Survival benefit associated with first-line androgen receptor pathway inhibitors for de novo metastatic castration-sensitive prostate cancer.

Background: Limited real-world data exist on the effectiveness of treatment intensification (TI) with androgen receptor pathway inhibitors (ARPI) in de novo metastatic castration-sensitive prostate cancer (mCSPC). This study compared outcomes of TI or first-generation nonsteroidal antiandrogens (NSAAs) to androgen-deprivation therapy (ADT) alone in US patients with de novo mCSPC.

Methods: Veterans Affairs patients with de novo mCSPC (February 2018-June 2020) confirmed via chart review were grouped into ADT alone, ADT + NSAAs, or ADT + ARPI cohorts using predefined recruitment quotas.

Chemosensory Tobacco Product Toxicology Part 2: Toxicological Testing, Assays, and State of the Science.

The toxicologic impacts to normative function of the chemosensory system and loss of its contribution to organism protection and homeostasis remain an underrepresented area of interest in the published literature. The impact of chemical constituents in ENDS e-liquids or aerosol on the chemosensory system is even less known, as are the effects on product selection and use behavior-and may be an overlooked impact on the public health. This review is a snapshot of the current state of the science and opportunities for improving and increasing the volume of publications in chemosensory toxicology, on the potential impacts of tobacco products.

Circulating Tumor DNA (ctDNA) is Reliably Detected in Patients with Metastatic Malignant Phyllodes Tumors, a Feasibility Study.

Background: Malignant phyllodes tumors (MPT) are biologically aggressive breast neoplasms, with high local and distant recurrence rates and a median survival of 12 months when metastatic. With a disease-free interval often less than 2 years, circulating tumor DNA (ctDNA) may allow for earlier identification of patients with MPT at risk for recurrence. Here, we aim to determine the feasibility of detecting ctDNA in (1) patients with known, active metastatic disease and (2) patients with nonmetastatic MPT prior to surgical resection.

Genomic Evaluation of Canine Prostatic Carcinomas as a Model for the Human Disease.

Spontaneous canine prostate cancer (PC) is widely considered a pertinent clinical model for the human disease. While over 95% of PC in men are adenocarcinomas, arising from prostatic glandular epithelium, it is increasingly recognised that many canine PC are of urothelial origin, arising within the prostatic urethra or ducts, or through invasion from a primary urinary bladder tumour. At diagnosis, canine prostatic tumours are often poorly differentiated and widely disseminated, masking the primary site and limiting the sensitivity of cellular biomarkers.

Qualitative study of Black and Latino (a/e) caregiver participation on family-centered rounds.

Background: Family-centered rounds (FCR), multi-disciplinary rounds at bedside that involve the patient and family, has become the standard of care in pediatric hospitalizations. Caregiver participation on FCR improves shared-decision making and communication among providers, patients, and families. Evidence suggests Black and Latino (a/e) caregivers participate less during FCR than White caregivers, likely due to interpersonal and structural inequities, however contributing factors have not been adequately explored.

Improving lung cancer tumor-infiltrating lymphocyte (TIL) manufacturing.

Background: The successful treatment of melanoma using autologous in vitro expanded tumor infiltrating lymphocytes (TILs) has sparked clinical trials for the assessment of TIL efficacy against other cancers, including non-small cell lung cancer (NSCLC). This rise in clinical applications of TILs has increased the need for improved, more streamlined and cost-effective manufacturing protocols. The aim of this study was to simplify and reduce the cost of traditional TIL manufacturing protocols while maintaining GMP manufacturing compliance, yields, and quality of the TIL product.

Quantifying Preferences for CAR-T Compared to Standard of Care as a First-Line Treatment Among Patients With Multiple Myeloma.

Background: CAR-T therapy is approved for the treatment of relapsed refractory multiple myeloma (MM) and is being studied for newly diagnosed MM (NDMM). The use of novel therapies in early-line MM raises questions on the acceptability of upfront risks in exchange for extended relapse-free periods without the treatment burden and limitations on daily activities associated with maintenance therapy.

Methods: A discrete-choice experiment was designed to elicit adults' preferences for hypothetical NDMM treatments.

STHD: probabilistic cell typing of single spots in whole transcriptome spatial data with high definition.

Recent advances in spatial transcriptomics technologies have enabled gene expression profiling across the transcriptome in spots with subcellular resolution, but high sparsity and dimensionality present significant computational challenges. We present STHD for probabilistic cell typing of single spots in whole-transcriptome spatial transcriptomics with high definition. With a machine learning model combining count statistics with neighbor regularization, STHD accurately predicts cell type identities of subcellular spots, revealing both global tissue architecture and local multicellular neighborhoods.

Prognostic gene expression and microRNA profiling signatures and genetic alterations in primary testicular diffuse large B-cell lymphoma.

Primary testicular (PT) diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive lymphoma with distinct clinical and molecular characteristics. To identify prognostic biomarkers in PT-DLBCL, in this study we analyzed DNA and RNA samples of PT-DLBCL tumors from 206 patients using next-generation sequencing platforms and assays. Genetic alteration analysis found that multiple chromosomal copy number variations (CNVs), TP53 transcript mutations with high variant allele frequency, and MCD subtype had significantly adverse prognostic effects, whereas elevated microsatellite instability had a significantly favorable prognostic effect in PT-DLBCL.

Practice-Level Severity Case Mix and Treatment Patterns for Premenopausal Noncancerous Hysterectomy.

Hysterectomy for noncancerous conditions is a patient-preference-sensitive procedure. Therefore, gynecological practices may provide hysterectomy at varying levels of symptom severity. We assess whether practice-level severity case mix associates with segregation of patients by race and ethnicity or insurance status.

Frequency, Risk Factors, and Outcomes of Strokes in Patients With Primary Glioma After Cranial Radiation Therapy.

Background And Objectives: Radiation therapy is the mainstay of therapy for patients with glioma. While this treatment modality can improve survival, treatment-related complications may include radiation-induced vasculopathy and increased risk of stroke. We aimed to evaluate the stroke frequency, associated risk factors, and outcomes after cranial radiation therapy in patients with glioma.

Matching-adjusted indirect comparison of enzalutamide versus darolutamide doublet in mHSPC.

Aims: To compare the efficacy of enzalutamide + androgen-deprivation therapy (ADT) versus darolutamide + ADT for treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) using a matching-adjusted indirect comparison (MAIC).

Patients And Methods: Individual patient data from ARCHES (NCT02677896; enzalutamide + ADT,  = 1150) were weighted and adjusted to match published aggregated data on baseline characteristics from ARANOTE (NCT04736199; darolutamide + ADT,  = 669). The MAIC was anchored on the common comparator, placebo + ADT, and provided a (matching-adjusted) hazard ratio (HR) of enzalutamide versus darolutamide.

Efficacy of Anti-PD-(L)1 Immunotherapy in Patients with DNA Mismatch Repair-deficient Metastatic Castration-resistant Prostate Cancer.

Background And Objective: Up to 5% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbour loss-of-function alterations in mismatch repair genes (dMMR) resulting in microsatellite instability (MSI-H). Data on the efficacy of immune checkpoint inhibitors (ICIs) in dMMR mCRPC are limited, and reimbursement for these agents is not universally available.

Methods: We performed an international, multicentre, retrospective study to investigate the efficacy of anti-PD-(L)1 monotherapy in dMMR mCRPC.

Molecular characteristics by race and ethnicity of patients with high tumor mutational burden, high microsatellite instability, and mismatch repair deficiency: Real-world data from the multi-institutional Endometrial cancer Molecularly Targeted Therapy Consortium (ECMT2).

Objective: Mismatch repair deficiency (dMMR), high microsatellite instability (MSI-H), and high tumor mutation burden (TMB-H) are predictive and prognostic biomarkers in endometrial cancer. We aimed to characterize the racial/ethnic distribution of molecular markers and the clinical characteristics among endometrial cancer patients with TMB-H and MSI-H/dMMR.

Methods: The Endometrial Cancer Molecularly Targeted Therapy Consortium is a centrally verified clinical and molecular repository.

Neoadjuvant, Perioperative, and Adjuvant Immunotherapy in Early-Stage Surgically Resectable Non-Small Cell Lung Cancer: Updates and Future Perspectives.

Historically, systemic therapy for resectable non-small cell lung cancer (NSCLC) has been associated with a modest impact on overall survival. The current treatment options for early-stage resectable NSCLC include neoadjuvant, adjuvant, and perioperative immunotherapy in combination with chemotherapy. In this review, we explore the current treatment paradigms and emerging opportunities for improved survival outcomes from using immunotherapeutic approaches in the treatment of early-stage resectable NSCLC.

Expanding the workforce of clinical trial investigators committed to gynecologic cancer research: the GOG Foundation, Inc's Scholar Career Development Award and New Investigator Program.

Objective: Training and supporting early-career investigators are essential for developing a resilient and competent clinical research workforce in gynecologic oncology. To address persistent gaps in mentorship, protected time, funding, and leadership pathways, the Gynecologic Oncology Group Foundation, Inc (GOG-F) launched two-tiered development programs: the GOG-F New Investigator Program and the GOG-F Scholar Career Development Award. This 5-year evaluation reports academic, leadership, accrual, and funding outcomes.

Improvement of bullous pemphigoid following salvage radiation in PSA-recurrent prostate cancer: a potential paraneoplastic association.

This case describes a man in his 70s with a 12-year history of bullous pemphigoid (BP) and recurrent prostate cancer, both diagnosed in the same year. Initially managed with active surveillance, his prostate cancer progressed, requiring hormonal therapy, surgery, and, eventually due to recurrence, salvage radiation therapy (RT). Concurrently, his BP, characterised by blistering skin lesions, was managed with corticosteroids, azathioprine and methotrexate, though full control of disease activity was difficult.

Cancer outcomes in women without upfront surgery for ductal carcinoma in situ: observational cohort study.

Objective: To determine the risk of subsequent ipsilateral invasive breast cancer in women who do not receive upfront surgery on diagnosis of ductal carcinoma in situ (DCIS).

Design: Observational cohort study using data abstracted directly from patients' medical records and from a national cancer registry in patients with primary DCIS diagnosed between 2008 and 2015.

Setting: Commission on Cancer accredited facilities (n=1330) in the US.

RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE).

Purpose: Effective treatment options for melanoma after immune checkpoint blockade failure are limited. RP1 (vusolimogene oderparepvec) is a herpes simplex virus type 1-based oncolytic immunotherapy, here evaluated in combination with nivolumab in anti-PD-1-failed melanoma.

Methods: Patients had advanced melanoma that had confirmed progression on anti-PD-1 (≥8 weeks, last prior treatment).

Evaluating axillary lymph node metastasis risks in breast cancer patients via Semi-ALNP: a multicenter study.

Background: Accurately evaluating axillary lymph nodes (ALNs) is essential for guiding both staging and treatment strategies in breast cancer (BC) patients. Currently, traditional pathological staging methods still rely on invasive biopsies or surgeries. This study aimed to construct, evaluate, and validate a semisupervised classifier utilizing radiomic and machine learning (ML) techniques to noninvasively identify axillary nodal disease.

Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR.

Allogeneic hematopoietic cell transplantation (HCT) remains a curative therapy for many patients with hematologic malignancies, bone marrow failure syndromes, inborn errors of immunity and metabolic disorders. Current donor selection strategies typically prioritize the selection of an HLA-matched donor over HLA mismatched ("alternative") donor sources, with a hierarchical approach to the donor search. More recent data challenge this rubric, particularly in the context of novel graft-versus-host disease (GVHD) prophylaxis strategies that demonstrate improved outcomes in alternative donor HCT recipients.

QT STAR: concomitant QTc-prolonging medication use among patients with HR+/HER2- metastatic breast cancer receiving a CDK4/6 inhibitor in first line.

Background: The risk of drug-induced corrected QT interval (QTc) prolongation is an important consideration in clinical decision-making for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). This retrospective analysis described concomitant QTc-prolonging medication use in patients with HR+/HER2- mBC who received first-line (1L) treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus an aromatase inhibitor (AI).

Methods: This retrospective claims analysis utilized the Optum Clinformatics Data Mart database to identify patients with HR+/HER2- mBC who initiated 1L CDK4/6i plus AI treatment between January 2017 and March 2022.

Untrustworthiness, ineffective communication, and discrimination: The real issues behind lower utilization of labor epidural analgesia by Black Americans.

Background: Non-Hispanic Black pregnant individuals utilize up to 50% less labor epidural analgesia compared to non-Hispanic White individuals.

Purpose: This Outlook and Perspectives aims to evaluate the factors contributing to racial differences in the utilization of labor epidural analgesia.

Methods: Literature on scientific evidence regarding racial disparities in maternal outcomes and labor pain management was reviewed and summarized.

Pansarcoma Analysis of Cyclin-Dependent Kinase and Cyclin Outlier Gene Expression Highlights CDK7 as a Potential Therapeutic Target in Chordoma.

Purpose: Cyclin-dependent kinase (CDK)4/6 inhibitors are approved for the treatment of breast cancer, and they have more recently been used in patients with well-differentiated/dedifferentiated liposarcomas (WD-LPSs/DD-LPSs). However, targeting of these and other CDKs, including transcriptional CDKs, remains a promising avenue of investigation for various cancers. Therefore, we sought to characterize outlier overexpression of CDK and cyclin genes in sarcomas.