Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC.

Introduction: In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status.

Methods: In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts.

Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.

A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear.

Analysis of Physical Activity Using Wearable Health Technology in US Adults Enrolled in the All of Us Research Program: Multiyear Observational Study.

Background: To date, no studies have examined adherence to the 2018 Physical Activity Guidelines for Americans (PAGA) in real-world longitudinal settings using objectively measured activity monitoring data. This study addresses this gap by using commercial activity monitoring (Fitbit) data from the All of Us dataset.

Objective: The primary objectives were to describe the prevalence of adherence to the 2018 PAGA and identify associated sociodemographic determinants.

Weekly Cisplatin Cycles and Outcomes for Chemoradiation in Head and Neck Cancer.

Importance: National Comprehensive Cancer Network guidelines recommend weekly cisplatin as an alternative concurrent systemic therapy for definitive chemoradiation in patients with head and neck cancer. However, the impact of different levels of adherence to weekly cisplatin on outcomes stratified by human papillomavirus p16 status remains unclear.

Objective: To evaluate the association between the number of weekly cisplatin cycles and outcomes.

Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.

Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.

Methods: This was an open-label, two-part, phase II, single-arm, multicenter study.

Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma.

The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient's own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system.

Factors influencing pursuit of management roles by clinically trained pharmacists: A modified Delphi survey.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Proinflammatory Dietary Pattern and Risk of Total and Subtypes of Breast Cancer Among U.S. Women.

Background: Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been associated with certain cancers. Investigating whether this dietary pattern is associated with breast cancer-where the role of inflammation is less well-defined-could provide valuable insights and potentially improve strategies for preventing this cancer.

Methods: We prospectively followed 76,386 women from Nurses' Health Study (NHS, 1984-2018) and 92,886 women from Nurses' Health Study II (NHSII, 1991-2019).

Design Guidelines for Improving Mobile Sensing Data Collection: Prospective Mixed Methods Study.

Background: Machine learning models often use passively recorded sensor data streams as inputs to train machine learning models that predict outcomes captured through ecological momentary assessments (EMA). Despite the growth of mobile data collection, challenges in obtaining proper authorization to send notifications, receive background events, and perform background tasks persist.

Objective: We investigated challenges faced by mobile sensing apps in real-world settings in order to develop design guidelines.

Effects of a culturally tailored patient navigation program on unmet supportive care needs in Hispanic/Latino cancer survivors: A randomized controlled trial.

Background: Patient navigation (PN) is a promising yet underused approach to address Hispanic/Latino (H/L) cancer survivors' unmet supportive care needs. The authors conducted a randomized trial to evaluate the effect of a culturally tailored PN program with the LIVESTRONG Foundation's Cancer Navigation Services (PN-LCNS) on reducing unmet needs in H/L survivors.

Methods: From 2012 to 2015 at two US sites, 288 H/L survivors diagnosed with breast, prostate, or colorectal cancer were randomized to a PN-LCNS program or to standard PN.

N-substituted-4-(pyridin-4-ylalkyl)piperazine-1-carboxamides and related compounds as Leishmania CYP51 and CYP5122A1 inhibitors.

CYP5122A1, an enzyme involved in sterol biosynthesis in Leishmania, was recently characterized as a sterol C4-methyl oxidase. Screening of a library of compounds against CYP5122A1 and CYP51 from Leishmania resulted in the identification of two structurally related classes of inhibitors of these enzymes. Analogs of screening hit N-(3,5-dimethylphenyl)-4-(pyridin-4-ylmethyl)piperazine-1-carboxamide (4a) were generally strong inhibitors of CYP51 but were less potent against CYP5122A1 and typically displayed weak inhibition of L.

Laterality of Radiation Therapy in Breast Cancer is Not Associated With Increased Risk of Coronary Artery Disease in the Contemporary Era.

Purpose: External beam radiation therapy (EBRT) is a critical component of breast cancer (BC) therapy. Given the improvement in technology in the contemporary era, we hypothesized that there is no difference in the development of or worsening of existing coronary artery disease (CAD) in patients with BC receiving left versus right-sided radiation.

Methods And Materials: For the meta-analysis portion of our study, we searched PubMed, Web of Science, and Scopus and included studies from January 1999 to September 2022.

Combinatorial targeting of glutamine metabolism and lysosomal-based lipid metabolism effectively suppresses glioblastoma.

Antipsychotic drugs have been shown to have antitumor effects but have had limited potency in the clinic. Here, we unveil that pimozide inhibits lysosome hydrolytic function to suppress fatty acid and cholesterol release in glioblastoma (GBM), the most lethal brain tumor. Unexpectedly, GBM develops resistance to pimozide by boosting glutamine consumption and lipogenesis.

Radiosurgery Society Case-Based Guide to Stereotactic Body Radiation Therapy for Challenging Cases of Spinal Metastases.

Purpose: Spinal stereotactic body radiation therapy (SBRT) has become the standard of care in management of patients with limited sites of metastatic disease, radioresistant histologies, painful vertebral metastases with long life expectancy and cases of reirradiation. Our case-based guidelines aim to assist radiation oncologists in the appropriate utilization of SBRT for common, yet challenging, cases of spinal metastases.

Methods And Materials: Cases were selected to include scenarios of large volume sacral disease with nerve entrapment, medically inoperable disease abutting the thecal sac, and local failure after prior SBRT.

Menin Inhibition With Revumenib for -Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

Purpose: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with -rearranged () acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) acute leukemia.

Methods: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.