Can Language Models Identify Side Effects of Breast Cancer Radiation Treatments?
Authors: Natalie Seah, Danielle S. Bitterman, Daphna Spiegel, Thomas Hartvigsen
Organizations: University of Virginia · Mass General Brigham, Dana-Farber Cancer Institute, Harvard Medical School
Abstract
Accurately communicating the side effects of cancer treatments to cancer survivors is critical, particularly in settings such as informed consent, where clinicians must clearly and comprehensively convey potential treatment toxicities. However, this task remains challenging due to clinical knowledge deficits about adverse treatment effects and fragmentation across electronic health record (EHR) systems. Large language models (LLMs) have the potential to assist in this task, though their reliability in oncology survivorship contexts remains poorly understood. We present a deployment-oriented stress-testing framework for evaluating LLM-generated radiation side effect lists in breast cancer treatment and survivorship care. Using 21 breast cancer patient profiles, we construct paired patient clinical scenarios that differ only in radiotherapy regimens to evaluate seven instruction-tuned LLMs under multiple prompting regimes. We then compare LLM outputs to a clinician-curated reference derived from informed consent documents at two major academic medical centers and developed by a team including more than seven breast radiation oncologists. The reference maps radiation dose-fractionation, fields, and locations to associated toxicities, broken down by frequency and temporal onset. Across models, we reveal sensitivity to minor documentation changes, trade-offs between precision and recall, and systematic under-recall of rare and long-term side effects. When used alone, constraints on the number of side effects generated reduce precision, and grounding outputs in clinician-curated side effect lists substantially improves reliability and robustness. These findings highlight important limitations of LLM use in oncology and suggest practical design choices for safer and more informative survivorship-focused applications.
Large language models (LLMs) are increasingly being explored for clinical decision support, but their reliability in complex oncology treatment planning remains unclear. We evaluated agentic LLM systems for breast cancer treatment recommendation generation using 72 real clinical cases across stages I to IV and 1,147 case-specific rubrics generated through Asymmetric Information Rubric Generation (AIRG), in which the rubric generator had access to real clinical decisions unavailable to the evaluated models. Seven pipelines were compared, including single-LLM baselines, tool-augmented systems, and multi-agent architectures with fact checking and autonomous subagent spawning. The best-performing configuration, Claude Opus 4.8 with the D&C+SA pipeline, achieved a global score of 0.594 ± 0.025. Tool use and increased agent autonomy had mixed effects, improving performance in some settings but degrading it in others. Performance varied by clinical domain and disease stage, and oncologist-led error analysis revealed persistent clinically relevant failures, including incorrect or missing recommendations, flawed justifications, citation errors, outdated claims, and overconfidence. These findings suggest that agentic LLM systems can generate clinically relevant breast cancer recommendations, but remain insufficient for unsupervised clinical use.
Vinicius Anjos de Almeida, Nícolas Henrique Borges, Leonardo Vicenzi +5
Treatment planning in precision oncology requires synthesizing heterogeneous patient information with rapidly evolving clinical guidelines to ensure guideline-concordant care. While large language models (LLMs) show promise in many diagnostic tasks, their adoption for high-stakes treatment planning is hindered by complex reasoning, adherence to timely clinical guidelines, and safety concerns. In this study, we present GatorOnco, an agentic LLM for colorectal cancer (CRC) treatment planning. GatorOnco is developed using a total of 282 billion tokens of biomedical text, including healthcare system-scale clinical text comprising 166 billion tokens from UF Health. We implemented a domain-adaptation method that integrates pre-training, model merging, a two-stage post-training approach, and agent-based reinforcement learning. An agentic retrieval-augmented generation (RAG) approach dynamically integrates time-sensitive clinical guidelines into the reasoning process. In a blind, randomized clinical evaluation conducted by five UF Health oncologists, GatorOnco significantly outperformed open-source LLMs (P < 0.01) and achieved expert-level performance comparable to UF Health oncologists. Compared with expert oncologists, GatorOnco received significantly higher ratings for readability (4.46 vs. 4.19, P < 0.01) and completeness (3.91 vs. 3.52, P < 0.01), while showing statistically comparable performance in correctness (4.09 vs. 4.11, P = 0.921), currency (4.04 vs. 3.98, P = 0.478), and safety (4.22 vs. 4.22, P = 0.999). These findings demonstrate that integrating agentic reasoning with large-scale domain adaptation can help bridge the gap for generative AI in high-stakes cancer treatment planning.
Breast cancer remains a leading cause of cancer-related mortality among women. Its clinical management requires multimodal reasoning across a clinical workflow that spans \textit{screening}, \textit{diagnosis} and \textit{treatment planning}, where each stage involves distinct imaging modalities, task objectives, and reasoning patterns. However, constrained by data scarcity and model versatility, existing medical MLLMs are typically evaluated on isolated modalities or narrow task families, limiting their ability to support workflow-level clinical reasoning. In this work, we first introduce \textbf{BreastStage}, a workflow-aligned breast imaging instruction corpus comprising 1.86M instruction-following pairs curated from 17 sub-datasets across 5 imaging modalities and 136 task templates. Its held-out split, \textbf{BreastStage-Bench}, provides a comprehensive benchmark for evaluating multimodal reasoning across the breast cancer care continuum. Building on this corpus, we propose \textbf{BreastGPT}, a unified MLLM equipped with a dual-branch visual encoder and concept-preserving token compression to bridge the scale gap between standard radiology and gigapixel pathology. On BreastStage-Bench, BreastGPT achieves 75.66% closed-ended accuracy and 89.92% open-ended score, outperforming both general-purpose and medical-specific MLLMs across clinical stages and task formats. These results suggest that workflow-aligned data and cross-scale visual modeling are critical for clinically grounded medical MLLMs. All data, code, and model checkpoints are released at https://yangyy-liu.github.io/BreastGPT.io.