Multidimensional Healthcare Access Barriers to Prostate-Specific Antigen Testing: A Nation-Wide Panel Study in the United States From 2006 to 2020.

Background: Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors.

IFNγ Is Critical for CAR T Cell-Mediated Myeloid Activation and Induction of Endogenous Immunity.

Chimeric antigen receptor (CAR) T cells mediate potent antigen-specific antitumor activity; however, their indirect effects on the endogenous immune system are not well characterized. Remarkably, we demonstrate that CAR T-cell treatment of mouse syngeneic glioblastoma (GBM) activates intratumoral myeloid cells and induces endogenous T-cell memory responses coupled with feed-forward propagation of CAR T-cell responses. IFNγ production by CAR T cells and IFNγ responsiveness of host immune cells are critical for tumor immune landscape remodeling to promote a more activated and less suppressive tumor microenvironment.

Occult Colonic Perforation in a Patient With Coronavirus Disease 2019 After Interleukin-6 Receptor Antagonist Therapy.

Background: Interleukin-6 blockade (IL-6) has become a focus of therapeutic investigation for the coronavirus disease 2019 (COVID-19).

Methods: We report a case of a 34-year-old with COVID-19 pneumonia receiving an IL-6 receptor antagonist (IL-6Ra) who developed spontaneous colonic perforation. This perforation occurred despite a benign abdominal exam and in the absence of other known risk factors associated with colonic perforation.

Extended 5-Year Follow-up Results of a Phase Ib Study (BRIM7) of Vemurafenib and Cobimetinib in -Mutant Melanoma.

Purpose: To report the 5-year overall survival (OS) landmark and the long-term safety profile of vemurafenib plus cobimetinib (BRAF plus MEK inhibition, respectively) in the BRIM7 study.

Patients And Methods: This phase Ib, dose-finding, and expansion study evaluated combination treatment with vemurafenib and cobimetinib in two cohorts of patients with advanced -mutated melanoma: patients who were BRAF inhibitor (BRAFi)-naïve ( = 63) or patients who had progressed on prior treatment with BRAFi monotherapy [vemurafenib monotherapy-progressive disease (PD); = 66]. Patients in the dose-escalation phase received vemurafenib at 720 or 960 mg twice daily in combination with cobimetinib at 60, 80, or 100 mg/d for 14 days on/14 days off, 21 days on/7 days off, or continuously.

Elevated Levels of Mutant Circulating Tumor DNA and Circulating Hepatocyte Growth Factor Are Associated With Poor Prognosis in Patients With Metastatic Melanoma.

Purpose: We performed a retrospective exploratory analysis to evaluate the prognostic and predictive effect of two circulating biomarkers, mutant circulating tumor DNA (ctDNA) and circulating hepatocyte growth factor (cHGF), in metastatic melanoma.

Materials And Methods: This study evaluated patients from BRIM-3, a phase III trial comparing vemurafenib and dacarbazine in 675 patients with mutated advanced melanoma. ctDNA was measured using droplet digital polymerase chain reaction, and cHGF was measured by enzyme-linked immunosorbent assay.

Modeled Prognostic Subgroups for Survival and Treatment Outcomes in BRAF V600-Mutated Metastatic Melanoma: Pooled Analysis of 4 Randomized Clinical Trials.

Importance: Prognostic models may provide insight into clinical trial results and inform the clinical management of patients with BRAF V600-mutated metastatic melanoma.

Objective: To identify subgroups with distinct survival outcomes based on clinical and genomic characteristics and to assess survival in identified prognostic subgroups across cohorts treated with dacarbazine, vemurafenib, or cobimetinib plus vemurafenib.

Design, Setting, And Participants: This retrospective and exploratory recursive partitioning analysis (RPA) modeled associations between prespecified covariates and survival outcomes using pooled data from the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies.

Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.

BRAF mutations are found in ~50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAF-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported.

Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial.

Background: The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF(V600)-mutant advanced melanoma, as previously reported in the coBRIM study. In this Article, we report updated efficacy results, including overall survival and safety after longer follow-up, and selected biomarker correlative studies.

Methods: In this double-blind, randomised, placebo-controlled, multicentre study, adult patients (aged ≥18 years) with histologically confirmed BRAF(V600) mutation-positive unresectable stage IIIC or stage IV melanoma were randomly assigned (1:1) using an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily).

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Osteo-/odontogenic differentiation of induced mesenchymal stem cells generated through epithelial-mesenchyme transition of cultured human keratinocytes.

Introduction: Revascularization of necrotic pulp has been successful in the resolution of periradicular inflammation; yet, several case studies suggest the need for cell-based therapies using mesenchymal stem cells (MSCs) as an alternative for de novo pulp regeneration. Because the availability of MSCs may be limited, especially in an aged population, the current study reports an alternative approach in generating MSCs from epidermal keratinocytes through a process called epithelial-mesenchymal transition (EMT).

Methods: We induced EMT in primary normal human epidermal keratinocytes (NHEKs) by transient transfection of small interfering RNA targeting the p63 gene.

Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study.

Background: Addition of a MEK inhibitor to a BRAF inhibitor enhances tumour growth inhibition, delays acquired resistance, and abrogates paradoxical activation of the MAPK pathway in preclinical models of BRAF-mutated melanoma. We assessed the safety and efficacy of combined BRAF inhibition with vemurafenib and MEK inhibition with cobimetinib in patients with advanced BRAF-mutated melanoma.

Methods: We undertook a phase 1b study in patients with advanced BRAF(V600)-mutated melanoma.

Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study.

Background: In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600) mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF(V600E) and BRAF(V600K) mutation subgroups.

Methods: Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF(V600) mutations were eligible.

Quality of care and cancer survivorship: the challenge of implementing the institute of medicine recommendations.

As the population ages, maintaining the quality of care for new patients with cancer will be challenged by an anticipated shortage of health professionals to care for the increased number of newly diagnosed and surviving patients with cancer.

Outcomes from the Moving Beyond Cancer psychoeducational, randomized, controlled trial with breast cancer patients.

Purpose: Evidence suggests that the re-entry phase (ie, early period after medical treatment completion) presents distinct challenges for cancer patients. To facilitate the transition to recovery, we conducted the Moving Beyond Cancer (MBC) trial, a multisite, randomized, controlled trial of psychoeducational interventions for breast cancer patients.

Methods: Breast cancer patients were registered within 6 weeks after surgery.

Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life.

This article reviews the symptoms and everyday problems associated with tamoxifen adjuvant therapy and their impact on patients' quality of life. In addition, the purported toxic effects of tamoxifen therapy (e.g.