Key Regulatory Elements of the TGFβ-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across Cancer Types.

Transforming growth factor-beta (TGFβ) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGFβ have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen expressed by mesenchymal-derived cancer cells and cancer-associated fibroblasts (CAFs).

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT.

Body composition as a determinant of the therapeutic index with androgen signaling inhibition.

Background: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI.

Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis.

Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9).

Monostotic Scapular Caffey Disease: A Case Report With MRI Correlate.

Caffey disease, also referred to as infantile cortical hyperostosis, is a self-limiting inflammatory disease of bone, typically diagnosed in infancy (ages less than five months). This disease is characterized by asymmetric, often polyostotic bony hyperostosis and expansion, with a predilection for the mandible (70-90%). We present a unique case of a two-month-old boy with monostotic scapular hyperostosis.

Development of a Strategic Initiative at MD Anderson Cancer Center to Improve Outcomes in Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for many cancer types. The clinical use of ICIs is increasing rapidly, including in combinations associated with increased risk of toxicities, termed "immune-related adverse events" (irAEs). Therefore, MD Anderson Cancer Center (MDACC) in Houston, Texas has proactively responded by developing a priority endeavor known as the Immuno-Oncology Toxicity (IOTOX) initiative.

Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments.

(AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of , , and (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed.

Impact of Selective Immunosuppressive Therapy on Subsequent Immune-Related Adverse Events After Immune Checkpoint Inhibitor-Induced Colitis Treatment.

Objectives: Immune checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs) such as colitis. irAEs can be managed by selective immunosuppressive therapy (SIT) agents such as infliximab and vedolizumab. We aimed to elucidate the incidence of subsequent new irAEs after exposure to SIT by describing patients' clinical course.

Immune checkpoint therapy-current perspectives and future directions.

Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries.

Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers.

Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients.

Use of behavioural change taxonomies in systematic reviews and meta-analyses regarding obesity management.

We investigated the prevalence of behavioural change taxonomies in systematic reviews and meta-analyses related to obesity management. In addition, we analysed the funding sources, author conflicts of interest statements, risk of bias, and favorability of the results in such studies to determine if there was a relationship between methodological quality and taxonomy use. We searched several databases including MEDLINE, Epistemonikos, Cochrane EDSR, Pubmed and Embase for systematic reviews and meta-analyses regarding the behavioural treatment of obesity.

Characteristics and outcomes of cancer patients with pre-existing microscopic colitis after exposure to PD-1 and PD-L1 inhibitors.

Purpose: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment.

Methods: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries.

Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers.

Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients.

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer.

The addition of atezolizumab (anti-PD-L1) to enzalutamide (androgen receptor antagonist) did not prolong survival in metastatic prostate cancer. Efficacy with immunotherapies in prostate cancer will require additional studies to elucidate and target mechanisms of resistance within the prostate tumor microenvironment.

A composite T cell biomarker in pre-treatment blood samples correlates with detection of immune-related adverse events.

Finding biomarkers for predicting anti-tumor responses and immune-related adverse events (irAEs) with immune checkpoint therapy remains a challenge. Lozano et al. have developed a composite biomarker score that includes the frequency of effector-memory CD4 T cells and TCR clonality of CD4 T cells in peripheral blood as a potentially predictive biomarker of irAEs.

Analysis of Systematic Reviews in Clinical Practice Guidelines for Head and Neck Cancer.

Objective: Clinical practice guidelines (CPGs) are essential to clinical decision-making as their recommendations are supported by published literature. Systematic reviews are considered the highest quality of evidence used to underpin these guidelines. However, research to support these recommendations may lack compliance to quality reporting among systematic reviews (SRs).