapy was a complete response (CR) for 26 (11.3%), a partial response (PR) for 184 patients (79.6%), and stable disease (SD) for 21 patients (9.1%). Univariate analysis revealed the 3-year failure-free survival (FFS) rates in the CR (88.5% vs 61.9%; P =.017) and PR (81.2% vs 61.9%; P = .01) groups, and the 3-year overall survival rates for the CR (96.2% vs 76.2%; P =.048) and PR (93.4% vs 76.2%; P =.025) groups were obviously higher compared with that of the SD group. In multivariate analysis, CR was established as a favorable prognostic factor for FFS (hazard ratio [HR], 0.210; 95% confidence interval [95% CI], 0.057-0.779 [P =.02]), and PR for FFS (HR, 0.447; 95% CI, 0.213-0.936 [P =.033]) and OS (HR, 0.361; 95% CI, 0.132-0.986 [P =.047]) when compared with SD. No survival difference was observed between the CR and PR groups.Conclusions: Tumor response to TPF may be a properly powerful prognosis predictor and help to develop individualized treatment strategies for patients with locoregionally advanced NPC. Cancer 2017;123:1643-1652. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to determine the predictive value of pretreatment serum uric acid (SUA) for metastasis in locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy. Methods This retrospective study examined 1063 patients with locally advanced NPC. Multivariate survival analysis was used. Results High pretreatment SUA level (>353.4 μmol/L) independently predicted distant metastasis-free survival ( p = .013) and was associated with high white blood cell ( p = .005), lymphocyte counts ( p < .001), and male sex ( p < 0.001). In addition, SUA levels were significantly elevated in patients with T1 to T3 classification ( p = .042). For patients with subsequent lung metastases after treatment, markedly higher pretreatment SUA levels were detected compared with patients who had other distant metastases ( p =.012) and patients without distant metastasis ( p = .024). Conclusion Pretreatment SUA may be a useful biomarker for evaluating treatment options for patients with locally advanced NPC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 492-497, 2017 [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to assess the prognostic value of ABO blood group in nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Patients and Methods: We retrospectively reviewed the data on 1397 patients with non-metastatic, newly diagnosed NPC treated using IMRT. Patient survival between different ABO blood groups were compared using log-rank test. Cox hazards model was adopted to establish independent prognostic factors. Results: In our study, the distribution of the A, B, AB and O blood groups was 26.6% (372/1397), 26.2% (366/1397), 5.2% (73/1397) and 42.0% (586/1397), respectively. The cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA based on disease-free survival (DFS) was 1355 copies/ml (area under curve [AUC], 0.649; sensitivity, 0.76; specificity, 0.496) for the whole cohort. Estimated four-year DFS, overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates were 81.7%, 89.2%, 89.4% and 92.3% for blood group A; 82.1%, 89.3%, 89.0% and 92.0% for group B; 83.3%, 88.1%, 86.2% and 95.5% for group AB, 80.9%, 90.7%, 88.4% and 90.2% for group O (P > 0.05 for all rates). Multivariate analysis revealed ABO blood group was not an independent prognostic factor for DFS, OS, DMFS or LRRFS (P > 0.05 for all rates) after adjusting for plasma EBV DNA in either the whole cohort or subgroup analysis by gender. Conclusions: The prognostic value of ABO blood group may be limited for patients with NPC in the era of IMRT, and no substantial correlation between ABO blood group and plasma EBV DNA was observed. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was to evaluate the prognostic value of the cumulative cisplatin dose (CCD) for long-term survival outcomes after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods. Patients were included in an open-label phase III multicenter randomized controlled trial performed at seven institutions in China, and the 298 patients receiving CCRT only were assessed. Patient survival between different CCD groups were compared. Results. Median CCD for the 298 patients was 240 mg/m² (range, 40-320 mg/m²); 113 (37.9%) patients received a CCD of <240 (≤200) mg/m², and 185(62.1%) received a CCD of ≥240 mg/m². For CCD of ≥240 mg/m² vs. <240 mg/m², the estimated 5-year overall survival, disease-free survival, locoregional relapse-free survival, and distant metastasis-free survival rates were 83.2% vs. 76.2% (p = .403), 73.5% vs. 67.8% (p = .461), 90.4% vs. 86.8% (p = .551), and 82.6% vs. 79.7% (p = .632), respectively. Multivariate analysis demonstrated that CCD (240 mg/m²) was not an independent prognostic factor in either the entire cohort or stage III/IV subgroup. Conclusion. A CCD of ≥240 mg/m² was not an independent prognostic factor in patients with locoregionally advanced NPC at high risk of distant metastasis, and 200 mg/m² cisplatin may be adequate to achieve a survival benefit. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study investigated the prevalence and prognostic value of chronic hepatitis B virus (HBV) infection in patients with nasopharyngeal carcinoma (NPC) from an area in southern China in which HBV and NPC are endemic. METHODS A total of 1301 patients with nonmetastatic, histologically proven NPC who were treated with radiotherapy or chemoradiotherapy were retrospectively reviewed. RESULTS In this series, 142 of the 1301 patients (10.9%) had chronic HBV infection (hepatitis B surface antigen [HBsAg] seropositive). The percentages of non-cancer-related deaths (15.0% vs 12.1%; P = .618) and severe hepatic adverse events (3.5% vs 0.9%; P = .145) were similar among patients with NPC with and without HBV infection. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRFS) rates for patients with NPC with or without HBV infection were 70.9% and 80.8% ( P = .003), 63.7% and 73.0% ( P = .016), and 81.7% and 88.2% ( P = .035), respectively. Multivariate analysis identified chronic HBV infection in patients with NPC as an independent unfavorable prognostic factor for OS (hazards ratio [HR], 1.684; P = .003), PFS (HR, 1.451; P = .015), and LRFS (HR, 1.573; P = .048). Further analysis revealed that chronic HBV infection was an unfavorable, independent prognostic factor in patients with locoregionally advanced NPC, but not those with early-stage disease. In patients with stage III/IV NPC, HBsAg-positive patients had poorer OS (64.0% vs 77.2%; P = .003), PFS (56.2% vs 70.6%; P = .004), and LRFS (76.2% vs 88.3%; P = .002) compared with HBsAg-negative patients. On multivariate analysis, chronic HBV infection was found to be an independent adverse prognostic predictor for OS (HR, 1.734; P = .004), PFS (HR, 1.644; P = .003), and LRFS (HR, 2.108; P = .003) in patients with stage III/IV NPC. CONCLUSIONS Chronic HBV infection is an independent adverse prognostic factor in patients with locoregionally advanced NPC. Cancer 2014;120:68-76. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

The metastatic rate of nasopharyngeal carcinoma (NPC) is the highest among head and neck tumours. Additionally, distant metastasis is the main cause of therapy failure and mortality in NPC. Thus, novel biomarkers are needed for designing new therapeutic strategies to improve the prognosis of this disease. In this study, qRT-PCR and western blotting revealed that the expression of the WD repeat domain phosphoinositide interacting 1 (WIPI-1) was markedly decreased in NPC cells and tissues. Furthermore, low WIPI-1 expression closely correlated with poor prognosis in NPC patients. In vitro functional experiments revealed that overexpression or knockdown of WIPI-1 repressed or facilitated the migration, colony formation, and proliferation of NPC cells. Consistent with the in vitro studies, WIPI-1 significantly inhibited tumour growth, invasion and metastasis in popliteal lymph node metastasis, lung metastasis, and xenograft mouse models in vivo. Mechanistically, WIPI-1 directly interacted with tripartite motif containing 21 (TRIM21) and enhanced starvation-induced autophagy by interacting with TRIM21 in NPC cells. Moreover, MYC gene expression was markedly increased in the WIPI-1 knockdown group, as demonstrated by RNA-seq analysis and qRT-PCR validation. Altogether, WIPI-1 acts as a tumour suppressor gene in NPC that inhibits tumour growth and metastasis. Targeting WIPI-1 may be a novel treatment approach for NPC. [ABSTRACT FROM AUTHOR]

Objective: In nasopharyngeal carcinoma (NPC), the staging category of parotid lymph node (PLN) metastasis is not explicitly defined, resulting in varied classifications and treatment strategies in clinical practice. This study aimed to determine the prognostic value and optimal staging category of PLN metastasis in NPC.Materials and Methods: With the NPC database from a big-data platform, 10,126 patients with primarily diagnosed, non-metastatic NPC and treated with intensity modulated radiotherapy at our center from 2009 to 2015 were analyzed in this study.Results: In total, 43/10126 patients (0.4%) were diagnosed with histologically verified PLN metastasis at initial diagnosis. Of these, 88.4% (38/43) had enlarged lymph nodes in level II and 34.9% (15/43) in level Ib. Compared with patients without PLN metastasis, those with PLN metastasis had higher risk of disease failure (adjusted hazard ratio [HR], 1.770), distant metastasis (HR, 1.907), and regional recurrence (HR, 3.649), with similar 3-year disease-free survival (70.0% vs. 71.1%) and distant metastasis-free survival (74.8% vs. 77.4%) with patients with N3 disease. Of note, 10/43 patients had regional recurrence: six had recurrent lymph nodes in level Ib; and four of these six patients had no identifiable level Ib lymph nodes on pretreatment imaging.Conclusion: PLN metastasis was associated with high risk of distant metastasis and regional recurrence, and patients with PLN metastasis had similar outcome compared with patients with N3 disease. Regional recurrences in rare levels, such as level Ib, were common in patients with PLN metastasis at initial diagnosis. [ABSTRACT FROM AUTHOR]

The prognostic value of the primary lesion pretreatment apparent diffusion coefficient (ADC), which is obtained by diffusion-weighted magnetic resonance imaging (MR-DWI), remains unknown in nasopharyngeal carcinoma (NPC). Thus, to investigate whether the pretreatment ADC value as measured from the primary site on MR-DWI is an independent prognostic factor in NPC, we retrospectively reviewed a cohort of 541 patients with histologically-proven stage I-IVB NPC. All patients underwent MRI using a 3-Tesla system (Trio Tim; Siemens, Erlangen Germany). To calculate ADC, the primary lesion was designated on the ADC map at the level of the largest tumor diameter to cover most of the lesion, avoiding cystic or necrotic components. Median and mean (±SD) pretreatment ADC were 0.713 and 0.716 ± 0.079 × 10−3 mm2/s, respectively. Univariate and multivariate analysis confirmed high pretreatment ADC was a good prognostic factor for poor local relapse-free survival and disease-free survival. Furthermore, the area under the ROC curve for prediction of local failure significantly increased when pretreatment ADC was combined with T classification (P = 0.004). Thus, pretreatment ADC might provide useful information for predicting outcome and selecting high-risk patients appropriate for more aggressive therapy. Further studies are warranted to investigate the biological basis of this observation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to optimize the cycle for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) receiving neoadjuvant chemotherapy (NCT) in the era of intensity-modulated radiotherapy (IMRT).Materials and Methods: Data on 569 locoregionally advanced NPC patients treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between different NCT cycle groups were compared.Results: The median cycle of NCT was 2 (range, 2-4 cycles) for the whole cohort, and patients were therefore stratified as low cycle (=2) and high cycle (>2) groups. In total, 247 pairs of NPC patients were selected by PSM. Univariate analysis found no significantly prognostic difference between the low cycle and high cycle groups, and multivariate analysis did not establish NCT cycle as an independent factor. However, stratified analysis revealed patients in the low cycle group had better OS than those of patients in the high cycle group (92.4% vs. 80.8%, P=0.029), and NCT was identified as an independent prognostic factor for OS in patients with N2-3 category (HR, 2.252; 95% CI, 1.024-4.953; P=0.043).Conclusion: Two cycles of NCT may be enough and additional more cycles are not associated with improved survival outcomes for patients with locoregionally advanced NPC in the era of IMRT. [ABSTRACT FROM AUTHOR]

Objective: In cancer trials, prior cancer is a common exclusion criterion. We evaluated the characteristics of prior cancer exclusion criteria in nasopharyngeal carcinoma (NPC) trials and determined its prognostic effect on patients with NPC.Methods: We reviewed NPC trials for prior cancer exclusion criteria. Then we estimated the effect of prior cancer among NPC patients using the Surveillance, Epidemiology, and End Results database.Propensity score-matching was used to compensate for differences in baseline characteristics between patients with and without prior cancer.Results: There were 109 clinical trials involving 10,437 patients; 49 trials (45%) excluded patients with prior cancer. Prior cancer exclusion was more common in recent or phase III trials. We identified 10,195 NPC patients; 6.2% had prior cancer. More than 70% of these cancers were in situ/localized/regional and diagnosed relatively close to the NPC diagnosis (median 3.3 years). Patients with certain prior cancer type (prostate, breast, gynecological, hematological), time of diagnosis (>5 years ago), or stage (in situ/localized) did not have inferior survival compared with patients with no prior cancer. We tested one form of prior cancer exclusion criteria in an NPC cohort resembling a modern trial population: it did not adversely affect overall and NPC-specific survival.Conclusions: Many NPC trials excluded patients with prior cancer, whichimpacts trialaccrual and generalizability. Our findings suggest that broader inclusion in trials of patients with NPC with prior cancer might not affect trial outcomes. More research is needed to understand the appropriateness of this exclusion policy across cancer types and trials. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed at identifying the optimal induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy.Materials and Methods: We identified eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between September 2009 and May 2015. Survival outcomes and grade 3-4 toxicities were compared between different IC regimen groups.Results: In total, 3738 patients were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%) receiving TPF, PF and TP, respectively. In the whole population, multivariate analysis found that TPF seems to be better than PF and TP. Howerver, subgroup analysis revealed TPF and TP had same effectiveness in patients receiving a cumulative cisplatin dose (CCD) ≥200mg/m2 in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD<200mg/m2. Grade 3-4 toxicities were similar between TPF and TP groups, but were relatively higher than that in PF group.Conclusions: Our study concluded that induction TP regimen may be enough for patients receiving a CCD≥200mg/m2, while TPF may be superior to TP and PF for patients receiving a CCD<200mg/m2, although grade 3-4 toxic events were more common but tolerable. Further studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Objectives: The subgroups of patients with nasopharyngeal carcinoma (NPC) who benefit from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) remain unclear.Materials and Methods: We established prognostic nomograms for overall survival (OS) and disease-free survival (DFS), and validated the nomograms in 1230 patients with NPC and subgroup of 923 patients with locoregionally advanced NPC (LANPC). Three well-matched risk groups (i.e., low, intermediate and high risk) were created via recursive partitioning and 1-to-1 propensity score matching; IC+CCRT was compared with CCRT in each risk group.Results: Histological type, T category, N category, plasma Epstein-Barr virus deoxyribonucleic acid (and the same factors plus age and neutrophil-lymphocyte ratio) were included in the nomograms for DFS (and OS). Both nomograms had higher c-indexes than the 7th edition staging system in both NPC/LANPC (all P-values≤0.010). The nomogram for OS also had a higher c-index in LANPC than the 8th edition staging system (P-value=0.052). OS was significantly different between all three risk groups in the individualized risk stratification (all P-values<0.001), while the 7th and 8th edition staging systems failed to clearly separate OS for stage II and III disease (P-value=0.415 and 0.347, respectively). IC+CCRT improved OS in intermediate and high risk patients with LANPC compared to CCRT alone (P-value<0.001 and P-value=0.002, respectively).Conclusion: These prognostic nomograms could accurately guide treatment of individual patients with NPC. IC+CCRT could improve OS for patients with LANPC at intermediate to high risk. [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 and purpose The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized. Material and methods Using the Adult Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of comorbidity and developed, validated and confirmed a predictive score model in a training set ( n = 658), internal validation set ( n = 658) and independent set ( n = 652) using area under the receiver operating curve analysis. Results Comorbidity was present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%). Compared to an ACE-27 score ⩽1, patients with an ACE-27 score >1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P < 0.001), similar results were obtained in the other sets ( P < 0.05). In multivariate analysis, ACE-27 score was a significant independent prognostic factor for OS and DFS. The combined risk score model including ACE-27 had superior prognostic value to TNM stage alone in the internal validation set (0.70 vs. 0.66; P = 0.02), independent set (0.73 vs. 0.67; P = 0.002) and all patients (0.71 vs. 0.67; P < 0.001). Conclusions Comorbidity significantly affects prognosis, especially in stages II and III, and should be incorporated into the TNM staging system for NPC. Assessment of comorbidity may improve outcome prediction and help tailor individualized treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: The development of improved diagnostic and therapeutic techniques has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study is to revaluate the prognostic value of parapharyngeal extension in NPC in the IMRT era. Material and methods: We retrospectively reviewed data from 749 biopsy-proven non-metastatic NPC patients. All patients were examined with magnetic resonance imaging (MRI) and received intensity-modulated radiotherapy (IMRT) as the primary treatment. Results: The incidence of parapharyngeal extension was 72.1%. A significant difference was observed in the disease-free survival (DFS; 70.3% vs. 89.1%, P <0.001), distant metastasis-free survival (DMFS; 79.3% vs. 92.0%, P <0.001), and local relapse-free survival (LRFS; 92.8% vs. 99.0%, P =0.002) of patients with and without parapharyngeal extension. Parapharyngeal extension was an independent prognostic factor for DFS and DMFS in multivariate analysis (P =0.001 and P =0.015, respectively), but not LRFS. The difference between DMFS in patients with or without parapharyngeal space extension was statistically significant in patients with cervical lymph node metastasis (P <0.001). Conclusions: In the IMRT era, parapharyngeal extension remains a poor prognosticator for DMFS in NPC, especially in patients with positive lymph node metastasis. Additional therapeutic improvements are required to achieve a favorable distant control in NPC with parapharyngeal extension. [Copyright &y& Elsevier]

Summary: Background: MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods: We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings: 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio [HR] 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 [95% CI 0·60–0·76] vs 0·60 [0·52–0·67]; p=0·013), the internal validation set (0·70 [0·61–0·78] vs 0·61 [0·54–0·68]; p=0·012), and the independent set (0·70 [0·62–0·78] vs 0·63 [0·56–0·69]; p=0·032). Interpretation: Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding: Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities. [Copyright &y& Elsevier]

Purpose: To investigate the prognostic significance of prevertebral space involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: A retrospective review of data from 506 biopsy-proven, nonmetastatic NPCs was performed. Patients underwent magnetic resonance imaging examinations and received IMRT as their primary treatment. Results: In this series, 161 NPC patients (31.8%) had PSI. Parapharyngeal space (p < 0.001), skull base (p < 0.001), and paranasal sinuses (p = 0.009) were associated with PSI after multivariate analysis. The 4-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis–free survival (DMFS) for NPC patients with and without PSI was 69.1% and 89.2% (p < 0.0001), 83.9% and 96.4% (p < 0.0001), and 71.6% and 89.6% (p < 0.0001), respectively. Multivariate analysis identified PSI as an independent negative prognostic factor for both OS (HR = 1.478–4.380; p = 0.001) and DMFS (HR = 1.389–4.174; p = 0.002). Patients with PSI had similar survival rates in OS and DMFS (p = 0.241 and p = 0.493, respectively) to that of T4 disease, while the differences between PSI and T3 disease in both OS and DMFS were distinctly significant (p = 0.029 and p = 0.029, respectively). Conclusions: For NPC patients treated with IMRT, PSI was found to be an independent prognostic factor for both OS and DMFS. It seems reasonable that PSI should be classified as a T4 disease on the basis of the current American Joint Committee on Cancer staging classification criteria. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic value of baseline serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Cases of NPC (n = 465) that involved treatment with IMRT with or without chemotherapy were retrospectively analyzed. Results: The mean (±SD) and median baseline serum LDH levels for this cohort were 172.77 ± 2.28 and 164.00 IU/L, respectively. Levels of LDH were significantly elevated in patients with locoregionally advanced disease (p = 0.016). Elevated LDH levels were identified as a prognostic factor for rates of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), with p values <0.001 in the univariate analysis and p < 0.001, p = 0.004, and p = 0.003, respectively, in the multivariate analysis. Correspondingly, the prognostic impact of patient LDH levels was found to be statistically significant for rates of OS, DFS, and DMFS (p = 0.028, 0.024, and 0.020, respectively). For patients who experienced subsequent liver failure after treatment, markedly higher pretreatment serum LDH levels were detected compared with patients experiencing distant metastasis events at other sites (p = 0.032). Conclusions: Elevated baseline LDH levels are associated with clinically advanced disease and are a poor prognosticator for OS, DFS, and DMFS for NPC patients. These results suggest that elevated serum levels of LDH should be considered when evaluating treatment options. [ABSTRACT FROM AUTHOR]