Pancreatic Cancer
Horseshoe Forests for High-Dimensional Causal Survival Analysis
Jacobs, Tijn, van Wieringen, Wessel N., van der Pas, Stéphanie L.
We develop a Bayesian tree ensemble model to estimate heterogeneous treatment effects in censored survival data with high-dimensional covariates. Instead of imposing sparsity through the tree structure, we place a horseshoe prior directly on the step heights to achieve adaptive global-local shrinkage. This strategy allows flexible regularisation and reduces noise. We develop a reversible jump Gibbs sampler to accommodate the non-conjugate horseshoe prior within the tree ensemble framework. We show through extensive simulations that the method accurately estimates treatment effects in high-dimensional covariate spaces, at various sparsity levels, and under non-linear treatment effect functions. We further illustrate the practical utility of the proposed approach by a re-analysis of pancreatic ductal adenocarcinoma (PDAC) survival data from The Cancer Genome Atlas.
Into the Single Cell Multiverse: an End-to-End Dataset for Procedural Knowledge Extraction in Biomedical Texts
Here we describe the additional details of FlaMBé's curation including structured guidelines for each annotation task, corpus curation, and file assembly. All manual curation in FlaMBé was conducted by three annotators who have doctorate level expertise in computational biology. For named entity tagging annotations a set of structured guidelines were followed to ensure consistency. The guidelines given to reviewers are in the annotator guidelines section below. B.1 Tissue and cell type entities Generally, all terms, related synonyms, and text entities that can be mapped to an entry from the tissue, organ, body part, fluid, and cell type branches of the NCI thesaurus were labeled. Instead of a rigid vocabulary fixed on exact matches of NCIThesaurus (NCIT) terms and synonyms, annotators were encouraged to tag any word with the same meaning as an ontology term. For example, "Pancreatic ductal adenocarcinoma" describes cancer of the pancreas, which can be related back to the NCI Thesaurus, and thus was tagged as a "TISSUE". An initial set of rules was provided to each annotator. When one annotator encountered a corner case (e.g., "is neuron a tissue or cell type?") all annotators discussed, reached a consensus, then added the corner case to the set of annotation rules.
Cognitive bias in LLM reasoning compromises interpretation of clinical oncology notes
Kenaston, Matthew W., Ayub, Umair, Parmar, Mihir, Anjum, Muhammad Umair, Naqvi, Syed Arsalan Ahmed, Kumar, Priya, Rawal, Samarth, Chaudhuri, Aadel A., Zakharia, Yousef, Heath, Elizabeth I., Bekaii-Saab, Tanios S., Tao, Cui, Van Allen, Eliezer M., Zhou, Ben, Choi, YooJung, Baral, Chitta, Riaz, Irbaz Bin
Despite high performance on clinical benchmarks, large language models may reach correct conclusions through faulty reasoning, a failure mode with safety implications for oncology decision support that is not captured by accuracy-based evaluation. In this two-cohort retrospective study, we developed a hierarchical taxonomy of reasoning errors from GPT-4 chain-of-thought responses to real oncology notes and tested its clinical relevance. Using breast and pancreatic cancer notes from the CORAL dataset, we annotated 600 reasoning traces to define a three-tier taxonomy mapping computational failures to cognitive bias frameworks. We validated the taxonomy on 822 responses from prostate cancer consult notes spanning localized through metastatic disease, simulating extraction, analysis, and clinical recommendation tasks. Reasoning errors occurred in 23 percent of interpretations and dominated overall errors, with confirmation bias and anchoring bias most common. Reasoning failures were associated with guideline-discordant and potentially harmful recommendations, particularly in advanced disease management. Automated evaluators using state-of-the-art language models detected error presence but could not reliably classify subtypes. These findings show that large language models may provide fluent but clinically unsafe recommendations when reasoning is flawed. The taxonomy provides a generalizable framework for evaluating and improving reasoning fidelity before clinical deployment.
Generalist Models in Medical Image Segmentation: A Survey and Performance Comparison with Task-Specific Approaches
Moglia, Andrea, Leccardi, Matteo, Cavicchioli, Matteo, Maccarini, Alice, Marcon, Marco, Mainardi, Luca, Cerveri, Pietro
Following the successful paradigm shift of large language models, leveraging pre-training on a massive corpus of data and fine-tuning on different downstream tasks, generalist models have made their foray into computer vision. The introduction of Segment Anything Model (SAM) set a milestone on segmentation of natural images, inspiring the design of a multitude of architectures for medical image segmentation. In this survey we offer a comprehensive and in-depth investigation on generalist models for medical image segmentation. We start with an introduction on the fundamentals concepts underpinning their development. Then, we provide a taxonomy on the different declinations of SAM in terms of zero-shot, few-shot, fine-tuning, adapters, on the recent SAM 2, on other innovative models trained on images alone, and others trained on both text and images. We thoroughly analyze their performances at the level of both primary research and best-in-literature, followed by a rigorous comparison with the state-of-the-art task-specific models. We emphasize the need to address challenges in terms of compliance with regulatory frameworks, privacy and security laws, budget, and trustworthy artificial intelligence (AI). Finally, we share our perspective on future directions concerning synthetic data, early fusion, lessons learnt from generalist models in natural language processing, agentic AI and physical AI, and clinical translation.
MiniGPT-Pancreas: Multimodal Large Language Model for Pancreas Cancer Classification and Detection
Moglia, Andrea, Nastasio, Elia Clement, Mainardi, Luca, Cerveri, Pietro
Problem: Pancreas radiological imaging is challenging due to the small size, blurred boundaries, and variability of shape and position of the organ among patients. Goal: In this work we present MiniGPT-Pancreas, a Multimodal Large Language Model (MLLM), as an interactive chatbot to support clinicians in pancreas cancer diagnosis by integrating visual and textual information. Methods: MiniGPT-v2, a general-purpose MLLM, was fine-tuned in a cascaded way for pancreas detection, tumor classification, and tumor detection with multimodal prompts combining questions and computed tomography scans from the National Institute of Health (NIH), and Medical Segmentation Decathlon (MSD) datasets. The AbdomenCT-1k dataset was used to detect the liver, spleen, kidney, and pancreas. Results: MiniGPT-Pancreas achieved an Intersection over Union (IoU) of 0.595 and 0.550 for the detection of pancreas on NIH and MSD datasets, respectively. For the pancreas cancer classification task on the MSD dataset, accuracy, precision, and recall were 0.876, 0.874, and 0.878, respectively. When evaluating MiniGPT-Pancreas on the AbdomenCT-1k dataset for multi-organ detection, the IoU was 0.8399 for the liver, 0.722 for the kidney, 0.705 for the spleen, and 0.497 for the pancreas. For the pancreas tumor detection task, the IoU score was 0.168 on the MSD dataset. Conclusions: MiniGPT-Pancreas represents a promising solution to support clinicians in the classification of pancreas images with pancreas tumors. Future research is needed to improve the score on the detection task, especially for pancreas tumors.
Cross-Representation Benchmarking in Time-Series Electronic Health Records for Clinical Outcome Prediction
Chen, Tianyi, Zhu, Mingcheng, Luo, Zhiyao, Zhu, Tingting
Electronic Health Records (EHRs) enable deep learning for clinical predictions, but the optimal method for representing patient data remains unclear due to inconsistent evaluation practices. We present the first systematic benchmark to compare EHR representation methods, including multivariate time-series, event streams, and textual event streams for LLMs. This benchmark standardises data curation and evaluation across two distinct clinical settings: the MIMIC-IV dataset for ICU tasks (mortality, phenotyping) and the EHRSHOT dataset for longitudinal care (30-day readmission, 1-year pancreatic cancer). For each paradigm, we evaluate appropriate modelling families--including Transformers, MLP, LSTMs and Retain for time-series, CLMBR and count-based models for event streams, 8-20B LLMs for textual streams--and analyse the impact of feature pruning based on data missingness. Our experiments reveal that event stream models consistently deliver the strongest performance. Pre-trained models like CLMBR are highly sample-efficient in few-shot settings, though simpler count-based models can be competitive given sufficient data. Furthermore, we find that feature selection strategies must be adapted to the clinical setting: pruning sparse features improves ICU predictions, while retaining them is critical for longitudinal tasks. Our results, enabled by a unified and reproducible pipeline, provide practical guidance for selecting EHR representations based on the clinical context and data regime.
CECT-Mamba: a Hierarchical Contrast-enhanced-aware Model for Pancreatic Tumor Subtyping from Multi-phase CECT
Gong, Zhifang, Gao, Shuo, Zhao, Ben, Xu, Yingjing, Yang, Yijun, Ju, Shenghong, Zhou, Guangquan
Contrast-enhanced computed tomography (CECT) is the primary imaging technique that provides valuable spatial-temporal information about lesions, enabling the accurate diagnosis and subclassification of pancreatic tumors. However, the high heterogeneity and variability of pancreatic tumors still pose substantial challenges for precise subtyping diagnosis. Previous methods fail to effectively explore the contextual information across multiple CECT phases commonly used in radiologists' diagnostic workflows, thereby limiting their performance. In this paper, we introduce, for the first time, an automatic way to combine the multi-phase CECT data to discriminate between pancreatic tumor subtypes, among which the key is using Mamba with promising learnability and simplicity to encourage both temporal and spatial modeling from multi-phase CECT. Specifically, we propose a dual hierarchical contrast-enhanced-aware Mamba module incorporating two novel spatial and temporal sampling sequences to explore intra and inter-phase contrast variations of lesions. A similarity-guided refinement module is also imposed into the temporal scanning modeling to emphasize the learning on local tumor regions with more obvious temporal variations. Moreover, we design the space complementary integrator and multi-granularity fusion module to encode and aggregate the semantics across different scales, achieving more efficient learning for subtyping pancreatic tumors. The experimental results on an in-house dataset of 270 clinical cases achieve an accuracy of 97.4% and an AUC of 98.6% in distinguishing between pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNETs), demonstrating its potential as a more accurate and efficient tool.
Optimizing Prognostic Biomarker Discovery in Pancreatic Cancer Through Hybrid Ensemble Feature Selection and Multi-Omics Data
Zobolas, John, George, Anne-Marie, López, Alberto, Fischer, Sebastian, Becker, Marc, Aittokallio, Tero
Prediction of patient survival using high-dimensional multi-omics data requires systematic feature selection methods that ensure predictive performance, sparsity, and reliability for prognostic biomarker discovery. We developed a hybrid ensemble feature selection (hEFS) approach that combines data subsampling with multiple prognostic models, integrating both embedded and wrapper-based strategies for survival prediction. Omics features are ranked using a voting-theory-inspired aggregation mechanism across models and subsamples, while the optimal number of features is selected via a Pareto front, balancing predictive accuracy and model sparsity without any user-defined thresholds. When applied to multi-omics datasets from three pancreatic cancer cohorts, hEFS identifies significantly fewer and more stable biomarkers compared to the conventional, late-fusion CoxLasso models, while maintaining comparable discrimination performance. Implemented within the open-source mlr3fselect R package, hEFS offers a robust, interpretable, and clinically valuable tool for prognostic modelling and biomarker discovery in high-dimensional survival settings.
Early Detection of Pancreatic Cancer Using Multimodal Learning on Electronic Health Records
Aouad, Mosbah, Choudhary, Anirudh, Farooq, Awais, Nevers, Steven, Demirkhanyan, Lusine, Harris, Bhrandon, Pappu, Suguna, Gondi, Christopher, Iyer, Ravishankar
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest c ancers, and early detection remains a major clinical challenge due to the absence of spec ific symptoms and reliable biomarkers. In this work, we propose a new multimodal appro ach that integrates longitudinal diagnosis code histories and routinely collected laborato ry measurements from electronic health records to detect PDAC up to one year prior to clin ical diagnosis. Our method combines neural controlled differential equations to model irregular lab time series, pretrained language models and recurrent networks to learn diagnosis code trajectory representations, and cross-attention mechanisms to capture in teractions between the two modalities. We develop and evaluate our approach on a real-world dat aset of nearly 4,700 patients and achieve significant improvements in AUC ranging from 6.5 % to 15.5% over state-of-the-art methods. Furthermore, our model identifies diagnosis codes and laboratory panels associated with elevated PDAC risk, including both established and new biomarkers.
Leveraging Fine-Tuned Large Language Models for Interpretable Pancreatic Cystic Lesion Feature Extraction and Risk Categorization
Rasromani, Ebrahim, Kang, Stella K., Xu, Yanqi, Liu, Beisong, Luhadia, Garvit, Chui, Wan Fung, Pasadyn, Felicia L., Hung, Yu Chih, An, Julie Y., Mathieu, Edwin, Gu, Zehui, Fernandez-Granda, Carlos, Javed, Ammar A., Sacks, Greg D., Gonda, Tamas, Huang, Chenchan, Shen, Yiqiu
Background: Manual extraction of pancreatic cystic lesion (PCL) features from radiology reports is labor-intensive, limiting large-scale studies needed to advance PCL research. Purpose: To develop and evaluate large language models (LLMs) that automatically extract PCL features from MRI/CT reports and assign risk categories based on guidelines. Materials and Methods: We curated a training dataset of 6,000 abdominal MRI/CT reports (2005-2024) from 5,134 patients that described PCLs. Labels were generated by GPT-4o using chain-of-thought (CoT) prompting to extract PCL and main pancreatic duct features. Two open-source LLMs were fine-tuned using QLoRA on GPT-4o-generated CoT data. Features were mapped to risk categories per institutional guideline based on the 2017 ACR White Paper. Evaluation was performed on 285 held-out human-annotated reports. Model outputs for 100 cases were independently reviewed by three radiologists. Feature extraction was evaluated using exact match accuracy, risk categorization with macro-averaged F1 score, and radiologist-model agreement with Fleiss' Kappa. Results: CoT fine-tuning improved feature extraction accuracy for LLaMA (80% to 97%) and DeepSeek (79% to 98%), matching GPT-4o (97%). Risk categorization F1 scores also improved (LLaMA: 0.95; DeepSeek: 0.94), closely matching GPT-4o (0.97), with no statistically significant differences. Radiologist inter-reader agreement was high (Fleiss' Kappa = 0.888) and showed no statistically significant difference with the addition of DeepSeek-FT-CoT (Fleiss' Kappa = 0.893) or GPT-CoT (Fleiss' Kappa = 0.897), indicating that both models achieved agreement levels on par with radiologists. Conclusion: Fine-tuned open-source LLMs with CoT supervision enable accurate, interpretable, and efficient phenotyping for large-scale PCL research, achieving performance comparable to GPT-4o.