Explainable AI for Precision Oncology: A Task-Specific Approach Using Imaging, Multi-omics, and Clinical Data

Abstract

Abstract Despite continued advances in oncology, cancer remains a leading cause of global mortality, highlighting the need for diagnostic and prognostic tools that are both accurate and interpretable. Unimodal approaches often fail to capture the biological and clinical complexity of tumors. In this study, we present a suite of task-specific AI models that leverage CT imaging, multi-omics profiles, and structured clinical data to address distinct challenges in segmentation, classification, and prognosis. We developed three independent models across large public datasets. Task 1 applied a 3D U-Net to segment pancreatic tumors from CT scans, achieving a Dice Similarity Coefficient (DSC) of 0.7062. Task 2 employed a hierarchical ensemble of omics-based classifiers to distinguish tumor from normal tissue and classify six major cancer types with 98.67% accuracy. Task 3 benchmarked classical machine learning models on clinical data for prognosis prediction across three cancers (LIHC, KIRC, STAD), achieving strong performance (e.g., C-index of 0.820 in KIRC, AUC of 0.978 in LIHC). Across all tasks, explainable AI methods such as SHAP and attention-based visualization enabled transparent interpretation of model outputs. These results demonstrate the value of tailored, modality-aware models and underscore the clinical potential of applying such tailored AI systems for precision oncology. Technical Foundations Segmentation (Task 1): A custom 3D U-Net was trained using the Task07_Pancreas dataset from the Medical Segmentation Decathlon (MSD). CT images were preprocessed with MONAI-based pipelines, resampled to (64, 96, 96) voxels, and intensity-windowed to HU ranges of –100 to 240. Classification (Task 2): Multi-omics data from TCGA—including gene expression, methylation, miRNA, CNV, and mutation profiles—were log-transformed and normalized. Five modality-specific LightGBM classifiers generated meta-features for a late-fusion ensemble. Stratified 5-fold cross-validation was used for evaluation. Prognosis (Task 3): Clinical variables from TCGA were curated and imputed (median/mode), with high-missing-rate columns removed. Survival models (e.g., Cox-PH, Random Forest, XGBoost) were trained with early stopping. No omics or imaging data were used in this task. Interpretability: SHAP values were computed for all tree-based models, and attention-based overlays were used in imaging tasks to visualize salient regions.

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