Purpose: Lymphopenia is a common adverse event following radiotherapy, but its prognostic relevance following comprehensive involved-site radiation (ISRT) for oligometastatic disease is unknown. We evaluated lymphocyte kinetics after ISRT for oligometastases and tested whether treatment-related lymphopenia was associated with overall survival (OS) and modified progression-free survival (mPFS). Patients and Methods: We performed a single-institution registry study of consecutive patients with 1 to 5 distant metastases treated with comprehensive ISRT by a single radiation oncologist from 2014 to 2023. Systemic therapy was administered at clinician discretion. Absolute lymphocyte count (ALC) was collected at baseline, during radiation and at 1, 3 and 12 months after radiotherapy. Lymphopenia was graded using CTCAE v5.0 (grade 1, ALC < 1000 cells/µL; grade ≥ 3, ALC < 500 cells/µL). OS and mPFS (defined as death or metastatic progression not salvageable with further local therapy) were estimated by the Kaplan–Meier method. Associations were evaluated using univariable and multivariable Cox proportional hazards models. Results: Among 177 patients, the 5-year OS was 39.6% and the median OS was 42.8 months. Median ALC declined from 1400 cells/µL at baseline to 800 cells/µL during radiotherapy (p < 0.01) and 700 cells/µL at a median of 0.7 months after radiation (p < 0.01). Partial recovery was observed at 1000 cells/µL at 3 months (p < 0.001) and 1000 cells/µL at 1 year (p < 0.01). Baseline ALC <1000 cells/µL was associated with worse OS on univariable analysis (p = 0.04) but not on multivariable analysis. Although 27% developed grade ≥ 3 lymphopenia within 3 months of radiation, the 5-year overall survival was 41.4% without lymphopenia versus 31.9% with lymphopenia (p = 0.60). On multivariable analysis, ECOG performance status (HR 1.9, p < 0.01), age (HR 1.04, p < 0.01), albumin (HR 0.6, p = 0.03), and pre-radiation chemotherapy (HR 3.1, p < 0.01) independently predicted overall survival. Conclusions: Comprehensive ISRT for oligometastatic disease was associated with a sustained decrease in median ALC. Treatment-related lymphopenia was not independently associated with OS in this heterogeneous cohort. The disease control benefit of metastasis-directed therapy may outweigh potential detrimental immunologic effects of radiation-induced lymphopenia.

Glucagon-like peptide-1 (GLP-1)-based therapies have been observed to produce cardiovascular benefits in cardiometabolic diseases; however, their impact on heart failure-specific outcomes is only becoming known through dedicated randomized controlled trials (RCTs). This scoping review consolidates the most recent randomized data that examine how GLP-1-based therapies affect heart failure-specific symptoms, functional capacity, and the occurrence of clinical events. Literature searches were conducted in PubMed, Google Scholar, and CINAHL for RCTs and prespecified analyses between 2021 and 2026 evaluating GLP-1-based therapies and reporting heart failure-specific outcomes. Five RCT-based studies met inclusion criteria, including randomized trials and prespecified RCT-derived analyses evaluating semaglutide and tirzepatide. Among patients with heart failure with preserved ejection fraction (HFpEF) and obesity, semaglutide significantly improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and 6-minute walk distance compared to placebo. Tirzepatide exhibited improvements across symptoms and functional and event-based outcomes, with prespecified trajectory analyses confirming favorable shifts in New York Heart Association functional class, Patient Global Impression of Severity, health-related quality of life, and background heart failure medication use. Among patients with type 2 diabetes mellitus and chronic kidney disease, semaglutide was associated with a significantly reduced rate of cardiovascular death or worsening heart failure events. Although the available evidence comes from a small number of recent randomized and prespecified RCT-based studies, current findings suggest that GLP-1-based therapies are associated with improvements in symptoms and functional capacity and reductions in heart failure events in certain patient populations, especially those with HFpEF and obesity. These beneficial effects support a potential role for the integration of GLP-1-based therapies in population-specific heart failure management.