Dexrazoxane Significantly Reduces Anthracycline-induced Cardiotoxicity in Pediatric Solid Tumor Patients: A Systematic Review
Bibliographic record
Abstract
Cardiotoxicity is a dose-limiting and potentially lethal complication of anthracycline administration. Previous studies failed to determine definitive toxic doses or cardioprotective factors. Current dosing strategies may utilize unnecessarily high anthracycline doses, such that survival benefit may not outweigh increased toxicity rates. A systematic review of randomized controlled trials and prospective/retrospective studies investigating anthracycline treatment in pediatric solid tumors was performed from PubMed/MEDLINE and Cochrane databases. Generalized linear models mapping survival, cardiotoxicity, and cardiotoxicity-free survival adjusted for male-to-female ratio, follow-up time, and concomitant chemotherapeutic drugs or cardioprotective agents (dexrazoxane) were generated using R. Survival rose linearly with increasing cumulative anthracycline dose whereas cardiotoxicity demonstrated exponential increases both without (dose, >200 mg/m) and with (dose, >400 mg/m) dexrazoxane. Maximum cardiotoxicity-free survival was 268.2 mg/m without and 431.8 mg/m with dexrazoxane. Despite increasing cardiotoxicity-free dose by >150 mg/m, dexrazoxane minimally improved projected survival (71.9% vs. 75.4%). Cardiotoxicity increased linearly as a function of follow-up time with rates doubling from 5 to 20 years, without evidence of plateau. On the basis of our model, current dosing regimens-doxorubicin doses >375 mg/m without dexrazoxane-overvalue increased anthracycline administration and may contribute to devastating cardiotoxicity. The linear increase of cardiotoxicity without evidence of plateau confirms the necessity for lifelong cardiac monitoring.
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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 | 0.003 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.007 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".