Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas

Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare endocrine malignancies that are associated with high rates of morbidity and mortality because of their large tumor burden and location, progression, and release of catecholamines. Systemic therapies for MPPGs are limited. MPPGs are characterized by pseudohypoxia that may prevent immune system recognition. We conducted a phase II clinical trial of pembrolizumab in patients with progressive MPPGs. The primary endpoint was the non-progression rate at 27 weeks. The secondary endpoints included the objective response and clinical benefit rates, progression free and overall survival duration, and safety. We also determined whether PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor were associated with clinical response and hereditary background. Eleven patients were included in this trial, four (36%) with germline mutations and seven (64%) with hormonally active tumors. Four patients (40%, 95% confidence interval (CI) 12–74%) achieved the primary endpoint. The objective response rate was 9% (95% CI: 0–41%). The clinical benefit rate was 73% (95% CI: 39–94%). Four patients had grade 3 adverse events related to pembrolizumab. No patients experienced grade 4 or 5 adverse events or a catecholamine crisis. Progression free survival time was 5.7 months (95% CI: 4.37—not reached). The median survival duration was 19 months (95% CI: 9.9—not reached). PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor did not seem to be associated with disease response. Single-agent pembrolizumab has modest treatment efficacy in patients with progressive MPPGs. Positive responses seemed to be independent of patients’ hereditary backgrounds, tumor hormonal status, and the presence of infiltrating mononuclear inflammatory cells or PDL-1 expression in the primary tumor

A Technical Analysis Investigating Energy Sustainability Utilizing Reliable Renewable Energy Sources to Reduce CO2 Emissions in a High Potential Area

©2020 Elsevier Ltd. All rights reserved. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1016/j.renene.2020.09.042Reduction of carbon dioxide (CO 2) emissions will have a positive impact on the environment by preventing adverse effects of global warming. To achieve an eco-environment, the primary source of energy needs to shift from fossil fuels to clean renewable energy. Thus, increased utilization of renewable energy overtime reduces air pollution and contributes to securing sustainable energy supply to satisfy future energy needs. The main purpose of this study is to investigate several sustainable hybrid renewable systems for electricity production in Iran. In this regard, critical indicators that have the strongest impact on the environment and energy sustainability are presented in this study. After a comprehensive review of environmental issues, data was collected from the meteorological organization and a techno-economic assessment was performed using HOMER software. It was concluded that the hybrid configuration composed of photovoltaic (PV), wind turbine, diesel generator and battery produced the best outcome with an energy cost of 0.151$/kWh and 15.6% return on investment. In addition, the results showed that with a higher renewable fraction exceeding 72%, this hybrid system can reduce more than 2000 Kg of CO 2 emission per household annually. Although excess electricity generation is a challenge in stand-alone systems, by using the fuel cell, an electrolyzer, and a hydrogen tank unit, the amount of energy loss was reduced to less than one-sixth. These results show that selecting useful indicators such as appropriate implementation of policies of new enabling technologies and investments on renewable energy resources, has three potential benefits namely: CO 2 reduction, greater sustainable electricity generation and provides an economic justication for stakeholders to invest in the renewable energy sector.Peer reviewe