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Purpose/Objective(s) Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal squamous cell carcinoma, but long-term survival remains suboptimal, warranting an improved approach. Immunotherapy has been studied in the metastatic and unresectable recurrent setting, but additional data are needed to assess its role in definitive therapy. The study hypothesis was that the use of immunotherapy in conjunction with chemoradiation would be safe and result in improved laryngectomy-free survival (LFS) compared to standard of care chemoradiation. Materials/Methods This trial was an open-label, single-arm, prospective, multi-institutional study. The study included a Phase I run-in portion to assess safety in the first 6 enrolled patients and a planned subsequent Phase II component. Due to slow accrual, the study was closed after enrollment of 9 patients and the data were allowed to mature. The primary endpoint of the Phase II portion was LFS at 18 months. Study patients had Stage III or IV (T1-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given as a 200 mg flat dose 3 weeks prior to the start of chemoradiation and was then given q21 days until the completion of chemoradiation. Cisplatin was given at a dose of 100 mg/m2 q21 days during radiation with allowed dose modifications for toxicities. Radiation was prescribed to a total dose of 70 Gy in 35 daily fractions using IMRT with an elective nodal dose of 56-63 Gy. Results A total of 9 patients with a median age of 54 were enrolled from 2017 to 2019. The median follow-up time was 30.1 months. None of the enrolled patients required laryngectomy, resulting in 100% LFS at 18 months for evaluable patients. The 18-month overall survival (OS) rate was 66.7%; of the 3 patient deaths, 2 were due to co-morbid conditions (diabetes, peripheral arterial disease) rather than malignancy. The remaining 6 patients were alive at the time of last follow-up and the median duration of OS was not reached. There were 27 Grade 3 toxicities, with 2 attributable to pembrolizumab. Nearly all Grade 4 (n = 4) and Grade 5 (n = 1) toxicities occurred in a single patient with poorly-controlled diabetes; the Grade 5 toxicity was due to diabetic ketoacidosis. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation; the edema has since resolved and the tracheostomy was reversed. Conclusion The use of concurrent pembrolizumab with chemoradiation for locally advanced larynx cancer resulted in high LFS. Most toxicities were attributable to chemoradiation and the majority of Grade 4 and 5 toxicities occurred in a patient with poorly-controlled diabetes. A case of late Grade 4 laryngeal edema could have been related to immunotherapy. Future studies with concurrent immunotherapy with chemoradiation should account for this possibility.

This paper presents a methodology to design an optimal bidding strategy for a generator according to his or her degree of risk aversion. A typical thermal plant is assumed to be located in the Ontario electricity system to apply this methodology for two types of participants: risk averse and risk seeker.

This paper introduces a method for forecasting energy prices using artificial intelligence methods, such as neural networks and fuzzy logic, and a combination of the two. The new approach is compared with some of the exiting methods. Various factors affecting the market clearing price are investigated. Results for the Ontario electricity market are presented.

This paper introduces a method for forecasting energy prices using artificial intelligence methods such as neural networks and fuzzy logic and a combination of the two. The forecasted price is then used to design an optimal bidding strategy for a generator according to his/her degree of risk aversion. A typical thermal plant is assumed to be located in the Ontario electricity system to apply this methodology for two types of participants: risk averse and risk seeker. Results for the Ontario electricity market are presented.

A large-scale implementation of distributed generation (DG) in the power system can cause a gradual transition from the current 'vertically-operated power system', which is supported mainly by several huge centralized generators, into a future 'horizontally-operated power system', having also a large number of small to medium-size distributed (renewable) generators. In this paper the transient stability of a power system that undergoes such a ' vertical-to-horizontal' transformation is studied on a real time digital simulator (RTDS). A 9-bus power system with 3 centralized generators is used as a test system. Scenarios to simulate the 'vertical-to-horizontal' transformation of the test system are developed by shutting down centralized generators in the test system and by replacing them with DG units implemented in the load buses. The DG units are implemented as converter-connected units, synchronous machines, or a combination of those. To study the transient stability in each scenario, 3-phase temporary faults are applied in order to determine the critical clearing time (CCT)