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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Jacqueline Lammert - , EUropean Network for RAre CANcers (EURACAN) Initiative, partner site Munich, Munich, Germany., Deutsches Konsortium für Translationale Krebsforschung (DKTK) - München, Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Tobias Dreyer - , Deutsches Konsortium für Translationale Krebsforschung (DKTK) - München, Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Sonja Mathes - , Klinikum Rechts der Isar (MRI TUM), Universitätsmedizin Mainz (Autor:in)
  • Leonid Kuligin - , Google München – Cloud Space (Autor:in)
  • Kai J Borm - , Klinikum Rechts der Isar (MRI TUM), Bayerische Zentrum für Krebsforschung (BZKF) (Autor:in)
  • Ulrich A Schatz - , Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Marion Kiechle - , Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Alisa M Lörsch - , Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Johannes Jung - , Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Sebastian Lange - , Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Nicole Pfarr - , Klinikum Rechts der Isar (MRI TUM), Technische Universität München (Autor:in)
  • Anna Durner - , Klinikum Rechts der Isar (MRI TUM) (Autor:in)
  • Kristina Schwamborn - , Klinikum Rechts der Isar (MRI TUM), Technische Universität München (Autor:in)
  • Christof Winter - , Klinikum Rechts der Isar (MRI TUM), Deutsches Konsortium für Translationale Krebsforschung (DKTK) - München (Autor:in)
  • Dyke Ferber - , Else Kröner Fresenius Zentrum für Digitale Gesundheit, Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg, Universitätsklinikum Heidelberg (Autor:in)
  • Jakob Nikolas Kather - , Medizinische Klinik und Poliklinik I, Else Kröner Fresenius Zentrum für Digitale Gesundheit, Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Carolin Mogler - , Klinikum Rechts der Isar (MRI TUM), Deutsches Konsortium für Translationale Krebsforschung (DKTK) - München, Technische Universität München (Autor:in)
  • Anna L Illert - , Klinikum Rechts der Isar (MRI TUM), Deutsches Konsortium für Translationale Krebsforschung (DKTK) - München, Bayerische Zentrum für Krebsforschung (BZKF) (Autor:in)
  • Maximilian Tschochohei - , Google München – Cloud Space (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummere2400478
Seiten (von - bis)e2400478
FachzeitschriftJCO precision oncology
Jahrgang8
PublikationsstatusVeröffentlicht - Okt. 2024
Peer-Review-StatusJa

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

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