# Enhancing Lung Cancer Treatment Outcome Prediction through Semantic Feature Engineering Using Large Language Models

arXiv: https://arxiv.org/abs/2512.20633 · HTML: https://mlsanity.com/paper/2512.20633/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 8 of its 37 references that are in the map.
- First posted on arXiv 1 Dec 2025.

## Builds on (most cited first, 8 of 8)

- [A Unified Approach to Interpreting Model Predictions](https://mlsanity.com/paper/1705.07874/) (2017)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [Med-BERT: pre-trained contextualized embeddings on large-scale structured electronic health records for disease prediction](https://mlsanity.com/paper/2005.12833/) (2020)
- [Can Generalist Foundation Models Outcompete Special-Purpose Tuning? Case Study in Medicine](https://mlsanity.com/paper/2311.16452/) (2023)
- [Towards Generalist Biomedical AI](https://mlsanity.com/paper/2307.14334/) (2023)
- [Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis](https://mlsanity.com/paper/1912.08937/) (2019)
- [Medical Hallucinations in Foundation Models and Their Impact on Healthcare](https://mlsanity.com/paper/2503.05777/) (2025)
- [Gecko: Versatile Text Embeddings Distilled from Large Language Models](https://mlsanity.com/paper/2403.20327/) (2024)

## Abstract (arXiv)

Accurate prediction of treatment outcomes in lung cancer remains challenging due to the sparsity, heterogeneity, and contextual overload of real-world electronic health data. Traditional models often fail to capture semantic information across multimodal streams, while large-scale fine-tuning approaches are impractical in clinical workflows. We introduce a framework that uses Large Language Models (LLMs) as Goal-oriented Knowledge Curators (GKC) to convert laboratory, genomic, and medication data into high-fidelity, task-aligned features. Unlike generic embeddings, GKC produces representations tailored to the prediction objective and operates as an offline preprocessing step that integrates naturally into hospital informatics pipelines. Using a lung cancer cohort (N=184), we benchmarked GKC against expert-engineered features, direct text embeddings, and an end-to-end transformer. Our approach achieved a mean AUROC of 0.803 (95% CI: 0.799-0.807) and outperformed all baselines. An ablation study further confirmed the complementary value of combining all three modalities. These results show that the quality of semantic representation is a key determinant of predictive accuracy in sparse clinical data settings. By reframing LLMs as knowledge curation engines rather than black-box predictors, this work demonstrates a scalable, interpretable, and workflow-compatible pathway for advancing AI-driven decision support in oncology.