arXiv subjects

Cornelis Verhoef

Publications and source records attributed to Cornelis Verhoef.

9 recordsLinked to original sources

arXiv2026

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.

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arXiv2026

Bivariate deconvolution for cancer detection after surgery

Detection of minimal residual disease (MRD) in cancer patients after surgery can provide an early marker for disease recurrence and guide subsequent treatment decisions. Accurate and sensitive estimation of tumour burden after cancer surgery may be obtained through liq- uid biopsies, measuring circulating tumour DNA (ctDNA) using, for example, mutation-based Variant Allele Frequency (VAF) values. However, to be applicable to all patients this ei- ther requires tumour-informed, patient-specific mutation panels or sensitive, tumour-agnostic genome-wide measurements. We propose a solution that accounts for patient-specific charac- teristics in genome-wide screens. For that, we introduce a bivariate deconvolution model to estimate tumour proportion from circulating cell-free DNA (cfDNA) methylation profiles of patients before and after surgery. The observations are modelled as a convolution of two bivariate latent variables, corresponding to tumour and background signals, mixed by the tumour proportion at each measurement. This bivariate approach links pre- and post-surgery measurements improving estimation of the tumour proportion after surgery, when the tumour signal is potentially very weak, or absent. We approximate likelihood of the convolution through a discretisation of the bivariate density for each latent variable into a two-dimensional grid for each pair of observations which allows for fast maximum likelihood estimation. We evaluate the predictive performance of the estimated post-surgery tumour proportions based on cfDNA methylation against available mutation-based VAF values in one-year recurrence-free survival.

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arXiv2025

Evaluating Open-Weight Large Language Models for Structured Data Extraction from Narrative Medical Reports Across Multiple Use Cases and Languages

Large language models (LLMs) are increasingly used to extract structured information from free-text clinical records, but prior work often focuses on single tasks, limited models, and English-language reports. We evaluated 15 open-weight LLMs on pathology and radiology reports across six use cases, colorectal liver metastases, liver tumours, neurodegenerative diseases, soft-tissue tumours, melanomas, and sarcomas, at three institutes in the Netherlands, UK, and Czech Republic. Models included general-purpose and medical-specialised LLMs of various sizes, and six prompting strategies were compared: zero-shot, one-shot, few-shot, chain-of-thought, self-consistency, and prompt graph. Performance was assessed using task-appropriate metrics, with consensus rank aggregation and linear mixed-effects models quantifying variance. Top-ranked models achieved macro-average scores close to inter-rater agreement across tasks. Small-to-medium general-purpose models performed comparably to large models, while tiny and specialised models performed worse. Prompt graph and few-shot prompting improved performance by ~13%. Task-specific factors, including variable complexity and annotation variability, influenced results more than model size or prompting strategy. These findings show that open-weight LLMs can extract structured data from clinical reports across diseases, languages, and institutions, offering a scalable approach for clinical data curation.

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arXiv2025

Improving Survival Models in Healthcare by Balancing Imbalanced Cohorts: A Novel Approach

We explore whether survival model performance in underrepresented high- and low-risk subgroups - regions of the prognostic spectrum where clinical decisions are most consequential - can be improved through targeted restructuring of the training dataset. Rather than modifying model architecture, we propose a novel risk-stratified sampling method that addresses imbalances in prognostic subgroup density to support more reliable learning in underrepresented tail strata. We introduce a novel methodology that partitions patients by baseline prognostic risk and applies matching within each stratum to equalize representation across the risk distribution. We implement this framework on a cohort of 1,799 patients with resected colorectal liver metastases (CRLM), including 1,197 who received adjuvant chemotherapy and 602 who did not. All models used in this study are Cox proportional hazards models trained on the same set of selected variables. Model performance is assessed via Harrell's C index, time-dependent AUC, and Integrated Calibration Index (ICI), with internal validation using Efron's bias-corrected bootstrapping. External validation is conducted on two independent CRLM datasets. Cox models trained on risk-balanced cohorts showed consistent improvements in internal validation compared to models trained on the full dataset while noticeably enhancing stratified C-index values in underrepresented high- and low-risk strata of the external cohorts. Our findings suggest that survival model performance in observational oncology cohorts can be meaningfully improved through targeted rebalancing of the training data across prognostic risk strata. This approach offers a practical and model-agnostic complement to existing methods, especially in applications where predictive reliability across the full risk continuum is critical to downstream clinical decisions.

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arXiv2024

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.

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arXiv2024

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.

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arXiv2021

An automated machine learning framework to optimize radiomics model construction validated on twelve clinical applications

Predicting clinical outcomes from medical images using quantitative features (``radiomics'') requires many method design choices, Currently, in new clinical applications, finding the optimal radiomics method out of the wide range of methods relies on a manual, heuristic trial-and-error process. We introduce a novel automated framework that optimizes radiomics workflow construction per application by standardizing the radiomics workflow in modular components, including a large collection of algorithms for each component, and formulating a combined algorithm selection and hyperparameter optimization problem. To solve it, we employ automated machine learning through two strategies (random search and Bayesian optimization) and three ensembling approaches. Results show that a medium-sized random search and straight-forward ensembling perform similar to more advanced methods while being more efficient. Validated across twelve clinical applications, our approach outperforms both a radiomics baseline and human experts. Concluding, our framework improves and streamlines radiomics research by fully automatically optimizing radiomics workflow construction. To facilitate reproducibility, we publicly release six datasets, software of the method, and code to reproduce this study.

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arXiv2020

Differential diagnosis and molecular stratification of gastrointestinal stromal tumors on CT images using a radiomics approach

Distinguishing gastrointestinal stromal tumors (GISTs) from other intra-abdominal tumors and GISTs molecular analysis is necessary for treatment planning, but challenging due to its rarity. The aim of this study was to evaluate radiomics for distinguishing GISTs from other intra-abdominal tumors, and in GISTs, predict the c-KIT, PDGFRA,BRAF mutational status and mitotic index (MI). All 247 included patients (125 GISTS, 122 non-GISTs) underwent a contrast-enhanced venous phase CT. The GIST vs. non-GIST radiomics model, including imaging, age, sex and location, had a mean area under the curve (AUC) of 0.82. Three radiologists had an AUC of 0.69, 0.76, and 0.84, respectively. The radiomics model had an AUC of 0.52 for c-KIT, 0.56 for c-KIT exon 11, and 0.52 for the MI. Hence, our radiomics model was able to distinguish GIST from non-GISTS with a performance similar to three radiologists, but was not able to predict the c-KIT mutation or MI.

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arXiv2020

Extending Unsupervised Neural Image Compression With Supervised Multitask Learning

We focus on the problem of training convolutional neural networks on gigapixel histopathology images to predict image-level targets. For this purpose, we extend Neural Image Compression (NIC), an image compression framework that reduces the dimensionality of these images using an encoder network trained unsupervisedly. We propose to train this encoder using supervised multitask learning (MTL) instead. We applied the proposed MTL NIC to two histopathology datasets and three tasks. First, we obtained state-of-the-art results in the Tumor Proliferation Assessment Challenge of 2016 (TUPAC16). Second, we successfully classified histopathological growth patterns in images with colorectal liver metastasis (CLM). Third, we predicted patient risk of death by learning directly from overall survival in the same CLM data. Our experimental results suggest that the representations learned by the MTL objective are: (1) highly specific, due to the supervised training signal, and (2) transferable, since the same features perform well across different tasks. Additionally, we trained multiple encoders with different training objectives, e.g. unsupervised and variants of MTL, and observed a positive correlation between the number of tasks in MTL and the system performance on the TUPAC16 dataset.

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