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This study examined the preparation of isobornyl acetate/isoborneol from camphene using an α-hydroxyl carboxylic acid (HCA) composite catalyst. Through the study of the influencing factors, it was found that HCA and boric acid exhibited significant synergistic catalysis. Under optimal conditions, when tartaric acid–boric acid was used as the catalyst, the conversion of camphene and the gas chromatography (GC) content and selectivity of isobornyl acetate were 92.9%, 88.5%, and 95.3%, respectively. With the increase in the ratio of water to acetic acid, the GC content and selectivity of isobornol in the product increased, but the conversion of camphene decreased. The yield of isobornol was increased by adding ethyl acetate or titanium sulfate/zirconium sulfate to form a ternary composite catalyst. When a ternary complex of titanium sulfate, tartaric acid, and boric acid was used as the catalyst, the GC content of isobornol in the product reached 55.6%. Under solvent-free conditions, mandelic acid–boric acid could catalyze the hydration reaction of camphene, the GC content of isoborneol in the product reached 26.1%, and the selectivity of isoborneol was 55.9%. The HCA–boric acid composite catalyst can use aqueous acetic acid as a raw material, which is also beneficial for the reuse of the catalyst. [ABSTRACT FROM AUTHOR]

Arch dams are typically built in the mountain and gorge regions with complex terrain. In the current engineering practice, foundation models are commonly simplified as the half-space with the canyon of regular geometry. The complex topography conditions above the dam crest are neglected. This study investigates the effect of realistic valley topography on the dynamic response of arch dams. The direct finite element method is generalized and applied to the dam-reservoir-foundation system with realistic valley topography. The input ground motions are transformed into the effective earthquake loads at the truncated boundaries by performing several dynamic reaction calculations using one-dimensional (1D) and two-dimensional (2D) auxiliary finite element models. The effect of valley topography on the seismic response of the Baihetan arch dam is evaluated as a case study. Results indicate that the valley topographic irregularities significantly influence the dynamic responses of the arch dam, including relative displacement and stress distribution. Notably, the valley topography effect on the seismic response of arch dams depends on the incident ground motions and is hardly predicted in advance, demonstrating the necessity to account for the realistic topography conditions. • The direct finite element method is generalized to realistic topography sites. • Procedure to obtain the seismic forces for realistic topography sites is presented. • The effect of valley topography on the seismic response of arch dams is analyzed. [ABSTRACT FROM AUTHOR]

Attached outlets are integral components of arch dams to discharge flood. However, they are usually neglected in the current seismic analysis of arch dams for simplicity. This paper aims to analyze the effect of attached outlets on the nonlinear seismic response of arch dams. For this purpose, a 235 m high arch dam is analyzed as a case study. The results indicate that the effect of attached outlets on the seismic response of arch dams depends on the ground motion intensity. For the ground motions with a low peak ground acceleration (PGA), the effect of attached outlets on the concrete damage is slight and local, which is consistent with the existing perception. However, as the ground motion intensity increases, their effect extends to the entire dam body. In contrast, the influence of attached outlets on the joint opening is typically observed at the middle contraction joints. Furthermore, the model analysis demonstrates that the inertia effect of attached structures is the primary contribution to these phenomena. Finally, a simplified simulation approach is used for incorporating the influence of attached outlets by coalescing the mass to the dam surface. • The effect of attached outlets on the nonlinear response of arch dams is investigated. • Mechanism of the attached outlets' effect is analyzed. • A simplified simulation approach of the attached structures is investigated. [ABSTRACT FROM AUTHOR]

Abstract Large quantities of molybdenum (Mo) slag are generated as a by-product during mining and smelting, which not only occupy huge stretches of arable land and natural habitats but also threaten the local ecosystem and environment. How to recycle this Mo slag is becoming an urgent issue. Here, we reported the toxicity assessment of Mo slag as a mineral fertilizer for slag recycling in agricultural practices. The results showed the following: (1) Lower rates of slag (1.0%, 2.5%, and 5.0%) fertilization, especially 5.0% slag, increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase), the contents of chlorophyll, and both the maximum quantum yield and quantum efficiency of photosystem II; decreased the content of malondialdehyde and the non-photochemical quenching of photosystem II; and eventually increased the height, leaf area, and biomass of pakchoi seedlings; (2) Higher rates (7.5% and 10.0%) of Mo slag application resulted in a reduction in the aforementioned physiological and morphological parameters (except for peroxidase activity) of pakchoi seedlings; and (3) Although fertilization with 5.0% slag increased the accumulation of the non-essential elements arsenic (As), lead (Pb), and cadmium (Cd) in pakchoi seedlings, their contents were still lower than the maximum levels of the Codex Alimentarius Commission, European Union, and standards of China. From the perspectives of plant nutrition and food safety, our results showed that Mo slag fertilization at rates lower than 5.0% can be applied as a mineral fertilizer for pakchoi grown on calcareous soils. Graphical abstract Image 1 Highlights • Low rates of Mo slag improve the physiology and growth of pakchoi seedlings. • High rates of Mo slag stunt pakchoi seedling growth and yield. • Contents of non-essential elements in seedlings meet the maximum levels in food standards. • Low rates of Mo slag can be a potential mineral fertilizer in agricultural practices. [ABSTRACT FROM AUTHOR]

The active structural change of actin cytoskeleton is a general host response upon pathogen attack. This study characterized the function of the cotton (Gossypium hirsutum) actin-binding protein VILLIN2 (GhVLN2) in host defense against the soilborne fungus Verticillium dahliae. Biochemical analysis demonstrated that GhVLN2 possessed actin-binding,-bundling, and -severing activities. A low concentration of GhVLN2 could shift its activity from actin bundling to actin severing in the presence of Ca2+. Knockdown of GhVLN2 expression by virus-induced gene silencing reduced the extent of actin filament bundling and interfered with the growth of cotton plants, resulting in the formation of twisted organs and brittle stems with a decreased cellulose content of the cell wall. Upon V. dahliae infection, the expression of GhVLN2 was downregulated in root cells, and silencing of GhVLN2 enhanced the disease tolerance of cotton plants. The actin bundles were less abundant in root cells of GhVLN2-silenced plants than in control plants. However, upon infection by V. dahliae, the number of actin filaments and bundles in the cells of GhVLN2-silenced plants was raised to a comparable level as those in control plants, with the dynamic remodeling of the actin cytoskeleton appearing several hours in advance. GhVLN2-silenced plants exhibited a higher incidence of actin filament cleavage in the presence of Ca2+, suggesting that pathogen-responsive downregulation of GhVLN2 could activate its actin-severing activity. These data indicate that the regulated expression and functional shift of GhVLN2 contribute to modulating the dynamic remodeling of the actin cytoskeleton in host immune responses against V. dahliae. [ABSTRACT FROM AUTHOR]

We report the use of five alpha-hydroxy acids (citric, tartaric, mandelic, lactic and glycolic acids) as catalysts in the synthesis of terpineol from alpha-pinene. The study found that the hydration rate of pinene was slow when only catalyzed by alpha-hydroxyl acids. Ternary composite catalysts, composed of AHAs, phosphoric acid, and acetic acid, had a good catalytic performance. The reaction step was hydrolysis of the intermediate terpinyl acetate, which yielded terpineol. The optimal reaction conditions were as follows: alpha-pinene, acetic acid, water, citric acid, and phosphoric acid, at a mass ratio of 1:2.5:1:(0.1–0.05):0.05, a reaction temperature of 70 °C, and a reaction time of 12–15 h. The conversion of alpha-pinene was 96%, the content of alpha-terpineol was 46.9%, and the selectivity of alpha-terpineol was 48.1%. In addition, the catalytic performance of monolayer graphene oxide and its composite catalyst with citric acid was studied, with acetic acid used as an additive. [ABSTRACT FROM AUTHOR]

SurA is the primary periplasmic molecular chaperone that facilitates the folding and assembling of outer membrane proteins (OMPs) in Gram-negative bacteria. Deletion of the surA gene in Escherichia coli leads to a decrease in outer membrane density and an increase in bacterial drug susceptibility. Here, we conducted mutational studies on SurA to identify residues that are critical for function. One mutant, SurAv37c, significantly reduced the activity of SurA. Further characterization indicated that SurAv37c was structurally similar to, but less stable than, the wild-type protein. The loss of activity in SurAv37G could be restored through the introduction of a pair of Cys residues and the subsequent formation of a disulfide bond. Inspired by this success, we created three additional SurA constructs, each containing a disulfide bond at different regions of the protein between two rigid secondary structural elements. The formation of disulfide bond in these mutants has no observable detrimental effect on protein activity, indicating that SurA does not undergo large-scale conformational change while performing its function. [ABSTRACT FROM AUTHOR]

The article provides information on a study which examined the clinicopathologic characteristics, treatment outcomes and prognostic factors of radiation-induced sarcoma (RIS) following radiotherapy for nasopharyngeal carcinoma (NPC). A brief review of the related literature on RIS is offered. Data reviewed were from institutional electronic medical records of patients with NPC treated with definitive radiotherapy between February 1964 and 2003. A discussion on the findings of the study is detailed.

Glycopeptide antibiotics are widely used in the treatment of infections caused by Gram-positive bacteria. They inhibit the biosynthesis of the bacterial cell wall through binding to the D-alanyl-D-alanine (D-Ala-D-Ala) terminal peptide of the peptidoglycan precursor. Taking advantage of this highly specific interaction, we developed a direct fluorescence polarization based method for the detection of glycopeptide antibiotics. Briefly, we labeled the acetylated tripeptide Ac-L-Lys-D-Ala-D-Ala-OH with a fluorophore to create a peptide probe. Using three glycopeptide antibiotics, vancomycin, teicoplanin, and telavancin, as model compounds, we demonstrated that the fluorescence polarization of the peptide probe increased upon binding to antibiotics in a concentration dependent manner. The dissociation constants (Kd) between the peptide probes and the antibiotics were consistent with those reported between free D-Ala-D-Ala and the antibiotics in the literature. The assay is highly reproducible and selective toward glycopeptide antibiotics. Its detection limit and work concentration range are 0.5 μM and 0.5-4 μM for vancomycin, 0.25 μM and 0.25-2 μM for teicoplanin, and 1 μM and 1-8 μM for telavancin. Furthermore, we compared our assay in parallel with a commercial fluorescence polarization immunoassay (FPIA) kit in detecting teicoplanin spiked in human blood samples. The accuracy and precision of the two methods are comparable. We expect our assay to be useful in both research and clinical laboratories. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To determine the feasibility of using limited four-dimensional computed tomography (4DCT) images for treatment planning. Materials and methods: The 4DCT scans of 16 patients with hepatocellular carcinoma (HCC) were analyzed. Gross tumor volumes (GTVs) were manually contoured on all 10 respiratory phases, and different internal clinical target volumes (ICTVs) were derived by encompassing volumes of the respective CTVs. Volume, position, and shape of ICTVs were calculated and compared. Results: The ICTV2 phases, ICTV3 phases, ICTV4 phases, and ICTV6 phases all showed excellent agreement with ICTV10 phases, and the ICTV2 phases encompassed ICTV10 phases by 94.1±1.8% on average. The 3D shift between the centers of mass of the ICTVs was only 0.6mm. The surface distance between ICTV10 phases and ICTV2 phases was 1.7±0.8mm in the left-right (LR) and anteroposterior (AP) directions. Conclusions: Contouring two extreme phases at end-inhalation and end-exhalation is a reasonably safe and labor-saving method of deriving ITV for liver radiotherapy with low and medium tumor motion amplitude (⩽1.6cm). Whether the larger tumor movement affects the results is the subject of ongoing research. [Copyright &y& Elsevier]

Purpose: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. Methods and Materials: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m2 on Day 1) weekly during RT, followed by cisplatin (80 mg/m2 on Day 1) and fluorouracil (800 mg/m2 on Days 1–5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. Results: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. Conclusions: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China. [Copyright &y& Elsevier]

AIB1, a candidate oncogene in breast cancer, is commonly amplified and overexpressed in several types of human cancers. In this study, expression and amplification of AIB1 in nasopharyngeal carcinoma (NPC) were studied by immunohistochemical analysis and fluorescence in situ hybridization using tissue microarrays, including 80 specimens of NPC and 20 specimens of nonneoplastic nasopharyngeal mucosa. In this NPC cohort, overexpression and amplification of AIB1 was detected in 36 (51%) of 71 and 3 (7%) of 46 NPCs, respectively. Overexpression of AIB1 was observed more frequently in NPCs in late T stages (T3/T4, 24/35 [69%]) than in earlier stages (T1/T2, 12/36 [33%]; P 05). In addition, 18 (72%) of 25 NPCs with lymph node metastasis (N1-3) showed overexpression of AIB1; the frequency was significantly higher than that in NPCs without node metastasis (N0, 18/49 [39%]; P 05). These findings suggest that overexpression of AIB1 in NPCs may be important in the acquisition of an invasive and/or metastatic phenotype. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Abstract: Background and purpose: To define individualized internal target volume (ITV) for hepatocellular carcinoma using four-dimensional computed tomography (4DCT). Materials and methods: Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured on all 10 respiratory phases of 4DCT scans in 10 patients with hepatocellular carcinoma. The 3D and 4D treatment plans were performed for each patient using two different planning target volumes (PTVs): (1) PTV3D was derived from a single CTV plus conventional margins; (2) PTV4D was derived from ITV4D, which encompassed all 10 CTVs plus setup margins (SMs). The volumes of PTVs and dose distribution were compared between the two plans. Results: The average PTV volume of the 4D plans (328.4±152.2cm3) was less than 3D plans (407.0±165.6cm3). The 4D plans spared more surrounding normal tissues than 3D plans, especially normal liver. Compared with 3D plans, the mean dose to normal liver (MDTNL) decreased from 22.7 to 20.3Gy. Without increasing the normal tissue complication probability (NTCP), the 4D plans allowed for increasing the calculated dose from 50.4±1.3 to 54.2±2.6Gy, an average increase of 7.5% (range 4.0–16.0%). Conclusions: The conventional 3D plans can result in geometric miss and include excess normal tissues. The 4DCT-based plans can reduce the target volumes to spare more normal tissues and allow dose escalation compared with 3D plans. [Copyright &y& Elsevier]

Seismic analysis of dam-foundation systems is inherently complex due to uncertainties in material properties. This study investigates the effects of material randomness and heterogeneity on the seismic response of gravity dam-foundation systems using the stochastic spectral finite element method (SSFEM) based on the Karhunen Loève expansion and the polynomial chaos expansion. The Pine Plane dam is taken as an analysis example. First, the appropriate Karhunen Loève expansion modes and polynomial chaos order are determined for SSFEM by comparing them with the Monte-Carlo simulations. Subsequently, the seismic response of the dam is analyzed in the stochastic and deterministic models, respectively. Results indicate that material randomness and heterogeneity may reduce the seismic response of gravity dams, and the deterministic model may overestimate dynamic responses. Subsequently, the parametric analysis of the correlation length, which measures the spatial correlation between variables in different positions and indicates the size of heterogeneity material patches, is conducted. It is demonstrated that the correlation length would not significantly affect the mean responses, but a larger correlation length leads to greater dispersions in responses. Finally, the effects of randomness in the foundation are investigated. The heterogeneities in the foundation affect the response of the dam in the high-frequency range. Therefore, the uncertainty in material properties should be fully considered in a structural assessment and risk analysis. • Parameters of SSFEM are determined in stochastic simulation for the Pine Plane dam. • The effect of the correlation length on the seismic response of gravity dam-foundation system is analyzed. • The effect of randomness in the foundation on the seismic response is analyzed. [ABSTRACT FROM AUTHOR]

Background: Despite 3‐year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression‐free survival at 3 years (3‐year PFS) and overall survival (OS) among patients with ESCC. Methods: We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age‐ and sex‐matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data. Results: The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3‐year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5‐year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9–17.5). Conversely, the SMR for patients who achieved 3‐year PFS was 0.9 (95% CI, 0.6–1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88–0.90). The strongest correlation was observed between 3‐year PFS and 5‐year OS in RCTs and retrospective studies. Conclusions: Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3‐year PFS had excellent outcomes. Our study supports 3‐year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between systemic inflammatory response and short‐term mortality in patients with non‐cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil‐to‐lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet‐to lymphocyte ratio (PLR), and monocyte‐to‐lymphocyte ratio (MLR). Methods: Data were collected from two prospectively enrolled CATCH‐LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90‐day liver transplant (LT)‐free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90‐day LT‐free mortality. Kaplan–Meier method was used to estimate the 90‐year LT‐free survival. Results: The prevalence of CSH was 20.5% (226/1103). The 28‐day and 90‐day LT‐free mortality rates were 17.7% and 26.1%, respectively, for patients with non‐cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90‐day LT‐free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection. Conclusions: NLR may be an independent risk factor for 90‐day LT‐free mortality in patients with non‐cirrhotic chronic liver disease. A NLR of 2.9 as the cut‐off value can be used to predict disease aggravation in CSH patients without infection. [ABSTRACT FROM AUTHOR]

Background: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC).Methods: We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events.Results: Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (probability, 61%) and PFS (probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (probability, 37%) and PFS (probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively.Conclusions: This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC.Trial Registration: PROSPERO registration number: (CRD 42021261554). [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to define individualized internal target volume (ITV) for hepatocellular carcinoma (HCC) using 4D computed tomography (4DCT), and to determine the geometric and dosimetric benefits of respiratory gating. Gross tumor volumes (GTVs) were contoured on 10 respiratory phases of 4DCT images for 12 patients with HCC. Three treatment plans were prepared using different planning target volumes (PTVs): (1) PTV3D, derived from a single helical clinical target volume (CTV) plus conventional margins; (2) PTV10 phases, derived from ITV10 phases, which encompassed all 10 CTVs plus an isotropic margin of 0.8 cm; (3) PTVgating, derived from ITVgating, which encompassed three CTVs within gating-window at end-expiration plus an isotropic margin of 0.8 cm. The PTV3D was the largest volume for all patients. The ITV-based plans and gating plans spared more normal tissues than 3D plans, especially the liver. Without increasing normal tissue complication probability of the 3D plans, the ITV-based plans allowed for increasing the calculated dose from 50.8 Gy to 54.7 Gy on average, and the gating plans could further escalate the dose to 58.5 Gy. Compared with ITV-based plans, the dosimetric gains with gating plan strongly correlated with GTV mobility in the craniocaudal direction. The ITV-based plans can ensure target coverage with less irradiation of normal tissues compared with 3D plans. Respiratory-gated radiotherapy can further reduce the target volumes to spare more surrounding tissues and allow dose escalation, especally for patients with tumor mobility >1 cm. [Copyright &y& Elsevier]

Purpose The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. Results With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. Conclusion No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen. [ABSTRACT FROM AUTHOR]

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are, respectively, the main etiologies. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European Consortium Acute-on-Chronic Liver Failure in Cirrhosis Study is urgently needed in Asia, where the prevalence of HBV is high. A multicenter prospective cohort of 2,600 patients was designed, drawing from 14 nationwide liver centers from tertiary university hospitals in China, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and noncirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization, and follow-ups were performed once a month, with plans to follow all patients until 36 months after hospital discharge. Of these patients, 1,859 (71.5%) had HBV-related disease, 1,833 had cirrhotic disease, and 767 had noncirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented. [ABSTRACT FROM AUTHOR]

A previous study demonstrated that p300 is overexpressed in nasopharyngeal carcinoma (NPC), and that its expression is an independent prognostic factor. The aim of the present study is to investigate the role of p300 in human NPC development. A small hairpin (sh) RNA lentiviral expression vector targeting the p300 gene was constructed to suppress the expression of p300 in NPC cells. Knockdown of p300 was verified by reverse transcription-quantitative polymerase chain reaction and western blotting. Wound-healing, invasion, immunofluorescence and immunoprecipitation assays were performed to assess the influence of p300 on nasopharyngeal tumorigenesis and metastasis in vitro. The expression of p300 was upregulated in NPC cell lines. After knockdown of p300, the migration and invasion ability of shp300 cells were significantly inhibited (P<0.05). Furthermore, the depletion of p300 expression in NPC cell lines resulted in the upregulation of epithelial phenotype marker E-cadherin and a-catenin, and downregulation of mesenchymal phenotype markers N-cadherin and vimentin. p300 promotes epithelial-mesenchymal transition (EMT) through the acetylation of Smad2 and Smad3 in the tumor growth factor-β signaling pathway. In conclusion, p300 may be involved in the invasion and metastasis of NPC through the induction of EMT. [ABSTRACT FROM AUTHOR]

Background and purpose Genetic single nucleotide polymorphisms (SNP) play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between insulin-like growth factor binding protein-3 ( IGFBP-3 ) gene polymorphisms and ESCC patients risk and survival after definitive chemoradiotherapy (CRT). Materials and methods We undertook a case-control study to analyze two IGFBP-3 polymorphisms (rs2854744 A > C and rs2854746 G > C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 110 ESCC patients treated with CRT and 128 control participants, and performed IGFBP-3 genotyping using DNA sequencing. Results The obtained results indicated that overall, no statistically significant association was observed in rs2854746 G > C. However, rs2854744 A > C genotype was at increased risk of ESCCs ( P = 0.032; odds ratio (OR) = 1.201, CI 95%:1.014–1.423). Moreover, rs2854744 A > C genotype ESCCs were more significantly common in patients with tumor size of >6 cm than A allele ESCC and in cases of lower T stage. Furthermore, ESCC patients with rs2854744CC genotype have the poorer CRT response and shorter survival time than GG + GC genotype ESCC. Conclusions In conclusion, polymorphism in IGFBP-3 rs2854744 A > C might be a potential predictor of ESCC risk and patient survival. Nevertheless, further investigation with a larger sample size is needed to support our results. [ABSTRACT FROM AUTHOR]

Background Data on cervical esophageal cancer (CEC) based on modern radiotherapy technique are rare. We aimed to analyze the clinical efficacy and failure pattern of patients with CEC who underwent definitive chemoradiotherapy. Methods Between February 2002 and October 2013, 102 patients with CEC treated with definitive chemoradiotherapy were retrospectively analyzed. All patients received concurrent platinum-based chemotherapy with conformal radiotherapy (50–70 Gy in 25–35 fractions, 5 fractions per week over 5–7 weeks). Overall survival (OS), progression-free survival (PFS) and loco-regional failure-free survival (LRFFS) were calculated. Results The 3-year OS, PFS and LRFFS rates for the entire sample were 39.3%, 33.6% and 35.3%, respectively. During follow-up, 32, 26, and 41 patients had developed local, regional, and distant failure, respectively. Sex and hoarseness were independent prognostic indicators for OS ( P = 0.011, P < 0.001; respectively) and PFS ( P = 0.008, P = 0.001; respectively). Hoarseness was the only independent prognostic factor for LRFFS ( P = 0.002). Conclusions Distant metastasis was the most common failure pattern in CEC patients undergoing definitive chemoradiotherapy. Hoarseness was an independent prognostic factor for OS, PFS, and LRFFS. [ABSTRACT FROM AUTHOR]

Background To compare the clinical outcomes of neoadjuvant chemoradiotherapy (CRT) with cisplatin/vinorelbine versus cisplatin/fluorouracil in patients with locally advanced esophageal cancer. Methods Between 2000 and 2012, 279 patients with thoracic esophageal squamous cell carcinoma (SCC) undergoing neoadjuvant CRT followed by surgery were reviewed. Through a matched case–control study, 57 patients treated with cisplatin/vinorelbine were matched 1:1 to patients who received cisplatin/fluorouracil according to age, sex, performance status, tumor location, tumor length, and pretreatment TNM stage. Results Patient and disease-related characteristics were comparable between the two groups. The pathologic complete response (pCR) rate was 47.4% for the cisplatin/vinorelbine group and 28.1% for the cisplatin/fluorouracil group ( P = 0.034). Median overall survival (OS) in the cisplatin/vinorelbine group was significantly better compared with the cisplatin/fluorouracil group (52.8 vs. 25.2 months), with 3-year OS rates of 64.3% vs. 31.3%, respectively ( P = 0.001). However, cisplatin/vinorelbine was associated with a significantly higher rate of grade 3–4 leukopenia than cisplatin/fluorouracil ( P = 0.03). Multivariate analysis showed that being female, age ⩾55 years, pCR after CRT, and chemotherapy with cisplatin/vinorelbine were independent positive prognostic factors for survival. Conclusions Cisplatin/vinorelbine might lead to a higher pCR rate and better survival outcomes than cisplatin/fluorouracil in esophageal SCC. The incidence of hematologic toxicity is increased with cisplatin/vinorelbine, but is tolerable and manageable. Prospective controlled studies are required to confirm the efficacy of this regimen. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). Material and Methods: 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68–70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. Results: The median follow-up period was 37.3 months (range, 6.3–45.1 months). The 3-year estimated local failure–free survival, regional failure–free survival, locoregional failure–free survival, distant metastasis–free survival, disease–free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2–3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. Conclusions: VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. Methods: From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50–68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). Results: The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. Conclusions: Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival. [ABSTRACT FROM AUTHOR]

Background and purpose: The benefit of concurrent chemoradiotherapy (CCRT) in elderly patients with inoperable esophageal squamous cell carcinoma (SCC) is controversial. This study aimed to assess the efficiency and safety of CCRT in elderly thoracic esophageal cancer patients. Methods and materials: Between January 2002 and December 2011, 128 patients aged 65 years or older treated with CCRT or radiotherapy (RT) alone for inoperable thoracic esophageal SCC were analyzed retrospectively (RT alone, n = 55; CCRT, n = 73). Results: No treatment-related deaths occurred and no patients experienced any acute grade 4 non-hematologic toxicities. Patients treated with CCRT developed more severe acute toxicities than patients who received RT alone. The 3-year overall survival (OS) rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008). Multivariate analysis identified T stage and treatment modality as independent prognostic factors for survival. Further analysis revealed that survival was significantly better in the CCRT group than in the RT alone group for patients ≤ 72 years. Nevertheless, the CCRT group had a similar OS to the RT group for patients > 72 years. Conclusion: Our results suggest that elderly patients with inoperable thoracic esophageal SCC could benefit from CCRT, without major toxicities. However, for patients older than 72 years, CCRT is not superior to RT alone in terms of survival benefit. [ABSTRACT FROM AUTHOR]

The majority of membrane proteins function as oligomers. However, it remains largely unclear how the oligomer stability of protein complexes correlates with their function. Understanding the relationship between oligomer stability and activity is essential to protein research and to virtually all cellular processes that depend on the function of protein complexes. Proteins make lasting or transient interactions as they perform their functions. Obligate oligomeric proteins exist and function exclusively at a specific oligomeric state. Although oligomerization is dearly critical for such proteins to function, a direct correlation between oligomer affinity and biological activity has not yet been reported. Here, we used an obligate trimeric membrane transporter protein, AcrB, as a model to investigate the correlation between its relative trimer affinity and efflux activity. AcrB is a component of the major multidrug efflux system in Escherichia coli. We created six AcrB constructs with mutations at the transmembrane intersubunit interface, and we determined their activities using both a drug susceptibility assay and an ethidium bromide accumulation assay. The relative trimer affinities of these mutants in detergent micelles were obtained using blue native polyacrylamide gel electrophoresis. A correlation between the relative trimer affinity and substrate efflux activity was observed, in which a threshold trimer stability was required to maintain efflux activity. The trimer affinity of the wild-type protein was approximately 3 kcal/mol more stable than the threshold value. Once the threshold was reached, an additional increase of stability in the range observed had no observable effect on protein activity. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prognostic significance of unilateral cervical lymph nodal metastasis (CLNM) in patients with inoperable thoracic esophageal squamous cell carcinoma (SCC) and to identify significant prognostic factors in these patients. Patients and methods: This retrospective study involved 395 patients with inoperable esophageal SCC treated with concurrent chemoradiotherapy. The patients were classified into three groups according to their cervical lymph node status: group A, no evidence of CLNM; group B, unilateral CLNM; group C, other distant metastases. Overall survival (OS) and progression-free survival (PFS) were calculated. Significant prognostic factors were identified using univariate and multivariate analyses. Results: The 3-year OS rates in groups A, B and C were 46.7%, 33.5% and 8.3%, respectively (p<0.001, log-rank test). The corresponding PFS rates were 40.7%, 26.4% and 4.7% (p<0.001, log-rank test). Group B had a similar prognosis to that of group A and better 3-year OS (p = 0.009) and PFS (p = 0.006) rates than those of group C. Multivariate analysis demonstrated that T stage, chemotherapy regimen and cervical lymph node involvement were independent prognostic factors affecting OS and PFS. Conclusions: Compared to other distant metastases, unilateral CLNM is associated with longer OS in esophageal SCC and should be regarded as a regional disease. Sex, T stage, concurrent chemotherapy modality and cervical lymph node involvement are independent predictors of survival in esophageal SCC. [ABSTRACT FROM AUTHOR]

Multidrug efflux pumps play important roles in bacteria drug resistance. A major multidrug efflux system in Gram-negative bacteria is composed of the inner membrane transporter AcrB, outer membrane protein channel TolC, and membrane fusion protein AcrA. These three proteins form a large complex that spans both layers of cell membranes and the periplasmic space. AcrB exists and functions as a homotrimer. To identify residues at the trimer interface that play important roles in AcrB function, we conducted site directed mutagenesis and discovered a key residue, R780. Although R780K was partially functional, all other R780 mutants tested were completely nonfunctional. Replacement of R780 by other residues disrupted trimer association. However, a decrease of trimer stability was not the lone cause for the observed loss of activity, because the activity loss could not be restored by strengthening trimer interaction. Using both heat and chemical denaturation methods, we found that the mutation decreased protein stability. Finally, we identified a repressor mutation, M774K, through random mutagenesis. It restored the activity of AcrBR780A to a level close to that of the wild-type protein. To examine the mechanism of activity restoration, we monitored denaturation of AcrBR780A/M774K and found that the repressor mutation improved protein stability. These results suggest that R780 is critical for AcrB stability. When R780 was replaced by Ala, the protein retained the overall structure, still trimerized in the cell membrane, and interacted with AcrA. However, local structural rearrangement might have occurred and lead to the decrease of protein stability and loss of substrate efflux activity. [ABSTRACT FROM AUTHOR]

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

Background: To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC). Materials and methods: Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30–48 Gy) in six fractions during two weeks. Results: The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy. Conclusions: VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients. [ABSTRACT FROM AUTHOR]

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

Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light--generated heat to destroy tumor cells. However, complete tumor eradication by PTA therapy alone is difficult because heterogeneous heat distribution can lead to sublethal thermal dose in some areas of the tumor. Successful PTA therapy requires selective delivery of photothermal conducting nanoparticles to mediate effective PTA of tumor cells, and the ability to combine PTA with other therapy modalities. Here, we synthesized multifunctional doxorubicin (DOX)-loaded hollow gold nanospheres (DOX@HAuNS) that target EphB4, a member of the Eph family of receptor tyrosine kinases overexpressed on the cell membrane of multiple tumors and angiogenic blood vessels. Increased uptake of targeted nanoparticles T-DOX@HAuNS was observed in three EphB4-positive tumors both in vitro and in vivo. In vivo release of DOX from DOX@HAuNS, triggered by NIR laser, was confirmed by dualradiotracer technique. Treatment with T-DOX@HAuNS followed by NIR laser irradiation resulted in significantly decreased tumor growth when compared with treatments with nontargeted DOX@HAuNS plus laser or HAuNS plus laser. The tumors in 6 of the 8 mice treated with T-DOX@HAuNS plus laser regressed completely with only residual scar tissue by 22 days following injection, and none of the treatment groups experienced a loss in body weight. Together, our findings show that concerted chemo-photothermal therapy with a single nanodevice capable of mediating simultaneous PTA and local drug release may have promise as a new anticancer therapy. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC). The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody) on ESCC radiotherapy (RT) and underlying mechanisms. Methods: Nimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3) in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model. Results: Nimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression) in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR) induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (P<0.05), and even after the administration of Nimotuzumab, the RT response of IGFBP-3 silenced KYSE30 cells was not enhanced (P>0.05). In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029), and also with IGFBP-3 up-regulation in tumor tissue. Conclusions: Nimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Radiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child–Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT). Methods and materials: A total of 114 eligible patients (mean age 45years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3±308.1) cm3. A median dose of 53Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6Gy (range: 4–6Gy). Results: Patients were followed up for 1–79months (median 19months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5–40Gy irradiations (V5–40) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V20 were independent predictors. Using V20 as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively. Conclusions: Our data suggest that V20 is the unique significant dosimetric predictor for RILD risks in PLC patients with Child–Pugh Grade A cirrhosis after hypofractionated CRT. [Copyright &y& Elsevier]

Purpose: To define by MRI the local extension patterns in patients presenting with nasopharyngeal carcinoma (NPC) and to improve clinical target volume delineation. Methods and Materials: Consecutive patients (N = 943) with newly diagnosed and untreated NPC were included in this study. All patients underwent MRI of the nasopharynx and neck, which was reviewed by two radiologists. Results: According to the incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were initially classified into three risk grades: high risk (≥ 35%), medium risk (≥ 5–35%), and low risk (< 5%). Incidence rates of tumor invasion into anatomic sites at medium risk were increased, reaching 55.2%, when adjacent high-risk anatomic sites were involved. However, the rates were substantially lower, mostly < 10%, when adjacent high-risk sites were not involved. The incidence rates of concurrent tumor invasion into bilateral sites were < 10%, except in the case of prevertebral muscle involvement (13.1%). Among the 178 incidences of cavernous sinus invasion, there were often two or more simultaneous infiltration routes (60.6%); when only one route was involved, the foramen ovale was the most common (26.4%). Conclusions: In patients presenting with NPC, local disease spreads stepwise from proximal sites to more distal sites. Tumors extend quickly through privileged pathways such as neural foramina. The anatomic sites surrounding the nasopharynx are at low risk of concurrent bilateral tumor invasion. Selective radiotherapy of the local disease in NPC may be feasible. [Copyright &y& Elsevier]

Purpose: To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. Methods and Materials: We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment. Results: The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b and T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages. Conclusion: Using the 6th American Joint Committee on Cancer staging system produces 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 recategorizing the T, N, and group stage criteria. [Copyright &y& Elsevier]

The aim of this study is to evaluate the quality of life (QoL) of nasopharyngeal carcinoma (NPC) survivors. 192 NPC survivors treated in 1999 and 2000 were enrolled in this study. Median follow up was 3.6 years (range 2.4–4.6 years). The Chinese SF-36 questionnaire and a self-reported symptom checklist consisting of 14 items were completed at clinics. Sociodemographic factors and clinical information were also collected. Most functional domains of the Chinese SF-36 were significantly worse in NPC survivors compared to the normal population. Xerostomia, hearing loss, hypomnesia, dysphagia, and trismus were frequently reported symptoms. Sociodemographic variables including gender, age, dialect, educational level, monthly income, economic status, and number of comorbidities were univariate predictors of different SF-36 domains and symptoms. Patients with earlier T and N stage, irradiated by linear accelerator, with lower dose and weekly dose to nasopharynx and neck, and those who had anterior nasal radiation field reported better QoL. Multiple stepwise regression analysis showed that the number of comorbidities, monthly income, age, and T stage were independent factors affecting global QoL. We concluded that NPC survivors had worse QoL than the normal population and improving radiotherapy might increase physical and functional domain of QoL. [ABSTRACT FROM AUTHOR]