The Next Layer: Augmenting Foundation Models With Structure-Preserving and Attention-Guided Learning for Local Patches to Global Context Awareness in Computational Pathology

Authors

Muhammad Waqas
Rukhmini Bandyopadhyay
Eman Showkatian
Amgad Muneer
Anas Zafar
Frank R Alvarez
Maricel Corredor Marin
Wentao Li
David Jaffray
Cara Haymaker
John V Heymach
Natalie Vokes
Luisa M Solis Soto
Jianjun Zhang
Jia Wu

Language

English

Publication Date

2-4-2026

Journal

npj Precision Oncology

DOI

10.1038/s41698-026-01312-5

PMID

41639188

Abstract

Foundation models have emerged as powerful feature extractors in computational pathology. However, they typically omit mechanisms for leveraging the global spatial structure of tissues and the local contextual relationships among diagnostically relevant regions-key elements for understanding the tumor microenvironment. Multiple instance learning (MIL) remains an essential next step following the foundation model, designing a framework to aggregate patch-level features into slide-level predictions. We present EAGLE-Net, a structure-preserving, attention-guided MIL architecture designed to augment prediction and interpretability. EAGLE-Net integrates multi-scale absolute spatial encoding to capture global tissue architecture, a top-K neighborhood-aware loss to focus attention on local microenvironments, and background suppression loss to minimize false positives. We benchmarked EAGLE-Net on large pan-cancer datasets, including three cancer types for classification tasks (10,701 slides) and seven cancer types for survival prediction (4,172 slides), using three distinct histology foundation backbones (REMEDIES, Uni-V1, Uni2-h). Across tasks, EAGLE-Net achieved up to 3% higher classification accuracy and the top concordance indices in 6 of 7 cancer types, producing smooth, biologically coherent attention maps that aligned with expert annotations and highlighted invasive fronts, necrosis, and immune infiltration. These results position EAGLE-Net as a generalizable, interpretable framework that complements foundation models, enabling improved prognostic and diagnostic performance.

Published Open-Access

yes

Recommended Citation

Waqas, Muhammad; Bandyopadhyay, Rukhmini; Showkatian, Eman; et al., "The Next Layer: Augmenting Foundation Models With Structure-Preserving and Attention-Guided Learning for Local Patches to Global Context Awareness in Computational Pathology" (2026). Faculty, Staff and Student Publications. 5816.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5816