60 Use of the Combined Positive Score (CPS) with the companion diagnostic PD-L1 IHC 22C3 pharmDx provides precise evaluation of PD-L1 expression across multiple tumor indications and cutoffs

BackgroundThe Combined Positive Score (CPS)1 algorithm includes tumor and immune cells for determination of Programed Death-Ligand 1 (PD-L1) protein expression in tumor tissues and has been analytically and clinically validated for use with PD-L1 IHC 22C3 pharmDx across multiple indications and cutoffs.2 PD-L1 22C3 IHC pharmDx is a qualitative immunohistochemical assay using anti-PD-L1, Clone 22C3 to detect PD-L1 in formalin-fixed, paraffin-embedded (FFPE) tumor tissues using Autostainer Link 48. PD-L1 IHC 22C3 pharmDx is FDA-approved as an aid in identifying patients for treatment with KEYTRUDA® for six tumor indications at clinically validated CPS diagnostic cutoffs2: gastric or gastroesophageal junction (GC/GEJ) adenocarcinoma (CPS ≥ 1), cervical cancer (CPS ≥ 1), urothelial carcinoma (CPS ≥ 10), head and neck squamous cell carcinoma (HNSCC) (CPS ≥ 1), esophageal squamous cell carcinoma (ESCC) (CPS ≥ 10)3, and triple-negative breast cancer (TNBC) (CPS ≥ 10).MethodsPrecision of PD-L1 IHC 22C3 pharmDx using CPS was assessed for all six indications at the corresponding clinically validated diagnostic cutoffs and at additional exploratory cutoffs under normal, day-to-day testing conditions. Precision testing included Combined Precision (inter-instrument/operator/run (day)), Intra-Run Repeatability, and Observer (inter-/intra-) Scoring Reproducibility studies. FFPE specimens were stained with PD-L1 IHC 22C3 pharmDx and scored using CPS as described in the package insert.2 Four CPS cutoffs were evaluated: CPS ≥ 1 (GC/GEJ, urothelial carcinoma, ESCC, cervical cancer, HNSCC, TNBC), CPS ≥ 10 (GC/GEJ, urothelial carcinoma, ESCC, TNBC), CPS ≥ 20 (HNSCC), and CPS ≥ 50 (HNSCC). Data were analyzed using negative percent agreement (NPA), positive percent agreement (PPA), and overall agreement (OA) with two-sided 95% percentile bootstrap confidence intervals (CIs) based on PD-L1 binary status at the applicable cutoff(s). For each study, data from each CPS cutoff-indication pair were individually analyzed. Meta-analyses were also performed by pooling data from all indications per (i) study and cutoff, and (ii) per study for all tested cutoffs.ResultsNearly all agreement analyses (142/144) for each CPS cutoff-indication pair showed NPA/PPA/OA point estimates (PE) ≥ 90% and CI lower bounds (CILB) ≥ 85%. Meta-analyses showed PE ≥ 90% for NPA/PPA/OA and CILB ≥ 85% per study and cutoff, and per study for all tested cutoffs. Discordant comparisons accounted for <5% of total comparisons performed for each study type.ConclusionsCPS used with PD-L1 IHC 22C3 pharmDx provides precise evaluation of PD-L1 expression across multiple tumor indications and cutoffs under normal, day-to-day testing conditions.AcknowledgementsWe thank the IUSCC Cancer Center at Indiana University School of Medicine, for the use of the Tissue Procurement and Distribution Core, which provided Dako North America, Inc. service.The data and biospecimens used in this project were provided by US Biolab (Gaithersburg, MD, USA), Sofia Bio LLC (New York, NY, USA), Contract Research Ltd (Charlestown, Nevis), and Centre Hospitalier Universitaire (CHU) de Nice (Nice, France) with appropriate ethics approval and through Trans-Hit Biomarkers Inc. Tissue samples were provided by the Cooperative Human Tissue Network which is funded by the National Cancer Institute. Other investigators may have received specimens from the same subjects. Tissue samples supplied by BioIVT (Hicksville, NY, USA).Trial RegistrationN/AReferencesCPS = (# PD-L1 staining cells (tumor cells, lymphotcytes, macrophages))/(Total # viable tumor cells )×100PD-L1 IHC 22C3 pharmDx [Instructions for Use]. Available at: www.agilent.com/library/eifu. Code SK006. Accessed July 2, 2021ESCC was analytically validated as a subtype of esophageal cancer [2].Ethics ApprovalN/AConsentN/A

Utilization of cell proliferation markers to diagnose cystic jaw pathologies

Markers of cell proliferation are widely used as diagnostic and prognostic tools. Coincident estimation of these markers increases the precise evaluation of the proliferative status of different tissues and can also be helpful in determining progression, aggressiveness and prognosis of the lesions. The current study investigated the expression of PCNA and MCM3 cell proliferation markers in 40 formalin fixed paraffin embedded tissue blocks of odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) cases using immunohistochemistry method. Markers` expression based on the intensity, percentage of positively stained cells and localization of reaction through the cyst lining epithelium was separately analyzed for each marker using Chi square test, the results of which were significant for the two markers (P < 0.05). Both markers revealed statistically significant differences between OKC and UA cases regarding markers expression intensity, positivity score and localization of reaction through the epithelium. Mural UA histologic variant was significantly different than luminal and intraluminal variants. The correlation coefficient between the two markers was found to be 0.86.

High precision evaluation of the combustion enthalpy by ab-intio computations

Accurate evaluation of combustion enthalpy is of high scientific and industrial importance. Although via ab-initio computation of heat of reactions, as one of the promising and well-established approaches in computational chemistry, this goal should in principle be achievable, examples of reliable and precise evaluation of heat of combustion by ab-initio methods has surprisingly not yet been reported. A handful of works carried out for this purpose report significant inconsistencies between the ab-initio evaluated and experimentally determined combustion enthalpies and suggest empirical corrections to improve the accuracy of predicted data. With this background, the main aims of the present study is to investigate the reasons behind those reported inconsistencies and propose guidelines for highly accurate evaluation of combustion enthalpy via ab-initio computations. Through the provided guidelines, the most accurate results ever reported, with average absolute deviation, mean unsigned error and correlation coefficient of 1.556 kJ/mole, 0.072% and 0.99999, respectively, is achieved for theoretically computed combustion enthalpies of 40 studied hydrocarbons.

An Almost Comprehensive Approach for the Choice of Motor and Transmission in Mechatronic Applications: Torque Peak of the Motor

The choice of motor and transmission to move a joint must ensure that the torque peaks of the motor lie inside its dynamic operating range. With this aim, this paper proposes an approach in which all the candidate transmissions are processed one by one to find among all the candidate motors those they could execute the reference task with. Consequently, all the transmission parameters, and not only its transmission ratio, are taken into consideration in advance. For rectangular dynamic operating ranges, this approach allows a direct and precise evaluation of all the admissible motor-transmission couples, without any approximation and further check. Apart from an entirely automated procedure, the method also provides diagrams through which the designer can concisely compare the admissible solutions. Furthermore, the method provides a solution for the drive systems in which the limit torque of the dynamic operating range does depend on the motor speed.

Contemporary possibilities in the diagnostics of anterior and posterior eye diseases with the use of new-generation OCT

Optical coherence tomography is a non-contact imaging method of the anterior and posterior segments of the eye that is based on laser scanning in spectral domain. This study presents diagnostic possibilities of the new generation Solix FullRange™ OCT&OCTA apparatus (Optovue) to examine meibomian glands, cornea, anterior chamber, as well iridocorneal angles and lens. In the posterior segment of the eye it allows for the precise evaluation of the vitreous body, choroid, retina, optic nerve and blood-flow measurements.