Foundation-model-guided radiogenomic discovery linking cancer genomes to cancer scans

Accurate preoperative subtype classification of renal cell carcinoma (RCC) from contrast-enhanced computed tomography remains clinically challenging. Radiomics provides structured tumour descriptors, whereas foundation representations offer transferable image features. However, it remains unclear whether radiomics still adds value beyond pretrained representations, and how 2D and 3D MedVAE encoders compare in this setting. We compared handcrafted radiomics, 2D MedVAE, 3D MedVAE, and their fusion for binary clear-cell RCC versus non-clear-cell RCC classification on KiTS23 under a unified preprocessing pipeline. Concatenation, cross-attention, and gated fusion were evaluated as representative integration strategies, and radiomics feature importance was analysed to support decision-centric interpretability. Fusion consistently improved discrimination over image-only MedVAE branches. The best overall performance was achieved by 3D gated fusion, with an AUC of 82.7%, outperforming the best 2D fusion model (79.6%), the radiomics baseline (74.4%), and the single-modality MedVAE branches. Ablation analysis further showed clear gains of the full fusion model over both image-only and radiomics-only variants, indicating complementary contributions from radiomics and image representations. These findings suggest that radiomics remains relevant for RCC CT classification in the presence of foundation representations, and that its integration with MedVAE is more effective in the 3D setting. More broadly, the study supports a complementary role for radiomics and foundation representations in clinically meaningful imaging decision support.

Radiomics provides quantitative descriptions of tumour appearance that may complement disease-specific foundation models in small labelled cohorts. We investigate this complementarity for computed tomography-based classification of clear cell renal cell carcinoma. Our framework uses radiomics to modulate RenalCLIP features through feature-wise linear modulation (FiLM), while retaining a direct radiomics contribution. Internal testing and external validation compare it with conventional fusion strategies and reference classifiers. The FiLM model achieves an area under the receiver operating characteristic curve (AUC) of 0.804 internally and 0.854 externally, with the highest mean AUC among the evaluated RenalCLIP fusion strategies in both cohorts. Pathway ablations examine the contributions of conditional modulation and the direct radiomics residual, while feature permutation highlights the role of tumour texture. These findings support radiomics as a useful complement to RenalCLIP in a small labelled cohort and identify FiLM as an effective approach to integrating their representations for robust renal tumour classification.

Lung cancer remains one of the leading causes of cancer- related mortality worldwide. Although targeted therapies have improved outcomes for patients with non-small cell lung cancer (NSCLC), they rely on mutation profiling through tissue biopsy, an invasive procedure with several limitations. This study investigates PET/CT-based radio- genomic prediction of epidermal growth factor receptor (EGFR), tumour protein 53 (TP53), and Kirsten rat sarcoma viral oncogene (KRAS) mutations using deep learning. We further evaluate whether pairwise multi-label learning improves mutation prediction compared with conventional single-gene classification. To the best of our knowledge, this is among the first studies to systematically investigate multi-label learning for PET/CT radiogenomic mutation prediction in NSCLC. Experiments were conducted on a novel UK-based radiogenomics cohort. Joint pre- diction of KRAS and TP53 improved AUC from 0.58 to 0.64 for KRAS and from 0.69 to 0.71 for TP53. For the EGFR/KRAS pair, only EGFR benefited from joint learning, while no improvement was observed for the EGFR/TP53 pair. These findings demonstrate that the effectiveness of multi-label learning depends on the specific combination of gene mutations being modelled, suggesting that mutation-specific modelling strategies may be preferable for PET/CT radiogenomic prediction.