Empirical investigation of 3D CT Foundation Models and Unsupervised Adaptation for Head and Neck Cancer Recurrence Prediction

The rapid emergence of 3D CT foundation models has opened new avenues for predictive modeling from CT imaging, offering a compelling alternative to traditional radiomics which is known to suffer from reproducibility issues and sensitivity to acquisition protocol variations. Yet, as these models grow in availability, a critical need arises to evaluate how well their learned representations generalize across diverse clinical settings and whether adaptation to specific downstream tasks is necessary to unlock their full potential. To address these questions, we benchmarked several 3D CT foundation models for predicting recurrence-free survival in head and neck cancer across two public datasets totaling 3,644 patients, evaluating various adaptation strategies and modality fusion mechanisms. Our findings reveal persistent difficulty in identifying features that generalize consistently across different imaging distributions, as evidenced by significant performance drops on external validation cohorts. Ultimately, the integration of imaging features with clinical data remains the most accurate approach for prognostic prediction, though achieving universal generalization across varied clinical contexts continues to represent a substantial challenge for the current generation of models.