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Biologically active bacterial cellulose (BC) was efficiently synthesized in situ using wine pomace and its hydrolysate. The structural and biomechanical properties together with the biological functions of the BC were investigated. Functional BC from wine pomace and its enzymatic hydrolysate were of high purity and had higher crystallinity indexes (90.61% and 89.88%, respectively) than that from HS medium (82.26%). FTIR results proved the in-situ bindings of polyphenols to the functionalized BC. Compared to BC from HS medium, wine pomace-based BC had more densely packed ultrafine fibrils, higher diameter range distributions of fiber ribbon, but lower thermal decomposition temperatures, as revealed by the SEM micrographs and DSC data. Meanwhile, wine pomace-based BC exhibited higher loads in tensile strength and higher hardness (4.95 ± 0.31 N and 5.13 ± 0.63 N, respectively) than BC in HS medium (3.43 ± 0.14 N). Furthermore, BC synthesized from wine pomace hydrolysate exhibited a slower release rate of phenolic compounds, and possessed more antioxidant activities and better bacteriostatic effects than BC from wine pomace. These results demonstrate that BC synthesized in situ from wine pomace (especially from enzymatic hydrolysate) is a promising biomolecule with a potential application in wound dressing, tissue engineering, and other biomedical fields.

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.

Evaluation of principal residual stress with X-Ray diffraction for metals has been widely practiced, but not for polymers due to a large fraction of amorphous phase, though it is very important for many engineering applications. Such a method is established for rigid semicrystalline polymer with rubber amorphous which, in the present work, are defined as the polymers with an amorphous rubber phase and a crystal matrix (rigid crystal network) providing its plastic modulus. An equal strain model between crystal and amorphous phases and the Young's modulus contributed by both crystal and amorphous phases, instead of moduli from crystal region, are justified for the stress evaluation for rigid semicrystalline polymers. The principal residual stresses obtained with our approach show a very good correlation with crystal orientation and the anisotropic mechanical properties of the polymer films studied. The established method can be widely used for rigid semicrystalline polymers with rubbery amorphous.

The miscibility, crystalline structure and morphology, as well as, properties of Polyamide 6 (PA6)/polyvinylidene fluoride (PVDF) blends (with up to 50 wt% of PVDF) were studied. Small Angle X-ray Scattering study above the melting point of PVDF shows that the blends have very limited miscibility with approximately 5 wt% of PVDF inclusion in PA6 amorphous lamellar region. SAXS results also indicate a certain degree of PA6 inclusion into PVDF region though quantitative evaluation is unavailable with the limited blends studied in this work. The fine PVDF dispersion in the PA6 blends with up to 50 wt% of PVDF with an average size about 150 nm is supposed to be the result of the partial miscibility. The partial miscibility has great effects on the morphology and properties of the blends. Crystallization of both components are suppressed in the blends, especially on the PVDF component, which shows a significantly lowered crystallization temperature (up to 30 °C) during a cooling and a dramatic drop in crystallinity. Morphological studies together with Small Angle Light Scattering (SALS) show that spherulites, consisting of PA6 skeleton with dispersed PVDF domains (∼150 nm) engulfed among PA6 fibrils, are formed in the blends. The PA6 based spherulites become more defective with the increase in PVDF content, resulting in short/broken fibrils and undetectable PA6 spherulites for the blends with 30–50 wt% of PVDF at the temperature over the melting point of PVDF, say 185 °C. The blends show a significantly improved toughness compared with neat PA6, due to the partial miscibility which leads to the fine dispersion of PVDF domains in PA6 spherulites.

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.

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.

In this study, a yeast-like fungal strain (LG-8), newly isolated from spontaneous Tibet kefir in China, was identified as Geotrichum candidum on the basis of its morphological characteristics and ITS5.8S gene sequence. Interestingly, the strain was able to remove more than 99% of Pb2+ ions in water at low concentrations and a maximum of 325.68 mg lead/g of dry biomass. The results of selective passivation experiments suggested that phosphate, amide and carboxyl groups on the cell wall contributed to lead removal. Scanning electron microscopy (SEM) photomicrographs revealed that large amounts of micro/nanoparticles formed on the cell wall, and energy dispersive X-ray spectroscopy (EDX) results further indicated the presence of lead along with phosphorus and chlorine in the particles. Furthermore, the results of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses revealed that the particles were composed of pyromorphite [Pb5(PO4)3Cl)], a highly insoluble lead mineral. Importantly, this is the first time that the biomineralization of lead into pyromorphite has been observed as the major mechanism for lead removal by G. candidum LG-8, providing a new strategy to scavenge heavy metals from aquatic environment in an eco-friendly manner.

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.

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.

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.

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.

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.

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.

The correlation of foreign exchange rates in currency markets is investigated based on the empirical data of DKK/USD, NOK/USD, CAD/USD, JPY/USD, KRW/USD, SGD/USD, THB/USD and TWD/USD for a period from 1995 to 2002. Cross-SampEn (cross-sample entropy) method is used to compare the returns of every two exchange rate time series to assess their degree of asynchrony. The calculation method of confidence interval of SampEn is extended and applied to cross-SampEn. The cross-SampEn and its confidence interval for every two of the exchange rate time series in periods 1995–1998 (before the Asian currency crisis) and 1999–2002 (after the Asian currency crisis) are calculated. The results show that the cross-SampEn of every two of these exchange rates becomes higher after the Asian currency crisis, indicating a higher asynchrony between the exchange rates. Especially for Singapore, Thailand and Taiwan, the cross-SampEn values after the Asian currency crisis are significantly higher than those before the Asian currency crisis. Comparison with the correlation coefficient shows that cross-SampEn is superior to describe the correlation between time series.

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.