Prediction of High-Dose Methotrexate Blood Concentration in Osteosarcoma Patients Using Machine Learning

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Publicado en:Drug Design, Development and Therapy vol. 19 (2025), p. 3631
Autor principal: Zhao, J
Otros Autores: Dai, S, He J, Liu, N, Zhang, B, Li S
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Taylor & Francis Ltd.
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022 |a 1177-8881 
024 7 |a 10.2147/DDDT.S515535  |2 doi 
035 |a 3204750504 
045 2 |b d20250101  |b d20251231 
100 1 |a Zhao, J 
245 1 |a Prediction of High-Dose Methotrexate Blood Concentration in Osteosarcoma Patients Using Machine Learning 
260 |b Taylor & Francis Ltd.  |c 2025 
513 |a Journal Article 
520 3 |a Introduction: High-dose methotrexate is a typical chemotherapy that is widely used in the treatment of osteosarcoma. However, the unique dose-response relationship of methotrexate makes its treatment window relatively narrow, and its clinical use is in a dilemma: either the drug concentration in the patient’s body cannot reach the effective concentration level, or adverse reactions may occur due to drug overdose. For this circumstance, monitoring and predicting the drug concentration in the patient’s body is well founded and necessary. While pharmacokinetic models exist, they often oversimplify patient-specific covariates. This study addresses the unmet need for early-exposure prediction through interpretable machine learning, enabling data-driven decisions before toxicity manifestation.Methods: In this article, 68 osteosarcoma patients’ information including demography, administration and assay was gathered. We analyzed medical data and selected 10 important features using a random forest, including hydration status, red blood cell distribution width coefficient of variation, platelet distribution width, creatinine, γ-glutamyl transferase, large platelet ratio, serum potassium, lactate dehydrogenase, weight, and prealbumin. Then, cross-validation and SHAP has been conducted to confirm the robust and interpretation of the model.Results: On this basis, 7 machine learning regression models was built to predict the blood concentration of methotrexate. R2, MSE, RMSE, MAE are the evaluation metrics. Finally, LightGBM was selected as the best prediction model with a performance of R2=0.87, MSE=0.020, RMSE=0.141, MAE=0.065.Discussion: This machine learning framework addresses a critical gap in high-dose methotrexate therapeutic monitoring by achieving early and personalized blood drug concentration prediction, allowing for personalized dosing of patients based on predicted concentrations. The interpretability of SHAP-derived feature importance enhances clinical utility, offering a paradigm shift from reactive toxicity management to proactive precision dosing in osteosarcoma therapy. 
653 |a Erythrocytes 
653 |a Datasets 
653 |a Metastasis 
653 |a Bone cancer 
653 |a Regression analysis 
653 |a Telemedicine 
653 |a Machine learning 
653 |a Toxicity 
653 |a Prediction models 
653 |a Methotrexate 
653 |a Decision trees 
653 |a Pharmacokinetics 
653 |a Medical prognosis 
653 |a Creatinine 
653 |a Dosage 
653 |a Hospitals 
653 |a Platelets 
653 |a Missing data 
653 |a Algorithms 
653 |a Chemotherapy 
653 |a Patients 
653 |a Dihydrofolate reductase 
653 |a Regression models 
653 |a Normal distribution 
653 |a Data processing 
653 |a Oncology 
653 |a Blood levels 
653 |a Health services 
653 |a Monitoring 
653 |a Demography 
653 |a L-Lactate dehydrogenase 
653 |a Hydration 
653 |a Customization 
653 |a Learning algorithms 
653 |a Drug dosages 
653 |a Overdose 
653 |a Coefficient of variation 
653 |a Osteosarcoma 
653 |a Lactate dehydrogenase 
653 |a Variables 
653 |a Clinical decision making 
700 1 |a Dai, S 
700 1 |a He J 
700 1 |a Liu, N 
700 1 |a Zhang, B 
700 1 |a Li S 
773 0 |t Drug Design, Development and Therapy  |g vol. 19 (2025), p. 3631 
786 0 |d ProQuest  |t Nursing & Allied Health Database 
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856 4 0 |3 Full Text + Graphics  |u https://www.proquest.com/docview/3204750504/fulltextwithgraphics/embedded/75I98GEZK8WCJMPQ?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3204750504/fulltextPDF/embedded/75I98GEZK8WCJMPQ?source=fedsrch