AMO-ENE: Attention-based Multi-Omics Fusion Model for Outcome Prediction in Extra Nodal Extension and HPV-associated Oropharyngeal Cancer

Extranodal extension (ENE) is an emerging prognostic factor in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC), although it is currently omitted as a clinical staging criteria. Recent works have advocated for the inclusion of iENE as a prognostic marker in HPV-positive OPC staging. However, several practical limitations continue to hinder its clinical integration, including inconsistencies in segmentation, low contrast in the periphery of metastatic lymph nodes on CT imaging, and laborious manual annotations. To address these limitations, we propose a fully automated end-to-end pipeline that uses computed tomography (CT) images with clinical data to assess the status of nodal ENE and predict treatment outcomes. Our approach includes a hierarchical 3D semi-supervised segmentation model designed to detect and delineate relevant iENE from radiotherapy planning CT scans. From these segmentations, a set of radiomics and deep features are extracted to train an imaging-detected ENE grading classifier. The predicted ENE status is then evaluated for its prognostic value and compared with existing staging criteria. Furthermore, we integrate these nodal features with primary tumor characteristics in a multimodal, attention-based outcome prediction model, providing a dynamic framework for outcome prediction. Our method is validated in an internal cohort of 397 HPV-positive OPC patients treated with radiation therapy or chemoradiotherapy between 2009 and 2020. For outcome prediction at the 2-year mark, our pipeline surpassed baseline models with 88.2% (4.8) in AUC for metastatic recurrence, 79.2% (7.4) for overall survival, and 78.1% (8.6) for disease-free survival. We also obtain a concordance index of 83.3% (6.5) for metastatic recurrence, 71.3% (8.9) for overall survival, and 70.0% (8.1) for disease-free survival, making it feasible for clinical decision making.

An arithmetic method algorithm optimizing k-nearest neighbors compared to regression algorithms and evaluated on real world data sources

Linear regression analysis focuses on predicting a numeric regressand value based on certain regressor values. In this context, k-Nearest Neighbors (k-NN) is a common non-parametric regression algorithm, which achieves efficient performance when compared with other algorithms in literature. In this research effort an optimization of the k-NN algorithm is proposed by exploiting the potentiality of an introduced arithmetic method, which can provide solutions for linear equations involving an arbitrary number of real variables. Specifically, an Arithmetic Method Algorithm (AMA) is adopted to assess the efficiency of the introduced arithmetic method, while an Arithmetic Method Regression (AMR) algorithm is proposed as an optimization of k-NN adopting the potentiality of AMA. Such algorithm is compared with other regression algorithms, according to an introduced optimal inference decision rule, and evaluated on certain real world data sources, which are publicly available. Results are promising since the proposed AMR algorithm has comparable performance with the other algorithms, while in most cases it achieves better performance than the k-NN. The output results indicate that introduced AMR is an optimization of k-NN.