Background: Progression-free survival (PFS) is a crucial endpoint in cancer drug research. Clinician-confirmed cancer progression, namely real-world PFS (rwPFS) in unstructured text (ie, clinical notes), serves as a reasonable surrogate for real-world indicators in ascertaining progression endpoints. Response evaluation criteria in solid tumors (RECIST) is traditionally used in clinical trials using serial imaging evaluations but is impractical when working with real-world data. Manual abstraction of clinical progression from unstructured notes remains the gold standard. However, this process is a resource-intensive, time-consuming process. Natural language processing (NLP), a subdomain of machine learning, has shown promise in accelerating the extraction of tumor progression from real-world data in recent years. Objectives: We aim to configure a pretrained, general-purpose health care NLP framework to transform free-text clinical notes and radiology reports into structured progression events for studying rwPFS on metastatic breast cancer (mBC) cohorts. Methods: This study developed and validated a novel semiautomated workflow to estimate rwPFS in patients with mBC using deidentified electronic health record data from the Nference nSights platform. The developed workflow was validated in a cohort of 316 patients with hormone receptor–positive, human epidermal growth factor receptor-2 (HER-2) 2-negative mBC, who were started on palbociclib and letrozole combination therapy between January 2015 and December 2021. Ground-truth datasets were curated to evaluate the workflow’s performance at both the sentence and patient levels. NLP-captured progression or a change in therapy line were considered outcome events, while death, loss to follow-up, and end of the study period were considered censoring events for rwPFS computation. Peak reduction and cumulative decline in Patient Health Questionnaire-8 (PHQ-8) scores were analyzed in the progressed and nonprogressed patient subgroups. Results: The configured clinical NLP engine achieved a sentence-level progression capture accuracy of 98.2%. At the patient level, initial progression was captured within ±30 days with 88% accuracy. The median rwPFS for the study cohort (N=316) was 20 (95% CI 18-25) months. In a validation subset (n=100), rwPFS determined by manual curation was 25 (95% CI 15-35) months, closely aligning with the computational workflow’s 22 (95% CI 15-35) months. A subanalysis revealed rwPFS estimates of 30 (95% CI 24-39) months from radiology reports and 23 (95% CI 19-28) months from clinical notes, highlighting the importance of integrating multiple note sources. External validation also demonstrated high accuracy (92.5% sentence level; 90.2% patient level). Sensitivity analysis revealed stable rwPFS estimates across varying levels of missing source data and event definitions. Peak reduction in PHQ-8 scores during the study period highlighted significant associations between patient-reported outcomes and disease progression. Conclusions: This workflow enables rapid and reliable determination of rwPFS in patients with mBC receiving combination therapy. Further validation across more diverse external datasets and other cancer types is needed to ensure broader applicability and generalizability.

Background: Immunotherapy-based regimens have expanded the treatment landscape for unresectable hepatocellular carcinoma (uHCC); however, real-world data are limited. Methods: This retrospective, observational study used data from electronic medical records from Mayo Clinic sites across the United States. Patients with uHCC who initiated a first-line (1L) systemic therapy between June 2020–October 2022 with ≥2 follow-up visits were included. Treatment patterns, overall survival (OS), and post-index gastrointestinal (GI) bleeding were assessed by GI bleeding risk defined by Child–Pugh Class B or C, pre-index GI bleeding, uncontrolled hypertension, or significant varices and band ligation. Results: Of 186 included patients, 68.8% had GI bleeding risk and 31.2% did not. Atezolizumab plus bevacizumab was the most common 1L systemic therapy in patients with or without GI bleeding risk (72.7% and 29.3%, respectively). Median OS (95% confidence interval) with atezolizumab plus bevacizumab was 12.8 (8.0–19.3) months and not reached in patients with and without GI bleeding risk, respectively. OS rates with atezolizumab plus bevacizumab in patients with or without GI bleeding risk, respectively, were 52.3% and 70.6% at 12 months, 41.6% and 57.8% at 18 months, and 34.6% and 51.3% at 24 months. Post-index GI bleeding with atezolizumab plus bevacizumab occurred in 19.4% and 5.9% of patients with and without GI bleeding risk, respectively. Conclusions: During this study period, atezolizumab + bevacizumab was the most common 1L therapy for patients with uHCC, regardless of GI bleeding risk. OS rates with atezolizumab + bevacizumab were lower in patients with versus without GI bleeding risk. Findings highlight the unmet need for guidance on characteristics-driven treatment decisions.

Background: Glucagon-like peptide-1 (GLP-1) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists reduce cardiovascular events, but the underlying cardiac structural remodeling remains unclear. Objectives: This study evaluated longitudinal cardiac remodeling associated with semaglutide and tirzepatide in a real-world cohort and determined its weight-loss dependency. Methods: Using electronic health records from a federated network, we analyzed longitudinal echocardiograms of patients prescribed semaglutide or tirzepatide, stratified by 12-month weight loss into super-responders (>15%), moderate-responders (5%-15%), and minimal-responders (5% weight loss were propensity-matched with non-GLP-1/GIP weight-loss medication control patients on demographics and baseline body mass index. Results: Among 3,500 GLP-1/GIP patients (422 weight-loss super-responders, 1,426 moderate-responder, 1,652 minimal-responders), left ventricular (LV) mass decreased across all groups proportional to weight loss (super-responders: 198.4 ± 69.6 to 176.6 ± 66.0 g; moderate-responders: 210.7 ± 74.0 to 195.8 ± 68.1 g; minimal-responders: 216.1 ± 68.4 to 204.8 ± 67.4 g; p < 0.001). Left atrial volume and LV systolic and diastolic function did not change. Among weight-loss super-responders, semaglutide (n = 159) showed greater LV mass reduction than tirzepatide (n = 89) (Cohen’s d = -0.389 vs. -0.263), while tirzepatide showed small improvements in right ventricular function. Compared to matched non-GLP-1/GIP controls (n = 118/group), GLP-1/GIP patients exhibited significant LV mass reduction not observed in controls despite similar weight loss. Conclusions: Real-world findings demonstrate that incretin-based therapies are associated with reverse cardiac remodeling characterized by weight-loss-dependent and incretin-specific mechanisms, with potentially distinct structural targets among agents.