# Predicting Targeted Therapy Resistance in Non-Small Cell Lung Cancer Using Multimodal Machine Learning

arXiv: https://arxiv.org/abs/2503.24165 · HTML: https://mlsanity.com/paper/2503.24165/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 6 of its 29 references that are in the map.
- First posted on arXiv 31 Mar 2025.

## Builds on (most cited first, 6 of 6)

- [Self-Normalizing Neural Networks](https://mlsanity.com/paper/1706.02515/) (2017)
- [HoVer-Net: Simultaneous Segmentation and Classification of Nuclei in Multi-Tissue Histology Images](https://mlsanity.com/paper/1812.06499/) (2018)
- [Pathologist-level classification of histologic patterns on resected lung adenocarcinoma slides with deep neural networks](https://mlsanity.com/paper/1901.11489/) (2019)
- [Attention-Based Deep Neural Networks for Detection of Cancerous and Precancerous Esophagus Tissue on Histopathological Slides](https://mlsanity.com/paper/1811.08513/) (2018)
- [MHAttnSurv: Multi-Head Attention for Survival Prediction Using Whole-Slide Pathology Images](https://mlsanity.com/paper/2110.11558/) (2021)
- [Masked Pre-Training of Transformers for Histology Image Analysis](https://mlsanity.com/paper/2304.07434/) (2023)

## Built on by (most cited first, 1 of 1)

- [A Narrative Review on Large AI Models in Lung Cancer Screening, Diagnosis, and Treatment Planning](https://mlsanity.com/paper/2506.07236/) (2025)

## Abstract (arXiv)

Lung cancer is the primary cause of cancer death globally, with non-small cell lung cancer (NSCLC) emerging as its most prevalent subtype. Among NSCLC patients, approximately 32.3% have mutations in the epidermal growth factor receptor (EGFR) gene. Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), has demonstrated remarkable efficacy in the treatment of NSCLC patients with activating and T790M resistance EGFR mutations. Despite its established efficacy, drug resistance poses a significant challenge for patients to fully benefit from osimertinib. The absence of a standard tool to accurately predict TKI resistance, including that of osimertinib, remains a critical obstacle. To bridge this gap, in this study, we developed an interpretable multimodal machine learning model designed to predict patient resistance to osimertinib among late-stage NSCLC patients with activating EGFR mutations, achieving a c-index of 0.82 on a multi-institutional dataset. This machine learning model harnesses readily available data routinely collected during patient visits and medical assessments to facilitate precision lung cancer management and informed treatment decisions. By integrating various data types such as histology images, next generation sequencing (NGS) data, demographics data, and clinical records, our multimodal model can generate well-informed recommendations. Our experiment results also demonstrated the superior performance of the multimodal model over single modality models (c-index 0.82 compared with 0.75 and 0.77), thus underscoring the benefit of combining multiple modalities in patient outcome prediction.