Expert-Guided Large Language Models for Clinical Decision Support in Precision Oncology

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jacqueline Lammert - , EUropean Network for RAre CANcers (EURACAN) Initiative, partner site Munich, Munich, Germany., German Cancer Consortium (DKTK) partner site Munich, Klinikum Rechts der Isar (MRI TUM) (Author)
  • Tobias Dreyer - , German Cancer Consortium (DKTK) partner site Munich, Klinikum Rechts der Isar (MRI TUM) (Author)
  • Sonja Mathes - , Klinikum Rechts der Isar (MRI TUM), University Medical Center Mainz (Author)
  • Leonid Kuligin - , Google Munich Cloud Space (Author)
  • Kai J Borm - , Klinikum Rechts der Isar (MRI TUM), Bavarian Center for Cancer Research (BZKF) (Author)
  • Ulrich A Schatz - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Marion Kiechle - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Alisa M Lörsch - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Johannes Jung - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Sebastian Lange - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Nicole Pfarr - , Klinikum Rechts der Isar (MRI TUM), Technical University of Munich (Author)
  • Anna Durner - , Klinikum Rechts der Isar (MRI TUM) (Author)
  • Kristina Schwamborn - , Klinikum Rechts der Isar (MRI TUM), Technical University of Munich (Author)
  • Christof Winter - , Klinikum Rechts der Isar (MRI TUM), German Cancer Consortium (DKTK) partner site Munich (Author)
  • Dyke Ferber - , Else Kröner Fresenius Center for Digital Health, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg (Author)
  • Jakob Nikolas Kather - , Department of Internal Medicine I, Else Kröner Fresenius Center for Digital Health, National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Carolin Mogler - , Klinikum Rechts der Isar (MRI TUM), German Cancer Consortium (DKTK) partner site Munich, Technical University of Munich (Author)
  • Anna L Illert - , Klinikum Rechts der Isar (MRI TUM), German Cancer Consortium (DKTK) partner site Munich, Bavarian Center for Cancer Research (BZKF) (Author)
  • Maximilian Tschochohei - , Google Munich Cloud Space (Author)

Abstract

PURPOSE: Rapidly expanding medical literature challenges oncologists seeking targeted cancer therapies. General-purpose large language models (LLMs) lack domain-specific knowledge, limiting their clinical utility. This study introduces the LLM system Medical Evidence Retrieval and Data Integration for Tailored Healthcare (MEREDITH), designed to support treatment recommendations in precision oncology. Built on Google's Gemini Pro LLM, MEREDITH uses retrieval-augmented generation and chain of thought.

METHODS: We evaluated MEREDITH on 10 publicly available fictional oncology cases with iterative feedback from a molecular tumor board (MTB) at a major German cancer center. Initially limited to PubMed-indexed literature (draft system), MEREDITH was enhanced to incorporate clinical studies on drug response within the specific tumor type, trial databases, drug approval status, and oncologic guidelines. The MTB provided a benchmark with manually curated treatment recommendations and assessed the clinical relevance of LLM-generated options (qualitative assessment). We measured semantic cosine similarity between LLM suggestions and clinician responses (quantitative assessment).

RESULTS: MEREDITH identified a broader range of treatment options (median 4) compared with MTB experts (median 2). These options included therapies on the basis of preclinical data and combination treatments, expanding the treatment possibilities for consideration by the MTB. This broader approach was achieved by incorporating a curated medical data set that contextualized molecular targetability. Mirroring the approach MTB experts use to evaluate MTB cases improved the LLM's ability to generate relevant suggestions. This is supported by high concordance between LLM suggestions and expert recommendations (94.7% for the enhanced system) and a significant increase in semantic similarity from the draft to the enhanced system (from 0.71 to 0.76, P = .01).

CONCLUSION: Expert feedback and domain-specific data augment LLM performance. Future research should investigate responsible LLM integration into real-world clinical workflows.

Details

Original languageEnglish
Article numbere2400478
Pages (from-to)e2400478
JournalJCO precision oncology
Volume8
Publication statusPublished - Oct 2024
Peer-reviewedYes

Keywords

Sustainable Development Goals

Keywords

  • Humans, Precision Medicine/methods, Decision Support Systems, Clinical, Medical Oncology/methods, Neoplasms/therapy