Cross-Attention Multimodal Learning for Predicting Response to Neoadjuvant Imatinib in Gastrointestinal Stromal Tumors: A Multicenter Retrospective Study

Background: Response to neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs) is highly variable and cannot be reliably predicted using current clinical or molecular markers. This study developed and evaluated an explainable multimodal deep learning framework integrating computed tomography (CT) imaging and clinical variables to predict treatment response. Methods: Patients from four tertiary centers were retrospectively included between 2000-2023 in independent pretraining (n=935) and prediction (n=213) cohorts. A cross-attention framework integrating clinical variables and tumor-centered CT imaging was developed to predict response to neoadjuvant imatinib. Two training strategies were evaluated: (1) self-supervised pretraining with low-rank adaptation and (2) training from scratch. Hyperparameters were optimized using SMAC3. Performance was assessed through internal cross-validation and external testing. Ablation analyses and attention-based explanations were used to quantify modality contributions. Results: Among 213 patients (54.5% responders), responders had larger tumors (112 vs. 89 mm, P=0.026), higher mitotic index (3 vs. 0, P<0.001), and more frequent KIT mutations (69.0% vs. 56.7%, P=0.019). Cross-attention models achieved the highest internal performance (AUC up to 0.99) but lower external performance (AUC 0.60-0.63). Clinical-only performance was moderate (AUC 0.66), whereas imaging-only models showed limited generalizability (AUC 0.56-0.66). Explainability analyses identified significant differences in feature importance between responders and non-responders, including CD117, BRAF, PDGFRA, age, sex, disease status, and comorbidities (FDR-adjusted P<=0.036). Conclusion: The cross-attention framework shows potential for improving imatinib response prediction in GIST while providing interpretable insights into multimodal determinants of treatment response.

AI in radiological imaging of soft-tissue and bone tumours: a systematic review evaluating against CLAIM and FUTURE-AI guidelines

Soft-tissue and bone tumours (STBT) are rare, diagnostically challenging lesions with variable clinical behaviours and treatment approaches. This systematic review provides an overview of Artificial Intelligence (AI) methods using radiological imaging for diagnosis and prognosis of these tumours, highlighting challenges in clinical translation, and evaluating study alignment with the Checklist for AI in Medical Imaging (CLAIM) and the FUTURE-AI international consensus guidelines for trustworthy and deployable AI to promote the clinical translation of AI methods. The review covered literature from several bibliographic databases, including papers published before 17/07/2024. Original research in peer-reviewed journals focused on radiology-based AI for diagnosing or prognosing primary STBT was included. Exclusion criteria were animal, cadaveric, or laboratory studies, and non-English papers. Abstracts were screened by two of three independent reviewers for eligibility. Eligible papers were assessed against guidelines by one of three independent reviewers. The search identified 15,015 abstracts, from which 325 articles were included for evaluation. Most studies performed moderately on CLAIM, averaging a score of 28.9$\pm$7.5 out of 53, but poorly on FUTURE-AI, averaging 5.1$\pm$2.1 out of 30. Imaging-AI tools for STBT remain at the proof-of-concept stage, indicating significant room for improvement. Future efforts by AI developers should focus on design (e.g. define unmet clinical need, intended clinical setting and how AI would be integrated in clinical workflow), development (e.g. build on previous work, explainability), evaluation (e.g. evaluating and addressing biases, evaluating AI against best practices), and data reproducibility and availability (making documented code and data publicly available). Following these recommendations could improve clinical translation of AI methods.

Minimally Interactive Segmentation of Soft-Tissue Tumors on CT and MRI using Deep Learning

Segmentations are crucial in medical imaging to obtain morphological, volumetric, and radiomics biomarkers. Manual segmentation is accurate but not feasible in the radiologist's clinical workflow, while automatic segmentation generally obtains sub-par performance. We therefore developed a minimally interactive deep learning-based segmentation method for soft-tissue tumors (STTs) on CT and MRI. The method requires the user to click six points near the tumor's extreme boundaries. These six points are transformed into a distance map and serve, with the image, as input for a Convolutional Neural Network. For training and validation, a multicenter dataset containing 514 patients and nine STT types in seven anatomical locations was used, resulting in a Dice Similarity Coefficient (DSC) of 0.85$\pm$0.11 (mean $\pm$ standard deviation (SD)) for CT and 0.84$\pm$0.12 for T1-weighted MRI, when compared to manual segmentations made by expert radiologists. Next, the method was externally validated on a dataset including five unseen STT phenotypes in extremities, achieving 0.81$\pm$0.08 for CT, 0.84$\pm$0.09 for T1-weighted MRI, and 0.88\pm0.08 for previously unseen T2-weighted fat-saturated (FS) MRI. In conclusion, our minimally interactive segmentation method effectively segments different types of STTs on CT and MRI, with robust generalization to previously unseen phenotypes and imaging modalities.