Cary Dehing-Oberije

Development and External Validation of Prognostic Model for 2-Year Survival of Non–Small-Cell Lung Cancer Patients Treated With Chemoradiotherapy

PURPOSE Radiotherapy, combined with chemotherapy, is the treatment of choice for a large group of non-small-cell lung cancer (NSCLC) patients. Recent developments in the treatment of these patients have led to improved survival. However, the clinical TNM stage is highly inaccurate for the prediction of survival, and alternatives are lacking. The objective of this study was to develop and validate a prediction model for survival of NSCLC patients, treated with chemoradiotherapy. PATIENTS AND METHODS The clinical data from 377 consecutive inoperable NSCLC patients, Stage I-IIIB, treated radically with chemoradiotherapy were collected. A prognostic model for 2-year survival was developed, using 2-norm support vector machines. The performance of the model was expressed as the area under the curve of the receiver operating characteristic and assessed using leave-one-out cross-validation, as well as two external data sets. RESULTS The final multivariate model consisted of gender, World Health Organization performance status, forced expiratory volume in 1 s, number of positive lymph node stations, and gross tumor volume. The area under the curve, assessed by leave-one-out cross-validation, was 0.74, and application of the model to the external data sets yielded an area under the curve of 0.75 and 0.76. A high- and low-risk group could be clearly identified using a risk score based on the model. CONCLUSION The multivariate model performed very well and was able to accurately predict the 2-year survival of NSCLC patients treated with chemoradiotherapy. The model could support clinicians in the treatment decision-making process.

The importance of patient characteristics for the prediction of radiation-induced lung toxicity

PURPOSE Extensive research has led to the identification of numerous dosimetric parameters as well as patient characteristics, associated with lung toxicity, but their clinical usefulness remains largely unknown. We investigated the predictive value of patient characteristics in combination with established dosimetric parameters. PATIENTS AND METHODS Data from 438 lung cancer patients treated with (chemo)radiation were used. Lung toxicity was scored using the Common Toxicity Criteria version 3.0. A multivariate model as well as two single parameter models, including either V(20) or MLD, was built. Performance of the models was expressed as the AUC (Area Under the Curve). RESULTS The mean MLD was 13.5 Gy (SD 4.5 Gy), while the mean V(20) was 21.0% (SD 7.3%). Univariate models with V(20) or MLD both yielded an AUC of 0.47. The final multivariate model, which included WHO-performance status, smoking status, forced expiratory volume (FEV(1)), age and MLD, yielded an AUC of 0.62 (95% CI: 0.55-0.69). CONCLUSIONS Within the range of radiation doses used in our clinic, dosimetric parameters play a less important role than patient characteristics for the prediction of lung toxicity. Future research should focus more on patient-related factors, as opposed to dosimetric parameters, in order to identify patients at high risk for developing radiation-induced lung toxicity more accurately.

Comparison of Bayesian network and support vector machine models for two-year survival prediction in lung cancer patients treated with radiotherapy.

PURPOSE Classic statistical and machine learning models such as support vector machines (SVMs) can be used to predict cancer outcome, but often only perform well if all the input variables are known, which is unlikely in the medical domain. Bayesian network (BN) models have a natural ability to reason under uncertainty and might handle missing data better. In this study, the authors hypothesize that a BN model can predict two-year survival in non-small cell lung cancer (NSCLC) patients as accurately as SVM, but will predict survival more accurately when data are missing. METHODS A BN and SVM model were trained on 322 inoperable NSCLC patients treated with radiotherapy from Maastricht and validated in three independent data sets of 35, 47, and 33 patients from Ghent, Leuven, and Toronto. Missing variables occurred in the data set with only 37, 28, and 24 patients having a complete data set. RESULTS The BN model structure and parameter learning identified gross tumor volume size, performance status, and number of positive lymph nodes on a PET as prognostic factors for two-year survival. When validated in the full validation set of Ghent, Leuven, and Toronto, the BN model had an AUC of 0.77, 0.72, and 0.70, respectively. A SVM model based on the same variables had an overall worse performance (AUC 0.71, 0.68, and 0.69) especially in the Ghent set, which had the highest percentage of missing the important GTV size data. When only patients with complete data sets were considered, the BN and SVM model performed more alike. CONCLUSIONS Within the limitations of this study, the hypothesis is supported that BN models are better at handling missing data than SVM models and are therefore more suitable for the medical domain. Future works have to focus on improving the BN performance by including more patients, more variables, and more diversity.

Privacy-preserving cox regression for survival analysis

Privacy-preserving data mining (PPDM) is an emergent research area that addresses the incorporation of privacy preserving concerns to data mining techniques. In this paper we propose a privacy-preserving (PP) Cox model for survival analysis, and consider a real clinical setting where the data is horizontally distributed among different institutions. The proposed model is based on linearly projecting the data to a lower dimensional space through an optimal mapping obtained by solving a linear programming problem. Our approach differs from the commonly used random projection approach since it instead finds a projection that is optimal at preserving the properties of the data that are important for the specific problem at hand. Since our proposed approach produces an sparse mapping, it also generates a PP mapping that not only projects the data to a lower dimensional space but it also depends on a smaller subset of the original features (it provides explicit feature selection). Real data from several European healthcare institutions are used to test our model for survival prediction of non-small-cell lung cancer patients. These results are also confirmed using publicly available benchmark datasets. Our experimental results show that we are able to achieve a near-optimal performance without directly sharing the data across different data sources. This model makes it possible to conduct large-scale multi-centric survival analysis without violating privacy-preserving requirements.

Survival Prediction in Lung Cancer Treated with Radiotherapy: Bayesian Networks vs. Support Vector Machines in Handling Missing Data

Missing data is a given in the medical domain, so machine learning models should have satisfactory performance even when missing data occurs. Our previous work has focused on support vector machines (SVM), but we hypothesize that Bayesian networks (BN) can handle missing data better. To test the hypothesis, we trained a BN and SVM model for 2 year survival on 322 lung cancer patients and compared their performance in three separate external datasets (35, 47, 33 patients), each with their own characteristics in terms of missing data. The models used tumor size, clinical T and N stage, involved lymph nodes and WHO performance as prognostic features. We found that the BN model performed better than SVM (AUC 0.77, 0.72. 0.70 vs. 0.71, 0.68, 0.69), especially if tumor size was missing. We conclude that BN models are better suited for the medical domain, as they can handle missing data better.