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This work describes the adaptive use of a conventional stainless steel acupuncture needle as the electrode substrate for construction of a molybdenum disulfide (MoS2) and platinum nanoparticles (PtNPs) layer-modified microneedle sensor for real-time monitoring of hydrogen peroxide (H2O2) release from living cells. To construct the nanocomposite-functionalized microneedle, the needle surface was first coated with a gold film by ion sputtering to enhance the conductivity. Subsequently, an electrochemical deposition method was successfully employed to deposit MoS2 nanosheet and Pt nanoparticles on the needle tip as the sensing interface. Electrochemical study demonstrated that the MoS2/PtNPs nanocomposite-modified needle exhibited excellent catalytic performance and low over-potential toward the reduction of H2O2. Not only did the microneedle achieve a wide linear range from 1 to 100 μmol L−1 with a limit of detection down to 0.686 μmol L−1, but it also realized the highly specific detection of H2O2. Owing to these remarkable analytical advantages, the prepared microneedle was applied to determine H2O2 release from living cells with satisfactory results. The MoS2/PtNPs nanocomposite-functionalized microneedle sensor is simple and affordable, and can serve as a promising electrochemical nonenzymatic sensing platform. Moreover, this superfine needle sensor shows great potential for real-time monitoring of reactive oxygen species in vivo with minimal damage. [ABSTRACT FROM AUTHOR]

Purpose: Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept. Methods: We searched databases such as PubMed and Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings for records up to August 2013 to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating aflibercept in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95 % confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of included studies. Results: A total of 3,060 patients with a variety of solid tumors from ten clinical trials were included in our analysis. The overall incidence of FAEs associated with aflibercept was 5.1 % (95%CI: 3.8-6.8 %). The use of aflibercept significantly increased the risk of FAEs compared to patients treated with control medication (OR 1.81, 95 % CI: 1.20-2.72, p = 0.004). Additionally, the most common causes of FAEs were infection (38.8 %), hemorrhage (5.9 %) and GI perforation (5.9 %), respectively. Conclusions: With available evidence, the use of aflibercept is associated with an increased risk of FAEs compared to controls. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept remains justified in its approved indications. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to gain a better understanding of the overall incidence and risk of osteonecrosis of the jaw (ONJ) in cancer patients receiving denosumab. Methods: We performed a meta-analysis of relevant randomized controlled trials identified in Pubmed, Embase, and Cochrane databases. Abstracts presented at the conferences were also searched. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: A total of 8963 patients with a variety of solid tumors from 7 randomized controlled trials (RCTs) were included for the meta-analysis. The overall incidence of ONJ in cancer patients receiving denosumab was 1.7 % [95 % CI: 0.9-3.1 %]. Also, the use of denosumab was associated with significantly increased risk of ONJ in comparison with bisphosphonates (BPs)/placebo treatment (RR 1.61, 95 % CI: 1.05-2.48, P = 0.029). Subgroup analysis based on controlled therapies demonstrated an increased risk of ONJ in denosumab therapy, when compared with BPs (RR 1.48, 95 % CI: 0.96-2.29, P = 0.078) or placebo (RR 16.28, 95 % CI: 1.68-158.05, P = 0.017). Similar results were observed in prostate cancer (RR 3.358, 95 % CI: 1.573-7.166, P = 0.002) while there was a non-significantly increased risk of denosumab-related osteonecrosis of the jaw (DONJ) in non-prostate cancers (RR 1.142, 95 % CI: 0.678-1.921, P = 0.618). Conclusions: The use of denosumab is associated with an increased risk of developing ONJ when compared with BP treatment or placebo, although the increased risk was not statistically significant between denosumab and BP treatment. Further studies are still needed to establish guidelines for the prevention and effective treatment of ONJ. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy of doublet versus single third-generation cytotoxic agent as first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC). Methods: Several databases including PubMed, Embase, and Cochrane databases were searched. The endpoints were overall survival (OS), time to progression (TTP), 1-year survival rate (1-year SR), overall response rate (ORR), and grade 3 or 4 adverse event (AE). We performed a meta-analysis of the randomized controlled trials using a fixed-effects model and an additional random-effects model when applicable. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). A subgroup meta-analysis was performed based on chemotherapy regimens. Results: Ten eligible trials involving 2,510 patients were identified. The intention-to-treatment (ITT) analysis demonstrated that doublet therapy was superior to single agent in terms of OS (HR = 0.84, 95 % CI = 0.71-1.00, p = 0.053), TTP (HR = 0.76, 95 % CI = 0.60-0.96, p = 0.022), 1-year SR (RR = 1.17, 95 % CI = 1.02-1.35, p = 0.03), and ORR (RR = 1.54, 95 % CI = 1.36-1.73, p = 0.000). Subgroup analysis also favored platinum-based doublet therapy in terms of 1-year SR (RR = 1.40, 95 % CI = 1.09-1.81, p = 0.009) and ORR (RR = 1.64, 95 % CI = 1.38-1.96, p = 0.000). Though gemcitabine-based doublet significantly increased ORR compared with single agent (RR = 1.45, 95 % CI = 1.23-1.71, p = 0.000), it did not translate into an increase in survival benefits. In addition, more incidences of grade 3 or 4 anemia, thrombocytopenia, and neurotoxicity were observed in the doublet combination group. With respect to grade 3 or 4 neutropenia and nonhematologic toxicities such as diarrhea, fatigue, nausea, and vomiting, equivalent frequencies were found between the two groups. Conclusions: Our results indicated that doublet therapy was superior to a single third-generation cytotoxic agent for elderly patients with advanced NSCLC. The optimal dosage and schedule of platinum-based doublet should be investigated in future prospective clinical trials. Gemcitabine-based doublet could be considered for elderly patients who were not suitable for platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer Methods: We systematically searched for randomized clinical trials that compared pemetrexed-based doublet with single-agent pemetrexed in patients with histologically proven non-small-cell lung cancer. The primary end point was overall survival. Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, Texas, USA). Results: Five randomized clinical trials (totally 1,186 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (HR 0.82, 95% CI 0.71-0.95, P = 0.007) and overall response rate (OR 2.39, 95% CI 1.58-3.62, P = 0.000) in pemetrexed-based doublet group, compared with pemetrexed alone, though the pooled HR for overall survival (HR 0.89, 95% CI 0.76-1.04; P = 0.129) showed no significant difference between the two groups. However, there were more incidences of grade 3 or 4 neutropenia (OR 2.3, 95% CI 1.4-3.77, P = 0.001), thrombocytopenia (OR 6.41, 95% CI 2.57-16.0, P = 0.000), and leucopenia (OR 2.45, 95% CI 1.13-5.34, P = 0.024) in pemetrexed-based doublet group. With regard to the risk of grade 3 or 4 anemia (OR 0.71, 95% CI 0.17-2.91, P = 0.629) and fatigue (OR 1.47, 95% CI 0.92-2.35, P = 0.104), there was no significant difference between the two groups. Conclusion: Pemetrexed-based doublet therapy didn't gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and leucopenia were observed in pemetrexed-based doublet group. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the efficacy and toxicity of vandetanib in the second-line treatment for advanced non-small cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared therapy with vandetanib versus standard second-line treatment, including docetaxel, pemetrexed, erlotinib, or gefitinib, as second-line treatment for patients with histologically proven non-small-cell lung cancer. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, overall response rate, and grade 3 or 4 toxicity. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, TX, USA). Results: Four randomized clinical trials ( N = 3,292 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (hazards ration (HR), 0.91; 95% confidence interval (CI), 0.83−1.00; P = 0.039) and overall response rate (relative risk (RR), 1.49; 95% CI, 1.04−2.14; P = 0.03) in therapy with vandetanib group compared with standard second-line therapy group, although the pooled HR for overall survival (HR, 0.95; 95% CI, 0.88−1.03; P = 0.191) showed no significant difference between the two groups. In addition, there were less incidences of grade 3 or 4 anemia (RR, 0.39; 95% CI, 0.22−0.67; P = 0.001) in therapy with vandetanib group. With regard to the risk of grade 3 or 4 neutropenia (RR, 1.19; 95% CI, 1.0-1.43; P = 0.054), diarrhea (RR, 1.38; 95% CI, 1.0−1.94; P = 0.059), nausea and vomiting (RR, 0.77; 95% CI, 0.48−1.26; P = 0.308), rash (RR, 2.83; 95% CI, 0.73−10.9; P = 0.131), cough (RR, 1.19; 95% CI, 1.0−1.43; P = 0.054), and fatigue (RR, 1.0; 95% CI, 0.747−1.35; P = 0.971), there was no significant difference between the two groups. Conclusions: Therapy with vandetanib offered a clinically meaningful and statistically significant improvement in PFS and ORR in patients with advanced NSCLC but did not benefit overall survival. Therapy with vandetanib regimens might be suggested as second-line treatment for advanced NSCLC based on a similar toxicity profile compared with standard second-line therapy. [ABSTRACT FROM AUTHOR]

Water splitting driven by solar energy to produce hydrogen, which is highly dependent on the designing of semiconductor photocatalyst, is an efficient technology to address energy shortage problems and environment issues simultaneously. Here, the halogen and potassium binary-doped graphitic carbon nitride (named as X-K-C 3 N 4 , X = F, Cl, Br, I) photocatalysts were synthetized via simply one pot thermal polymerization method, which shown optimized band structure, enhanced optical absorption, higher separation rate of photogenerated carriers, and thus improved photocatalytic performance under visible light irradiation. As result, F–K–C 3 N 4 is demonstrated to be highly efficient in the separation and transfer of carriers owing to the existence of C–F bond, C N triple bond and K junction. The F–K–C 3 N 4 shows a highest H 2 evolution rate of 1039 μmol g−1 h−1 and a remarkable stability under visible light irradiation (λ ≥ 420 nm), which is about 8.5 times higher than that of pristine g-C 3 N 4. • We systematically studied the effect of K and halogen binary-doped graphitic carbon nitride on photocatalytic performance. • The significantly enhanced photocatalytic activity is described to the double accelerations of F, K binary doping. • F–K–C 3 N 4 exhibits improved visible light harvesting ability and photogenerated charge separation rate. • The F–K–C 3 N 4 exhibits 8.5 times higher H 2 generation rate than that of pristine C 3 N 4. [ABSTRACT FROM AUTHOR]

Monitoring the dynamic pH changes in vivo remains very essential to comprehend the function of pH in various physiological processes. In this study, we report a high-performance electrochemical pH microneedle based on an acupuncture needle (AN) for real-time monitoring of pH changes in a rat brain. The pH microneedle was prepared by a layer-to-layer assembly of molybdenum disulfide (MoS2) nanosheets and polyaniline (PAN), with an attempt to achieve a highly sensitive detection of hydrogen ions (H+). The as-prepared PAN/MoS2/AN exhibited a high Nernstian response of −51.2 mV per pH over a wide pH range from 3.0 to 9.0, and excellent selectivity toward pH against other potential interfering species in the brain. Moreover, the corresponding open circuit potential rapidly increased and decreased when Na2CO3 or NaH2PO4 was injected into the rat brain, respectively, demonstrating that the PAN/MoS2/AN has an excellent response toward pH changes in vivo. This work provides a new potentiometric method for real-time monitoring of dynamic pH changes in vivo with high reliability and stability. [ABSTRACT FROM AUTHOR]

Purpose: Non-small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting epidermal growth factor receptor (EGFR) mutations have been developed, most advanced NSCLC is still incurable and new targets for anticancer drugs are in demand. BRCA1-associated protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS). UPS has emerged as a potential target for anticancer drugs. The aim of the present study was to investigate the expression of BAP1 protein in patients with NSCLC.Methods: BAP1 expression was measured using Western blot analysis in 103 cases patients with advanced NSCLC.Results: Results revealed 49 (47.5%) patients were classified with high expression of BAP1. Squamous cell carcinomas were more likely to be observed in BAP1 high expressers compared with adenocarcinomas (55.8% vs. 32.3%, p = 0.001). High BAP1 expression was associated with no lymph node metastasis (p = 0.002). There was also a significant association between BAP1 expression and histological type (p = 0.014), while expression of BAP1 was not correlated with other clinical or pathological characteristics. Kaplan-Meier survival analysis showed that patients with high BAP1 expression had a longer median survival compared with patients with low BAP1 expression (23.2 vs. 14.7 months, p = 0.021). Multivariate analysis revealed that high BAP1 expression was an independent lower risk for all 103 patients (HR = 0.61, 95% CI 0.32-0.71, p = 0.003).Conclusions: BAP1 may be a useful prognostic factor of NSCLC patients and potential target for anticancer drugs. [ABSTRACT FROM AUTHOR]

Purpose Arterial thromboembolic events (ATEs) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR–TKIs) have emerged as a serious concern, we perform a meta-analysis of randomized controlled trials (RCTs) to determine the incidence and risk of ATEs in cancer patients treated with these agents. Methods The databases of PubMed and Web of Science were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR), and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 9711 patients from 19 RCTs were included. The overall incidence of ATEs was 1.5% (95%CI: 1.0–2.3%). The use of VEGFR–TKIs significantly increased the risk of developing ATEs when compared with controls (OR 2.26, 95%CI: 1.38–3.68, p = 0.001). Sensitivity analysis indicated that the significance estimate of pooled ORs was not significantly influenced by omitting any single study. In subgroup analyses, the odds ratio of ATEs did not significantly vary with tumor types ( p = 0.70), VEGFR–TKIs ( p = 0.32), treatment regimens ( p = 0.76), phase of trials ( p = 0.37) and sample size ( p = 0.89). Additionally, the most common events for ATEs were cardiac ischemia/infarction (67.4%), CNS ischemia (7.9%) and cerebrovascular accident (6.7%). Conclusion In this largest meta-analysis to date, we find that treatment with VEGFR–TKIs significantly increase the risk of developing ATEs. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of these drugs remains justified in their approved indications. [ABSTRACT FROM AUTHOR]

AIMS: Congestive heart failure (CHF) associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has emerged as a relevant problem in clinical and scientific communities. We performed an up-to-date, comprehensive meta-analysis to determine the overall incidence and risk of CHF in cancer patients receiving VEGFR-TKIs. METHODS: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to August 31 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 10 553 patients from 36 clinical trials were included. The overall incidence of all grade and high grade CHF associated with VEGFR-TKIs was 3.2% (95% CI 1.8%, 5.8%) and 1.4% (95% CI 0.9%, 2.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all grade (OR 2.37, 95% CI 1.76, 3.20, P < 0.001) and high grade (OR 3.51, 95% CI 1.74, 7.05, P < 0.001) CHF. In subgroup analyses, the risk of CHF did not significantly vary with tumour types (P = 0.071 for all grade; P = 0.72 for high grade) and VEGFR-TKIs (P = 0.55 for all grade; P = 0.99 for high grade). Meta-regression indicated that CHF might possibly occur early in the treatment of VEGFR-TKIs. No evidence of publication bias was observed. CONCLUSION: The use of VEGFR-TKIs is associated with a significantly increased risk of developing congestive heart failure in cancer patients. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event. Materials and methods: We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95 % CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036). Conclusions: Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients. [ABSTRACT FROM AUTHOR]

Background: Aflibercept is currently approved as second-line treatment for patients with metastatic colorectal cancer, and its application in other types of tumors is undergoing clinical evaluation. Hypertension is one of its major adverse effects with a substantial variation in the reported incidences and has not been systematically investigated. Methods: We searched PubMed, EMBASE, and Cochrane Library databases from January 2000 to August 2013 and abstracts presented at annual meetings from 2004 to 2013 to identify relevant studies. Eligible studies were phase II and III prospective clinical trials of aflibercept in patients with any type of cancer describing events of hypertension. Summary incidence rates, odds ratios (OR), and 95 % confidence intervals (CIs) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: A total of 15 trials with 4,451 patients were included for the meta-analysis. The summary incidences of all-grade and high-grade hypertension were 42.4 % (95 % CI 35.0-50.3) and 17.4 % (95 % CI 13.7-21.9), respectively. The use of aflibercept in cancer patients was associated with a significantly increased risk of all-grade (OR 4.47, 95 % CI 3.84-5.22, p < 0.001) and high-grade (OR 4.97, 95 % CI 3.95-6.27, p < 0.001) hypertension. The risk of developing hypertension with aflibercept was significantly higher than that of bevacizumab (all-grade: OR 1.93, 95 % CI 1.61-2.32, p < 0.001; high-grade: OR 2.06, 95 % CI 1.79-2.37, p < 0.001). Conclusions: The use of aflibercept is associated with a significantly increased risk of developing all-grade and high-grade hypertension compared with control. Close monitoring and adequate managements are highly recommended to decrease cardiovascular complication. [ABSTRACT FROM AUTHOR]

Abstracts: Background: The use of vascular-endothelial growth factor (VEGF) antibody bevacizumab is associated with an increased risk of gastrointestinal (GI) perforation, but the incidence and risk of GI perforation associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has not been well described. We conduct a systematic review and meta-analysis of published trials to evaluate the overall incidence and risk of GI perforation associated with VEGFR-TKIs. Methods: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to March 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on GI perforation. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. Results: A total of 5352 patients with a variety of solid tumors from 20 clinical trials were included in our analysis. The incidence of GI perforation was 1.3% (95%CI: 0.8–2.0%) among patients receiving VEGFR-TKIs, with a mortality of 28.6% (15.0–47.6%). Patients treated with VEGFR-TKIs did not significantly increase the risk of GI perforation compared with patients treated with control medication, with an OR of 2.99 (95%CI: 0.85–10.53, p =0.089). Sub-group analysis showed that the incidence of GI perforation did not significantly vary with tumor types, VEGFR-TKIs and treatments regimens. No evidence of publication bias was observed. Conclusions: The use of VEGFR-TKIs dose not significantly increase the risk of GI perforation in comparison with the controls. Further studies are recommended to investigate this association and the risk differences among different tumor types, VEGFR-TKIs or treatment regimens. [Copyright &y& Elsevier]

Objective: Ovarian cancer is the most deadly deadliest gynecological tumor in the female reproductive system. Therefore, the present study sought to determine the diagnostic performance of International Ovarian Tumor Analysis Simple Rules (IOTA SR), the Ovarian-Adnexal Reporting and Data System (O-RADS), and Cancer Antigen 125 (CA125) in discriminating benign and malignant ovarian tumors. The study also assessed whether a combination of the two ultrasound categories systems and CA125 can improve the diagnostic performance. Methods: A total of 453 patients diagnosed with ovarian tumors were retrospectively enrolled from Fujian Cancer Hospital between January 2017 and September 2020. The data collected from patients included age, maximum lesion diameter, location, histopathology, levels of CA125, and detailed ultrasound reports. Additionally, all ultrasound images were independently assessed by two ultrasound physicians with more than 5 years of experience in the field, according to the IOTA simple rules and O-RADS guidelines. Furthermore, the area under the curve (AUC), sensitivity, and specificity of the above mentioned predictors were calculated using the receiver operating characteristic curve. Results: Out of the 453 patients, 184 had benign lesions, while 269 had malignant ovarian tumors. In addition, the AUCs of IOTA SR, O-RADS, and CA125 in the overall population were 0.831, 0.804, and 0.812, respectively, and the sensitivities of IOTA SR, O-RADS, and CA125 were 94.42, 94.42, and 80.30%, respectively. On the other hand, the AUCs of IOTA SR combined with CA125, O-RADS combined with CA125, and IOTA SR plus O-RADS combined with CA125 were 0.900, 0.891, and 0.909, respectively. The findings also showed that the AUCs of a combination of the three approaches were significantly higher than those of individual strategies (p<0.05) but not significantly higher than the AUC of a combination of two methods (p>0.05). Conclusion: The findings showed that a combination of IOTA SR or O-RADS in combination with CA125 may improve the ability to distinguish benign from malignant ovarian tumors. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event. Materials and methods: We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95 % CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036). Conclusions: Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients. [ABSTRACT FROM AUTHOR]

Ultrasound elastography has been introduced into clinical practice for a decade and arisen continuous increasing attention worldwide. Shear wave elastography (SWE) is a further extension of ultrasound elastography on the basis of strain elastography, providing a two-dimensional distribution map of tissue stiffness and quantitative measurement of the tissue stiffness in Young's modulus (kPa) and/or shear wave speed (m/s). The Society of Ultrasound in Medicine, Chinese Medical Association (CMA) has recently released a series of guidelines for the use of SWE, including the technique and principle of SWE, and use of SWE in liver fibrosis, breast, thyroid, and musculoskeletal system. Herein, a part of SWE in thyroid nodules is presented. In this guideline, the background, classification and technology of SWE, examination methods, diagnostic performance, prognosis evaluation, reproducibility, and limitations are discussed and recommendations are given. The recommendations are based on the published literatures with regard to SWE with different levels of evidence, particularly a mid-term result of the prospective multi-center clinical trial of SWE in thyroid, as well as the Society of Ultrasound in Medicine, CMA expert's consensus. The document provides an overall analysis of SWE in thyroid from clinical perspective, which aimed to provide recommendations to the clinicians with regard to the management of thyroid nodules by the assistance of SWE. [ABSTRACT FROM AUTHOR]

Aims Gemcitabine has been associated with an increased risk of arterial and venous thromboembolic events ( ATEs and VTEs), although the overall risk remains unclear. As indications for its use in oncology are expanding, a comprehensive characterization of these complications becomes imperative. Methods Pubmed was searched for articles published from 1 January 1990 to 31 December 2012. Eligible studies included prospective randomized controlled phase II and III trials evaluating gemcitabine based vs. non-gemcitabine based chemotherapy in patients with solid tumours. Data on VTEs and ATEs were extracted. Overall incidence rates, odds ratio ( OR), and 95% confidence intervals ( CIs) were calculated employing fixed or random effects models depending on the heterogeneity of included trials. Results A total of 4845 patients from 19 trials were included. Among patients treated with gemcitabine based chemotherapy, the overall incidence of VTEs (13 studies comprising 3823 patients) and ATEs (eight studies consisting of 2431 patients) was 2.1% (95% CI 1.2%, 3.8%) and 2.2% (95% CI 1.4%, 3.2%). The associated ORs of VTEs and ATEs were 1.56 (95% CI 0.86, 2.83, P = 0.15) and 1.82 (95% CI 0.89, 3.75, P = 0.10) compared with non-gemcitabine based therapy. A tendency to increase the risk of ATE and VTEs was also detected in any prespecified subgroup. Conclusion The use of gemcitabine does not significantly increase the risk of VTEs and ATEs in patients with solid tumours when compared with non-gemcitabine based chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Purpose: The aim of this study is to evaluate the frequency and relative risk of hypocalcemia in cancer patients receiving denosumab. Methods: We searched the PubMed (data from 1966 to October 2012), Embase (data from 1980 to October 2012) and Cochrane Library (up to October 2012) electronic databases for relevant randomized controlled trials (RCTs). Abstracts presented at conferences were also searched. Phase II and III trials of denosumab in patients with any type of cancer that reported occurrence of hypocalcemia were eligible. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity among included trials. Results: A total of 8990 patients with a variety of solid tumors from seven RCTs were included for the meta-analysis. The overall incidences of all-grade and high-grade hypocalcemia in cancer patients were 5.2% (95% confidence interval [CI]: 2.8-9.3%) and 2.0% (95% CI: 0.7-5.5%), respectively. The use of denosumab was associated with significantly increased risk of developing all-grade (RR 1.932, 95% CI: 1.590-2.347, p < 0.001) and high-grade hypocalcemia (RR 4.027, 95% CI: 2.346-6.912, p < 0.001) in comparison with controls. Conclusions: The use of denosumab is associated with a significantly increased risk of developing hypocalcemia (p < 0.001). Physicians should be aware of this adverse effect and should monitor cancer patients receiving denosumab. [ABSTRACT FROM AUTHOR]

Aim To perform a systematic review and meta-analysis of published clinical trials to determine incidence rate and overall risk of hypertension with vandetanib in cancer patients. Methods A comprehensive literature search for studies published up to March 2012 was performed. Summary incidence rates, relative risk ( RR), and 95% confidence intervals ( CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results A total of 11 trials with 3154 patients were included for the meta-analysis. The summary incidences of all-grade and high-grade hypertension in patients with cancer were 24.2% [95% confidence interval (CI), 18.1-30.2%] and 6.4% (95% CI, 3.3-9.5%), respectively. Subgroup analysis demonstrated that the pooled incidences of all-grade and high-grade hypertension were 21.8% [95% CI, 15-30.5%] and 7.6% (95% CI, 2.8-18.8%), respectively, among non-small-cell lung cancer (NSCLC) patients, and 32.1% (95% CI: 27.3-37.3%) and 8.8% (5.9%-12.9%), respectively, among MTC patients, and 15.4 (95% CI: 3.2-33.7%) and 3.4% (95% CI: 1%-11.1%) respectively, among non-MTC/NSCLC tumors patients. Furthermore, vandetanib was associated with a significant increased risk of all-grade hypertension (RR 5.1, 95% CI: 3.76-6.92, P = 0.000) and high-grade hypertension (RR 8.06, 95% CI: 3.41-19.04, P = 0.000) in comparison with controls. Conclusions There is a significant risk of developing hypertension in cancer patients receiving vandetanib. Appropriate monitoring and treatment is strongly recommended to prevent cardiovascular complications. [ABSTRACT FROM AUTHOR]

Purposes: To gain a better understanding of the overall incidence and risk of hypertension in cancer patients who receive pazopanib and to compare the differences in incidence among sorafenib, sunitinib, and pazopanib. Methods: Several databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned single drug pazopanib 800 mg/day with data on hypertension available. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials. Results: A total of 1,651 patients with a variety of solid tumors from 13 clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade hypertension in cancer patients were 35.9 % (95 % CI 31.5-40.6 %) and 6.5 % (95 % CI 5.2-8.0 %), respectively. The use of pazopanib was associated with an increased risk of developing all-grade (RR 4.97, 95 % CI 3.38-7.30, p < 0.001) and high-grade hypertension (RR 2.87, 95 % CI 1.16-7.12, p = 0.023). Additionally, there was no significant difference in the incidence of all-grade (RR 1.21, 95 % CI 0.96-1.53, p = 0.11) and high-grade hypertension (RR 1.29, 95 % CI 0.80-2.07, p = 0.30) between RCC and non-RCC patients. Interestingly, the risk of all-grade hypertension with pazopanib was substantially higher than sorafenib (RR 1.99; 95 % CI 1.73-2.29, p = 0.00) and sunitinib (RR 2.20; 95 % CI 1.92-2.52, p = 0.00), while the risk of pazopanib-induced high-grade hypertension was similar to sorafenib (RR 0.98; 95 % CI 0.75-1.30, p = 0.90) and sunitinib (RR 0.81; 95 % CI 0.62-1.06, p = 0.12). Conclusions: The use of pazopanib is associated with a significantly increased risk of developing hypertension. Close monitoring and appropriate managements are recommended during the therapy. Future studies are still needed to investigate the risk reduction and possible use of pazopanib in selected patients. [ABSTRACT FROM AUTHOR]

Background: Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC. Methods: Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95%CI: 0.82–0.99, p = 0.024), PFS (HR 0.83, 95%CI: 0.72–0.97, p = 0.018), and ORR (OR 1.35, 95%CI 1.01–1.80, P = 0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy. Conclusions: With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cancer that originates in the bone, termed primary bone cancer, is rare. Osteosarcoma (OS) occurs primarily in growing bone tissue and is more prevalent in children and adolescents. OS in adults is rare, with 3 to 5 cases per million population per year worldwide. There are limited data on treatment-related prognosis and adverse reactions in adults reported in the literature. Objectives: The aims of this study were to investigate factors that influence serum methotrexate (MTX) concentrations used in chemotherapy in Chinese adult patients with OS, and to determine the correlations (based on age, sex, and dosage), if any, between MTX and prognosis, in terms of disease-free survival (DFS) and overall survival (OAS), and tolerability. Methods: Adult patients aged ≥30 years with OS received ≥3 courses (2 courses before surgery and 3–4 courses postsurgery) of high-dose MTX (6 or 8 g/m2) combined chemotherapy. The regimen consisted of day 1: MTX + folinic acid (herein referred to as citrovorum factor rescue); day 8: cisplatin; days 21 to 25: ifosfamide + mesna; and day 21: doxorubicin. Serum MTX concentrations were assessed immediately after the end of infusion (baseline) and at 24 and 48 hours using high-performance liquid chromatography. Changes in serum MTX concentrations, factors that influence serum MTX concentrations, and the relationship between serum MTX concentrations and prognosis and tolerability (determined by adverse reactions) were analyzed. Patients received a second course of treatment after a 3-week period. Results: Ninety patients (58 men, 32 women; age range, 30–67 years) with OS were included in the study. A total of 532 courses of combined chemotherapy were administered. The serum MTX concentrations ranged widely at baseline (244.31–929.68 mol/L, Cmin and Cmax, respectively) and at 24 hours (0.73–28.24 mol/L, respectively), suggesting that the serum MTX concentrations varied significantly between different individuals and within the same individual at different time points. The serum MTX concentrations in ~23% of cases (122/532) determined at 24 and/or 48 hours were numerically higher than the safety values (according to Nirenberg''s reference: irreversible damage if MTX concentration was >10 umol/L and > 1 umol/L at 24 and 48 hours, respectively). No correlation was found between high serum MTX concentration at baseline and high serum MTX concentration at 24 hours (r = 0.401). The prevalences of the 3 most common adverse reactions in these patients were depressed white blood cell count (44.03%), dental ulcer (23.0%), and rash (18.0%). However, in the remaining 410 courses in which serum MTX concentrations were lower than the safety values, these prevalences were 14.6%, 3–9%, and 2.4%, respectively. Neither age nor sex was significantly associated with MTX Cmax, but dosage was (P < 0.05). Patients with a serum MTX Cmax concentration >500 μmol/L at baseline had a significantly longer DFS rate than those with ≤500 umol/L (P = 0.040). There were no significant between-group differences in the OAS rates. conclusions: In these Chinese patients with OS, serum MTX concentrations measured at different time points were varied. The findings suggest that adverse reactions occurred in patients whose serum MTX concentrations at 24 and/or 48 hours were higher than the safety values. The dosage appeared to have influenced MTX Cmax, while sex and age did not, and the Cmax was significantly related to DFS but not OAS. [Copyright &y& Elsevier]

Purpose: To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients. Methods: Fluorescent quantitative real-time PCR was applied to study the mRNA levels of Ezrin, CD44 and Six1 genes in 32 osteosarcoma patient samples and 10 adjacent normal tissues and MG63 osteosarcoma cell lines. The analysis of relationships between pulmonary metastasis and overall survival time were carried out based on the clinical data. Results: mRNA levels of Ezrin and Six1 genes in osteosarcoma tissues were higher than those in adjacent normal tissues (P=0.015, 0.025). The mRNA levels of Ezrin, CD44 and Six1 genes were closely correlated with Enneking GTM clinical staging, while no correlations were demonstrated between the mRNA level of these genes with sex, age, location or pathological types. In addition, we demonstrated that the high mRNA level of Ezrin gene was related to shorter lung metastasis-free and overall survival time of the Chinese patients with osteosarcoma (P<0.001). Conclusion: Our data suggest that Ezrin, but not CD44 and Six1, could be a prognostic factor and a predictor of potential lung metastasis in osteosarcoma. Further large sample studies need to be done to confirm the potential value of Ezrin as a new therapeutic target. [ABSTRACT FROM AUTHOR]