Tumor-anchored deep feature random forests for out-of-distribution detection in lung cancer segmentation

Accurate segmentation of cancerous lesions from 3D computed tomography (CT) scans is essential for automated treatment planning and response assessment. However, even state-of-the-art models combining self-supervised learning (SSL) pretrained transformers with convolutional decoders are susceptible to out-of-distribution (OOD) inputs, generating confidently incorrect tumor segmentations, posing risks for safe clinical deployment. Existing logit-based methods suffer from task-specific model biases, while architectural enhancements to explicitly detect OOD increase parameters and computational costs. Hence, we introduce a plug-and-play and lightweight post-hoc random forests-based OOD detection framework called RF-Deep that leverages deep features with limited outlier exposure. RF-Deep enhances generalization to imaging variations by repurposing the hierarchical features from the pretrained-then-finetuned backbone encoder, providing task-relevant OOD detection by extracting the features from multiple regions of interest anchored to the predicted tumor segmentations. Hence, it scales to images of varying fields-of-view. We compared RF-Deep against existing OOD detection methods using 1,916 CT scans across near-OOD (pulmonary embolism, negative COVID-19) and far-OOD (kidney cancer, healthy pancreas) datasets. RF-Deep achieved AUROC > 93.50 for the challenging near-OOD datasets and near-perfect detection (AUROC > 99.00) for the far-OOD datasets, substantially outperforming logit-based and radiomics approaches. RF-Deep maintained similar performance consistency across networks of different depths and pretraining strategies, demonstrating its effectiveness as a lightweight, architecture-agnostic approach to enhance the reliability of tumor segmentation from CT volumes.