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Purpose: We aimed to evaluate the value of deep learning on positron emission tomography with computed tomography (PET/CT)–based radiomics for individual induction chemotherapy (IC) in advanced nasopharyngeal carcinoma (NPC). Experimental Design: We constructed radiomics signatures and nomogram for predicting disease-free survival (DFS) based on the extracted features from PET and CT images in a training set (n = 470), and then validated it on a test set (n = 237). Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were applied to evaluate the discriminatory ability of radiomics nomogram, and compare radiomics signatures with plasma Epstein–Barr virus (EBV) DNA. Results: A total of 18 features were selected to construct CT-based and PET-based signatures, which were significantly associated with DFS (P < 0.001). Using these signatures, we proposed a radiomics nomogram with a C-index of 0.754 [95% confidence interval (95% CI), 0.709–0.800] in the training set and 0.722 (95% CI, 0.652–0.792) in the test set. Consequently, 206 (29.1%) patients were stratified as high-risk group and the other 501 (70.9%) as low-risk group by the radiomics nomogram, and the corresponding 5-year DFS rates were 50.1% and 87.6%, respectively (P < 0.0001). High-risk patients could benefit from IC while the low-risk could not. Moreover, radiomics nomogram performed significantly better than the EBV DNA-based model (C-index: 0.754 vs. 0.675 in the training set and 0.722 vs. 0.671 in the test set) in risk stratification and guiding IC. Conclusions: Deep learning PET/CT-based radiomics could serve as a reliable and powerful tool for prognosis prediction and may act as a potential indicator for individual IC in advanced NPC.

We analyzed the number of circulating tumor cells (CTCs) and Epstein-Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first-line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first-line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first-line chemotherapy was associated with significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first-line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first-line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.

Background The purpose of this study was to verify 10-year results of survival and late toxicities and assess the ultimate therapeutic ratio of intensity-modulated radiotherapy (IMRT) versus two-dimensional radiotherapy (2DRT) in patients with nasopharyngeal carcinoma (NPC). Materials and Methods We retrospectively reviewed the data from 1,276 patients with nonmetastatic NPC who received IMRT or 2DRT from January 2003 to December 2006. Results Of the 1,276 patients, 512 were treated with IMRT and 764 with 2DRT. Median follow-up was 115 months. At 10 years, the IMRT group demonstrated significantly better results than the 2DRT group in local failure-free survival (L-FFS; 90% vs. 84%; hazard ratio [HR], 0.57, 95% confidence interval [CI], 0.40–0.81; p = .001), failure-free survival (FFS; 69% vs. 58%; HR, 0.69, 95% CI, 0.57–0.83; p Conclusion IMRT demonstrated an improved ultimate therapeutic ratio compared with 2DRT in patients with NPC after a 10-year follow-up, with significant improvement of L-FFS, FFS, and OS and decrease in most late toxicities. Implications for Practice The ultimate therapeutic ratio of intensity-modulated radiotherapy versus two-dimensional radiotherapy in patients with nasopharyngeal carcinoma is unclear. In this retrospective study of 1,276 patients with nonmetastatic nasopharyngeal carcinoma with a follow-up of 115 months, intensity-modulated radiotherapy demonstrated an improved ultimate therapeutic ratio compared with two-dimensional radiotherapy, with significant improvement of local failure-free survival, failure-free survival, and overall survival and decrease in most late toxicities and noncancer deaths. However, distant control remains insufficient with this treatment modality.

Background Enlarged retropharyngeal lymph nodes (RLNs) are very common in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The most suitable treatment option for enlarged RLNs depends on the pathological results. However, RLN sampling is difficult and imminent in the clinic setting. We recently developed a novel minimally invasive technique termed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for sampling RLN tissues sufficient for pathological or cytological diagnosis. Methods We enrolled 30 post-radiotherapy patients with NPC with suspected RLN metastasis detected via magnetic resonance imaging (MRI). The EUS probe was introduced into the nasopharynx via the nostrils, and EUS was then used to scan the retropharyngeal space and locate the RLN in the anterior carotid sheath. EUS-FNA was subsequently performed. The safety and efficacy of using EUS-FNA to sample the RLN tissues were assessed. Results Strips of tissue were successfully sampled from all patients using EUS-FNA. Of the 30 patients, 23 were confirmed to have cancer cells in the biopsied tissues via pathology or cytology examinations with 1 EUS-FNA biopsy session. The seven cases without confirmed cancer cells were subsequently reanalyzed by using another EUS-FNA biopsy session, and two more cases were confirmed possessing cancer cells. The other five patients without confirmed cancer cells were closely followed with MRI every month for 3 months. After follow-up for 3 months, three patients were still considered cancer-free due to the presence of RLNs with stable or shrinking diameters. The rest two patients who showed progressive disease underwent a third EUS-FNA biopsy procedure and were further confirmed to be cancer cell-positive. In the whole cohort reported here, the EUS-FNA procedure was not associated with any severe complications. Conclusion EUS-FNA is a safe and effective diagnostic approach for sampling tissues from the RLNs in patients with suspected recurrent NPC.

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma.In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p0·0001), disease-free survival (HR 3·51, 2·43-5·07; p0·0001), and overall survival (HR 3·22, 2·18-4·76; p0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status.The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.The National Natural Science Foundation of China, the National ScienceTechnology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the HealthMedical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities.

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).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.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).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.

Background: In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN. Methods: Thirty-eight PN patients with small fiber involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed medical history and small fiber neuropathy were investigated, and symptom inventory questionnaire was conducted, as well as the visual analog scale. Nerve conduction studies and skin biopsies were also performed. The differences among the groups were analyzed using analysis of variance and Kruskal-Wallis test. Results: Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber density (IENFD) weakly correlated with motor conduction velocity (MCV) ( r = 0.372, P = 0.025), and proximal ( r = 0.383, P = 0.021) and distal ( r = 0.358, P = 0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also weakly correlated with MCV of the peroneal nerve ( r = 0.399, P = 0.016). IENFD was shown to be significantly different among all groups ( χ 2 = 9.901, P = 0.007). IENFD was significantly decreased ( χ 2 = 23.000, P = 0.003) in the MS-related PN group compared to the idiopathic PN group. The MCV of the tibial nerve was significantly different among all groups ( χ 2 = 8.172, P F = 4.336, P = 0.021) and distal ( F = 3.262, P = 0.049) CMAP of the tibial nerve was also significantly different among all groups. Conclusions: IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.

To better manage patients with de novo metastatic NPC (mNPC) including easily identifying individuals' survival outcomes and accurately choosing the most suitable treatment.Three independent cohorts of mNPC patients (a training set of n = 462, an internal prospective validation set of n = 272 and an external prospective validation set of n = 243) were studied. The radiological characteristics of distant metastases, including number of metastatic locations, number of metastatic lesions and size of metastatic lesions, were carefully defined based on imaging data. These three factors and other potential prognostic factors were comprehensively analysed and were further integrated into new subdivisions of stage M1 using a Cox proportional hazards model.We successfully subdivided the M1 stage into three categories: M1a, oligo metastasis without liver involvement; M1b, multiple metastases without liver involvement; and M1c, liver involvement irrespective of metastatic lesions. The 3-year overall survival ranged from 54.5% to 72.8%, from 34.3% to 41.6% and from 22.6.0%-23.6% for M1a, M1b and M1c, respectively (P 0.001). Systemic chemotherapy combined with radical loco-regional radiotherapy may benefit patients in M1a and M1b, not in M1c. Further aggressive treatment of metastatic lesions based on systemic chemotherapy and definitive loco-regional radiotherapy showed no survival benefit, even for patients in M1a (P 0.05).The subdividing of M1 provided promising prognostic value and could aid clinicians in choosing the most suitable treatment for de novo mNPC patients.

Background: Few studies have focused on peripheral nerve conduction during exposure to microgravity. The −6° head-down tilt (HDT) comprises an experimental model used to simulate the space flight environment. This study investigated nerve conduction characteristics of rhesus monkeys before and after prolonged exposure to HDT. Methods: Six rhesus monkeys (3–4 years old) were tilted backward 6° from the horizontal. Nerve conduction studies (NCSs) were performed on the median, ulnar, tibial, and fibular motor nerves. Analysis of variance with a randomized block design was conducted to compare the differences in the NCS before and 7, 21, and 42 days after the −6° HDT. Results: The proximal amplitude of the CMAP of the median nerve was significantly decreased at 21 and 42 days of HDT compared with the amplitude before HDT (4.38 ± 2.83 vs. 8.40 ± 2.66 mV, F = 4.85, P = 0.013 and 3.30 ± 2.70 vs. 8.40 ± 2.66 mV, F = 5.93, P = 0.004, respectively). The distal amplitude of the CMAP of the median nerve was significantly decreased at 7, 21, and 42 days of HDT compared with the amplitude before HDT (7.28 ± 1.27 vs. 10.25 ± 3.40 mV, F = 4.03, P = 0.039; 5.05 ± 2.01 vs. 10.25 ± 3.40 mV, F = 6.25, P = 0.04; and 3.95 ± 2.79 vs. 10.25 ± 3.40 mV, F = 7.35, P = 0.01; respectively). The proximal amplitude of the CMAP of the tibial nerve was significantly decreased at 42 days of HDT compared with the amplitude before HDT (6.14 ± 1.94 vs. 11.87 ± 3.19 mV, F = 5.02, P = 0.039). Conclusions: This study demonstrates that the compound muscle action potential amplitudes of nerves are decreased under simulated microgravity in rhesus monkeys. Moreover, rhesus monkeys exposed to HDT might be served as an experimental model for the study of NCS under microgravity. Key words: Compound Muscle Action Potential; Head-down Tilt; Microgravity; Nerve Conduction; Nerve Conduction Velocity

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.

Background The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy (IMRT) as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma (NPC), but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients. Endoscopic nasopharyngectomy (ENPG) was successfully applied in recurrent NPC with radiation free and relatively low medical costs. In this study, we examined whether ENPG could be an effective treatment for localized stage I NPC. Methods Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center. Simultaneously, the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort. The survival outcomes, quality of life (QOL), and medical costs between two groups were compared. Results After a median follow-up of 59.0 months (95% CI 53.4–64.6), no death, locoregional recurrence, or distant metastasis was observed in the 10 patients treated with ENPG. The 5-year overall survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients (100% vs. 99.1%, 100% vs. 97.7%, 100% vs. 99.0%, 100% vs. 97.4%, respectively, P > 0.05). In addition, compared with IMRT, ENPG was associated with decreased total medical costs ($ 4090.42 ± 1502.65 vs. $ 12620.88 ± 4242.65, P

Background The role of pretreatment Epstein-Barr virus DNA (pre-DNA) for individualized induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) still remains unknown. We aimed to address this clinical issue. Methods In total, data on 6218 patient with newly diagnosed LA-NPC receiving concurrent chemoradiotherapy (CCRT) with or without IC were retrospectively reviewed. Receiver operating characteristics (ROC) curve was adopted to calculate the cut-off value of pre-DNA based on disease-free survival (DFS). Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes between IC + CCRT and CCRT groups were compared. Results Among the original cohort, no survival difference between IC + CCRT and CCRT groups was found. The cut-off value of pre-DNA was 4650 copies/ml (area under curve [AUC], 0.620; sensitivity, 0.6224; specificity, 0.5673). For patients with Pre-DNA ≤ 4650 copies/ml, the IC + CCRT and CCRT groups also achieved comparable survival outcomes (P > 0.05 for all rates). However, IC + CCRT was associated with significantly improved 3-year DFS (78.6% vs. 74.8%, P = 0.03), overall survival (OS; 91.4% vs. 87.5%, P = 0.002) and distant metastasis-free survival (DMFS; 86.0% vs. 82.2%, P = 0.036) for patient with pre-DNA > 4650 copies/ml. Multivariate analysis also confirm that IC + CCRT was an independent prognostic factor for DFS (HR, 0.817; 95% CI, 0.683–0.977; P = 0.027), OS (HR, 0.675; 95% CI, 0.537–0.848; P = 0.001) and DMFS (HR, 0.782; 95% CI, 0.626–0.976; P = 0.03). Conclusions Pre-DNA may be a feasible and powerful consideration for individualized IC apart from other baseline clinical characteristics in LA-NPC. Electronic supplementary material The online version of this article (10.1186/s12885-018-5177-9) contains supplementary material, which is available to authorized users.

Purpose To investigate the prognostic value of skull-base invasion (SBI) for nasopharyngeal carcinoma (NPC), propose a subclassification of SBI. Methods 792 and 433 patients with pathologically proven NPC and complete clinical and magnetic resonance imaging records at Sun Yat-sen University Cancer Center and Foshan Hospital were enrolled, and investigated using heat map/cluster, network and survival analyses. Results The results of heat map/cluster analyses and network analysis showed that T3 patients with pterygoid process and/or base of the sphenoid bone invasion (T3 slight) had better treatment outcomes than those with other SBIs (T3 severe). Significant differences were observed between T3-slight and T3-severe groups with regard to 5-year overall survival (OS) (93.0% vs. 83.5%, p = 0.014) and progression-free survival (PFS) (82.5% vs. 74.1%, p = 0.044) rates. No significant difference was observed between T3-slight group and T2 patients with regard to 5-year OS (93.0% vs. 84.7%, p = 0.062) and PFS (82.5% vs. 78.9%, p = 0.459) rates. Therefore, we downgraded patients with T3 slight to T2, yielding a new T classification sample. The survival curves of the 5-year OS and PFS rates of T2 and T3 were more reasonable after sample redistribution than those before sample redistribution. The differences in the 5-year OS and PFS rates between T2 and T3 patients after sample redistribution approached significance (p = 0.075 and 0.051, respectively). Conclusions Different types of SBIs had different effects on the prognosis for NPC. We recommend patients with T3 slight not be defined as T3 but, rather, as T2.

// Rui Guo 1,* , Yan-Ping Mao 1,* , Lei chen 1 , Ling-Long Tang 1 , Guan-Qun Zhou 1 , Li-Zhi Liu 2 , Li Tian 2 , Mu-Sheng Zeng 3 , Wei-Hua Jia 3 , Jian-Yong Shao 4 , Ai-Hua Lin 5 , and 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 of Cancer Medicine, 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 of Cancer Medicine, People’s Republic of China 3 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, People’s Republic of China 4 Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, People’s Republic of China 5 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jun Ma, email: // Keywords : comorbidity, Initiation of chemotherapy, nasopharyngeal carcinoma, treatment outcome Received : September 11, 2015 Accepted : March 14, 2016 Published : April 06, 2016 Abstract Background: To assess the impact of comorbidity on the initiation of chemotherapy and its ultimate treatment outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: Data on 1316 patients with NPC treated between February 2003 and January 2007 was retrospectively reviewed. Comorbidity was assessed using the Adult Comorbidity Evaluation-27 (ACE-27) system. The association of various factors with chemotherapy was evaluated. And treatment outcomes of chemoradiotherapy regimes in patients with comorbidity were compared. Results: Comorbidity was present in 42.2% of patients; mild, moderate and severe comorbidity were observed in 33.6%, 8.1% and 0.5% of patients, respectively. Comorbidity (as indicated by ACE-27 score) was a negative prognostic factor for overall survival (OS) (hazard ratio HR=1.577; P 0), 5-year OS for the concomitant chemoradiotherapy group (CCRT) was 74.5% vs. 56.9% in the radiotherapy (RT) only group ( P = 0.008), the 5-year DFS rate was 64.0% in the CCRT group vs . 49.4% for RT only ( P = 0.015). Conclusions: Comorbidity should be assessed during treatment strategy decision-making to improve survival in NPC. Concomitant chemoradiotherapy is feasible and effective in patients with comorbidity in locoregionally advanced stages.

Background: Among patients with Charcot–Marie–Tooth disease (CMT), the X-linked variant (CMTX) caused by gap junction protein beta 1 (GJB1) gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 (CX32). CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods: We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People's Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX1. Results: Nine GJB1 mutations (c.283G>A, c.77C>T, c.643C>T, c.515C>T, c.191G>A, c.610C>T, c.490C>T, c.491G>A, and c.44G>A) were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were < 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C>T, c.191G>A, and c.610C>T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions: The three novel missense mutations within the GJB1 gene broaden the mutational diversity of CMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.

Scientific evidence linking vitamin D with various cancer types is growing, but the effects of vitamin D on ovarian cancer stem cell‑like cells (CSCs) are largely unknown. The present study aimed to examine whether vitamin D was able to restrain the stemness of ovarian cancer. A side population (SP) from malignant ovarian surface epithelial cells was identified as CSCs, in vitro and in vivo. Furthermore, 1α,25‑dihydroxyvitamin D3 [1α,25(OH)2D3] treatment inhibited the self‑renewal capacity of SP cells by decreasing the sphere formation rate and by suppressing the mRNA expression levels of cluster of differentiation CD44, NANOG, OCT4, SOX2, Kruppel‑like factor 4 and adenosine triphosphate binding cassette subfamily G member 2. Additionally, 1α,25(OH)2D3 treatment decreased the expression of Cyclin D1, whereas it increased the expression of β‑catenin and vitamin D receptor (VDR). Notably, immunofluorescence staining verified that 1α,25(OH)2D3 promoted the expression of β‑catenin in the cytoplasm. Furthermore, vitamin D3 delayed the onset of tumor formation derived from injection of ovarian CSCs to nude mice, by reducing CD44 and enhancing β‑catenin expressions in vivo. In conclusion, 1α,25(OH)2D3 restrains the stem cell‑like properties of ovarian cancer cells by enhancing the expression of VDR, by promoting the expression of β‑catenin in the cytoplasm, and by suppressing the expression of CD44. These findings provide a novel insight into the functions of vitamin D in diminishing the stemness of cancer CSCs.

The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA.In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT.The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P.001) and multivariate analysis (all P.05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P.001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance.The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

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 NRS20023 and ≥3 (original scale). However, patients with NRS2002 ≤3 vs3 (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.

Background Little is known about the prognostic difference of anti-EGFR therapy, cetuximab (CTX) or nimotuzumab (NTZ), concurrently with induction chemotherapy (IC, investigational arm) or RT (control arm) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We conducted this retrospective study to address this. Methods We identified 296 patients with newly diagnosed LA-NPC at Sun Yat-Sen University Cancer Center between January 2012 and May 2015. Patients were treated by IC with CCRT or RT and CTX/NTZ was delivered during IC or radiotherapy. Survival outcomes and toxicities between different arms were compared. Results In total, there were 149 patients in the investigational arm and 147 in control arm. The 3-year disease-free survival, overall survival, distant metastasis-free survival and locoregional relapse-free survival rates for investigational arm vs. control arm were 84.3% vs. 74.3% (P = 0.027), 94.0% vs. 92.1% (P = 0.673), 88.0% vs. 81.8% (P = 0.147) and 93.3% vs. 88.0% (P = 0.093). Multivariate analysis revealed patients in the control arm achieved significantly worse disease-free survival (HR, 1.497; 95% CI, 1.016–2.206; P = 0.026) compared with those in the investigational arm; however, no significant difference was identified for other endpoints. Patients in the investigational arm experienced more grade 3–4 skin reaction (15.4% vs. 2.0%, P

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

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) ≥ 200 mg/m2 in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD Conclusions Our study concluded that induction TP regimen may be enough for patients receiving a CCD ≥ 200 mg/m2, while TPF may be superior to TP and PF for patients receiving a CCD

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.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.Significant differences in local relapse-free survival (LRFS) and overall survival (OS) (P0.001, P0.001, 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, P0.001), but not for DMFS. IMRT improved local control in patients with carotid space (CS) involvement compared to 2D-CRT (P0.001). LRFS was significantly different between patients with and without CS extension in the 2D-CRT group (P0.001), but not in the IMRT group (P=0.215).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.

The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized.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.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 score1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P0.001), similar results were obtained in the other sets (P0.05). 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; P0.001).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.

Purpose/aim of the study: To date, there are no validated screening scales for small fibre neuropathy. This study investigated the small-fibre neuropathy and the symptom inventory questionnaire as well as the small fibre neuropathy screening list for small fibre neuropathy diagnosis.Fifty-five patients were divided into small fibre neuropathy and mixed fibre damage groups. Relevant scales, nerve conduction studies and skin biopsies were performed. Relationships between the intraepidermal nerve fibre density and different scales as well as the diagnostic and cut-off values (score at which Youden's index is largest) were determined.Compared with healthy Chinese participants, 20 patients were diagnosed with small fibre neuropathy. Intraepidermal nerve fibre density was moderately and highly correlated with the small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list, respectively. The diagnostic values were moderate and high for the small fibre neuropathy-symptom inventory questionnaire (cut-off value = 5, sensitivity = 80%, specificity = 81.8%) and small fibre neuropathy screening list (cut-off value = 8, sensitivity = 94.1%, specificity = 90.9%), respectively. There were no significant differences in the visual analogue scale between the small fibre neuropathy group, mixed small and large fibre neuropathy group, pure large fibre neuropathy group and the normal group.Small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list represent potential small fibre neuropathy screening tools. Abbreviations EMG electromyography ENA anti-extractable nuclear antigens ESR erythrocyte sedimentation rate IENFD intraepidermal nerve fibre density IGT impaired glucose tolerance NCS nerve conduction studies NDS neuropathy disability score OGTT oral glucose tolerance test PGP protein gene product PN peripheral neuropathy ROC receiver operating characteristic curve ROC-AUC area under the ROC curve SFN small fibre neuropathy SFN-SIQ small-fibre neuropathy and symptom inventory questionnaire SFNSL small fibre neuropathy screening list VAS visual analogue scale WHO World Health Organization.

To investigate the pattern of lymph node metastasis and treatment outcome after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC), and assess the possibility of replacing Ho's supraclavicular fossa (SCF) with the lower level (LL; cervical extension below caudal edge of cricoid cartilage) based on magnetic resonance imaging (MRI) as a criterion for N3 disease.We retrospectively reviewed 749 patients with biopsy-proven non-metastatic NPC treated with IMRT. Lymph node metastasis was mapped using the 2013 International Consensus Guidelines.Cervical lymph node (CLN) laterality, CLN greatest dimension (60 vs. ⩽60 mm) and Ho's SCF were independent prognostic factors for disease-free survival (DFS) and distant metastasis-free survival (DMFS; P0.01) in multivariate analysis. Replacing Ho's SCF with the LL was also predictive for DFS and DMFS (P0.01). Compared to the 7th UICC/AJCC, N-categories based on the LL provided more satisfactory distinction between hazard ratios for distant and disease failure for each N-category. N3a and N3b as defined by the 7th UICC/AJCC had similar DMFS (P=0.31) and DFS (P=0.21).Replacing Ho's SCF with the LL is simple and practical. The N-category staging system could be further simplified by merging N3 subcategories.

To derive a suitable method for grading masticator space invasion in nasopharyngeal carcinoma on the basis of magnetic resonance (MR) images and to determine its prognostic value in patients undergoing intensity-modulated radiation therapy.After institutional review board approval and informed consent were acquired, 808 patients with nasopharyngeal carcinoma who were treated with definitive intensity-modulated radiation therapy were analyzed retrospectively. The anatomic sites of masticator space involvement were identified with MR imaging. Overall survival, local relapse-free survival, and distant metastasis-free survival were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Potential prognostic factors were identified by means of multivariate analysis.Masticator space involvement was diagnosed in 163 of 808 patients (20.2%). Patients with lateral invasion (involvement of the lateral pterygoid muscle of the masticator space and beyond) had significantly poorer overall survival and distant metastasis-free survival than those with medial invasion (involvement of the medial pterygoid muscle of the masticator space) (P = .035 and P = .026, respectively). Furthermore, their overall survival, local relapse-free survival, and distant metastasis-free survival were significantly poorer compared with patients with stage T2 or T3 disease (all P ≤ .023) but similar to patients with stage T4 disease. The grade of masticator space involvement was an independent prognostic factor for overall survival, local relapse-free survival, and distant metastasis-free survival (all P ≤ .023).Masticator space involvement in nasopharyngeal carcinoma should be graded as medial (stage T2 disease) or lateral (stage T4 disease). This can facilitate staging of nasopharyngeal carcinoma and may be a suitable prognostic indicator of survival.

Background: To compare the imaging and clinical features of temporal lobe necrosis (TLN) in nasopharyngeal carcinoma (NPC) patients treated with two-dimensional radiotherapy (2D-RT) or those with intensity-modulated radiotherapy (IMRT). Methods: We retrospectively analysed NPC patients who underwent 2D-RT (72 patients, 128 temporal lobes) or IMRT (36 patients, 50 lobes) and developed radiation-induced, MRI-confirmed TLN. Results: White-matter lesions (WMLs), contrast-enhanced lesions, cysts and local mass effects were present in 128 out of 128 vs 48 out of 50 (P=0.078), 123 out of 128 vs 47 out of 50 (P=0.688), 10 out of 128 vs 1 out of 50 (P=0.185) and 57 out of 128 vs 13 out of 50 (P=0.023) temporal lobes, respectively, in the 2D-RT and IMRT groups. The WMLs were more extensive in the 2D-RT group (P0.05), whereas the difference in the incidence of severe debility was of marginal significance (18.1% vs 5.6%, P=0.077). Conclusions: The IMRT-induced TLN was less extensive and milder than 2D-RT-induced TLN, but both had similar clinical features.

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.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.The incidence of parapharyngeal extension was 72.1%. A significant difference was observed in the disease-free survival (DFS; 70.3% vs. 89.1%, P0.001), distant metastasis-free survival (DMFS; 79.3% vs. 92.0%, P0.001), 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 (P0.001).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.

Background: We previously reported that magnetic resonance imaging evidence of cranial nerve invasion was an unfavourable prognostic factor in nasopharyngeal carcinoma. However, the prognostic value of this evidence in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy remains unknown. Methods: We retrospectively analysed 749 nasopharyngeal carcinoma patients who underwent intensity-modulated radiotherapy. Results: Cranial nerve invasion was observed in 299 (39.9%) patients with T3–4 disease. In T3–4 nasopharyngeal carcinoma, magnetic resonance imaging-detected cranial nerve invasion was associated with inferior 5-year overall survival, distant metastasis-free survival, and locoregional relapse-free survival (P=0.002, 0.003, and 0.012, respectively). Multivariate analyses confirmed that cranial nerve invasion was an independent prognostic factor for distant metastasis-free survival (hazard ratio, 1.927; P=0.019) and locoregional relapse-free survival (hazard ratio, 2.605; P=0.032). Furthermore, the receiver-operating characteristic curves verified that the predictive validity of T classifications was significantly improved when combined with magnetic resonance imaging-detected cranial nerve invasion in terms of death, distant metastasis, and locoregional recurrence (P=0.015, 0.021 and 0.008, respectively). Conclusions: Magnetic resonance imaging-detected cranial nerve invasion is an independent adverse prognostic factor in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

Background The prognostic values of staging parameters require continual re-assessment amid changes in diagnostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non-metastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. Methods We reviewed the data from 749 patients with newly diagnosed, biopsy-proven, non-metastatic NPC in our cancer center (South China, an NPC endemic area) between January 2003 and December 2007. All patients underwent magnetic resonance imaging (MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insignificant explanatory variables. Results The 5-year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5-year survival rates were as follows: local relapse-free survival, 94.6%; nodal relapse-free survival, 97.0%; distant metastasis-free survival, 82.6%; disease-free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only significant prognostic factor for local failure (P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho’s location of the cervical lymph nodes were significant prognostic factors for both distant failure and disease failure (all P

This study aimed to investigate the association between Epstein-Barr virus (EBV)-related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA-IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0-1.85) in Stage I, 1.32 (0-3.51) in Stage II, 3.33 (0-4.30) in Stage III, 3.83 (2.85-4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation.

The prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma (NPC) has decreased with the extensive use of intensity-modulated radiotherapy (IMRT). We aimed to develop a prognostic scoring system (PSS) that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT. The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed. Age, pathologic classification, primary tumor extension, primary gross tumor volume (GTV-p), T and N categories, and baseline lactate dehydrogenase (LDH) level were analyzed. Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS. Independent prognostic factors for locoregional relapse included N2–3 stage, GTV-p ≥26.8 mL, and involvement of one or more structures within cluster 3. We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups: low risk (score 0), intermediate risk (score >0 and ≤1), high risk (score >1 and ≤2), and extremely high risk (score >2). The 5-year locoregional control rates for these groups were 97.4%, 93.6%, 85.2%, and 78.6%, respectively (P < 0.001). We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.

To propose a lymph node (N) staging system for nasopharyngeal carcinoma (NPC) based on the International Consensus Guidelines for lymph node (LN) levels and MRI-determined nodal variables.The MRI scans and medical records of 749 NPC patients receiving intensity modulated radiation therapy with or without chemotherapy were retrospectively reviewed. The prognostic significance of nodal level, laterality, maximal axial diameter, extracapsular spread, necrosis, and Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) size criteria were analyzed.Nodal level and laterality were the only independent prognostic factors for distant failure and disease failure in multivariate analysis. Compared with unilateral levels Ib, II, III, and/or Va involvement (hazard ratio [HR] 1), retropharyngeal lymph node involvement alone had a similar prognostic value (HR 0.71; 95% confidence interval [CI] 0.43-1.17; P=.17), whereas bilateral levels Ib, II, III, and/or Va involvement (HR 1.65; 95% CI 1.06-2.58; P=.03) and levels IV, Vb, and/or supraclavicular fossa involvement (HR 3.47; 95% CI 1.92-6.29; P.01) both significantly increased the HR for distant failure. Thus we propose that the N category criteria could be revised as follows: N0, no regional LN metastasis; N1, retropharyngeal lymph node involvement, and/or unilateral levels Ib, II, III, and/or Va involvement; N2, bilateral levels Ib, II, III, and/or Va involvement; N3, levels IV, Vb, and/or supraclavicular fossa involvement. Compared with the 7th edition of the UICC/AJCC criteria, the proposed N staging system provides a more satisfactory distinction between the HRs for regional failure, distant failure, and disease failure in each N category.The proposed N staging system defined by the International Consensus Guidelines and laterality is predictive and practical. However, because of no measurements of the maximal nodal diameter on MRI slices, the prognostic significance of LN size needs further evaluation.

To evaluate patterns of skull base invasion and its possible impact on tumor (T)-staging in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI).838 consecutive newly diagnosed by biopsy proven and untreated patients with NPC underwent MRI. The skull-base invasion of NPC was classified according to their incidence from proximal sites to more distant sites surrounding the nasopharynx as: high (≥35%), medium (≥5-35%), and low (5%) groups. A retrospective analysis of data consisting of a 5-year follow-up was carried out. The skull base invasion was related to their tumor (T) staging and prognosis at the 5-year follow-up after treatment with definitive radiation therapy. In addition, a survival health-related quality of life (QOL), overall survival (OS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were also assessed among the three groups.The total incidence of skull-base invasion was 65.51% (549/838). The differences in T-stage distribution, and the total survival health-related QOL, among the three groups were statistically significant (χ(2)=160.45, p0.005; χ(2)=38.43, p0.005, respectively). The differences between any two of the three groups were also significant, except when the medium grade was compared to the low grade. Significant differences were observed with regard to 5-year OS (83.2%, 74.7%, 59.2%, p=0.000) and DMFS (95.0%, 88.0%, 88.0%, p=0.016); no significant difference was observed in LRFS (95.3%, 95.6%, 91.23%, p=0.450).The results indicate that medium and low group displayed similar findings of skull base invasion, and survival status. We, therefore, propose that patients in these two groups be grouped under T4 in the TNM classification that might have a bearing in implementing optimum treatment.

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.

Background The aim was to develop and validate the quality of life scale for nasopharyngeal carcinoma (NPC) patients, the QOL-NPC (version 2), a specific instrument to measure quality of life for NPC patients. Methods The QOL-NPC was developed and validated according to standard procedures. The patients were assessed using the QOL-NPC, FACT-G, and FACT-H&N. Classical test theory was used to evaluate the reliability, validity, and responsiveness of the QOL-NPC. Results A total of 487 patients (97.4 %) completed the questionnaire. The QOL-NPC comprised four domains, as follows: physical function (eight items); psychological function (five items); social function (five items); and side effects (eight items). All of the items had a lower proportion of missing data. Cronbach's alpha values of the domains ranged from 0.72 to 0.84. The split-half reliability coefficients ranged from 0.77 to 0.84. All of the intra-class correlation coefficients were > 0.8. The normed fit index, non-normed fit index, and comparative fit index were >0.89. The root mean square error of approximation was 0.097, with a 90 % confidence interval (0.093, 0.100). The domain scores of the QOL-NPC were significantly correlated with the FACT-G and FACT-H&N (P

The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher’s exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.

The prognostic value of dynamic serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) hasn’t been explored. We retrospectively analyzed 1,428 cases of NPC treated with IMRT with or without chemotherapy. Elevated pre- and/or post-treatment LDH levels were found to be associated with unfavorable overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS), but not with local relapse-free survival (LRFS). The dynamic variations in LDH levels were prognostic factors for OS, DFS and DMFS, but not for LRFS. Multivariate analysis revealed that the N category, T category, post-treatment serum LDH level and age were independent prognostic factors for OS. Our results demonstrated that dynamic variations in LDH levels were associated with risk of distant failure and death, which may shed light on the dynamics of the disease and the response to therapy. We consider that LDH measurements will be of great clinical importance in the management of NPC, especially, when considering “decision points” in treatment algorithms. Therefore, we strongly recommend that LDH levels should be determined before and after treatment in NPC patients and the results integrated into decisions regarding treatment strategies.

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 subclassify patients with the T4 classification nasopharyngeal carcinoma (NPC), according to the seventh edition of the American Joint Committee on Cancer staging system, using magnetic resonance imaging (MRI), and to evaluate the prognostic value of subclassification after intensity-modulated radiotherapy (IMRT). Methods and Materials A total of 140 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated classification T4 NPC received IMRT as their primary treatment and were included in this retrospective study. T4 patients were subclassified into two grades: T4a was defined as a primary nasopharyngeal tumor with involvement of the masticator space only; and T4b was defined as involvement of the intracranial region, cranial nerves, and/or orbit. Results The 5-year overall survival (OS) rate and distant metastasis-free survival (DMFS) rate for T4a patients (82.5% and 87.0%, respectively), were significantly higher than for T4b patients (62.6% and 66.8%; p = 0.033 and p = 0.036, respectively). The T4a/b subclassification was an independent prognostic factor for OS (hazard ratio=2.331, p = 0.032) and DMFS (hazard ratio=2.602, p = 0.034), and had no significant effect on local relapse-free survival. Conclusions Subclassification of T4 patients, as T4a or T4b, using MRI according to the site of invasion, has prognostic value for the outcomes of IMRT treatment in NPC.

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.

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.

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 (

Purpose To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC). Methods and Materials A retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients. Results Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups. Conclusions A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies.

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

High intensity focused ultrasound (HIFU) is a noninvasive treatment modality that induces complete coagulative necrosis of a deep tumor through the intact skin. This study was conducted to analyze and evaluate the complications of HIFU for the treatments of hepatocellular carcinoma. A total of 59 patients with hepatocellular carcinoma, with a total of 72 lessions were enrolled in this study. Tumor size ranged from 2.5 to 14.0 cm in diameter, with a mean diameter of 7.6 cm. All patients had accepted HIFU treatment, and the median number of HIFU sessions was 1.32 per patient. Results: The common complications from HIFU therapy were skin burns of various grades (eight cases of grade 1 skin burns, 48 of grade 2, three cases of 3), and pain in the treatment regions (15 cases of mild pain, 37 cases of moderate pain, 7 cased of severe pain). Other systemic complications were relatively rare and included fever (5 cases), hypertension (8 cases), supraventricular tachycardia (3 cases), mild impairment of hepatic function (48 cases), and mild mpairment of renal function (2 cases). Local damage consisted of acute cholecystitis (2 cases), hematuria (6 cases), cholangiectasis (5 cases), light pericardial effusion (2 cases), impairment of peripheral nerves (10 cases), pleural effusion in the right thorax (3 cases), and impairment of vertebral column (1 case). No gastric or intestinal tract perforation, big vessel rupture, or hepatic rupture occurred. Conclusions: HIFU is a minimally invasive treatment for patients with hepatocellular carcinoma; however, there are some systemic and local complications that should be taken into consideration in evaluating HIFU for therapeutic use.

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.

// 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