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Objectives: Systemic therapies for pancreatic neuroendocrine tumors (PNETs) are limited. The combination of bevacizumab and temsirolimus showed significant antitumor activity, but the single-agent activity of bevacizumab was unknown. We conducted a single-arm, phase II trial to evaluate the efficacy of bevacizumab in PNETs. Methods: Patients with progressive disease by the Response EvaluationCriteria in Solid Tumors version 1.1 within 7 months of enrollment were eligible for bevacizumab 10 mg/kg every 2 weeks. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. The primary end point was response rate (RR).Results: Twenty-four patients were enrolled and followed up for a median duration of 36.1 months. Confirmed RR was 12.5%; 75.0% of patients had stable disease at 6 months. Median progression-free survival was 18.0 months; median overall survival was not reached. Common grade 3 adverse events were hypertension (45.8%) and proteinuria (8.3%). No grade 4 adverse events were observed.Conclusions: Bevacizumab demonstrated promising antitumor activity in progressive PNETs comparable to standard targeted therapy. Although this study failed to reject the null hypothesis (RR, 10%), bevacizumab seems a reasonable monotherapy and a potential component of combination therapies given clinical activity and low rates of adverse events.

Introduction: Prior AF screening trials demonstrated low yield, highlighting the need for more targeted approaches. An AI algorithm was developed to identify ECG signatures of AF risk during normal sinus rhythm, which has been validated in diverse external populations. Hypothesis: An AI-guided, targeted screening approach could improve the diagnosis of AF. Methods We conducted a pragmatic decentralized trial to prospectively recruit patients with stroke risk factors but no prior AF. The AI algorithm was applied to the ECGs performed in routine practice and divided patients into high- or low-risk groups. The primary endpoint was AF lasting ≥ 30 seconds on a subsequent 30-day continuous cardiac rhythm monitor. In a secondary analysis, trial participants were 1:1 propensity score-matched to real-world controls derived from the eligible but unenrolled population. Results A total of 1,003 patients from 40 U.S. states completed the study, with a mean age of 74 [SD 8.8] years. Over a mean of 22.3 days of continuous monitoring, AF was detected in 6 (1.6%) of low-risk patients and 48 (7.6%) of high-risk patients (OR 4.98 [2.11-11.75], p<0.001). Compared to usual care, AI-guided AF screening was associated with increased detection of AF (high-risk group: 4.2% vs. 11.1%, p<0.001; low-risk group: 0.9% vs. 2.4%, p=0.12) over a median follow-up of 10 months. Conclusions A prospective pragmatic study found that the AI a can risk-stratify a relatively uniform population (i.e., older adults at risk for stroke) to detect AF during short-term cardiac monitoring. Furthermore, when compared with usual care, AI-guided cardiac monitoring was associated with increased AF detection. As such, an AI-guided AF screening approach, leveraging existing EHR data and infrastructure, could be effective, patient-centered, and massively scalable, thereby reducing unnecessary health utilization and diagnosis-related anxiety (Clinicaltrials.gov: NCT04208971).

INTRODUCTION: We recently developed a fluorescence in situ hybridization probe set for evaluating suspicious biliary and pancreatic duct strictures (PB-FISH). We aimed to determine whether PB-FISH results in biliary brush cytology specimens are associated with outcomes of patients with cholangiocarcinoma (CCA). METHODS: We performed a retrospective study of patients with CCA tested by PB-FISH from January 2015 to August 2018. CCA was stratified by primary sclerosing cholangitis (PSC) into those with (PSC CCA) or without PSC ( de novo CCA). PB-FISH results were categorized as polysomy (gain of multiple loci), nonpolysomy (single locus gain, single locus gain with 9p21 loss, homozygous 9p21 loss, tetrasomy), and disomy (no abnormalities). Overall survival (OS) was estimated using Kaplan-Meier methods and compared between the PB-FISH results using log-rank tests. Cox models were adjusted for age, sex, CA 19-9, cytology results, source of brushing sample, and treatments. RESULTS: Characteristics of 264 eligible patients (median age 60.4; range 18–92) were comparable for patients with PB-FISH polysomy vs nonpolysomy vs disomy. The median OS was similar between disomy, nonpolysomy, and polysomy in the overall population (22.7 vs 22.7 vs 20.3 months, respectively). For de novo CCA, both polysomy and nonpolysomy were associated with worse OS compared with disomy (polysomy: hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.14–3.83; nonpolysomy: HR = 2.4, 95% CI = 0.54–2.46; P = 0.027). For PSC CCA, neither polysomy nor nonpolysomy were significantly associated with worse OS (polysomy: 0.90, 95% CI = 0.47–1.75; nonpolysomy: HR = 1.78, CI = 0.71–4.49; P = 0.27). DISCUSSION: PB-FISH alterations are associated with worse survival in de novo CCA, though statistical significance was lost when adjusting for confounding variables.