Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors

Background:. Accurate prediction of postoperative metastasis and mortality risks in patients undergoing lower-limb oncological resection and endoprosthetic reconstruction is essential for guiding adjuvant therapies and managing patient expectations. Current prediction methods are limited by variabil...

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Main Authors: Jiawen Deng, BHSc, Myron Moskalyk, BHSc, MSc, Madhur Nayan, MD, PhD, Ahmed Aoude, MEng, MD, FRCSC, Michelle Ghert, MD, FRCSC, Sahir Bhatnagar, PhD, Anthony Bozzo, MSc, MD, FRCSC
Format: Article
Language:English
Published: Wolters Kluwer 2025-06-01
Series:JBJS Open Access
Online Access:http://journals.lww.com/jbjsoa/fulltext/10.2106/JBJS.OA.24.00213
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author Jiawen Deng, BHSc
Myron Moskalyk, BHSc, MSc
Madhur Nayan, MD, PhD
Ahmed Aoude, MEng, MD, FRCSC
Michelle Ghert, MD, FRCSC
Sahir Bhatnagar, PhD
Anthony Bozzo, MSc, MD, FRCSC
author_facet Jiawen Deng, BHSc
Myron Moskalyk, BHSc, MSc
Madhur Nayan, MD, PhD
Ahmed Aoude, MEng, MD, FRCSC
Michelle Ghert, MD, FRCSC
Sahir Bhatnagar, PhD
Anthony Bozzo, MSc, MD, FRCSC
author_sort Jiawen Deng, BHSc
collection DOAJ
description Background:. Accurate prediction of postoperative metastasis and mortality risks in patients undergoing lower-limb oncological resection and endoprosthetic reconstruction is essential for guiding adjuvant therapies and managing patient expectations. Current prediction methods are limited by variability in patient-specific factors. This study aims to develop and internally validate explainable machine learning (ML) models to predict the 1-year risk of new distant metastases and mortality in these patients. Methods:. We performed a secondary analysis of data from the Prophylactic Antibiotic Regimens in Tumor Surgery trial, which included 604 patients. Candidate features were selected based on availability and clinical relevance and then narrowed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Boruta algorithms. Six ML classification algorithms were tuned and calibrated: logistic regression, support vector machines, random forest, Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost), and neural networks. Models were developed with and without including percent tumor necrosis due to its high missing data rate (>30%). Hyperparameters were tuned using Bayesian optimization. Internal validation was conducted using a 30% hold-out set. Model explainability was assessed using permutation-based feature importance and SHapley Additive exPlanations. Results:. LightGBM was identified as the best-performing algorithm for both outcomes. For 1-year mortality prediction without percent necrosis, LightGBM achieved an area under the receiver operating characteristic curve (AUC-ROC) of 0.78 (95% confidence interval [CI] 0.70-0.86) during cross-validation and 0.72 on internal validation. For distant metastasis prediction, the LightGBM model without percent necrosis achieved an AUC-ROC of 0.77 (95% CI 0.71-0.84) during cross-validation and 0.77 on internal validation. Including percent necrosis did not significantly improve model performance. The top predictors identified were patient age, largest tumor dimension, and tumor stage. Conclusions:. Explainable ML models can effectively predict the 1-year risk of mortality and new distant metastases in patients undergoing lower-limb oncological resection and endoprosthetic reconstruction. Further external validation and consideration of other data modalities are required before integrating these ML-driven risk assessments into routine clinical practice. Level of Evidence:. Level II, Prognostic Study. See Instructions for Authors for a complete description of levels of evidence.
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spelling doaj-art-b990c954f2a44875becce41160093acd2025-08-20T02:29:07ZengWolters KluwerJBJS Open Access2472-72452025-06-0110210.2106/JBJS.OA.24.00213JBJSOA2400213Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone TumorsJiawen Deng, BHSc0Myron Moskalyk, BHSc, MSc1Madhur Nayan, MD, PhD2Ahmed Aoude, MEng, MD, FRCSC3Michelle Ghert, MD, FRCSC4Sahir Bhatnagar, PhD5Anthony Bozzo, MSc, MD, FRCSC61 Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada2 Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada4 Department of Population Health, NYU Grossman School of Medicine, New York, New York5 Division of Orthopaedic Surgery, McGill University, Montréal, Quebec, Canada6 Division of Orthopaedic Surgery, McMaster University, Hamilton, Ontario, Canada8 Department of Epidemiology and Biostatistics, McGill University, Montréal, Quebec, Canada5 Division of Orthopaedic Surgery, McGill University, Montréal, Quebec, CanadaBackground:. Accurate prediction of postoperative metastasis and mortality risks in patients undergoing lower-limb oncological resection and endoprosthetic reconstruction is essential for guiding adjuvant therapies and managing patient expectations. Current prediction methods are limited by variability in patient-specific factors. This study aims to develop and internally validate explainable machine learning (ML) models to predict the 1-year risk of new distant metastases and mortality in these patients. Methods:. We performed a secondary analysis of data from the Prophylactic Antibiotic Regimens in Tumor Surgery trial, which included 604 patients. Candidate features were selected based on availability and clinical relevance and then narrowed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Boruta algorithms. Six ML classification algorithms were tuned and calibrated: logistic regression, support vector machines, random forest, Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost), and neural networks. Models were developed with and without including percent tumor necrosis due to its high missing data rate (>30%). Hyperparameters were tuned using Bayesian optimization. Internal validation was conducted using a 30% hold-out set. Model explainability was assessed using permutation-based feature importance and SHapley Additive exPlanations. Results:. LightGBM was identified as the best-performing algorithm for both outcomes. For 1-year mortality prediction without percent necrosis, LightGBM achieved an area under the receiver operating characteristic curve (AUC-ROC) of 0.78 (95% confidence interval [CI] 0.70-0.86) during cross-validation and 0.72 on internal validation. For distant metastasis prediction, the LightGBM model without percent necrosis achieved an AUC-ROC of 0.77 (95% CI 0.71-0.84) during cross-validation and 0.77 on internal validation. Including percent necrosis did not significantly improve model performance. The top predictors identified were patient age, largest tumor dimension, and tumor stage. Conclusions:. Explainable ML models can effectively predict the 1-year risk of mortality and new distant metastases in patients undergoing lower-limb oncological resection and endoprosthetic reconstruction. Further external validation and consideration of other data modalities are required before integrating these ML-driven risk assessments into routine clinical practice. Level of Evidence:. Level II, Prognostic Study. See Instructions for Authors for a complete description of levels of evidence.http://journals.lww.com/jbjsoa/fulltext/10.2106/JBJS.OA.24.00213
spellingShingle Jiawen Deng, BHSc
Myron Moskalyk, BHSc, MSc
Madhur Nayan, MD, PhD
Ahmed Aoude, MEng, MD, FRCSC
Michelle Ghert, MD, FRCSC
Sahir Bhatnagar, PhD
Anthony Bozzo, MSc, MD, FRCSC
Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors
JBJS Open Access
title Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors
title_full Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors
title_fullStr Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors
title_full_unstemmed Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors
title_short Development of Explainable Machine Learning Models to Identify Patients at Risk for 1-Year Mortality and New Distant Metastases Postendoprosthetic Reconstruction for Lower Extremity Bone Tumors
title_sort development of explainable machine learning models to identify patients at risk for 1 year mortality and new distant metastases postendoprosthetic reconstruction for lower extremity bone tumors
url http://journals.lww.com/jbjsoa/fulltext/10.2106/JBJS.OA.24.00213
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