Citations

PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.

Abstract Background While immune checkpoint inhibitors (ICIs) provide durable clinical benefit in a subset of patients, current biomarkers to predict response lack accuracy. Ex vivo cytokine profiling has shown promise for improved accuracy but has been mostly limited to ICIs targeting PD-1 [Voabil et al, 2021]. This poses the question of whether ICIs beyond αPD-1 – such as CTLA4 blockade, which has been reported to act within the draining lymph node – would be amenable to similar approaches. The Elephas platform characterizes response to ICIs in live tumor fragments (LTFs) from core needle biopsies (CNBs) and resections using longitudinal cytokine profiling. Using a panel of 7 clinically relevant ICI regimens, we demonstrate cytokine responses across diverse tumor types, characterize similarities and differences in cytokine response profiles across different ICIs, and explore specimen variability in responses across ICI treatments. Methods CNBs were collected through 3 observational clinical trials (NCT05478538, NCT05520099, NCT0634962) and a biobank collection study, while resections were procured from NCI CHTN. LTFs were generated using an automated cutting device and encapsulated in hydrogel. LTFs were treated with mono (αPD-1, αPD-L1, αCTLA4, αLAG-3) or combination therapy (αPD-1/αCTLA4, αPD-1/αLAG-3, αPD-L1/αCTLA4) using a sequential treatment strategy in which isotype control followed by ICI were added to the same tissue in a single well. This approach enabled the comparison of control and treatment conditions while mitigating the effects of tumor heterogeneity. Production rates for 46 cytokines were measured using a multiplex assay. Remaining T-cell reactivity was also evaluated at the end of the assay to better understand the presence of functional T cells in LTFs. Results Unsupervised hierarchical clustering of cytokine profiling data from CNB LTFs across 129 patients identified defined responder and non-responder clusters. Within the response cluster, 4 subclusters with distinct immune phenotypes were identified. While tight clustering of samples treated with the same ICI was not observed, some enrichment of samples treated with combination ICIs was observed within individual subclusters. Further, cytokine responses to αCTLA4 monotherapy were observed, suggesting that CTLA4 blockade may act beyond the draining lymph node. LTFs from resections enabled the characterization of cytokine response profiles across treatment conditions within individual specimens, including the magnitude of cytokine response and variability in cytokine response profiles. Evaluation of T-cell reactivity provided further insight into the presence of functional T-cells in LTFs and the extent of T-cell activation achieved by ICI treatment. Conclusions This study demonstrates the platform’s ability to recapitulate diverse mechanisms of immune activation ex vivo, enabling the characterization of cytokine responses to clinically relevant ICI mono or combination therapy in live tumor tissue and supporting future efforts to improve ICI response prediction beyond αPD-1. Citation Format: Pichet Adstamongkonkul, Pierre Cunin, Santanu Bhattacharya, Tanmay Kulkarni, Amreen Nasreen, Nathan Marhefke, Nina Chen, T S. Ramasubramanian, Laura Hrycyniak, Julie Zweng, Erika von Euw, Christina Vivelo, Sean Caenepeel, Debabrata Mukhopadhyay, Hinco Gierman, Hilario Ramos. Characterization of αPD1, αPD-L1, αCTLA4, and αLAG3 as mono and combination therapy in live tumor fragments using an ex vivo cytokine profiling platform [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B032.

Obesity is increasingly prevalent among living kidney donor candidates, presenting complex clinical, ethical, and logistical challenges. Although obesity is linked to increased post-donation hypertension, diabetes, proteinuria, and chronic kidney disease, the overall absolute risks are modest and may differ depending on metabolic health and patterns of fat distribution. Current reliance on body mass index alone fails to capture the full spectrum of obesity-related risks, leading to inconsistent donor selection practices and potential inequities. This review examines the pathophysiological mechanisms of obesity-related kidney injury and available evidence on comorbidities and postdonation outcomes related to obesity. We discuss tools for better risk stratification, such as imaging-based adiposity assessment and personalized weight management strategies, and note that some risks may remain after weight loss. Barriers such as rigid body mass index cutoffs, limited access to treatment, and lack of long-term follow-up exacerbate disparities in access to donation. We argue for a shift toward individualized, risk-based evaluation supported by multidisciplinary care. We underscore the importance of donor counseling and advocate for a comprehensive, rather than paternalistic approach to living kidney donor selection. Advancing safe and equitable living donation in the context of rising obesity rates will necessitate revised guidelines, improved access to treatment, and an ongoing commitment to donor well-being.

Stereotactic arrhythmia radiotherapy (STAR) is emerging as a highly effective treatment for ventricular tachycardia (VT). Growing evidence indicates that STAR favorably reprograms the electrical substrate by speeding conduction and/or prolonging repolarization via modulation of ion channel expression, although the mechanisms by which single-fraction radiation mediates durable changes in gene expression are incompletely understood. Here, we identify dynamic changes in the cardiomyocyte epigenome and transcriptome after irradiation (IR) in vivo and in vitro, including durably increased expression and chromatin accessibility of Scn5a (encodes the α subunit of the sodium channel, Na V 1.5), demonstrating a role for epigenetic memory in conduction velocity (CV) increases observed after STAR. Transcriptomic and epigenetic sequencing further identified dynamic changes in gene expression and regulatory regions involved in cellular repolarization, calcium handling, and metabolism after IR. These changes were mirrored by dose-dependent and cell-autonomous changes in repolarization, calcium flux, and mitochondrial respiration, highlighting important cellular processes that may mediate the therapeutic effects of STAR. Overall, we found that cardiomyocytes exposed to a single fraction of high-dose IR exhibited epigenetic reprogramming that mediated broad and dynamic physiologic responses.

Abstract Objective To test the effectiveness of a surgical web‐based decision aid (DA) in improving knowledge. Summary of Background Data DAs support decision making by providing information about the options. Methods A stepped wedge trial was conducted in 10 National Cancer Institute Community Oncology Research Program clinics (Alliance for Clinical Trials in Oncology). Clinics were randomized to time of transition from usual care (UC) to delivery of a web‐based DA. Patients with stage 0 through 3 breast cancer being considered for surgery were enrolled. Knowledge (primary outcome) was measured using the Breast Cancer Surgery Decision Quality Instrument and patients were asked, “How informed do you feel?” Intervention effects were tested with linear mixed‐effects models, accounting for surgeon and clinic‐level clustering, time, and enrollment after COVID. Additional models controlled for demographics. Results A total of 44% of DA arm patients reviewed the DA and 58% in UC arm reported reviewing “any information.” Being in the DA arm versus UC was not associated with knowledge. However, “review of information” was associated with higher knowledge. In addition, non‐White race and lower education were associated with lower knowledge. The DA arm was associated with higher perceptions of feeling informed (parameter estimate 1.36; 95% CI, 0.18–2.55; p = .02); this persisted even when controlling for review of information or demographics. Conclusion Improved knowledge was not demonstrate with a web‐based DA versus UC. Interestingly, the DA was associated with a higher likelihood of feeling informed. Future research will explore the discrepancy between patients feeling informed but having low knowledge, especially for disadvantaged patients. Trial Registration ClinicalTrials.gov Identifier: NCT0376600

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

Purpose: While acquired apraxia of speech (AOS) has been the focus of intervention research for decades, little information is reported about the demographic representation of study participants. This article examines the extent to which published AOS treatment studies report participants' age, sex/gender, race/ethnicity, language background, and socioeconomic status; identifies critical gaps in the literature; and considers implications for representativeness. This information supports the important call to capture these patient factors systematically and thereby advance equity in research and clinical care. Method: This study is part of a larger systematic review examining treatment outcomes for acquired AOS. A comprehensive search of databases from 1951 to April 2024 was completed to determine the proportion of treatment articles that reported demographic information related to diversity. Studies were reviewed by trained raters using a standardized data extraction protocol with a consensus protocol. Results: While participant age and sex/gender were reported in nearly all studies (99% and 100%, respectively), only 24% of studies reported on race/ethnicity, 15% provided information on participants' language background, and none reported socioeconomic status. Among studies that included race/ethnicity, 89% of the participants were White, with minimal representation of other racial/ethnic groups. Conclusions: The underreporting of race/ethnicity, language background, and socioeconomic factors limits the generalizability and ecological validity of AOS treatment research. The field must prioritize inclusive participant recruitment and consistent demographic reporting. We propose a practical template for use in both research and clinical contexts to support more thorough data collection and to inform future work in diagnosis, assessment, and intervention for AOS. Supplemental Material: https://doi.org/10.23641/asha.31172353