Jason Holmes

Jason Holmes, Zhengliang Liu, Lian Zhang et al.

We present the first study to investigate Large Language Models (LLMs) in answering radiation oncology physics questions. Because popular exams like AP Physics, LSAT, and GRE have large test-taker populations and ample test preparation resources in circulation, they may not allow for accurately assessing the true potential of LLMs. This paper proposes evaluating LLMs on a highly-specialized topic, radiation oncology physics, which may be more pertinent to scientific and medical communities in addition to being a valuable benchmark of LLMs. We developed an exam consisting of 100 radiation oncology physics questions based on our expertise at Mayo Clinic. Four LLMs, ChatGPT (GPT-3.5), ChatGPT (GPT-4), Bard (LaMDA), and BLOOMZ, were evaluated against medical physicists and non-experts. ChatGPT (GPT-4) outperformed all other LLMs as well as medical physicists, on average. The performance of ChatGPT (GPT-4) was further improved when prompted to explain first, then answer. ChatGPT (GPT-3.5 and GPT-4) showed a high level of consistency in its answer choices across a number of trials, whether correct or incorrect, a characteristic that was not observed in the human test groups. In evaluating ChatGPTs (GPT-4) deductive reasoning ability using a novel approach (substituting the correct answer with "None of the above choices is the correct answer."), ChatGPT (GPT-4) demonstrated surprising accuracy, suggesting the potential presence of an emergent ability. Finally, although ChatGPT (GPT-4) performed well overall, its intrinsic properties did not allow for further improvement when scoring based on a majority vote across trials. In contrast, a team of medical physicists were able to greatly outperform ChatGPT (GPT-4) using a majority vote. This study suggests a great potential for LLMs to work alongside radiation oncology experts as highly knowledgeable assistants.

Zhengliang Liu, Peilong Wang, Yiwei Li et al.

This paper presents RadOnc-GPT, a large language model specialized for radiation oncology through advanced tuning methods. RadOnc-GPT was finetuned on a large dataset of radiation oncology patient records from the Mayo Clinic in Arizona. The model employs instruction tuning on three key tasks - generating radiotherapy treatment regimens, determining optimal radiation modalities, and providing diagnostic descriptions/ICD codes based on patient diagnostic details. Evaluations conducted by comparing RadOnc-GPT outputs to general large language model outputs showed higher ROUGE scores in these three tasks. The study demonstrated the potential of using large language models fine-tuned using domain-specific knowledge like RadOnc-GPT to achieve transformational capabilities in highly specialized healthcare fields such as radiation oncology. However, our model's clinical relevance requires confirmation, and it specializes in only the aforementioned three specific tasks and lacks broader applicability. Furthermore, its evaluation through ROUGE scores might not reflect the true semantic and clinical accuracy - challenges we intend to address in future research.

Lian Zhang, Zhengliang Liu, Lu Zhang et al.

In this study, we evaluate the performance of the Segment Anything Model (SAM) in clinical radiotherapy. Our results indicate that SAM's 'segment anything' mode can achieve clinically acceptable segmentation results in most organs-at-risk (OARs) with Dice scores higher than 0.7. SAM's 'box prompt' mode further improves the Dice scores by 0.1 to 0.5. Considering the size of the organ and the clarity of its boundary, SAM displays better performance for large organs with clear boundaries but performs worse for smaller organs with unclear boundaries. Given that SAM, a model pre-trained purely on natural images, can handle the delineation of OARs from medical images with clinically acceptable accuracy, these results highlight SAM's robust generalization capabilities with consistent accuracy in automatic segmentation for radiotherapy. In other words, SAM can achieve delineation of different OARs at different sites using a generic automatic segmentation model. SAM's generalization capabilities across different disease sites suggest that it is technically feasible to develop a generic model for automatic segmentation in radiotherapy.

Yuzhen Ding, Hongying Feng, Yunze Yang et al.

Purpose: In some proton therapy facilities, patient alignment relies on two 2D orthogonal kV images, taken at fixed, oblique angles, as no 3D on-the-bed imaging is available. The visibility of the tumor in kV images is limited since the patient's 3D anatomy is projected onto a 2D plane, especially when the tumor is behind high-density structures such as bones. This can lead to large patient setup errors. A solution is to reconstruct the 3D CT image from the kV images obtained at the treatment isocenter in the treatment position. Methods: An asymmetric autoencoder-like network built with vision-transformer blocks was developed. The data was collected from 1 head and neck patient: 2 orthogonal kV images (1024x1024 voxels), 1 3D CT with padding (512x512x512) acquired from the in-room CT-on-rails before kVs were taken and 2 digitally-reconstructed-radiograph (DRR) images (512x512) based on the CT. We resampled kV images every 8 voxels and DRR and CT every 4 voxels, thus formed a dataset consisting of 262,144 samples, in which the images have a dimension of 128 for each direction. In training, both kV and DRR images were utilized, and the encoder was encouraged to learn the jointed feature map from both kV and DRR images. In testing, only independent kV images were used. The full-size synthetic CT (sCT) was achieved by concatenating the sCTs generated by the model according to their spatial information. The image quality of the synthetic CT (sCT) was evaluated using mean absolute error (MAE) and per-voxel-absolute-CT-number-difference volume histogram (CDVH). Results: The model achieved a speed of 2.1s and a MAE of <40HU. The CDVH showed that <5% of the voxels had a per-voxel-absolute-CT-number-difference larger than 185 HU. Conclusion: A patient-specific vision-transformer-based network was developed and shown to be accurate and efficient to reconstruct 3D CT images from kV images.

Zhengliang Liu, Tianyang Zhong, Yiwei Li et al.

The rise of large language models (LLMs) has marked a pivotal shift in the field of natural language processing (NLP). LLMs have revolutionized a multitude of domains, and they have made a significant impact in the medical field. Large language models are now more abundant than ever, and many of these models exhibit bilingual capabilities, proficient in both English and Chinese. However, a comprehensive evaluation of these models remains to be conducted. This lack of assessment is especially apparent within the context of radiology NLP. This study seeks to bridge this gap by critically evaluating thirty two LLMs in interpreting radiology reports, a crucial component of radiology NLP. Specifically, the ability to derive impressions from radiologic findings is assessed. The outcomes of this evaluation provide key insights into the performance, strengths, and weaknesses of these LLMs, informing their practical applications within the medical domain.

Tianyang Zhong, Zhengliang Liu, Yi Pan et al.

This comprehensive study evaluates the performance of OpenAI's o1-preview large language model across a diverse array of complex reasoning tasks, spanning multiple domains, including computer science, mathematics, natural sciences, medicine, linguistics, and social sciences. Through rigorous testing, o1-preview demonstrated remarkable capabilities, often achieving human-level or superior performance in areas ranging from coding challenges to scientific reasoning and from language processing to creative problem-solving. Key findings include: -83.3% success rate in solving complex competitive programming problems, surpassing many human experts. -Superior ability in generating coherent and accurate radiology reports, outperforming other evaluated models. -100% accuracy in high school-level mathematical reasoning tasks, providing detailed step-by-step solutions. -Advanced natural language inference capabilities across general and specialized domains like medicine. -Impressive performance in chip design tasks, outperforming specialized models in areas such as EDA script generation and bug analysis. -Remarkable proficiency in anthropology and geology, demonstrating deep understanding and reasoning in these specialized fields. -Strong capabilities in quantitative investing. O1 has comprehensive financial knowledge and statistical modeling skills. -Effective performance in social media analysis, including sentiment analysis and emotion recognition. The model excelled particularly in tasks requiring intricate reasoning and knowledge integration across various fields. While some limitations were observed, including occasional errors on simpler problems and challenges with certain highly specialized concepts, the overall results indicate significant progress towards artificial general intelligence.

Xinyu Gong, Jason Holmes, Yiwei Li et al.

Recent advances in Large Language Models (LLMs) have presented new opportunities for integrating Artificial General Intelligence (AGI) into biological research and education. This study evaluated the capabilities of leading LLMs, including GPT-4, GPT-3.5, PaLM2, Claude2, and SenseNova, in answering conceptual biology questions. The models were tested on a 108-question multiple-choice exam covering biology topics in molecular biology, biological techniques, metabolic engineering, and synthetic biology. Among the models, GPT-4 achieved the highest average score of 90 and demonstrated the greatest consistency across trials with different prompts. The results indicated GPT-4's proficiency in logical reasoning and its potential to aid biology research through capabilities like data analysis, hypothesis generation, and knowledge integration. However, further development and validation are still required before the promise of LLMs in accelerating biological discovery can be realized.

Jason Holmes, Rui Peng, Yiwei Li et al.

IMPORTANCE The response effectiveness of different large language models (LLMs) and various individuals, including medical students, graduate students, and practicing physicians, in pediatric ophthalmology consultations, has not been clearly established yet. OBJECTIVE Design a 100-question exam based on pediatric ophthalmology to evaluate the performance of LLMs in highly specialized scenarios and compare them with the performance of medical students and physicians at different levels. DESIGN, SETTING, AND PARTICIPANTS This survey study assessed three LLMs, namely ChatGPT (GPT-3.5), GPT-4, and PaLM2, were assessed alongside three human cohorts: medical students, postgraduate students, and attending physicians, in their ability to answer questions related to pediatric ophthalmology. It was conducted by administering questionnaires in the form of test papers through the LLM network interface, with the valuable participation of volunteers. MAIN OUTCOMES AND MEASURES Mean scores of LLM and humans on 100 multiple-choice questions, as well as the answer stability, correlation, and response confidence of each LLM. RESULTS GPT-4 performed comparably to attending physicians, while ChatGPT (GPT-3.5) and PaLM2 outperformed medical students but slightly trailed behind postgraduate students. Furthermore, GPT-4 exhibited greater stability and confidence when responding to inquiries compared to ChatGPT (GPT-3.5) and PaLM2. CONCLUSIONS AND RELEVANCE Our results underscore the potential for LLMs to provide medical assistance in pediatric ophthalmology and suggest significant capacity to guide the education of medical students.

Jason Holmes, Shuyuan Ye, Yiwei Li et al.

Purpose: The performance of three different large language models (LLMS) (GPT-3.5, GPT-4, and PaLM2) in answering ophthalmology professional questions was evaluated and compared with that of three different professional populations (medical undergraduates, medical masters, and attending physicians). Methods: A 100-item ophthalmology single-choice test was administered to three different LLMs (GPT-3.5, GPT-4, and PaLM2) and three different professional levels (medical undergraduates, medical masters, and attending physicians), respectively. The performance of LLM was comprehensively evaluated and compared with the human group in terms of average score, stability, and confidence. Results: Each LLM outperformed undergraduates in general, with GPT-3.5 and PaLM2 being slightly below the master's level, while GPT-4 showed a level comparable to that of attending physicians. In addition, GPT-4 showed significantly higher answer stability and confidence than GPT-3.5 and PaLM2. Conclusion: Our study shows that LLM represented by GPT-4 performs better in the field of ophthalmology. With further improvements, LLM will bring unexpected benefits in medical education and clinical decision making in the near future.

Jason Holmes, Lian Zhang, Yuzhen Ding et al.

Purpose: To introduce the concept of using large language models (LLMs) to re-label structure names in accordance with the American Association of Physicists in Medicine (AAPM) Task Group (TG)-263 standard, and to establish a benchmark for future studies to reference. Methods and Materials: The Generative Pre-trained Transformer (GPT)-4 application programming interface (API) was implemented as a Digital Imaging and Communications in Medicine (DICOM) storage server, which upon receiving a structure set DICOM file, prompts GPT-4 to re-label the structure names of both target volumes and normal tissues according to the AAPM TG-263. Three disease sites, prostate, head and neck, and thorax were selected for evaluation. For each disease site category, 150 patients were randomly selected for manually tuning the instructions prompt (in batches of 50) and 50 patients were randomly selected for evaluation. Structure names that were considered were those that were most likely to be relevant for studies utilizing structure contours for many patients. Results: The overall re-labeling accuracy of both target volumes and normal tissues for prostate, head and neck, and thorax cases was 96.0%, 98.5%, and 96.9% respectively. Re-labeling of target volumes was less accurate on average except for prostate - 100%, 93.1%, and 91.1% respectively. Conclusions: Given the accuracy of GPT-4 in re-labeling structure names of both target volumes and normal tissues as presented in this work, LLMs are poised to be the preferred method for standardizing structure names in radiation oncology, especially considering the rapid advancements in LLM capabilities that are likely to continue.

Jason Holmes, Federico Mastroleo, Mariana Borras-Osorio et al.

Objective: To describe the design and early clinical evaluation of The Daily Dose (TDD), an LLM-driven, automated clinical summarization and clinical-trial identification system integrated into routine radiation oncology practice. Design: Mixed-methods evaluation using a cross-sectional, anonymous clinician survey administered after 1 month of system deployment. Exposure: Daily automated delivery of physician-specific email summaries generated using RadOnc-GPT, including patient schedules, concise EHR-derived clinical-status summaries, and automated identification of potentially relevant clinical trials for new or consult visits. Main Outcomes and Measures: Primary outcomes included self-reported usability, satisfaction, perceived usefulness, perceived impact on workflow, time savings, and intention for continued use. Internal consistency reliability was assessed using Cronbach's $α$. Results: Among 55 respondents, 52 (94.5\%) worked in radiation oncology, and 38 (69.1\%) were attending physicians. Most participants (83.6\%) reported using TDD daily or several times per week. Mean (SD) scores were 3.89 (1.04) for usability and satisfaction, 3.43 (1.24) for perceived usefulness, and 3.80 (1.17) for impact and future use (5-point Likert scale). Overall satisfaction was positively associated with perceived time savings ($p < .001$). Participants reported variable time savings, with 27\% estimating $\geq 10$ minutes saved per day. The questionnaire demonstrated excellent internal consistency (overall Cronbach's $α$ = 0.97).

Yujin Oh, Sangjoon Park, Xiang Li et al.

Clinical decision-making reflects diverse strategies shaped by regional patient populations and institutional protocols. However, most existing medical artificial intelligence (AI) models are trained on highly prevalent data patterns, which reinforces biases and fails to capture the breadth of clinical expertise. Inspired by the recent advances in Mixture of Experts (MoE), we propose a Mixture of Multicenter Experts (MoME) framework to address AI bias in the medical domain without requiring data sharing across institutions. MoME integrates specialized expertise from diverse clinical strategies to enhance model generalizability and adaptability across medical centers. We validate this framework using a multimodal target volume delineation model for prostate cancer radiotherapy. With few-shot training that combines imaging and clinical notes from each center, the model outperformed baselines, particularly in settings with high inter-center variability or limited data availability. Furthermore, MoME enables model customization to local clinical preferences without cross-institutional data exchange, making it especially suitable for resource-constrained settings while promoting broadly generalizable medical AI.

Peilong Wang, Zhengliang Liu, Yiwei Li et al.

Background: The radiation oncology clinical practice involves many steps relying on the dynamic interplay of abundant text data. Large language models have displayed remarkable capabilities in processing complex text information. But their direct applications in specific fields like radiation oncology remain underexplored. Purpose: This study aims to investigate whether fine-tuning LLMs with domain knowledge can improve the performance on Task (1) treatment regimen generation, Task (2) treatment modality selection (photon, proton, electron, or brachytherapy), and Task (3) ICD-10 code prediction in radiation oncology. Methods: Data for 15,724 patient cases were extracted. Cases where patients had a single diagnostic record, and a clearly identifiable primary treatment plan were selected for preprocessing and manual annotation to have 7,903 cases of the patient diagnosis, treatment plan, treatment modality, and ICD-10 code. Each case was used to construct a pair consisting of patient diagnostics details and an answer (treatment regimen, treatment modality, or ICD-10 code respectively) for the supervised fine-tuning of these three tasks. Open source LLaMA2-7B and Mistral-7B models were utilized for the fine-tuning with the Low-Rank Approximations method. Accuracy and ROUGE-1 score were reported for the fine-tuned models and original models. Clinical evaluation was performed on Task (1) by radiation oncologists, while precision, recall, and F-1 score were evaluated for Task (2) and (3). One-sided Wilcoxon signed-rank tests were used to statistically analyze the results. Results: Fine-tuned LLMs outperformed original LLMs across all tasks with p-value <= 0.001. Clinical evaluation demonstrated that over 60% of the fine-tuned LLMs-generated treatment regimens were clinically acceptable. Precision, recall, and F1-score showed improved performance of fine-tuned LLMs.

Zhengliang Liu, Jason Holmes, Wenxiong Liao et al.

We present the Radiation Oncology NLP Database (ROND), the first dedicated Natural Language Processing (NLP) dataset for radiation oncology, an important medical specialty that has received limited attention from the NLP community in the past. With the advent of Artificial General Intelligence (AGI), there is an increasing need for specialized datasets and benchmarks to facilitate research and development. ROND is specifically designed to address this gap in the domain of radiation oncology, a field that offers many opportunities for NLP exploration. It encompasses various NLP tasks including Logic Reasoning, Text Classification, Named Entity Recognition (NER), Question Answering (QA), Text Summarization, and Patient-Clinician Conversations, each with a distinct focus on radiation oncology concepts and application cases. In addition, we have developed an instruction-tuning dataset consisting of over 20k instruction pairs (based on ROND) and trained a large language model, CancerChat. This serves to demonstrate the potential of instruction-tuning large language models within a highly-specialized medical domain. The evaluation results in this study could serve as baseline results for future research. ROND aims to stimulate advancements in radiation oncology and clinical NLP by offering a platform for testing and improving algorithms and models in a domain-specific context. The ROND dataset is a joint effort of multiple U.S. health institutions. The data is available at https://github.com/zl-liu/Radiation-Oncology-NLP-Database.

Peilong Wang, Jason Holmes, Zhengliang Liu et al.

Purpose: We present an updated study evaluating the performance of large language models (LLMs) in answering radiation oncology physics questions, focusing on the recently released models. Methods: A set of 100 multiple-choice radiation oncology physics questions, previously created by a well-experienced physicist, was used for this study. The answer options of the questions were randomly shuffled to create "new" exam sets. Five LLMs -- OpenAI o1-preview, GPT-4o, LLaMA 3.1 (405B), Gemini 1.5 Pro, and Claude 3.5 Sonnet -- with the versions released before September 30, 2024, were queried using these new exam sets. To evaluate their deductive reasoning ability, the correct answer options in the questions were replaced with "None of the above." Then, the explain-first and step-by-step instruction prompts were used to test if this strategy improved their reasoning ability. The performance of the LLMs was compared with the answers from medical physicists. Results: All models demonstrated expert-level performance on these questions, with o1-preview even surpassing medical physicists with a majority vote. When replacing the correct answer options with 'None of the above', all models exhibited a considerable decline in performance, suggesting room for improvement. The explain-first and step-by-step instruction prompts helped enhance the reasoning ability of the LLaMA 3.1 (405B), Gemini 1.5 Pro, and Claude 3.5 Sonnet models. Conclusion: These recently released LLMs demonstrated expert-level performance in answering radiation oncology physics questions, exhibiting great potential to assist in radiation oncology physics education and training.

Jason Holmes, Yuexing Hao, Mariana Borras-Osorio et al.

Manual labeling limits the scale, accuracy, and timeliness of patient outcomes research in radiation oncology. We present RadOnc-GPT, an autonomous large language model (LLM)-based agent capable of independently retrieving patient-specific information, iteratively assessing evidence, and returning structured outcomes. Our evaluation explicitly validates RadOnc-GPT across two clearly defined tiers of increasing complexity: (1) a structured quality assurance (QA) tier, assessing the accurate retrieval of demographic and radiotherapy treatment plan details, followed by (2) a complex clinical outcomes labeling tier involving determination of mandibular osteoradionecrosis (ORN) in head-and-neck cancer patients and detection of cancer recurrence in independent prostate and head-and-neck cancer cohorts requiring combined interpretation of structured and unstructured patient data. The QA tier establishes foundational trust in structured-data retrieval, a critical prerequisite for successful complex clinical outcome labeling.

Meiyun Cao, Shaw Hu, Jason Sharp et al.

Purpose: This study aims to use a large language model (LLM) to automate the generation of summaries from the CT simulation orders and evaluate its performance. Materials and Methods: A total of 607 CT simulation orders for patients were collected from the Aria database at our institution. A locally hosted Llama 3.1 405B model, accessed via the Application Programming Interface (API) service, was used to extract keywords from the CT simulation orders and generate summaries. The downloaded CT simulation orders were categorized into seven groups based on treatment modalities and disease sites. For each group, a customized instruction prompt was developed collaboratively with therapists to guide the Llama 3.1 405B model in generating summaries. The ground truth for the corresponding summaries was manually derived by carefully reviewing each CT simulation order and subsequently verified by therapists. The accuracy of the LLM-generated summaries was evaluated by therapists using the verified ground truth as a reference. Results: About 98% of the LLM-generated summaries aligned with the manually generated ground truth in terms of accuracy. Our evaluations showed an improved consistency in format and enhanced readability of the LLM-generated summaries compared to the corresponding therapists-generated summaries. This automated approach demonstrated a consistent performance across all groups, regardless of modality or disease site. Conclusions: This study demonstrated the high precision and consistency of the Llama 3.1 405B model in extracting keywords and summarizing CT simulation orders, suggesting that LLMs have great potential to help with this task, reduce the workload of therapists and improve workflow efficiency.

Junjie Cui, Peilong Wang, Jason Holmes et al.

Purpose: To develop a retrieval-augmented generation (RAG) system powered by LLaMA-4 109B for automated, protocol-aware, and interpretable evaluation of radiotherapy treatment plans. Methods and Materials: We curated a multi-protocol dataset of 614 radiotherapy plans across four disease sites and constructed a knowledge base containing normalized dose metrics and protocol-defined constraints. The RAG system integrates three core modules: a retrieval engine optimized across five SentenceTransformer backbones, a percentile prediction component based on cohort similarity, and a clinical constraint checker. These tools are directed by a large language model (LLM) using a multi-step prompt-driven reasoning pipeline to produce concise, grounded evaluations. Results: Retrieval hyperparameters were optimized using Gaussian Process on a scalarized loss function combining root mean squared error (RMSE), mean absolute error (MAE), and clinically motivated accuracy thresholds. The best configuration, based on all-MiniLM-L6-v2, achieved perfect nearest-neighbor accuracy within a 5-percentile-point margin and a sub-2pt MAE. When tested end-to-end, the RAG system achieved 100% agreement with the computed values by standalone retrieval and constraint-checking modules on both percentile estimates and constraint identification, confirming reliable execution of all retrieval, prediction and checking steps. Conclusion: Our findings highlight the feasibility of combining structured population-based scoring with modular tool-augmented reasoning for transparent, scalable plan evaluation in radiation therapy. The system offers traceable outputs, minimizes hallucination, and demonstrates robustness across protocols. Future directions include clinician-led validation, and improved domain-adapted retrieval models to enhance real-world integration.

Yuzhen Ding, Jason Holmes, Hongying Feng et al.

Purpose: Intensity-modulated proton therapy (IMPT) offers precise tumor coverage while sparing organs at risk (OARs) in head and neck (H&N) cancer. However, its sensitivity to anatomical changes requires frequent adaptation through online adaptive radiation therapy (oART), which depends on fast, accurate dose calculation via Monte Carlo (MC) simulations. Reducing particle count accelerates MC but degrades accuracy. To address this, denoising low-statistics MC dose maps is proposed to enable fast, high-quality dose generation. Methods: We developed a diffusion transformer-based denoising framework. IMPT plans and 3D CT images from 80 H&N patients were used to generate noisy and high-statistics dose maps using MCsquare (1 min and 10 min per plan, respectively). Data were standardized into uniform chunks with zero-padding, normalized, and transformed into quasi-Gaussian distributions. Testing was done on 10 H&N, 10 lung, 10 breast, and 10 prostate cancer cases, preprocessed identically. The model was trained with noisy dose maps and CT images as input and high-statistics dose maps as ground truth, using a combined loss of mean square error (MSE), residual loss, and regional MAE (focusing on top/bottom 10% dose voxels). Performance was assessed via MAE, 3D Gamma passing rate, and DVH indices. Results: The model achieved MAEs of 0.195 (H&N), 0.120 (lung), 0.172 (breast), and 0.376 Gy[RBE] (prostate). 3D Gamma passing rates exceeded 92% (3%/2mm) across all sites. DVH indices for clinical target volumes (CTVs) and OARs closely matched the ground truth. Conclusion: A diffusion transformer-based denoising framework was developed and, though trained only on H&N data, generalizes well across multiple disease sites.