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  • https://doi.org/10.1002/mp.12967Copy DOI Icon

Machine learning algorithms for outcome prediction in(chemo)radiotherapy: An empirical comparison of classifiers

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Abstract

Purpose:Machine learning classification algorithms (classifiers) forprediction of treatment response are becoming more popular in radiotherapyliterature. General Machine learning literature provides evidence in favorof some classifier families (random forest, support vector machine, gradientboosting) in terms of classification performance. The purpose of this studyis to compare such classifiers specifically for (chemo)radiotherapy datasetsand to estimate their average discriminative performance for radiationtreatment outcome prediction.Methods:We collected 12 datasets (3496 patients) from prior studies onpost-(chemo)radiotherapy toxicity, survival, or tumor control with clinical,dosimetric, or blood biomarker features from multiple institutions and fordifferent tumor sites, that is, (non-)small-cell lung cancer, head and neckcancer, and meningioma. Six common classification algorithms with built-infeature selection (decision tree, random forest, neural network, supportvector machine, elastic net logistic regression, Logit-Boost) were appliedon each dataset using the popular open-source R packagecaret. The R code and documentationfor the analysis are available online (https://github.com/timodeist/classifier_selection_code). Allclassifiers were run on each dataset in a 100-repeated nested fivefoldcross-validation with hyperparameter tuning. Performance metrics (AUC,calibration slope and intercept, accuracy, Cohen’s kappa, and Brierscore) were computed. We ranked classifiers by AUC to determine whichclassifier is likely to also perform well in future studies. We simulatedthe benefit for potential investigators to select a certain classifier for anew dataset based on our study (pre-selection based onother datasets) or estimating the best classifier for a dataset(set-specific selection based on information from thenew dataset) compared with uninformed classifier selection (randomselection).Results:Random forest (best in 6/12 datasets) and elastic net logisticregression (best in 4/12 datasets) showed the overall best discrimination,but there was no single best classifier across datasets. Both classifiershad a median AUC rank of 2. Preselection and set-specificselection yielded a significant average AUC improvement of 0.02 and 0.02over random selection with an average AUC rank improvementof 0.42 and 0.66, respectively.Conclusion:Random forest and elastic net logistic regression yield higherdiscriminative performance in (chemo)radiotherapy outcome and toxicityprediction than other studied classifiers. Thus, one of these twoclassifiers should be the first choice for investigators when buildingclassification models or to benchmark one’s own modeling resultsagainst. Our results also show that an informed preselection of classifiersbased on existing datasets can improve discrimination over randomselection.

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