Abstract 2550: N-terminal Pro-brain Natriuretic Peptide-defined Cardiomyopathy in Doxorubicin-treated Children with Acute Lymphoblastic Leukemia
Bibliographic record
Abstract
Background: Doxorubicin damages heart muscle, placing long-term survivors of childhood cancer at elevated risk of cardiac dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP), an independent predictor of mortality and cardiovascular events in other populations, may serve to indicate cardiomyopathy prior to irreversible damage in this population. Methods: To determine the diagnostic value of NT-proBNP in children receiving doxorubicin, the NCI Dana-Farber Cancer Institute ALL Consortium collected serial serum samples and echocardiograms from children with ALL between 1995 and 2000 randomized to receive doxorubicin alone (dox; n = 74; 1203 samples; median age = 6.4 yrs; 30 mg/m 2 /dose for 10 doses) or doxorubicin preceded by the cardioprotectant dexrazoxane (dex/dox; n = 80; 1338 samples; median age = 7.1 yrs; 300 mg/m 2 /dose). Results: Marked NT-proBNP elevation (NT-proBNP ≥ 100 pg/ml if age ≥ 1; proBNP ≥ 150 pg/ml if age > 1) was seen at baseline (treatment day 0; dox alone = 82.5% of patients abnormal; dex/dox = 87.4%; p = 0.527). During treatment, the percentage of patients with abnormal NT-proBNP levels fell to a minimum of 35.8% in the dox only group and 16.4% in the dex/dox group ( p < 0.001) before rising progressively at the end of treatment (treatment day 220; dox only = 70.8%; dex/dox = 5.3%; p < 0.001). After controlling for treatment, a patient with abnormal NT-proBNP six months after the start of doxorubicin had 2.39 times the odds of having myocardial injury as indicated by elevated cardiac troponin T (cTnT ≥0.01 ng/mL; OR = 2.39; 95%CI 1.156 - 4.946; p = 0.019). Further, at any given time and for either treatment, a patient with abnormal NT-proBNP had 2.36 times the odds of having abnormal LV fractional shortening (OR = 2.36; 95%CI 1.026 - 5.449; p = 0.047). Conclusion: Elevated serum NT-proBNP was significantly related to cumulative unprotected doxorubicin dose, left ventricular fractional shortening, and cTnT during doxorubicin therapy. A much higher percentage of patients exhibited levels of NT-proBNP suggestive of cardiomyopathy than showed death of cardiomyocytes as indicated by elevated cTnT levels. This might allow the testing of individualized preventative therapy for cancer patients at high risk for long-term cardiotoxicity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".