LGAISep 25, 2025

Knowledgeable Language Models as Black-Box Optimizers for Personalized Medicine

arXiv:2509.20975v1h-index: 37
Originality Highly original
AI Analysis

This work addresses the problem of generalizing surrogate models for personalized medicine, offering a novel method to improve treatment optimization for patients.

The paper tackles the challenge of optimizing personalized treatment plans by using large language models as black-box optimizers, leveraging domain knowledge without fine-tuning, and shows that their method outperforms existing approaches in real-world tasks.

The goal of personalized medicine is to discover a treatment regimen that optimizes a patient's clinical outcome based on their personal genetic and environmental factors. However, candidate treatments cannot be arbitrarily administered to the patient to assess their efficacy; we often instead have access to an in silico surrogate model that approximates the true fitness of a proposed treatment. Unfortunately, such surrogate models have been shown to fail to generalize to previously unseen patient-treatment combinations. We hypothesize that domain-specific prior knowledge - such as medical textbooks and biomedical knowledge graphs - can provide a meaningful alternative signal of the fitness of proposed treatments. To this end, we introduce LLM-based Entropy-guided Optimization with kNowledgeable priors (LEON), a mathematically principled approach to leverage large language models (LLMs) as black-box optimizers without any task-specific fine-tuning, taking advantage of their ability to contextualize unstructured domain knowledge to propose personalized treatment plans in natural language. In practice, we implement LEON via 'optimization by prompting,' which uses LLMs as stochastic engines for proposing treatment designs. Experiments on real-world optimization tasks show LEON outperforms both traditional and LLM-based methods in proposing individualized treatments for patients.

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