Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis.

Background: Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ≥2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma.

Methods: Patients with previously treated advanced/metastatic urothelial carcinoma, pooled from two cohorts of the phase Ib JAVELIN Solid Tumor trial, received avelumab 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity or withdrawal.

miR-19a/b and miR-20a Promote Wound Healing by Regulating the Inflammatory Response of Keratinocytes.

Persistent and impaired inflammation impedes tissue healing and is a characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. In this study, we show that in human wound-edge keratinocytes, the expressions of microRNA (miR)-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, are upregulated during wound repair.

The effect of ultraviolet C radiation against different N95 respirators inoculated with SARS-CoV-2.

Objectives: There are currently no studies that have examined whether one dosage can be uniformly applied to different respirator types to effectively decontaminate SARS-CoV-2 on N95 filtering facepiece respirators (FFRs). Health care workers have been using this disinfection method during the pandemic. Our objective was to determine the effect of UVC on SARS-CoV-2 inoculated N95 respirators and whether this was respirator material/model type dependent.

Executive Summary of the American Radium Society Appropriate Use Criteria for Operable Esophageal and Gastroesophageal Junction Adenocarcinoma: Systematic Review and Guidelines.

Purpose: Limited guidance exists regarding the relative effectiveness of treatment options for nonmetastatic, operable patients with adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). In this systematic review, the American Radium Society (ARS) gastrointestinal expert panel convened to develop Appropriate Use Criteria (AUC) evaluating how neoadjuvant and/or adjuvant treatment regimens compared with each other, surgery alone, or definitive chemoradiation in terms of response to therapy, quality of life, and oncologic outcomes.

Methods And Materials: Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was used to develop an extensive analysis of peer-reviewed phase 2R and phase 3 randomized controlled trials as well as meta-analyses found within the Ovid Medline, Cochrane Central, and Embase databases between 2009 to 2019.

Impact of a SBRT/SRS longitudinal telehealth training pilot course in Latin America.

Purpose: To assess the impact of longitudinal telehealth training in stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) for clinicians in Latin America.

Materials And Methods: Professionals from two Peruvian centers received an initial SBRT/SRS on-site training course and subsequently received follow-up telehealth training (interventional group) or not (negative control arm). Twelve live video conference sessions were scheduled.

Epidermal resident γδ T cell development and function in skin.

Epidermal resident γδ T cells, or dendritic epidermal T cells (DETCs) in mice, are a unique and conserved population of γδ T cells enriched in the epidermis, where they serve as the regulators of immune responses and sense skin injury. Despite the great advances in the understanding of the development, homeostasis, and function of DETCs in the past decades, the origin and the underlying molecular mechanisms remain elusive. Here, we reviewed the recent research progress on DETCs, including their origin and homeostasis in the skin, especially at transcriptional and epigenetic levels, and discuss the involvement of DETCs in skin diseases.

Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis.

Alveolar macrophages (AMs) derived from embryonic precursors seed the lung before birth and self-maintain locally throughout adulthood, but are regenerated by bone marrow (BM) under stress conditions. However, the regulation of AM development and maintenance remains poorly understood. Here, we show that histone deacetylase 3 (HDAC3) is a key epigenetic factor required for AM embryonic development, postnatal homeostasis, maturation, and regeneration from BM.

Peyronie disease: a clinicopathologic study of 71 cases with emphasis on histopathologic patterns and prevalent metaplastic ossification.

Peyronie disease (PD) is a benign, superficial fibromatosis involving the fascial structures of the penis, causing deformity, pain, and loss of function, for which there are few contemporary studies of the histopathology. We performed a multi-institutional review of 74 routine and consultation specimens submitted with clinical concern for PD. Of these, three non-PD lesions were identified and excluded (a myointimoma, a mammary-type myofibroblastoma, and fibrocalcific atherosclerosis).

Optimal Donor for African Americans with Hematologic Malignancy: HLA-Haploidentical Relative or Umbilical Cord Blood Transplant.

Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with hematologic malignancy between 2008 and 2016.

Gene fusion characterisation of rare aggressive prostate cancer variants-adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma: an analysis of 19 cases.

Aims: To evaluate the molecular underpinnings of the rare aggressive prostate cancer variants adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma.

Methods And Results: We retrieved 19 tumours with one or more variant(s), and performed ERG immunohistochemistry, a next-generation sequencing assay targeting recurrent gene fusions, and fluorescence in-situ hybridisation (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid carcinoma (n = 10), adenosquamous carcinoma (n = 7), and pleomorphic giant-cell carcinoma (n = 7).

Characteristics of Participation in Patient-Reported Outcomes and Electronic Data Capture Components of NRG Oncology Clinical Trials.

Purpose: To assess the reasons why patients do not consent to patient-reported outcome (PRO) and electronic PRO data capture components of clinical trials and potential selection bias by having a separate consent.

Methods And Materials: Selected NRG Oncology trials were included based on disease site and inclusion of PROs and electronic PRO data capture via VisionTree Optimal Care as separate consent questions. Reasons for not participating were assessed.

Molecular therapeutic targets in non-small cell lung cancer.

Introduction: Several targetable genetic alterations have been identified in non-small cell lung cancers (NSCLC) and drugs targeting these alterations have been approved for the management of advanced NSCLC patients. Driver mutations with emerging clinical trial data include exon 20 insertion mutations, amplification, point mutations, rearrangements, amplification and mutations, and amplification and translocations.

Areas Covered: We reviewed English-language articles indexed in Medline and PubMed up to the 1 of June 2020.

Single-Cell RNA-Seq Analysis Uncovers Distinct Functional Human NKT Cell Sub-Populations in Peripheral Blood.

Vα24-invariant human natural killer T (NKT) cells comprise a unique subset of CD1d-restricted T cells with potent immune regulatory function and are involved in the development of a variety of human diseases. However, the lack of comprehensive molecular subset identities limits their objective classification and clinical application. Using unbiased single-cell RNA sequencing (scRNA-seq) of over 4000 unstimulated and 7000 stimulated human peripheral blood NKT cells, we identified four and five clusters of NKT cells from each NKT group, respectively.

Executive summary of the American Radium Society® Appropriate Use Criteria for management of uterine carcinosarcoma.

Objective: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed.

Methods: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS.

Smad2/4 Signaling Pathway Is Critical for Epidermal Langerhans Cell Repopulation Under Inflammatory Condition but Not Required for Their Homeostasis at Steady State.

Epidermal Langerhans cells (LCs) are skin-resident dendritic cells that are essential for the induction of skin immunity and tolerance. Transforming growth factor-β 1 (TGFβ1) is a crucial factor for LC maintenance and function. However, the underlying TGFβ1 signaling pathways remain unclear.

The State of the Science in Patient-Reported Outcomes for Patients with Lung Cancer.

Traditionally, clinicians have assumed the primary responsibility for evaluating disease- and treatment-related outcomes. In the past few decades, however, a series of recommendations and standards promulgated by professional societies and regulatory agencies have resulted in increased use of patient-reported outcome (PRO) measures in cancer clinical trials. PROs, such as quality of life (QOL) measures, are important in establishing overall treatment effectiveness in cancer clinical trials, and they can inform clinical decision making.

Rapid multicontrast brain imaging on a 0.35T MR-linac.

Purpose: Magnetic resonance-guided radiation therapy (MRgRT) has shown great promise for localization and real-time tumor monitoring. However, to date, quantitative imaging has been limited for low field MRgRT. This work benchmarks quantitative T1, R2*, and Proton Density (PD)mapping in a phantom on a 0.

Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an ,,-Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product.

We describe the synthesis of 10-aza-9-oxakalkitoxin, an ,,-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC 2.4 ng mL) comparable to that of kalkitoxin itself (IC 3.

Charlson Comorbidity score influence on prostate cancer survival and radiation-related toxicity.

Introduction: In addition to survival endpoints, we explored the impact of Charlson Comorbidity-Index (CCI) on the acute and late toxicities in men with localized prostate cancer who received dose-escalated definitive radiotherapy (RT).

Materials And Methods: CCI scores at diagnosis and survival outcomes were identified for men with intermediate/high-risk prostate cancer treated with RT (1/2007-12/2012). Study-cohort was accordingly grouped into no, mild and severe comorbidity (CCI-0, 1 or 2+).

Pharmacological and genetic targeting of 5-lipoxygenase interrupts c-Myc oncogenic signaling and kills enzalutamide-resistant prostate cancer cells via apoptosis.

Much of the morbidity and mortality due to prostate cancer happen because of castration-resistant prostate cancer (CRPC) which invariably develops after anti-androgenic therapy. FDA-approved enzalutamide is commonly prescribed for CRPC which works by blocking androgen receptor function. However, even after initial good response, enzalutamide-resistant prostate cancer (ERPC) develops which eventually leads to widespread metastasis.

Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer.

Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others.

Heterogeneity at the invasion front of triple negative breast cancer cells.

Identifying better predictive and prognostic biomarkers for the diagnosis and treatment of triple negative breast cancer (TNBC) is complicated by tumor heterogeneity ranging from responses to therapy, mutational burden, and clonal evolution. To overcome the gap in our understanding of tumor heterogeneity, we hypothesized that isolating and studying the gene expression profile of invasive tumor cell subpopulations would be a crucial step towards achieving this goal. In this report, we utilized a fluidic device previously reported to be capable of supporting long-term three-dimensional growth and invasion dynamics of cancer cells.

The Efficacy of Surgical Excision Plus Adjuvant Multimodal Therapies in the Treatment of Keloids: A Systematic Review and Meta-Analysis.

Background: Research evaluating the efficacy of multimodal therapy for the treatment of keloids has reported combination regimens are most effective.

Objective: To compare recurrence rates for keloids treated with surgery plus one adjuvant intervention (dual therapy) versus surgery plus 2 or more adjuvant interventions (triple therapy).

Materials And Methods: Systematic literature review and meta-analysis of combination treatment for keloids.