Biomarker-Guided Cardioprotection for Patients Treated With Anthracyclines
Bibliographic record
Abstract
Importance: There are gaps in the understanding of the clinical actionability of cardiovascular biomarkers for risk stratification during cardiotoxic chemotherapy. Objectives: To gain insights into an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided approach for cardioprotection in patients with breast cancer or lymphoma treated with anthracyclines and quantify the feasibility, tolerability, and exploratory efficacy of an NT-proBNP-guided strategy compared with usual care. Design, Setting, and Participants: The NT-proBNP guide, a multicenter, randomized (stratified 1:1 by cancer type) clinical trial, included 100 participants with breast cancer or lymphoma initiating anthracyclines from March 18, 2021, to October 20, 2023, who were followed up for 12 months. Interventions: Study participants in the NT-proBNP-guided arm had biomarker concentrations measured prior to anthracycline initiation (baseline), at each cycle, and at 3, 6, 9, and 12 months. An elevated NT-proBNP concentration triggered the initiation or titration of neurohormonal therapy. Participants in the usual care arm received routine care without prospective monitoring of NT-proBNP concentrations. Main Outcomes and Measures: The primary outcomes were feasibility and safety of the NT-proBNP-guided approach. Feasibility was defined by recruitment, retention, and medication compliance rates. Safety outcomes were assessed according to the Common Terminology Criteria for Adverse Events, version 5.0, at each visit. Exploratory outcomes included differences in blinded, centrally quantified echocardiographic measures and NT-proBNP concentrations between the 2 arms. Analysis was performed on an intention-to-treat approach. Results: Across 100 participants (mean [SD] age, 52.2 [14.4] years; 86 women [86.0%]), 74 (74.0%) had breast cancer and 26 (26.0%) had lymphoma. At 12 months, the retention rate was 92.7% (89 of 96). In the NT-proBNP-guided arm, 27 participants had NT-proBNP elevations, with a median time from baseline to first elevation of 14 days (IQR, 0-76 days), and a median time between the first NT-proBNP elevation and neurohormonal therapy prescription of 1 day (IQR, 0.5-9 days). There were no significant differences in targeted adverse events between the NT-proBNP-guided (23 events) and usual care (16 events) arms (P = .13). At 3 months, left ventricular ejection fraction (LVEF) was modestly higher in the NT-proBNP-guided arm compared with usual care (mean difference, 2.0% [95% CI, 0.5%-3.5%]; P = .007). NT-proBNP concentrations increased in both arms over the study duration, but elevations were slightly attenuated in the NT-proBNP-guided arm. Conclusions and Relevance: This randomized clinical trial of an NT-proBNP-guided approach to neurohormonal therapy in patients with cancer treated with anthracyclines demonstrates the feasibility, safety, and potential modest, early improvement in LVEF of a biomarker-guided approach. These findings provide support for further study of an NT-proBNP-guided approach to cardioprotection for patients undergoing cancer treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04737265.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".