Developing a Bayesian workshop for full-time staff statisticians.

Introduction: There are two main schools of thought about statistical inference: frequentist and Bayesian. The frequentist approach relies solely on available data for predictions, while the Bayesian approach incorporates both data and prior knowledge about the event of interest. Bayesian methods were developed hundreds of years ago; however, they were rarely used due to computational challenges and conflicts between the two schools of thought.

Durvalumab and guadecitabine in advanced clear cell renal cell carcinoma: results from the phase Ib/II study BTCRC-GU16-043.

Epigenetic modulation is well established in hematologic malignancies but to a lesser degree in solid tumors. Here we report the results of a phase Ib/II study of guadecitabine and durvalumab in advanced clear cell renal cell carcinoma (ccRCC; NCT03308396). Patients received guadecitabine (starting at 60 mg/m subcutaneously on days 1-5 with de-escalation to 45 mg/m2 in case of dose limiting toxicity) with durvalumab (1500 mg intravenously on day 8).

SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas.

Background: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN , a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD.

Comprehensive T cell repertoire characterization of non-small cell lung cancer.

Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients.

Quantile Graphical Models: Bayesian Approaches.

Graphical models are ubiquitous tools to describe the interdependence between variables measured simultaneously such as large-scale gene or protein expression data. Gaussian graphical models (GGMs) are well-established tools for probabilistic exploration of dependence structures using precision matrices and they are generated under a multivariate normal joint distribution. However, they suffer from several shortcomings since they are based on Gaussian distribution assumptions.

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis.

Multiple myeloma is, in most patients, an incurable cancer. Its precursors can be identified with routine tests setting the stage for early intervention to prevent active myeloma. We investigated the efficacy and safety of pembrolizumab, an antiprogrammed cell death 1 antibody, in smoldering myeloma patients with intermediate/high risk of progression to symptomatic myeloma.

Guiding the first biopsy in glioma patients using estimated Ki-67 maps derived from MRI: conventional versus advanced imaging.

Background: Undersampling of gliomas at first biopsy is a major clinical problem, as accurate grading determines all subsequent treatment. We submit a technological solution to reduce the problem of undersampling by estimating a marker of tumor proliferation (Ki-67) using MR imaging data as inputs, against a stereotactic histopathology gold standard.

Methods: MR imaging was performed with anatomic, diffusion, permeability, and perfusion sequences, in untreated glioma patients in a prospective clinical trial.

Concomitant targeting of the mTOR/MAPK pathways: novel therapeutic strategy in subsets of -altered non-small cell lung cancer.

Despite a therapeutic paradigm shift into targeted-driven medicinal approaches, resistance to therapy remains a hallmark of lung cancer, driven by biological and molecular diversity. Using genomic and expression data from advanced non-small cell lung cancer (NSCLC) patients enrolled in the BATTLE-2 clinical trial, we identified alterations in a subset of lung adenocarcinomas and found expression to carry worse overall survival. RICTOR-altered cohort was significantly enriched in axis mutations, suggesting a co-oncogenic driver role in these molecular settings.

Hepatocellular Carcinoma Tumor Dose Response After Y-radioembolization With Glass Microspheres Using Y-SPECT/CT-Based Voxel Dosimetry.

Purpose: To investigate hepatocellular carcinoma tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative Y-single-photon emission computed tomography (SPECT)/computed tomography (CT) after Y-radioembilization with glass microspheres. We also investigated the relationship between normal liver D and toxicities.

Methods And Materials: Y-radioembolization activity distributions for 34 patients were based on quantitative Y-bremsstrahlung SPECT/CT.

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

Purpose: Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.

TUSC2 Immunogene Therapy Synergizes with Anti-PD-1 through Enhanced Proliferation and Infiltration of Natural Killer Cells in Syngeneic -Mutant Mouse Lung Cancer Models.

Expression of the multikinase inhibitor encoded by the tumor suppressor gene (also known as ) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two -mutant syngeneic mouse lung cancer models.

Integrating Clinical and Multiple Omics Data for Prognostic Assessment across Human Cancers.

Multiple omic profiles have been generated for many cancer types; however, comprehensive assessment of their prognostic values across cancers is limited. We conducted a pan-cancer prognostic assessment and presented a multi-omic kernel machine learning method to systematically quantify the prognostic values of high-throughput genomic, epigenomic, and transcriptomic profiles individually, integratively, and in combination with clinical factors for 3,382 samples across 14 cancer types. We found that the prognostic performance varied substantially across cancer types.

Subspecies Influences Proinflammatory Cytokine Expression and Monocyte Activation in Human Colorectal Tumors.

Chronic infection and associated inflammation have long been suspected to promote human carcinogenesis. Recently, certain gut bacteria, including some in the genus, have been implicated in playing a role in human colorectal cancer development. However, the species and subspecies involved and their oncogenic mechanisms remain to be determined.

Selective Internal Radiation Therapy With Yttrium-90 Glass Microspheres: Biases and Uncertainties in Absorbed Dose Calculations Between Clinical Dosimetry Models.

Purpose: To quantify differences that exist between dosimetry models used for Y selective internal radiation therapy (SIRT).

Methods And Materials: Retrospectively, 37 tumors were delineated on 19 post-therapy quantitative Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC).

Novel algorithmic approach predicts tumor mutation load and correlates with immunotherapy clinical outcomes using a defined gene mutation set.

Background: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements.

Methods: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts.

PCAN: Probabilistic correlation analysis of two non-normal data sets.

Most cancer research now involves one or more assays profiling various biological molecules, e.g., messenger RNA and micro RNA, in samples collected on the same individuals.

CDK5 Regulates Paclitaxel Sensitivity in Ovarian Cancer Cells by Modulating AKT Activation, p21Cip1- and p27Kip1-Mediated G1 Cell Cycle Arrest and Apoptosis.

Cyclin-dependent kinase 5 (CDK5) is a cytoplasmic serine/ threonine kinase. Knockdown of CDK5 enhances paclitaxel sensitivity in human ovarian cancer cells. This study explores the mechanisms by which CDK5 regulates paclitaxel sensitivity in human ovarian cancers.

Differentiation of low-attenuation intracranial hemorrhage and calcification using dual-energy computed tomography in a phantom system.

Objectives: Calcific and hemorrhagic intracranial lesions with attenuation levels of less than 100 Hounsfield units (HUs) cannot currently be reliably differentiated by single-energy computed tomography (SECT). The proper differentiation of these lesion types would have a multitude of clinical applications. A phantom model was used to test the ability of dual-energy CT (DECT) to differentiate such lesions.

Characteristics and outcomes of patients with multiple myeloma who develop therapy-related myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Background: Patients with multiple myeloma (MM) have had significant improvements in outcomes. An increased risk of therapy-related myeloid neoplasms (t-MNs) has also developed. Little is known about the characteristics and outcomes of these patients.

Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines.

Background: MET is a receptor tyrosine kinase that is activated by the ligand HGF and this pathway promotes cell survival, migration, and motility. In accordance with its oncogenic role, MET is constitutively active, mutated, or over-expressed in many cancers. Corollary to its impact, inhibition of MET kinase activity causes reduction of the downstream signaling and demise of cells.

Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity with dexamethasone.

NVP-BKM120 is a novel phosphatidylinositol 3-kinase (PI3K) inhibitor and is currently being investigated in phase I clinical trials in solid tumors. This study aimed to evaluate the therapeutic efficacy of BKM120 in multiple myeloma (MM). BKM120 induces cell growth inhibition and apoptosis in both MM cell lines and freshly isolated primary MM cells.

Contrast sensitivity of digital imaging display systems: contrast threshold dependency on object type and implications for monitor quality assurance and quality control in PACS.

The American Association of Physicists in Medicine Task Group 18 has published standards and quality control (QC) guidelines to ensure consistency and optimal quality for digital image display systems (DIDSs). In many of these recommended QC tests, static test patterns that contain low-contrast objects are often used to assess and validate the quality of a DIDS. These low-contrast objects often have the shape of circular disks or squares with sharp edges, neither of which resemble most of the diagnostic findings in medical images.

Targeting cell signaling pathways for drug discovery: an old lock needs a new key.

In this age of targeted therapy, the failure of most current drug-discovery efforts to yield safe, effective, and inexpensive drugs has generated widespread concern. Successful drug development has been stymied by a general focus on target selection rather than clinical safety and efficacy. The very process of validating the targets themselves is inefficient and in many cases leads to drugs having poor efficacy and undesirable side effects.