A Rule-based Method Applied to the Imbalanced Classification of Radiation Toxicity

This paper describes a rule-based classifier (DEQAR-C), which is set up by the combination of selected rules after a two-phase process. In the first phase, the rules are generated and sorted for each class, and then a selection is performed to obtain a final list of rules. A real imbalanced dataset regarding the toxicity during and after radiation therapy for prostate cancer has been employed in a comparison with other predictive methods (rule-based, artificial neural networks, trees, Bayesian and logistic regression). DEQAR-C produced excellent results in an evaluation regarding several performance measures (accuracy, Matthews correlation coefficient, sensitivity, specificity, precision, recall and F-measure) and by using cross-validation. Therefore, it was employed to obtain a predictive model using the full data. The resultant model is easily interpretable, combining three rules with two variables, and suggesting conditions that are mostly confirmed by the medical literature

Predictive Modelling Approach to Data-Driven Computational Preventive Medicine

This thesis contributes novel predictive modelling approaches to data-driven computational preventive medicine and offers an alternative framework to statistical analysis in preventive medicine research. In the early parts of this research, this thesis presents research by proposing a synergy of machine learning methods for detecting patterns and developing inexpensive predictive models from healthcare data to classify the potential occurrence of adverse health events. In particular, the data-driven methodology is founded upon a heuristic-systematic assessment of several machine-learning methods, data preprocessing techniques, models’ training estimation and optimisation, and performance evaluation, yielding a novel computational data-driven framework, Octopus. Midway through this research, this thesis advances research in preventive medicine and data mining by proposing several new extensions in data preparation and preprocessing. It offers new recommendations for data quality assessment checks, a novel multimethod imputation (MMI) process for missing data mitigation, a novel imbalanced resampling approach, and minority pattern reconstruction (MPR) led by information theory. This thesis also extends the area of model performance evaluation with a novel classification performance ranking metric called XDistance. In particular, the experimental results show that building predictive models with the methods guided by our new framework (Octopus) yields domain experts' approval of the new reliable models’ performance. Also, performing the data quality checks and applying the MMI process led healthcare practitioners to outweigh predictive reliability over interpretability. The application of MPR and its hybrid resampling strategies led to better performances in line with experts' success criteria than the traditional imbalanced data resampling techniques. Finally, the use of the XDistance performance ranking metric was found to be more effective in ranking several classifiers' performances while offering an indication of class bias, unlike existing performance metrics The overall contributions of this thesis can be summarised as follow. First, several data mining techniques were thoroughly assessed to formulate the new Octopus framework to produce new reliable classifiers. In addition, we offer a further understanding of the impact of newly engineered features, the physical activity index (PAI) and biological effective dose (BED). Second, the newly developed methods within the new framework. Finally, the newly accepted developed predictive models help detect adverse health events, namely, visceral fat-associated diseases and advanced breast cancer radiotherapy toxicity side effects. These contributions could be used to guide future theories, experiments and healthcare interventions in preventive medicine and data mining

Machine learning using radiomics and dosiomics for normal tissue complication probability modeling of radiation-induced xerostomia

In routine clinical practice, the risk of xerostomia is typically managed by limiting the mean radiation dose to parotid glands. This approach used to give satisfying results. In recent years, however, several studies have reported mean-dose models to fail in the recognition of xerostomia risk. This can be explained by a strong improvement of overall dose conformality in radiotherapy due to recent technological advances, and thereby a substantial reduction of the mean dose to parotid glands. This thesis investigated novel approaches to building reliable normal tissue complication probability (NTCP) models of xerostomia in this context. For the purpose of the study, a cohort of 153 head-and-neck cancer patients treated with radiotherapy at Heidelberg University Hospital was retrospectively collected. The predictive performance of the mean-dose to parotid glands was evaluated with the Lyman-Kutcher-Burman (LKB) model. In order to examine the individual predictive power of predictors describing parotid shape (radiomics), dose shape (dosiomics), and demographic characteristics, a total of 61 different features was defined and extracted from the DICOM files. These included the patient’s age and sex, parotid shape features, features related to the dose-volume histogram, the mean dose to subvolumes of parotid glands, spatial dose gradients, and three-dimensional dose moments. In the multivariate analysis, a variety of machine learning algorithms was evaluated: 1) classification methods, that discriminated patients between a high and a low risk of complication, 2) feature selection techniques, that aimed to select a number of highly informative covariates from a large set of predictors, 3) sampling methods, that reduced the class imbalance, 4) data cleaning methods, that reduced noise in the data set. The predictive performance of the models was validated internally, using nested cross-validation, and externally, using an independent patient cohort from the PARSPORT clinical trial. The LKB model showed fairly good performance on mild-to-severe (G1+) xerostomia predictions. The corresponding dose-response curve revealed that even small doses to parotid glands increase the risk of xerostomia and should be kept as low as possible. For the patients who did develop moderate-to-severe (G2+) xerostomia, the mean dose was not an informative predictor, even though the efficient sparing of parotid glands allowed to achieve low G2+ xerostomia rates. The features describing the shape of a parotid gland and the shape of a dose proved to be highly predictive of xerostomia. In particular, the parotid volume and the spatial dose gradients in the transverse plane explained xerostomia well. The results of the machine learning algorithms comparison showed that a particular choice of a classifier and a feature selection method can significantly influence predictive performance of the NTCP model. In general, support vector machines and extra-trees achieved top performance, especially for the endpoints with a large number of observations. For the endpoints with a smaller number of observations, simple logistic regression often performed on a par with the top-ranking machine learning algorithms. The external validation showed that the analyzed multivariate models did not generalize well to the PARSPORT cohort. The only features that were predictive of xerostomia both in the Heidelberg (HD) and the PARSPORT cohort were the spatial dose gradients in the right-left and the anterior-posterior directions. Substantial differences in the distribution of covariates between the two cohorts were observed, which may be one of the reasons for the weak generalizability of the HD models. The results presented in this thesis undermine the applicability of NTCP models of xerostomia based only on the mean dose to parotid glands in highly conformal radiotherapy treatments. The spatial dose gradients in the left-right and the anterior-posterior directions proved to be predictive of xerostomia both in the HD and the PARSPORT cohort. This finding is especially important as it is not limited to a single cohort but describes a general pattern present in two independent data sets. The performance of the sophisticated machine learning methods may indicate a need for larger patient cohorts in studies on NTCP models in order to fully benefit from their advantages. Last but not least, the observed covariate-shift between the HD and the PARSPORT cohort motivates, in the author’s opinion, a need for reporting information about the covariate distribution when publishing novel NTCP models

Modelling for Radiation Treatment Outcome

Modelling of tumour control probability (TCP) and normal tissue complication probability (NTCP) has been continuously used to estimate the therapeutic window of radiotherapy. In recent years, available data on tumour and normal tissue biology and from multimodal imaging have increased substantially, in particular, due to image-guided radiotherapy (see previous chapters of this book) and novel high-throughput sequencing technologies. Accordingly, more complex modelling algorithms are applied and issues of data quality, structured modelling procedures, and model validation need to be addressed. This chapter outlines general modelling principles in the era of big data, provides definitions of classical TCP and NTCP models, and presents two applications of outcome modelling in radiotherapy: the model-based approach for assigning patients to photon or proton-beam therapy and radiomics analyses based on clinical imaging data.</p

Modelling for Radiation Treatment Outcome

Modelling of tumour control probability (TCP) and normal tissue complication probability (NTCP) has been continuously used to estimate the therapeutic window of radiotherapy. In recent years, available data on tumour and normal tissue biology and from multimodal imaging have increased substantially, in particular, due to image-guided radiotherapy (see previous chapters of this book) and novel high-throughput sequencing technologies. Accordingly, more complex modelling algorithms are applied and issues of data quality, structured modelling procedures, and model validation need to be addressed. This chapter outlines general modelling principles in the era of big data, provides definitions of classical TCP and NTCP models, and presents two applications of outcome modelling in radiotherapy: the model-based approach for assigning patients to photon or proton-beam therapy and radiomics analyses based on clinical imaging data.</p

Towards Prediction of Radiation Pneumonitis Arising from Lung Cancer Patients Using Machine Learning Approaches

Radiation pneumonitis (RP) is a potentially fatal side effect arising in lung cancer patients who receive radiotherapy as part of their treatment. For the modeling of RP outcomes data, several predictive models based on traditional statistical methods and machine learning techniques have been reported. However, no guidance to variation in performance has been provided to date. In this study, we explore several machine learning algorithms for classification of RP data. The performance of these classification algorithms is investigated in conjunction with several feature selection strategies and the impact of the feature selection strategy on performance is further evaluated. The extracted features include patients demographic, clinical and pathological variables, treatment techniques, and dose-volume metrics. In conjunction, we have been developing an in-house Matlab-based open source software tool, called DREES, customized for modeling and exploring dose response in radiation oncology. This software has been upgraded with a popular classification algorithm called support vector machine (SVM), which seems to provide improved performance in our exploration analysis and has strong potential to strengthen the ability of radiotherapy modelers in analyzing radiotherapy outcomes data

Hybrid Deep Neural Network for Brachial Plexus Nerve Segmentation in Ultrasound Images

Ultrasound-guided regional anesthesia (UGRA) can replace general anesthesia (GA), improving pain control and recovery time. This method can be applied on the brachial plexus (BP) after clavicular surgeries. However, identification of the BP from ultrasound (US) images is difficult, even for trained professionals. To address this problem, convolutional neural networks (CNNs) and more advanced deep neural networks (DNNs) can be used for identification and segmentation of the BP nerve region. In this paper, we propose a hybrid model consisting of a classification model followed by a segmentation model to segment BP nerve regions in ultrasound images. A CNN model is employed as a classifier to precisely select the images with the BP region. Then, a U-net or M-net model is used for the segmentation. Our experimental results indicate that the proposed hybrid model significantly improves the segmentation performance over a single segmentation model.Comment: The first two authors contributed equall