Safety of Anti-Angiogenic Drugs in Pediatric Patients with Solid Tumors: A Systematic Review and Meta-Analysis

Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations

Efficacy and Comparison of Different Strategies for Selenium Biofortification of Tomatoes

At appropriate concentrations, selenium (Se) is beneficial for humans. Tomato appears to be one of the best commodities for producing Se-biofortified fruit for dietary supplementation. To assess the efficacy of different enrichment protocols, a total of four on-plant and off-plant trials were conducted. Hydroponically grown tomato plants were sprayed with: (i) chemically synthesized Se nanoparticles (SeNPs) at 0, 1, and 1.5 mg Se L−1 at blooming; (ii) sodium selenate (Na2SeO4) or SeNPs solution at 0, 5, and 10 mg Se L−1 when the fruit entered the immature green stage. With regard to the off-plant trials, harvested mature green fruit were immersed in Na2SeO4 solution: (iii) at 0, 5, 10, and 20 mg Se L−1 for 15 s under a vacuum; (iv) at 0, 40, and 80 mg Se L−1 for 1 h. Spraying Na2SeO4 induced higher Se accumulation in plant tissue than SeNPs: both protocols were effective in enriching tomatoes. Postharvest Se enrichment via vacuum infiltration caused textural damage, whereas passive immersion in solution induced fruit Se accumulation without causing any damage. SeNPs appear to be quantitatively less effective than Na2SeO4, but might be environmentally safer. Elemental Se carried by NPs may be more easily incorporated into organic forms, which are more bioavailable for humans. Passive immersion may represent an alternative Se-enrichment strategy, allowing for the biofortification of harvested tomato fruit directly, with lower risks of environmental pollution

Is there still a place for vinorelbine in advanced metastatic castration resistant prostate cancer?

The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60\u200amg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels 6550% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treate

Development and validation of a case-finding algorithm for the identification of non-small cell lung cancers in a region-wide Italian pathology registry

PurposeTo develop and validate a case-finding algorithm for the identification of Non-Small Cell Lung Cancer (NSCLC) cases in a region-wide Italian pathology registry (PR).Materials and methodsData collected between 2009 and 2017 in the PR and the Pharmacy Database of the University Hospital of Siena and the PR of Tuscany region were used. A NSCLC-identification algorithm based on free-text keywords and SNOMED morphology and topography codes was designed and tested on data from Siena: indication for drug use (i.e. NSCLC) was the reference standard for sensitivity (SE); positive predictive value (PPV) was estimated through manual review. Algorithm modifications were then tested to improve algorithm performance: PPV was calculated against validated dataset from PR of Siena; a range of SE [min-max] was estimated in PR of Tuscany using analytical formulae that assumed NSCLC incidence equal either to 80% or 90% of overall lung cancer incidence recorded in Tuscany. The algorithm modification with the best performance was chosen as the final version of the algorithm. A random sample of 200 cases was extracted from the PR of Tuscany for manual review.ResultsThe first version of the algorithm showed a PPV of 74.7% and SE of 79% in PR of Siena. The final version of the algorithm had a SE in PR of Tuscany that grew with calendar time (2009 = [24.7%-28%]; 2017 = [57.9%-65.1%]) and a PPV of 93%.ConclusionsThe final NSCLC-finding algorithm showed with very high PPV. SE was in line with the expected contribution of PR to overall cases captured in the regional Cancer Registry, with a trend of increase over calendar time. Given the promising algorithm validity and the wide use of SNOMED terminology in electronic pathology records, the proposed algorithm is expected to be easily adapted to other electronic databases for (pharmaco)epidemiology purposes

Association between neutropenia and response to ramucirumab and paclitaxel in patients with metastatic gastric cancer

PURPOSE: The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer.METHODS: This is a retrospective study of patients treated with ramucirumab plus paclitaxel.RESULTS: Fifty-three patients were evaluated. Among these, 10 patients (26.5%) developed grade ≥3 neutropenia. Patients with grade ≥3 neutropenia reported a progression-free survival of 6.6 months (95% confidence interval 3.3-8.4) and overall survival of 11 months (95% confidence interval 5.9-13.1) vs. 4.4 months (95% confidence interval 3.9-5.2) and 8.7 months (95% confidence interval 7.8-10.1) respectively in patients' group with lower grade events.CONCLUSION: Our analysis seems to suggest that the occurrence of neutropenia predicts response to treatment with ramucirumab and paclitaxel.</p

Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors: A meta-regression of randomised prospective studies

INTRODUCTION: To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors-based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors-based treatments. METHODS: The systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. RESULTS: Twenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R2 = 0.47; 95% confidence interval [CI], 0.03-0.77; P = 0.001; and R2 = 0.32; 95% CI, 0.02-0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non-small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte-associated antigen 4 checkpoint inhibitors. CONCLUSION: The results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009-2011) and 30.6% (2018-2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018-2019 vs. 2009-2011 was found (non-squamous: HR: 0.95 CI95%: 0.92-0.98; squamous: HR: 0.94 CI95%: 0.90-0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed

Effects of Se-enrichment on yield, fruit composition and ripening of tomato (Solanum lycopersicum) plants grown in hydroponics

Selenium appears to be effective in promoting plant development and delaying the onset of senescence. Besides the effects on the metabolism and physiology of different crops, controlled increases in Se concentrations enhance the health-related properties of the produce. To study the effects of selenium on fruit composition and ripening physiology, an experiment was carried out on tomato (Solanum lycopersicum) plants grown in hydroponics. Sodium selenate was added to the nutrient solution at a rate of 0 (control) and 1 mg Se L−1 . The selenium added to the nutrient solution was absorbed by the roots, and the Se concentration was higher in leaves than in fruits. The addition of Se did not significantly influence the cumulative yield of tomato plants, but a delay in the onset of fruit ripening was detected, and the harvesting of control plants began earlier than in Se-treated plants. The addition of Se did not significantly affect the qualitative parameters with the exception of -carotene content, which was lower in red ripe fruit treated with selenium. Since -carotene accumulation is a ripening-related event in tomato, the lower amount of this compound may be associated with a general delay of ripening. This is confirmed by the reduced biosynthetic rate of ethylene, observed in Se-treated tomatoes, which also showed a reduced rate in colour change. This thus confirmed that ripening-related processes, such as the degradation of chlorophyll and the synthesis of carotenoids, are affected by selenium - with potential benefits in terms of storage and shelf-life. Our results showed that 100 g of tomato hydroponically grown with a nutrient solution supplemented with Se provided a total of 58 g Se. Thus, the daily consumption of 100 g of enriched tomato does not lead to Se toxicity, but can even provide a rational Se supplementation. This suggests that the addition of Se in a nutrient solution is useful for producing tomatoes with greater beneficial properties for human health

Lack of neutralizing activity in nonconvalescent sera, regardless of ABO blood group and anti-A isoagglutinin titer

Summary: Background: Several ABO blood groups have been associated with the likelihood of infection, severity, and/or outcome of COVID-19 in hospitalized cohorts, raising the hypothesis that anti-A isoagglutinins in non-A-group recipients could act as neutralizing antibodies against SARS-CoV-2. Materials and methods: We run live virus neutralization tests using sera from 58 SARS-CoV-2 seronegative blood donors (27 O-group and 31 A-group) negatives for SARS-CoV-2 IgG to investigate what degree of neutralizing activity could be detected in their sera and eventual correlation with anti-A isoagglutinin titers. Results: We could not find clinically relevant neutralizing activity in any blood group, regardless of anti-isoagglutinin titer, Discussion: Our findings suggest that mechanisms other than neutralization explain the differences in outcomes from COVID19 seen in different ABO blood groups