Safety and efficacy of pembrolizumab in combination with acalabrutinib in advanced head and neck squamous cell carcinoma: Phase 2 proof-of-concept study

PURPOSE: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton\u27s tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti-PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC. PATIENTS AND METHODS: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety and overall response rate (ORR) were co-primary objectives. The secondary objectives were progression-free survival (PFS) and overall survival. RESULTS: Seventy-six patients were evaluated (pembrolizumab, n = 39; pembrolizumab + acalabrutinib, n = 37). Higher frequencies of grade 3-4 treatment-emergent adverse events (AE; 65% vs. 39%) and serious AEs (68% vs. 31%) were observed with combination therapy versus monotherapy. ORR was 18% with monotherapy versus 14% with combination therapy. Median PFS was 2.7 [95% confidence interval (CI), 1.4-6.8] months in the combination arm and 1.7 (95% CI, 1.4-4.0) months in the monotherapy arm. The study was terminated due to lack of clinical benefit with combination treatment. To assess how tumor immune contexture was affected by therapy in patients with pre- and post-treatment biopsies, spatial proteomic analyses were conducted that revealed a trend toward increased CD45+ leukocyte infiltration of tumors from baseline at day 43 with pembrolizumab (monotherapy, n = 5; combination, n = 2), which appeared to be higher in combination-treated patients; however, definitive conclusions could not be drawn due to limited sample size. CONCLUSIONS: Despite lack of clinical efficacy, immune subset analyses suggest that there are additive effects of this combination; however, the associated toxicity limits the feasibility of combination treatment with pembrolizumab and acalabrutinib in patients with recurrent or metastatic HNSCC

American Journal of Oral Medicine and Radiology THE ROLE OF PET-CT IN THE CLINICAL MANAGEMENT OF ESOPHAGEAL CARCINOMA AND ITS LIMITATIONS

ABSTRACT In patients with oesophageal carcinoma being considered for esophagectomy, conventional staging methods include upper endoscopic gastroduodenoscopy, endoscopic ultrasonography(US), and computed tomography (CT) of the thorax and abdomen. The routine use of integrated positron emission tomography (PET)/CT with 2-[fluorine 18]fluoro-2-deoxy-d-glucose(FDG) in evaluation of patients with oesophageal carcinoma is increasing and has been reported to be useful in initial staging of oesophageal carcinoma. Methodology: This observational study retrospectively evaluated 45 consecutive patients with carcinoma esophagus which was diagnosed histologically. PET/CT is performed on an integrated scanner that combines both multisection CT and PET capabilities in two sequential gantries, avoiding the need for patient motion between the CT and PET components of the study and thereby leading to accurate coregistration of the CT and PET data. Results: In our study, 45 patients with histologically proven carcinoma esophagus were evaluated with PET-CT imaging which included 64.44% (no. 29) patients who had imaging only for staging, 31.11% (no. 14) patients for staging and response evaluation to therapy and 4.44% (no. 2) patients had treatment elsewhere and had PET-CT imaging for detection of recurrence of malignancy. Conclusion: appropriate and accurate interpretation of PET/CT results requires an appreciation of the artifacts and interpretative pitfalls that can be encountered in PET/ CT

ZOOPLANKTON DIVERSITY AND ITS RELATIONSHIP WITH PHYSICO-CHEMICAL PARAMETERS IN MANI RESERVOIR OF WESTERN GHATS, REGION, HOSANAGAR TALUK, SHIVAMOGA DISTRICT KARNATAKA, INDIA

Studies on relationship between zooplankton abundance and water quality parameter in Mani reservoir were made between January 2008 and December 2008. In the current investigation, impact of different physico-chemical parameters on zooplankton population was found. Ten genera of zooplankton were identified. The relationship between zooplankton and water quality parameters was varied from place to place depending upon the condition of the reservoir water

ZOOPLANKTON DIVERSITY AND ITS RELATIONSHIP WITH PHYSICO-CHEMICAL PARAMETERS IN MANI RESERVOIR OF WESTERN GHATS, INDIA

Studies on relationship between zooplankton abundance and water quality parameter in Mani reservoir were made between January 2008 and December 2008.in the urrent investigation, impact of different physico-chemical parameters on zooplankton population was found. Ten genera of zooplankton were identified. The relationship between zooplankton and water quality parameters was varied from place to place depending upon the condition of the reservoir water

Novel fluorescent protein from Hydnophora rigida possess cyano emission

10.1016/j.bbrc.2010.04.136Biochemical and Biophysical Research Communications3963631-636BBRC

An Improved Efficiency of Solar Photo Voltaic System Applications by Using DC-DC Zeta Converter

This study investigates on how a DC-DC Zeta converter act as intermediate among SPV and VSI, in which it drags the maximum power from the solar photo voltaic (SPV) system and to drive a BLDC motor connected to a water pumping system application. Here INC-MPPT (Incremental Conductance Maximum Power Point Tracking) method is utilized smartly to control the zeta converter in order to drive brushless DC (BLDC) motor smoothly. Soft starting current prevents the influence of peak starting current on the BLDC motor windings. The fundamental frequency of Electronic computational from the BLDC motor is used to avoid the voltage source inverter losses. The proposed converter is also suitable to increase the voltage of DC link connected to the VSI. The major benefit of this configuration is designed and modelled in such a way that even under dynamic conditions, the performance of a solar photovoltaic application is not affected. The suggested system is developed by using MATLAB/Simulink softwar

Speed regulation enhancement for SRM drive in PHEV applications by using hybrid fuzzy logic controller

Speed regulation enhancement of a Switched Reluctance Motor (SRM) Driveby using modularfront-endintegrated multilevel converter for plug-in hybrid electric vehicle (PHEV) applications are studied and evaluated in this paper. Theoperating modes of the system are basing on Turn-On &Turn OFF of the switches in the converter circuit. In order to achievefast demagnetization and excitation, during generator driving mode, the battery bank is used to elevate the phase voltage. To get the multiple voltage responses and torque increment, an additional charging capacitor and a reframed four-level structure from the converter during battery driving mode is required. A hybrid Fuzzy Logic Controlleris proposedin orderto control the speed of the SRM motor. This paper mainly focuses on the comparison of the hybrid fuzzy logic controller with conventional P & PI and to prove the proposed controller provides the best performance and high robustness compared to a conventional P & PI controller. Matlab / Simulink is used to simulate

Performance analysis of distributed power flow controller with ultracapacitor for regulating the frequency deviations in restructured power system

This paper presents a novel approach for automatic generation control (AGC) of two-area deregulated system with unequal sources for sustaining the frequency and tie-line power at perturbations. The combination of ultracapacitor (UC) and various FACTS controllers such as Thyristor-controlled series capacitor (TCSC), Static synchronous series compensator (SSSC), Unified power flow controller (UPFC), and Distributed power flow controller (DPFC) have been investigated in AGC of interconnected system with thermal-wind and hydro-diesel generating units. An innovative metaheuristic method called bat algorithm (BA) is used to ascertain the optimal gain parameters of the two degree of freedom (2DOF) controllers using an integral squared error (ISE) criteria. Furthermore, the productive assessment of the bat tuned 2DOF controllers are also compared with teaching learning-based optimization (TLBO) and cuckoo search (CS) methods optimized 2DOF in distinct contract scenarios of the suggested restructured system. The effect of the coordinated performance of UC and DPFC has been mitigated the oscillatory response of the AGC system at various operating circumstances. The investigations disclose that the bat optimized 2DOF-PID yield the productive outcomes with coordination of DPFC and UC in all contract transactions of the restructured system