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.

Purpose: Subcortical functional brain mapping is a valuable technique, especially involving lesions within or near white matter tracts. Motor and language deficits caused by intraoperative damage to these subcortical fibers are associated with worse outcomes. However, there are variable approaches to performing subcortical functional brain mapping. This systematic review was performed to better understand indications and optimal stimulation parameters. Methods: A systematic review was performed by PRISMA guidelines, using PubMed, Scopus, and Medline databases. Search dates ranged from inception to November 30th, 2024. Studies included adults who underwent subcortical electrical stimulation for functional brain mapping. Results: A total of 55 articles (249 patients, mean age 44.8 years, 114 female) were included. The most common pathology was brain tumor (96.3%), primarily gliomas and metastases, and 24.4% of all cases had a history of epilepsy. The most frequently mapped white matter tracts were the arcuate fasciculus, corticospinal/pyramidal tract, and inferior fronto-occipital fasciculus, involving motor, language, and cognitive functions. Bipolar stimulation (50–60 Hz, 0.5–1 millisecond, 1–10 mA) was preferred over monopolar stimulation. Among 147 patients with outcome data, 89.1% did not suffer permanent adverse outcomes including neurologic deficits, although long-term outcomes were inconsistently reported. Conclusions: The methodologic variability of subcortical functional brain mapping and lack of long-term follow-up reported limits determination of optimal parameter selection for electrical stimulation although common trends are reported. Functional brain mapping approaches may be guided by the tract and network involved. Further studies are needed to develop a standardized approach and more definitive guideline to its performance.

The therapeutic landscape of hematologic malignancies has undergone a paradigm shift with the increasing incorporation of targeted therapies, including inhibitors of vascular endothelial growth factor (VEGF) signaling. While VEGF-directed agents have historically been developed and deployed in solid tumors, their application in hematologic cancers—particularly multiple myeloma, select leukemias, and rare lymphomas—has expanded in investigational and clinical settings. VEGF is fundamental to angiogenesis, maintenance of endothelial integrity, and regulation of vascular tone. As a result, therapeutic inhibition of VEGF signaling is associated with a characteristic spectrum of cardiovascular adverse effects. These include hypertension, endothelial dysfunction, heart failure, thromboembolic complications, and renal injury, all of which present important clinical challenges in patients with hematologic malignancies. This population frequently has additional vulnerability due to factors such as cytopenias, preexisting renal impairment, and prior exposure to cardiotoxic anticancer therapies. This review aims to provide a cardio-oncology–oriented overview of VEGF biology, the range of VEGF-targeted agents used in hematologic cancers, and the underlying mechanisms driving their cardiovascular toxicities.

Abstract Objective: Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration. Method: Former American football players ( n = 180) completed measures of global and domain-specific SCC, neuropsychiatric symptom questionnaires, neuropsychological testing, lumbar puncture, and MRI. Elastic net regression evaluated the relative importance of potential SCC correlates. Intraclass correlation coefficients measured concordance between self and informant reports. Multiple linear regressions tested associations between SCC and verbal memory and executive functioning scores. CSF Aβ 1-42 , p-tau 181 , t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC. Results: Rates of SCC ranged from 43 to 77% depending on the domain. Symptoms of depression, impulsivity, and anxiety were strongly associated with SCC. Self- and informant-reported SCC showed moderate inter-rater agreement. Adjusting for age, race, education, APOE ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests. Conclusions: SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.