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Background: To analyze the prognostic value of cervical node necrosis (CNN) observed on pretreatment magnetic resonance imaging (MRI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods: The medical records of 1423 NPC patients with cervical node metastasis who underwent IMRT were retrospectively reviewed. Lymph nodes in the axial plane of pretreatment MRI were classified as follows: grade 0 CNN, no hypodense zones; grade 1 CNN, ≤33% areas showing hypodense zones; and grade 2, >33% areas showing hypodense zones. Results: CNN was detectable in 470/1423 (33%) patients. Of these 470 patients, 213 (15%) and 257 (18%) exhibited grade 1 and grade 2 CNN. The grade 0 and grade 1 CNN groups showed significant differences with regard to distant metastasis-free survival (DMFS), but not overall survival (OS), regional relapse-free survival (RRFS), local relapse-free survival (LRFS), and disease-free survival (DFS). Significant differences were observed among the grade 0 and grade 2 CNN groups with regard to OS, RRFS, LRFS, DMFS, and DFS. Moreover, OS, LRFS, RRFS, and DFS were significantly different between the grade 1 and grade 2 CNN groups, whereas DMFS showed no significant differences. Univariate and multivariate analyses revealed CNN on MRI as a significant negative prognostic factor for OS, LRFS, RRFS, DMFS, and DFS in NPC patients. Conclusions: NPC patients with CNN of different grades show various prognosis and failure patterns after IMRT. CNN on MRI can be adopted as a predictive factor for formulating individualized treatment plans for NPC patients.

Background: The changes in the risk of disease failure over time in nasopharyngeal carcinoma (NPC) remains unknown. Methods: We analyzed 749 patients treated with intensity-modulated radiotherapy in a single center. The annual hazard rates of disease failure (recurrence or death from any cause) were estimated using the life-table method. Results: In total, 41 (5.5%), 22 (2.9%) and 129 (17.2%) patients developed local, regional and distant recurrences, respectively; 149 (19.9%) patients died. Of the 600 patients who were alive at the last follow-up, 496 (82.7%) had follow-up times longer than 6 years. The 6-year failure-free survival rate was 74.8%. Older age (> 50 years) and advanced stage (Ⅲ-ⅣB) were independent risk factors for disease failure in multivariate analysis. The hazard curve for failure risk in the whole cohort showed a sharp peak at 2 years, changed to a gradually decreasing plateau between years 3 and 5 and then declined sharply. Subgroup analyses revealed similar hazard curves in both sexes. However, the patterns of hazard curve significantly differed between high-risk (> 50 years or stage Ⅲ-ⅣB) and low-risk (≤ 50 years or stage Ⅰ-Ⅱ) patients. Interpretation: The failure hazard rate in NPC didn't decline in a linear manner, but displayed a sharp peak at 2 years. The patterns of hazard function significantly differed between patients with different age and stage. Further studies are warranted to confirm our results.

Background: To explore the value of chemoradiotherapy (CRT) in stage II nasopharyngeal carcinoma (NPC) compared to radiotherapy (RT) alone which includes two-dimensional radiotherapy (2D-RT) and intensity-modulated radiotherapy (IMRT). Methods: All topic-related comparative articles were identified by a comprehensive search of public databases (MEDLINE, EMBASE, Cochrane Library and CBMdisc). The primary outcomes were overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Secondary outcomes were grade 3-4 acute toxicity events. We performed subgroup analysis of CRT versus 2D-RT/IMRT alone to investigate the optimal modality. Sensitivity analysis focused on CRT versus IMRT alone was used to assess stability of the study results. Results: Eleven comparative studies (2138 patients) were eligible. CRT had significantly higher OS (HR = 0.67, 95% CI = 0.45-0.98, P = 0.04) and LRRFS (HR = 0.61, 95% CI = 0.46-0.80, P = 0.0003) than RT alone, but no significant difference was observed in DMFS (HR = 0.83, 95% CI = 0.52-1.31, P = 0.41). Meanwhile, CRT was associated with higher frequencies of grade 3-4 leukopenia, mucositis and nausea (P = 0.005, 0.03, < 0.0001, respectively). Subgroup analysis showed that IMRT alone could achieve equivalent OS, LRRFS and DMFS compared to CRT (P = 0.14, 0.06, 0.89, respectively). Significant value was only observed in LRRFS for CRT compared to 2D-RT alone (P = 0.01). Sensitivity analysis for the comparison of CRT and IMRT alone demonstrated generally stable outcomes, in support of the final conclusions. Conclusions: In the treatment of patients with stage II NPC, CRT was better than 2D-RT alone with significant benefit in LRRFS. IMRT alone was superior to CRT with equivalent survival outcomes and fewer grade 3-4 acute toxicities.

Background: The prognostic value of C-reactive protein/albumin ratio (CRP/Alb), a novel inflammation-based marker, remains unknown in nasopharyngeal carcinoma (NPC). Methods: We conducted a retrospective review of 1572 consecutive patients with non-metastatic NPC. Patients were randomly divided into a training set (n = 514) and validation set (n = 1058). The prognostic value of the CRP/Alb ratio and the modified Glasgow prognostic score (mGPS; a well-recognized inflammation-based score) was assessed. Results: Receiver-operating characteristic analysis identified 0.05 as the optimal CRP/Alb cut-off value for disease failure in the training set. Patients with a CRP/Alb > 0.05 had poorer overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the training set (all P < 0.05). These results were confirmed in the validation set (all P < 0.05) and the whole cohort (all P < 0.001). In multivariate analysis of the entire cohort, the pretreatment CRP/Alb ratio was an independent prognostic factor for OS (HR, 1.394; 95% CI, 1.004-1.937; P = 0.048) and DMFS (HR, 1.545; 95% CI, 1.124-2.122; P = 0.007), but not for DFS (P = 0.083). The mGPS had no significant independent prognostic value for any end-point. Conclusion: CRP/Alb ratio is an useful prognostic indicator in patients with NPC, independent of disease stage.

Background: The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to investigate the impact of clinical stage on radiation doses to organs at risk (OARs) in NPC. Material and Methods: One hundred and forty-eight patients with newly diagnosed and untreated NPC were prospectively enrolled. Based on the anatomic definition and pathogenesis of radiation induced injury, a total of 28 OARs surrounding the nasopharynx were contoured on axial computed tomography (CT) planning images in each patient. Dose-volume histograms, as well as the mean and maximal doses for each structure, were calculated. Results: Radiation doses to 15 OARs (including the brain stem, temporal lobe and eye) were positively correlated with T stage, the radiation doses to 13 OARs (including the brachial plexus, parotid and thyroid) increased significantly with N stage, and the radiation doses to the spinal cord and mandible had no association with T or N stage. Based on the characteristic of excess rates, 9 OARs (e.g. spinal cord, eye, trachea, and et al.) met tolerance doses easily in all stages, 9 OARs (e.g. brain stem, temporal lobe, brachial plexus, and et al.) easily in early stages but with difficulty in advanced stages, and 10 OARs (e.g. cochlea, parotid, thyroid, and et al.) with difficulty in all stages. Conclusions: The radiation doses to most of OARs are associated with T or N stage, and there are three kinds of patterns for them: 1) meet tolerance doses easily in all stages; 2) meet tolerance doses easily in early stages but with difficulty in advanced stages; and 3) meet tolerance doses with difficulty in all stages.

Background: To identify predictors for development of mastoiditis after intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC). Methods: Data for 146 NPC patients treated with IMRT was retrospectively reviewed under institutional ethics committee approval. Clinical factors associated with mastoiditis were analyzed. Dose-volume histogram analysis was performed for the Eustachian tube, tympanic cavity, mastoid air cells, cochlea, internal auditory canal and vestibular apparatus to relate doses to radiographic changes in the mastoid. Mastoiditis was assessed using magnetic resonance imaging and was classified as Grade 0 (none), 1 (mild), 2 (moderate) or 3 (severe); Grade 3 mastoiditis was the study end-point. Results: Eighty-eight ears (36%) had radiation-induced mastoiditis: 38/244 (15.6%) mastoid complexes had Grade 1-2 mastoiditis and 50/244 (20.5%) mastoid complexes had Grade 3 mastoiditis. Multivariate analysis revealed a mastoid mean dose > 35.93 Gy (odds ratio [OR]=4.22, P=.003), Eustachian tube mean dose > 53.43 Gy (OR=2.16, P=.034) and advanced T category (T3 and T4; OR=10.33, P=.032) were negative prognostic factors for Grade 3 mastoiditis. Conclusions: Radiation-induced mastoiditis remains a common late toxicity in NPC after radiotherapy. The mean dose to the mastoid air cells and Eustachian tube should be limited to reduce the risk of radiation-induced mastoiditis.

Background: Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the efficacy of NACT+CCRT as compared with CCRT alone. Methods: We comprehensively searched databases and extracted data from randomized controlled trials involving NPC patients who received NACT+CCRT, CCRT, NACT+radiotherapy (RT), or RT. Overall survival (OS) with hazard ratio (HR), and locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs), were concerned. Results: Nine trials involving 1988 patients were analyzed. In the network meta-analysis, there was significant benefit of NACT+CCRT over CCRT for DMR (RR=0.54, 95% credible interval [CrI]=0.27-0.94). However, NACT+CCRT had a tendency to worsen locoregional control significantly as compared with CCRT (RR =1.71, 95%CrI =0.94-2.84), and no significant improvement in OS was found (HR =0.73, 95%CrI=0.40-1.23). Conclusions: NACT+CCRT is associated with reduced distant failure as compared with CCRT alone, and whether the additional NACT can improve survival for locoregionally advanced NPC should be further explored. Optimizing regimens and identifying patients at high risk of metastasis may enhance the efficacy of NACT+CCRT.

Purpose: The objective of this study was to confirm the association between pretreatment Epstein-Barr virus (EBV) DNA (pre-DNA) load and survival outcomes after long-term follow-up in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Materials and Methods: Between November 2009 and February 2012, a total of 1036 patients with LA-NPC were enrolled. There were 762 patients in stage III and 274 in stage IVA-B. All patients were treated with radical radiotherapy with or without chemotherapy, and pre-DNA concentrations were quantified by a polymerase chain reaction assay. Patient outcomes were evaluated. Results: The 5-year overall survival (OS), distant metastasis-free surviva (DMFS), locoregional relapse-free survival (LRFS), and progression-free survival (PFS) rates were 84.7%, 87.0%, 90.2%, and 77.1%, respectively. By using previously defined pre-DNA cutoff value (1500 copies/ml pretreatment), pre-DNA was an independent prognostic predictor for OS, DMFS, and PFS using log-rank test. Multivariate Cox analysis also confirmed these results. Subgroup analysis indicated that the 5-year OS, DMFS, and PFS rates in patients staged IVA-B with pre-DNA < 1500 copies/ml were similar to those patients staged III with pre-DNA ≥ 1500 copies/ml, whereas patients staged IVA-B patients with pre-DNA ≥ 1500 copies/ml predicted worse outcome. Conclusions: In this expanded study, the prognostic significance of pre-DNA was confirmed using predefined cutoff value in an independent patient group, and pre-DNA was identified as an independent prognostic marker for the risk stratification in LA-NPC.

Purpose : To evaluate the prognostic value of magnetic resonance imaging (MRI)-detected tumor residue after intensity-modulated radiation therapy (IMRT) and its association with post-treatment plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA) in nasopharyngeal carcinoma (NPC). Methods and materials : A prospective database of patients with histologically-proven NPC was used to retrospectively analyze 664 cases. Pre- and post-treatment MRI scans were independently reviewed by two senior radiologists who were blinded to clinical findings. Factors significantly associated with MRI-detected tumor residue were identified and included in the following multivariate logistic regression model. Residual risk model were established. Receiver operating characteristic (ROC) identify the optimal cut-off risk score for tumor residue. Results : MRI-detected residual tumor at three months after IMRT was associated with poor prognosis. The 5-year survival rates for the non-residual and residual groups were: OS (93.8% vs. 76.6%, P