用病理切片预测癌症转移风险和转移部位,提升临床决策效率
HistoMet: A Pan-Cancer Deep Learning Framework for Prognostic Prediction of Metastatic Progression and Site Tropism from Primary Tumor Histopathology
- 分两步预测:先估转移风险,再对高危者预测转移部位
- 在95%敏感度下降低后续工作量,转移部位预测宏F1达74.6%
- 结合医学概念与视觉语言模型,结果可解释性强,适合临床部署
转移仍是癌症致死主因,但仅凭原发肿瘤病理切片预测是否转移及转移位置仍具挑战。尽管全幻灯片图像(WSIs)蕴含丰富形态信息,现有计算病理方法通常将转移状态与转移部位预测视为独立任务,未体现临床中先评估转移风险、再判断部位的决策流程。为此,我们提出一种决策感知、概念对齐的多实例学习框架HistoMet,用于从原发肿瘤WSIs中进行预后预测。该框架采用双模块流水线:先估计转移进展概率,再对高风险病例条件性预测转移部位。通过预训练病理视觉-语言模型整合语言定义与数据自适应的转移概念,指导表征学习并增强临床可解释性。我们在包含6504例患者的多机构泛癌队列上评估HistoMet,该队列具备转移随访与部位标注。在临床相关的高灵敏度筛查设置(95%敏感度)下,HistoMet显著降低下游工作负荷,同时保持高转移风险召回率。对已转移病例,其宏F1为74.6%(标准差1.3),宏OvR AUC达92.1%。结果表明,显式建模临床决策结构可实现从原发肿瘤病理直接推断转移进展与部位嗜性的鲁棒、可部署预测。
原文摘要 · Abstract (English)
Metastatic Progression remains the leading cause of cancer-related mortality, yet predicting whether a primary tumor will metastasize and where it will disseminate directly from histopathology remains a fundamental challenge. Although whole-slide images (WSIs) provide rich morphological information, prior computational pathology approaches typically address metastatic status or site prediction as isolated tasks, and do not explicitly model the clinically sequential decision process of metastatic risk assessment followed by downstream site-specific evaluation. To address this research gap, we present a decision-aware, concept-aligned MIL framework, HistoMet, for prognostic metastatic outcome prediction from primary tumor WSIs. Our proposed framework adopts a two-module prediction pipeline in which the likelihood of metastatic progression from the primary tumor is first estimated, followed by conditional prediction of metastatic site for high-risk cases. To guide representation learning and improve clinical interpretability, our framework integrates linguistically defined and data-adaptive metastatic concepts through a pretrained pathology vision-language model. We evaluate HistoMet on a multi-institutional pan-cancer cohort of 6504 patients with metastasis follow-up and site annotations. Under clinically relevant high-sensitivity screening settings (95 percent sensitivity), HistoMet significantly reduces downstream workload while maintaining high metastatic risk recall. Conditional on metastatic cases, HistoMet achieves a macro F1 of 74.6 with a standard deviation of 1.3 and a macro one-vs-rest AUC of 92.1. These results demonstrate that explicitly modeling clinical decision structure enables robust and deployable prognostic prediction of metastatic progression and site tropism directly from primary tumor histopathology.
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