Clinical Reasoning AI for Oncology Treatment Planning: A Multi-Specialty Case-Based Evaluation
Authors: Philippe E. Spiess, Md Muntasir Zitu, Alison Walker, Daniel A. Anaya, Robert M. Wenham, Michael Vogelbaum, Daniel Grass, Ali-Musa Jaffer, Amod Sarnaik, Caitlin McMullen, Christine Sam, John V. Kiluk, Tianshi Liu, Tiago Biachi, Julio Powsang, Jing-Yi Chern, Roger Li, Seth Felder, Samuel Reynolds, Michael Shafique, Alison Sheehan, Ashley Layman, Cydney A. Warfield, Derrick Legoas, Jaclyn Parrinello, Jena Schmitz, Kevin Eaton, Mark Honor, Luis Felipe, Issam ElNaqa, Elier Delgado, Talia Berler, Rachael V. Phillips, Frantz Francisque, Carlos Garcia Fernandez, Gilmer Valdes
Organizations: Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. · Innova Montréal Inc., IT Services and Consulting, Montréal, QC, Canada. · Oncobrain, Inc., Tampa, FL, USA. · Advanced Cancer Treatment Centers, 15211 Cortez Boulevard, Brooksville, Florida 34613, USA.
Background: More than 80% of U.S. cancer care is delivered in community settings, where survival remains worse than at academic centers. Clinicians must integrate genomics, staging, radiology, pathology, and changing guidelines, creating cognitive burden. We evaluated OncoBrain, an AI clinical reasoning platform for oncology treatment-plan generation, as an early step toward OGI. Methods: OncoBrain combines general-purpose LLMs with a cancer-specific graph retrieval-augmented generation layer, a gold-standard treatment-plan corpus as long-term memory, and a model-agnostic safety layer (CHECK) for hallucination detection and suppression. We evaluated clinician-enriched case summaries across gynecologic, genitourinary, neuro-oncology, gastrointestinal/hepatobiliary, and hematologic malignancies. Three clinician groups completed structured evaluations of 173 cases using a common 16-item instrument: subspecialist oncologists reviewed 50 cases, physician reviewers 78, and advanced practice providers 45. Results: Ratings were highest for scientific accuracy, evidence support, and safety, with lower but favorable scores for workflow integration and time savings. On a 5-point scale, mean alignment with evidence and guidelines was 4.60, 4.56, and 4.70 across subspecialists, physician reviewers, and advanced practice providers. Mean scores for absence of safety or misinformation concerns were 4.80, 4.40, and 4.60. Workflow integration averaged 4.50, 3.94, and 4.00; perceived time savings averaged 5.00, 3.89, and 3.60. Conclusions: In this multi-specialty vignette-based evaluation, OncoBrain generated oncology treatment plans judged guideline-concordant, clinically acceptable, and easy to supervise. These findings support the potential of a carefully engineered AI reasoning platform to assist oncology treatment planning and justify prospective real-world evaluation in community settings.
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.
Mengxian Lyu, Cheng Peng, Tim Jang +18
Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. · Division of Hematology & Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA · University of Florida Health Cancer Institute, Gainesville, FL, USA +8
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
Faculdade de Medicina, Universidade de S˜ao Paulo, Av. Dr. Arnaldo, 455, 01246-903, S˜ao Paulo, S˜ao Paulo, Brazil · Spesia · Laboratory of Artificial Intelligence Applied to Bioinformatics, SEPT, Universidade Federal do Paran´a (UFPR), Rua Alcides Vieira Arcoverde, 1225, 81520-260, Curitiba, Paran´a, Brazil +2
Clinical trials are essential for advancing cancer care and drug development, but many fail because of insufficient patient enrollment. While there is growing interest in using AI to support patient recruitment, existing systems largely perform eligibility assessment alone and have rarely been evaluated in real-world oncology workflows. Here we present TrialGPT 2.0, an AI-assisted clinical trial recommendation system designed for real-world deployment. Rather than asking only whether a patient may qualify, the system also assesses which trials warrant further consideration given the patient's current clinical needs and local workflow priorities, and provides structured, inspectable explanations for expert review. Importantly, we evaluated TrialGPT 2.0 retrospectively and prospectively across multiple oncology-focused settings, spanning government, academic cancer-center, patient-advocacy, and NIH referral workflows. In retrospective multicenter cohorts comprising 288 cases, TrialGPT 2.0 retrieved at least one clinician-recommended trial in its top 10 recommendations for approximately 91% of cases while reducing clinician screening time by 55.0%. In a six-month prospective evaluation embedded in an active precision oncology tumor board, TrialGPT 2.0 contributed additional trial opportunities missed by the routine workflow, expanding patient access to clinical trial participation by 90.9%. To support scientific reproducibility, we also introduce NIH-TrialBench, a clinician-authored dataset comprising 126 diverse synthetic patient vignettes and matching scenarios from 11 NIH Institutes and Centers. Together, these results support the value of AI to assist clinical trial matching by improving clinician efficiency and identifying frequently overlooked trial opportunities, ultimately helping to expand and accelerate accrual to cancer trials.
Yin Fang, Qiao Jin, Shubo Tian +24
Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. · UI Health, University of Illinois Chicago. Chicago, IL, USA. · University of Illinois Urbana-Champaign, Urbana, IL, USA. +6