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The prognostic value of diabetes remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 1489 patients with non-metastatic, histologically-proven NPC treated using IMRT. 81/1489 (5.4%) patients were diabetic, 168/1489 (11.3%) were prediabetic, and 1240/1489 (83.3%) were normoglycemic. The 4-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 77.1% vs. 82.4% (P = 0.358), 85.8% vs. 91.0% (P = 0.123), 90.9% vs. 91.7% (P = 0.884), and 85.5% vs. 89.2% (P = 0.445) for diabetic vs. normoglycemic patients, and 82.4% vs. 82.4% (P = 0.993), 88.7% vs. 91.0% (P = 0.285), 90.6% vs. 91.7% (P = 0.832) and 91.5% vs. 89.2% (P = 0.594) for preidabetic vs. normoglycemic patients. Multivariate analysis did not established diabetes as poor prognostic factors in NPC patients treated with IMRT (P = 0.332 for DFS, P = 0.944 for OS, P = 0.977 for LRRFS, P = 0.157 for DMFS), however, triglycerides and low density lipoprotein cholesterol were independent prognostic factors. In conclusion, diabetes does not appear to be a prognostic factor in NPC patients treated with IMRT, and attention should be paid to hyperglycemia-associated hyperlipaemia.

The prognostic value of plasma Epstein-Barr virus (EBV) DNA remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 584 newly diagnosed patients with nonmetastatic and biopsy-proven NPC treated using IMRT. Plasma EBV DNA concentration was measured before therapy (pre-DNA) and within 1 month of completing therapy (post-DNA) using real-time quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curves were generated to identify pre-DNA and post-DNA cut-off values. Prognostic value was assessed using a multivariate Cox proportional hazards model .Three-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free (DMFS) for pre-DNA >2010 vs.≤2010 were 78.1% vs. 93.6% (P P P = 0.004) and 85.5% vs. 96.6% (P 0 vs. = 0 were 49.9% vs. 88.5% (P P P = 0.019) and 60.5% vs. 93.3% (P

To evaluate the prognostic value of gross primary tumor volume (GTV-P) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT).A total of 694 nonmetastatic and histologically proven NPC patients who underwent IMRT were retrospectively reviewed. Samples were split randomly into a training set (n=232) and a test set (n=462) to analysis. The receiver operating characteristic (ROC) curves were calculated to identify the cut-off point and test the prognostic validity of the GTV-P. The correlations between GTV-P and the American Joint Committee on Cancer (AJCC) disease stages were also analyzed.The 5-year disease-free survival (DFS), overall survival (OS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) rates for NPC patients with GTV-P19 vs. ≥19 ml were 94.9% vs. 64.8%, 97.0% vs. 76.4%, 98.2% vs. 92.5% and 97.1% vs. 75.2%, respectively (all P0.05) in all patients. Multivariate analysis indicated GTV-P was an independent prognostic factor. The ROC curve verified that the predictive ability of T classifications was improved when combined with GTV-P (P0.001).GTV-P is an independent prognostic indicator for treatment outcome after IMRT, and significantly improves the prognostic validity of T classifications in NPC.

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 p 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.

Summary Background The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. Methods We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3–4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m 2 cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0–2·27 Gy per fraction with five daily fractions per week for 6–7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60–66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m 2 adjuvant cisplatin and 800 mg/m 2 per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. Findings 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3–61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81–90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78–88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49–1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). Interpretation Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. Funding Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010–178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).

Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%–30%), and low-risk (

Background. Our aim was to grade MRI–detected skull-base invasion in nasopharyngeal carcinoma and evaluate the prognostic value of the grading. Methods. The MRI scans and medical records of 924 patients with histologically diagnosed nondisseminated nasopharyngeal carcinoma were reviewed retrospectively. Results. MRI-detected skull-base invasion was not found to be an independent prognostic factor for overall survival, distant metastasis-free survival, or local relapse-free survival (p > .05 for all). Grading of skull-base erosion according to the site of invasion was found to be an independent prognostic factor for both overall survival (p = .003 and p = .006, respectively) and distant metastasis-free survival (p = .001 for both) in the 512 patients with skull-base invasions and 315 patients with T3 disease. Conclusions. MRI-detected skull-base invasion is not an independent prognostic factor for nasopharyngeal carcinoma. However, grading according to the site of invasion as either low grade or severe has prognostic value. © 2010 Wiley Periodicals, Inc. Head Neck, 2010

The abiotic cathodes usually require a catalyst such as Pt to enhance power production, increasing the cost and lowering the operational sustainability. In this paper, the performance of a biocathode microbial fuel cell biocatalyzed by ferro/manganese-oxidizing bacteria was investigated. A scanning electron microscopy with an energy-dispersive spectrometer (SEM-EDS) was used to characterize the cathode and analyze the element of cathode. The amount of ferro/manganese-oxidizing bacteria in the biocathode was examined. In batch-fed systems, the maximum open circuit voltage (OCV) was between 700 and 800 mV and the maximum cell potential difference was higher than 600 mV with an external resistance of 100 Ω. The maximum power density was 32 W m −3 MFC for batch-fed systems (20–40% Coulombic yield) and 28 W m −3 MFC for a continuous system with an acetate loading rate of 1.0 kg COD m −3 day −1 . The results of SEM-EDS clearly showed that cathode was impregnated with iron and manganese. The amount of ferro/manganese-oxidizing bacteria was (7.5–20.0) × 10 5 MPN mL −1 in the biocathode. Biocathodes alleviate the need to use noble catalysts for the reduction of oxygen, which step forward towards large-scale application of MFCs.

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.

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.

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.

// Hao Peng 1 , Lei Chen 1 , Yuan Zhang 1 , Rui Guo 1 , Wen-Fei Li 1 , Yan-Ping Mao 1 , Ling-Long Tan 1 , Ying Sun 1 , Fan Zhang 1 , Li-Zhi Liu 2 , Li Tian 2 , Ai-Hua Lin 3 , Jun Ma 1 1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China 2 Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China 3 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510275, People’s Republic of China Correspondence to: Jun Ma, e-mail: majun2@mail.sysu.edu.cn Keywords: nasopharyngeal carcinoma, Epstein-Barr virus, prognosis, advanced stage, intensity-modulated radiation therapy Received: October 30, 2015 Accepted: March 04, 2016 Published: March 17, 2016 ABSTRACT Purpose : The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results : Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) ( P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% ( P < 0.001), 93.6% vs. 85.9% ( P = 0.001), 96.7% vs. 84.8% ( P < 0.001) and 94.1% vs. 90.0% ( P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P

// Hao Peng 1 , Lei Chen 1 , Ling-Long Tang 1 , Yuan Zhang 1 , Wen-Fei Li 1 , Yan-Ping Mao 1 , Fan Zhang 1 , Rui Guo 1 , Li-Zhi Liu 2 , Li Tian 2 , Ai-Hua Lin 3 , Ying Sun 1 , Jun Ma 1 1 Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China 2 Imaging Diagnosis and Interventional Center, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China 3 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China Correspondence to: Jun Ma, e-mail: majun2@mail.sysu.edu.cn Keywords: nasopharyngeal carcinoma, primary tumor inflammation, gross tumor volume, prognosis, intensity-modulated radiation therapy Received: October 28, 2015 Accepted: January 31, 2016 Published: February 25, 2016 ABSTRACT Purpose: The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). Results: PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% ( P < 0.001), 73.4% vs. 85.1% ( P < 0.001), 85.0% vs. 92.1% ( P < 0.001) and 83.6% vs. 91.4% ( P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318–3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204–2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177–2.402, P = 0.004). Conclusions: Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Materials and Methods: Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared.

// Yuan Zhang 1, * , Wen-Fei Li 1, * , Yan-Ping Mao 1 , Guan-Qun Zhou 1 , Hao Peng 1 , Ying Sun 1 , Qing Liu 2 , Lei Chen 1 , Jun Ma 1 1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Canton, Guangdong, China 2 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Canton, Guangdong, China * These authors have contributed equally to this work Correspondence to: Jun Ma, e-mail: majun2@mail.sysu.edu.cn Lei Chen, e-mail: chenlei@sysucc.org.cn Keywords: nasopharyngeal neoplasms, metastasis, TNM staging, maximum standardized uptake value, recursive partitioning analysis Received: October 28, 2015 Accepted: January 27, 2016 Published: February 8, 2016 ABSTRACT Background: Previous studies reported a correlation between the maximum standardised uptake value (SUV max ) obtained by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) and distant metastasis in nasopharyngeal carcinoma (NPC). However, an integrated model incorporating SUV max and anatomic staging for stratifying metastasis risk has not been reported. Results: The median SUV max for primary tumour (SUV-T) and cervical lymph nodes (SUV-N) was 13.6 (range, 2.2 to 39.3) and 8.4 (range, 2.6 to 40.9), respectively. SUV-T (HR, 3.396; 95% CI, 1.451-7.947; P = 0.005), SUV-N (HR, 2.688; 95%CI, 1.250-5.781; P = 0.011) and N-classification (HR, 2.570; 95%CI, 1.422-4.579; P = 0.001) were identified as independent predictors for DMFS from multivariate analysis. Three valid risk groups were derived by RPA: low risk (N0-1 + SUV-T 10.45) and high risk (N2-3). The three risk groups contained 100 (22.3%), 226 (50.3%), and 123 (27.4%) patients, respectively, with corresponding 3-year DMFS rates of 99.0%, 91.5%, and 77.5% ( P

Supplemental Digital Content is available in the text, The purpose of the present study was to evaluate prognostic factors in patients with nasopharyngeal carcinoma (NPC) from the endemic area of southern China who have a positive family history (FH) of cancer. Retrospective analysis of 600 patients with nondisseminated NPC and a positive FH was conducted. The prognostic value of different factors for overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local relapse-free survival (LRFS) were assessed using Cox regression models. The 3-year OS, DMFS, DFS, and LRFS rates were 93.8%, 91.3%, 86.3%, and 93.8%, respectively. The FH tumor type was NPC for 226/600 (37.7%) patients and other cancers for 374/600 (62.3%) patients. The 3-year OS and DMFS rates for patients with an FH of NPC were 91.2% and 89.8%, respectively. Thirty of 600 (5.0%) patients had elevated pretreatment serum lactate dehydrogenase (LDH >245.0 IU/L). In multivariate analysis, N classification (HR 4.56, 95% CI 2.13–9.74, P

The prognostic value and staging category of parotid lymph node (PLN) metastasis in nasopharyngeal carcinoma (NPC) remain unknown. We retrospectively reviewed MRI scans and medical records for 1811 NPC patients who received intensity-modulated radiotherapy. The diagnosis of PLN metastasis was mainly based on MRI follow-up. Twenty-five positive PLNs in 21/1811 patients were identified; the incidence of PLN metastasis was 1.2%. PLN metastasis was significantly associated with advanced N-category and stage. Ten of the 21 patients received irradiation of the involved PLNs; the PLN recurrence rate was significantly higher for patients who received no irradiation; thus only patients with irradiated PLN were included in prognostic analyses. PLN metastasis was associated with significantly poorer progression-free survival, overall survival and distant metastasis-free survival (DMFS), but not regional or local relapse-free survival, in univariate analysis. In multivariate analysis, PLN metastasis was also significantly associated with poor DMFS. PLN involvement had a significantly higher hazard ratio (HR) for distant failure than N2 disease and similar HR to N3 disease. In conclusion, PLN metastasis is rare in NPC and was associated with similarly poor DMFS as N3 disease. PLN metastasis should be suspected in advanced nodal disease, but diagnosed with care before administering aggressive treatment.

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.

The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival.

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.

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.

Background Leucopenia or neutropenia during chemotherapy predicts better survival in several cancers. We aimed to assess whether leucopenia could be a biological measure of treatment and a marker of efficacy in advanced nasopharyngeal carcinoma (ANPC). Methods We retrospectively analyzed 3826 patients with ANPC who received chemoradiotherapy. Leucopenia was categorised on the basis of worst grade during treatment according to the National Cancer Institute Common Toxicity Criteria version 4.0: no leucopenia (grade 0), mild leucopenia (grade 1–2), and severe leucopenia (grade 3–4). Associations between leucopenia and survival were estimated by Cox proportional hazards model. Results Of the 3826 patients, 2511 (65.6 %) developed mild leucopenia (grade 1–2) and 807 (21.1 %) developed severe leucopenia (grade 3–4) during treatment; 508 (13.3 %) did not. A multivariate Cox model that included leucopenia determined that the hazard ratios (HR) of death for patients with mild and severe leucopenia were 0.69 [95 % confidence interval (95 %CI) 0.56-0.85, p

Here we employed quantitative real-time PCR (qPCR) assays for polyphosphate kinase 1 (ppk1) and 16S rRNA genes to assess relative abundances of dominant clades of Candidatus Accumulibacter phosphatis (referred to Accumulibacter) in 18 globally distributed full-scale wastewater treatment plants (WWTPs) from six countries. Accumulibacter were not only detected in the 6 WWTPs performing biological phosphorus removal, but also inhabited in the other 11 WWTPs employing conventional activated sludge (AS) with abundances ranging from 0.02% to 7.0%. Among the AS samples, clades IIC and IID were found to be dominant among the five Accumulibacter clades. The relative abundance of each clade in the Accumulibacter lineage significantly correlated (p

Background To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). Methods We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Results Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3–57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Conclusion Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

Dysregulation of microRNAs (miRNAs) has been demonstrated to contribute to malignant progression in nasopharyngeal carcinoma (NPC). We previously reported that miR-93 was significantly upregulated in NPC based on a microarray analysis. However, the potential role and mechanism of action of miR-93 in the initiation and progression of NPC remain largely unknown. Quantitative RT-PCR demonstrated that miR-93 was significantly upregulated in NPC cell lines and clinical specimens. The MTT assay, colony formation assay, anchorage-independent growth, and Transwell migration and invasion assays showed that depletion of miR-93 inhibited NPC cell growth, invasion and migration in vitro and suppressed tumor growth in vivo. Disabled homolog-2 (Dab2) was verified as a miR-93 target gene using Luciferase reporter assays, quantitative RT-PCR and Western blotting and was involved in miR-93-regulated NPC cell growth, invasion and migration. These results indicated that miR-93 plays an important role in the initiation and progression of NPC by targeting Dab2 and the miR-93/Dab2 pathway may contribute to the development of novel therapeutic strategies for NPC in the future.

Glycogen-accumulating organisms (GAOs) may compete with phosphate-accumulating organisms (PAOs) for short-chain fatty acids (VFAs) in anaerobic polyhydroxyalkanoates (PHA) synthesis, but no consequently aerobic polyphosphate accumulation in enhanced biological phosphorus removal (EBPR) process, thus deteriorating the EBPR process. They are detected frequently in the deteriorated EBPR process, but their metabolisms are still far from our comprehensions for there is seldom pure culture. In this study, a nearly complete draft genome of a GAOs in Defluviicoccus cluster II, GAO-HK, is recruited from the metagenome of activated sludge in a full-scale industrial anoxic/aerobic wastewater plant. Comparative genomics reveal similar metabolisms of PHA and glycogen in GAOs of GAO-HK, Defluviicoccus tetraformis TFO71 (TFO71) and Competibacter phosphatis clade IIA (CPIIA), and PAOs of Accumulibacter clade IIA UW-1 (UW-1) and Tetrasphaera elongata Lp2 (Lp2). Although there are similar gene cassettes related with polyphosphate metabolism in these GAOs and PAOs, especially for Defluviicoccus-relative bacteria and UW-1, ppk1 in GAOs are diverse from those in the identified PAOs, implying the difference of polyphosphate metabolism in GAOs and PAOs. Additionally, genes related to the dissimilatory denitrification are absent in TFO71 and GAO-HK, implying that additional nitrate or nitrite may favor PAOs over Defluviicoccus-relative GAOs. Therefore, PAOs suffering from competition of Defluviicoccus-relative GAOs might be rescued with the additional nitrate/nitrite, which is important to improve the stability of EBPR processes.

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 (

Background The incidence of diabetes is increasing. But the impact of diabetes and prediabetes on survival of patients with nasopharyngeal carcinoma (NPC) has received little evaluation. Methods In a cohort of 5,860 patients, we compared the disease specific survival (DSS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) of patients with diabetes, prediabetes and normoglycemia defined by pretreatment fasting plasma glucose (FPG) using Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results Comparing to normoglycemic patients, the diabetic and the prediabetic were generally older, fatter, had hypertension, heart diseases and hyperlipaemia and usually received radiotherapy alone. But both the diabetic and the prediabetic had similar DSS, LRFS and DMFS to normoglycemic patients, even adjusting for such important factors as age, gender, smoking, drinking, hypertension, heart diseases, body mass index, hyperlipaemia, titer of VCA-IgA and EA-IgA, pathology, T-stage, N-stage, chemotherapy and radiotherapy (P>0.05 for all). Additionally, the findings remained unchanged in sensitivity analysis by excluding patients with known diabetes history and in subgroups of the various factors. Conclusions The diabetic and prediabetic NPC patients had similar survival to normoglycemic NPC patients. These data, in the largest reported cohort, are the first to evaluate the association between diabetes, prediabetes and the survival in NPC. The findings are relevant to patient management and provided evidence of the effect on this disease exerted by comorbidities.

The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8–20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64–68 Gy in 29–31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9–111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse–free survival, distant metastasis–free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3–4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1–2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.

Background: There are few systematic evaluations regarding the sixth and seventh editions of the UICC/AJCC TNM Staging System (TNM6th, TNM7th) and Chinese 2008 Staging System (TNMc2008) for nasopharyngeal carcinoma (NPC). Methods: We classified 2333 patients into intensity-modulated radiotherapy (IMRT) cohort (n=941) and conventional radiotherapy (CRT) cohort (n=1392). Tumour staging defined by TNM6th, TNM7th and TNMc2008 was compared based on Akaike information criterion (AIC) and Harrell's concordance index (c-index). Results: For T-classification, TNM6th (AIC=2585.367; c-index=0.6390385) had superior prognostic value to TNM7th (AIC=2593.242; c-index=0.6226889) and TNMc2008 (AIC=2593.998; c-index=0.6237146) in the IMRT cohort, whereas TNMc2008 was superior (AIC=5999.054; c-index=0.623547) in the CRT cohort. For N-classification, TNMc2008 had the highest prognostic value in both cohorts (AIC=2577.726, c-index=0.6297874; AIC=5956.339, c-index=0.6533576). Similar results were obtained when patients were stratified by chemotherapy types, age and gender. Using staging models in the IMRT cohort, we failed to identify better stage migrations than TNM6th T-classification and TNMc2008 N-classification. We therefore proposed to combine these categories; resultantly, stage groups of the proposed staging system showed superior prognostic value over TNM6th, TNM7th and TNMc2008. Conclusion: TNM6th T-classification and TNMc2008 N-classification have superior prognostic value in the IMRT era. By combining them with slight modifications, TNM criteria can be unified and its prognostic value be improved.

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.A total of 1301 patients with nonmetastatic, histologically proven NPC who were treated with radiotherapy or chemoradiotherapy were retrospectively reviewed.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.Chronic HBV infection is an independent adverse prognostic factor in patients with locoregionally advanced NPC.

Background: ABO blood group is associated with aetiology of nasopharyngeal carcinoma (NPC); however, the effect of it on survival of patients diagnosed with NPC has not been explored. Methods: We retrospectively analysed two cohorts of southern Chinese patients with WHO histological type III: intensity-modulated radiotherapy (IMRT) cohort, 924 patients; and conventional radiotherapy (CRT) cohort, 1193 patients. Associations of ABO blood group with survival were estimated using Cox regression. Results: In IMRT cohort, we observed significant associations of blood type A with overall survival (OS) and distant metastasis-free survival (DMFS), compared with type O, after adjusting for prognostic factors. Compared with non-A blood types (B, AB, and O), type A patients had significantly lower OS and DMFS (adjusted hazard ratio (HR)=1.49, 95% CI 1.03–2.17, P=0.036; HR=1.68, 95% CI 1.13–2.51, P=0.011, respectively); similar results were obtained in CRT cohort. Subgroup analyses of the entire population showed that lower OS conferred by blood type A was not significantly modified by age, smoking status, drinking status, immunoglobulin A against Epstein–Barr virus viral capsid antigen (VCA-IgA) titre, or chemotherapy; however, lower OS was not observed in female patients or patients with early clinical stage disease. Conclusion: ABO blood group is associated with survival in NPC; patients with blood type A had significantly lower OS and DMFS than patients with non-A blood types.

Recent findings have reported that human serum microRNAs (miRNAs) can be used as prognostic biomarkers in various cancers. We aimed to explore the prognostic value of serum miRNAs in nasopharyngeal carcinoma (NPC) patients. The level of serum miRNA was retrospectively analyzed in 512 NPC patients recruited between January 2001 and December 2006. In the discovery stage, a microarray followed by reverse transcription-quantitative polymerase chain reaction was used to identify differentially altered miRNAs in eight patients with shorter survival and eight patients with longer survival who were well matched by age, sex and clinical stage. The identified serum miRNAs were then validated in all 512 samples, which were randomly divided into a training set and a validation set. Four serum miRNAs (miR-22, miR-572, miR-638 and miR-1234) were found to be differentially altered and were used to construct a miRNA signature. Risk scores were calculated to classify the patients into high- or low-risk groups. Patients with high-risk scores had poorer overall survival [hazard ratio (HR), 2.54; 95% confidence interval (CI), 1.57-4.12; p0.001] and distant metastasis-free survival (HR, 3.28; 95% CI, 1.82-5.94; p0.001) than those with low-risk scores in the training set; these results were confirmed in the validation and combined sets. The miRNA signature and TNM stage were independent prognostic factors. The combination of the miRNA signature and TNM stage had a better prognostic value than the TNM stage or miRNA signature alone. The four-serum miRNA signature may add prognostic value to the TNM staging system and provide information for personalized therapy in NPC.

Background This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future. Methods Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (Σ) and random (σ) errors. Results The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial–lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior–inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior–posterior (AP) direction. The corresponding Σ were 1.0–1.4 mm, 0.4–0.5 mm and 0.2–0.4 mm, while the corresponding σ were 0.7–0.8 mm, 0.6–0.7 mm and 0.5–0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4–4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7–2.2 mm. Conclusions CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans.

This work focused on studying the effect of the chemical oxidation demand to sulfide ratio (COD/S) on power generation and sulfide oxidation in microbial fuel cells treating sulfide-rich wastewater containing organic contaminants. The maximum power density achieved was 20 +/- 1 W m(-3) V(Anode) and the C(oulombic) yield was 20 +/- 2%. The COD/S ofinfluent played an important role in elemental sulfur and sulfate production because of competition between acetate oxidation and element sulfur oxidation to sulfate in the anode. When the COD/S was 12.50/1, more than 74.0% of sulfide was converted into elemental sulfur after 24 hours of operation. The effect of the COD/S on power generation was negligible when the COD/S ranged between 4.85/l and 18.53/l. After 24 hours, the COD removals were 110 +/- 6, 213 +/- 9, 375 +/- 8 and 410 +/- 10 mgl(-1) when the COD/S was 4.85/1, 8.9/1, 12.5/1 and 18.53/1, respectively. The COD removal increased with the increasing COD of the influent, which fitted to the model of first-order reaction kinetics.

The purpose of this study was to summarize the treatment outcomes and evaluate the feasibility of partial neck irradiation in patients with nasopharyngeal carcinoma (NPC) with only retropharyngeal lymph nodes (RLNs) metastasis.Between January 2003 and December 2007, 54 patients with NPC who received partial neck irradiation to levels II, III, and VA and 100 patients who received whole neck irradiation were reviewed.The 5-year disease free survival (DFS), disease metastasis-free survival, (DMFS) local relapse-free survival (LRFS), and regional relapse-free survival (RRFS) rates were 81.8%, 87.7%, 94.8%, and 98.1%, respectively. The 5-year RRFS and DFS rates for the partial neck irradiation group and whole neck irradiation group were 98.1% versus 98.0% (p = .882), 87.0% vs 77.0% (p = .117), respectively. Partial neck irradiation was not considered a significant prognostic factor for any endpoint in univariate and multivariate analyses.Partial irradiation of neck levels II, III, and VA might be acceptable for patients with NPC with only RLN metastasis.

Background and purposeTo recommend contouring methods and atlas of organs at risk (OARs) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy, in order to help reach a consensus on interpretations of OARs delineation.Methods and materialsTwo to four contouring methods for the middle ear, inner ear, temporal lobe, parotid gland and spinal cord were identified via systematic literature review; their volumes and dosimetric parameters were compared in 41 patients. Areas under the receiver operating characteristic curves for temporal lobe contouring were compared in 21 patients with unilateral temporal lobe necrosis (TLN).ResultsVarious contouring methods for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord lead to different volumes and dosimetric parameters (P

BACKGROUND The objective of this study was to evaluate the long-term survival and late toxicities of concurrent-adjuvant chemotherapy in patients with stage III through IVB nasopharyngeal carcinoma (NPC) from endemic regions of China. METHODS Patients with stage III to IVB NPC were assigned randomly to receive radiotherapy (RT) alone (the RT group) or RT plus concurrent adjuvant chemotherapy (the CRT group). CRT patients received concurrent cisplatin (40 mg/m2) weekly during RT followed by cisplatin (80 mg/m2) and fluorouracil (800 mg/m2 daily for 5 days) every 4 weeks for 3 cycles. The primary endpoint was overall survival. RESULTS In total, 316 patients underwent randomization, with 158 to each group. At a median follow-up of 70 months, the 5-year overall survival rate was 72% for the CRT group and 62% for the RT group (hazard ratio, 0.69; 95% confidence interval, 0.48-0.99; P = .043). Failure-free survival was significantly higher in the CRT group (P = .020). Most late toxicities were similar (33% vs 26%; P = .089), except for cranial neuropathy (P = .042), peripheral neuropathy (P = .041), and ear damage (P = .048), which were significantly increased in the CRT group. CONCLUSIONS The addition of concurrent adjuvant chemotherapy to RT provides survival benefits to patients with stage III through IVB NPC in endemic regions of China, and it does not increase most late toxicities apart from cranial neuropathy, peripheral neuropathy, and ear damage. Cancer 2013;119:2230–2238. © 2013 American Cancer Society.

To identify the prognostic value and staging categories of masticator space involvement in nasopharyngeal carcinoma (NPC) as determined with anatomic criteria ("anatomic masticator space involvement") to determine whether it is necessary for the masticator space described with criteria of the American Joint Committee on Cancer to exclude the medial and lateral pterygoid muscles.This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. NPC was diagnosed in 924 patients with magnetic resonance (MR) imaging, and medical records and imaging studies were retrospectively analyzed. The overall survival, local relapse-free survival, and distant metastasis-free survival of these patients were analyzed by using the Kaplan-Meier method; differences were compared by using the log-rank test.The frequency of anatomic masticator space involvement was 19.7% (182 of 924 patients). With use of multivariate analysis, anatomic masticator space involvement was identified as an independent prognostic factor for overall survival (P = .02). In addition, anatomic masticator space involvement was associated with a marginally significant decrease in local relapse-free survival (P = .05); however, it had no effect on distant metastasis-free survival. There were no statistically significant differences between different degrees of anatomic masticator space involvement with regard to overall survival and local relapse-free survival in NPC (P = .34 and P = .54, respectively) or between T3 or T4 disease and anatomic masticator space involvement with regard to overall survival and local relapse-free survival (P = .63 and P = .44, respectively).Anatomic masticator space involvement affects the overall survival and local relapse-free survival of patients with NPC. When masticator space involvement includes the medial and lateral pterygoid muscles, the disease should be classified as stage T4.

To investigate the prognostic significance of prevertebral space involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).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.In this series, 161 NPC patients (31.8%) had PSI. Parapharyngeal space (p0.001), skull base (p0.001), 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% (p0.0001), 83.9% and 96.4% (p0.0001), and 71.6% and 89.6% (p0.0001), 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).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.

Purpose To evaluate the 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC) in patients treated with intensity-modulated radiotherapy. Methods and materials We performed a retrospective data review from 512 patients with biopsy-proven, nonmetastatic NPC in our cancer center (South China) between January 2003 and December 2006. Results The local relapse-free survival rates (LRFS) and disease failure-free survival rates (DFS) in the 6th edition system T1 and T2a stages were not significantly different (P = 0.629 and P = 0.820), while the LRFS and DFS of T1 and T2 using the 7th edition system were significantly different (P = 0.019 and P = 0.009). The LRFS and DFS between T2 and T3 in the 7th edition systems were lack of significance (P = 0.874 and P = 0.589). The total difference in distant metastasis-free survival rate and DFS between N0 and N3 was slightly larger using the 7th edition system than the 6th edition. The nodal dimension of a cervical lymph node was not a significant prognostic factor. Conclusions We observed a better segregation of survival curves by using the 7th edition system. It seems reasonable to downstage T3 as T2 and reject nodal greatest dimension from the N-staging system in the future revised edition.

Background and objective The Chinese 2008 staging system for nasopharyngeal carcinoma (NPC) was a common set of recommendations by initial revision of the previous'92 staging system. This study was to verify the Chinese 2008 staging system and to provide evidence for its further revision. Methods Between January 2003 and December 2004, 924 consecutive patients with newly diagnosed, nondisseminated biopsy-proven NPC, presented at the Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, were entered into our study. All patients received magnetic resonance imaging examination of the neck and nasopharynx before treatment. According to the principle of the staging system, the indices of hazard consistency, hazard discrimination, prognostic value, and distribution were used to evaluate the Chinese 2008 staging system. Results According to the Chinese 2008 staging system, the distribution of stage group for the whole series was 4.9% for the stage I, 22.6% stage II, 38.0% stage III, and 34.5% stage IVA. As for hazard discrimination, the 4-year local relapse-free survival (LRFS) rates for T1-T4 patients were 95.4%, 93.7%, 90.5% and 79.1%, respectively. Although the separation of LRFS for all subclassifications of T-stage showed reasonable, the differences among the subgroups T1, T2, and T3 were still lack of significant statistically. The 4-year distant metastasis failure-free survival (DMFS) rates for N0-N3 patients were 89.4%, 84.3%, 73.6, and 59.2%, respectively. The 4-year overall survival (OS) rates for stage I-IV patients were 96.7%, 94.1%, 82.6% and 67.1%, respectively. As for hazard consistency, the distinctions between T3 with skull base involvement and T3 with medial pterygoid muscle in the hazard ratios of local failure (1.628 vs. 3.905) and disease failure (1.630 vs. 3.288) were large. Multivariate analyses showed that cervical nodal level, extranodal neoplastic spread, and laterality were independent prognostic factors for OS and DMFS, but maximal axial diameter was not. Conclusion Using the Chinese 2008 staging system for NPC produces an acceptable distribution of patient numbers. Stage group, T classification, and N classification represent independent prognosis factors for major endpoints. However, our study reveals several deficiencies in the current system yet.