arXiv:2503.24165cs.LGcs.AI2025-03被引 7

用多模态数据预测肺癌靶向药耐药,准确率超80%。

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

  • 融合病理图像、基因测序等多源数据,构建可解释的预测模型
  • 在多中心数据上达到c-index 0.82,显著优于单一数据模型
  • 为晚期肺癌患者精准用药提供实用工具,适合临床决策参考

肺癌是全球癌症死亡的主要原因,其中非小细胞肺癌(NSCLC)是最常见亚型。约32.3%的NSCLC患者携带表皮生长因子受体(EGFR)基因突变。奥希替尼作为第三代EGFR酪氨酸激酶抑制剂(TKI),对携带激活及T790M耐药突变的患者具有显著疗效。然而,药物耐药仍是患者充分获益的重大挑战。目前尚无标准工具可准确预测包括奥希替尼在内的TKI耐药性。为此,本研究开发了一种可解释的多模态机器学习模型,用于预测携带激活EGFR突变的晚期NSCLC患者对奥希替尼的耐药性,在多机构数据集上取得c-index 0.82。该模型利用患者就诊时常规收集的数据,涵盖组织病理图像、下一代测序(NGS)数据、人口统计学信息及临床记录,实现精准肺癌管理与治疗决策支持。实验表明,多模态模型性能优于单一模态模型(c-index 0.82 vs. 0.75和0.77),验证了多模态融合在患者预后预测中的优势。

原文摘要 · Abstract (English)

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.

肺癌多模态耐药预测机器学习

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