Baheti Bhakti, Rai Sunny, Innani Shubham, Mehdiratta Garv, Bell William Robert, Guntuku Sharath Chandra, Nasrallah MacLean P, Bakas Spyridon
Division of Computational Pathology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana.
Department of Computer and Information Science, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania.
Mod Pathol. 2025 May 24;38(9):100797. doi: 10.1016/j.modpat.2025.100797.
Glioblastoma (GBM) is the most common and aggressive malignant adult tumor of the central nervous system, with a grim prognosis and heterogeneous morphologic and molecular profiles. Since the adoption of the current standard-of-care treatment in 2005, no substantial prognostic improvement has been noticed. In this study, we seek the identification of prognostically relevant GBM characteristics from routinely acquired hematoxylin and eosin-stained whole slide images (WSIs) and clinical data, which when integrated via advanced computational methods could yield improved patient prognostic stratification and hence optimize clinical decision making and patient management. The proposed WSI analysis capitalizes on a comprehensive curation of apparent artifactual content and an interpretability mechanism via a weakly supervised attention-based multiple-instance learning approach that further utilizes clustering to constrain the search space. Patterns automatically identified by our approach as of high prognostic value classify each WSI as representative of short or long survivors. Further assessments of the prognostic relevance of the associated clinical patient data are performed both in isolation and in an integrated manner, using XGBoost and SHapley Additive exPlanations. The multimodal integration of WSI with clinical data yields enhanced stratification performance when compared with using either one of the modalities. Identifying tumor morphologic and clinical patterns associated with short and long survival will enable the clinical neuropathologist to provide additional relevant prognostic information to the treating team and suggest avenues of biological investigation for further understanding and potentially treating GBM.
胶质母细胞瘤(GBM)是成人中枢神经系统中最常见且侵袭性最强的恶性肿瘤,预后严峻,形态学和分子特征各异。自2005年采用当前的标准治疗方案以来,尚未观察到显著的预后改善。在本研究中,我们试图从常规获取的苏木精和伊红染色的全切片图像(WSIs)及临床数据中识别与预后相关的GBM特征,通过先进的计算方法将这些特征整合起来,有望改善患者的预后分层,从而优化临床决策和患者管理。拟议的WSI分析利用对明显人为因素内容的全面整理以及一种基于弱监督注意力的多实例学习方法的可解释机制,该方法进一步利用聚类来限制搜索空间。我们的方法自动识别出的具有高预后价值的模式将每个WSI分类为短生存期或长生存期患者的代表。使用XGBoost和SHapley加性解释法,分别对相关临床患者数据的预后相关性进行单独评估和综合评估。与单独使用任何一种模式相比,WSI与临床数据的多模态整合可提高分层性能。识别与短生存期和长生存期相关的肿瘤形态学和临床模式,将使临床神经病理学家能够为治疗团队提供额外的相关预后信息,并为进一步了解和潜在治疗GBM提出生物学研究途径。