用病理切片预测三阴性乳腺癌化疗反应,准确率超85%。
Predicting Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancer Using Pre-Treatment Histopathologic Images
- 基于注意力机制的多实例学习框架,从染色切片直接预测化疗效果。
- 内部验证AUC达0.85,外部验证AUC为0.78,表现稳健。
- 模型关注区域与免疫标记物空间重合度高,提升可解释性。
三阴性乳腺癌(TNBC)因其侵袭性强且缺乏靶向治疗手段,仍是重大临床挑战。准确预测新辅助化疗(NACT)反应对制定个体化治疗策略、改善预后至关重要。本研究提出一种基于注意力的多实例学习(MIL)框架,直接从术前苏木精-伊红(H&E)染色活检切片预测病理完全缓解(pCR)。模型在174例回顾性院内队列上训练,并在独立队列(n=30)上外部验证,五折交叉验证平均曲线下面积(AUC)为0.85,外部测试AUC为0.78,展现良好预测性能与泛化能力。为增强可解释性,将注意力图与多重免疫组化(mIHC)数据(PD-L1、CD8+ T细胞、CD163+巨噬细胞)空间配准,结果显示注意力区域与免疫富集区有中等空间重叠,平均交并比(IoU)分别为0.47(PD-L1)、0.45(CD8+ T细胞)、0.46(CD163+巨噬细胞)。高注意力区域内这些标志物的存在支持其与NACT反应的生物学关联。该结果不仅提升模型可解释性,亦为从H&E切片中直接识别临床可用的组织学生物标志物提供依据,推动精准肿瘤学在TNBC中的应用。
原文摘要 · Abstract (English)
Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive behavior and lack of targeted therapies. Accurate early prediction of response to neoadjuvant chemotherapy (NACT) is essential for guiding personalized treatment strategies and improving patient outcomes. In this study, we present an attention-based multiple instance learning (MIL) framework designed to predict pathologic complete response (pCR) directly from pre-treatment hematoxylin and eosin (H&E)-stained biopsy slides. The model was trained on a retrospective in-house cohort of 174 TNBC patients and externally validated on an independent cohort (n = 30). It achieved a mean area under the curve (AUC) of 0.85 during five-fold cross-validation and 0.78 on external testing, demonstrating robust predictive performance and generalizability. To enhance model interpretability, attention maps were spatially co-registered with multiplex immuno-histochemistry (mIHC) data stained for PD-L1, CD8+ T cells, and CD163+ macrophages. The attention regions exhibited moderate spatial overlap with immune-enriched areas, with mean Intersection over Union (IoU) scores of 0.47 for PD-L1, 0.45 for CD8+ T cells, and 0.46 for CD163+ macrophages. The presence of these biomarkers in high-attention regions supports their biological relevance to NACT response in TNBC. This not only improves model interpretability but may also inform future efforts to identify clinically actionable histological biomarkers directly from H&E-stained biopsy slides, further supporting the utility of this approach for accurate NACT response prediction and advancing precision oncology in TNBC.
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