Clustering of Largely Right-Censored Oropharyngeal Head and Neck Cancer Patients for Discriminative Groupings to Improve Outcome Prediction.

Clustering is the task of identifying groups of similar subjects according to certain criteria. The AJCC staging system can be thought as a clustering mechanism that groups patients based on their disease stage. This grouping drives prognosis and influences treatment. The goal of this work is to evaluate the efficacy of machine learning algorithms to cluster the patients into discriminative groups to improve prognosis for overall survival (OS) and relapse free survival (RFS) outcomes. We apply clustering over a retrospectively collected data from 644 head and neck cancer patients including both clinical and radiomic features. In order to incorporate outcome information into the clustering process and deal with the large proportion of censored samples, the feature space was scaled using the regression coefficients fitted using a proxy dependent variable, martingale residuals, instead of follow-up time. Two clusters were identified and evaluated using cross validation. The Kaplan Meier (KM) curves between the two clusters differ significantly for OS and RFS (p-value < 0.0001). Moreover, there was a relative predictive improvement when using the cluster label in addition to the clinical features compared to using only clinical features where AUC increased by 5.7% and 13.0% for OS and RFS, respectively.

Evaluating the Effect of Right-Censored End Point Transformation for Radiomic Feature Selection of Data From Patients With Oropharyngeal Cancer.

PURPOSE: To evaluate the effect of transforming a right-censored outcome into binary, continuous, and censored-aware representations on radiomics feature selection and subsequent prediction of overall survival (OS) and relapse-free survival (RFS) of patients with oropharyngeal cancer. METHODS AND MATERIALS: Different feature selection techniques were applied using a binary outcome indicating event occurrence before median follow-up time, a continuous outcome using the Martingale residuals from a proportional hazards model, and the raw right-censored time-to-event outcome. Radiomic signatures combined with clinical variables were used for risk prediction. Three metrics for accuracy and calibration were used to evaluate eight feature selectors and six predictive models. RESULTS: Feature selection across 529 patients on more than 3,800 radiomic features resulted in increases ranging from 0.01 to 0.11 in C-index and area under the curve (AUC) scores compared with clinical features alone. The ensemble model yielded the best scores for AUC and C-index (often > 0.7) and calibration (Nam-D'Agostino test statistic often < 15.5 with 8 df). The random forest feature selectors achieved the best performance considering all metrics. Random regression forest performed the best in OS prediction with the ensemble model (AUC, 0.75; C-index, 0.76; calibration, 8.7). Random survival forest performed the best in RFS prediction with the ensemble model (AUC, 0.71; C-index, 0.68; calibration, 19.1). CONCLUSION: Including a radiomic signature results in better prediction than using only clinical data. Signatures generated randomly or without considering the outcome result in poor calibration scores. The random forest feature selectors for each of the three transformations typically selected the greatest number of features and produced the best predictions at acceptable calibration levels. In particular, random regression forest and random survival forest performed best for OS and RFS, respectively.