Morphology signal in whole slide image foundation models can automatically triage slides

Patient exams in the cancer diagnosis and staging process typically generate several whole slide images (WSIs). One of the initial steps in training models on WSI data is identifying one or a few slides containing tumor or other diagnostic biomarkers necessary for downstream prediction tasks such as estimating recurrence risk or progression-free survival. This step requires tedious manual curation by experienced pathologists. Many published datasets make the artificial assumption of 1 slide per patient. Alternatively, all slides per patient may be used for model training, which may dilute the signal from the few slides containing tumor or other relevant information. In this paper, we present a pipeline to overcome these challenges using publicly available WSI foundation models (FMs). Our evaluations show that ranking WSIs based on predictions from zero-shot classification using WSI FMs accurately identifies slides with the most tumor, indicating that WSI FMs contain sufficient morphology signal to automatically triage slides. We also present a formulation for ranked evaluation to benchmark FM performance in slide triage. We show, on multiple datasets, that tumor slides are identified in the top-2 ranked slides for patients with up to 43 slides.

Test-Time Instance Selection for Improved Whole Slide Image Analysis

Whole Slide Image (WSI) analysis has been widely studied for cancer diagnosis. Conventionally, a gigapixel WSI is divided into small patches and processed by Multiple Instance Learning (MIL) models. However, existing MIL models typically process all patches, many of which contain redundant or non-informative tissue patterns. Although recent approaches have focused on instance selection to identify discriminative patches and reduce redundancy, these selection modules still require additional training. In this work, we propose Test-Time Instance Selection (TTIS), a training-free, plug-and-play framework that selects compact yet representative patches during inference. TTIS further incorporates a multi-view ensemble strategy to integrate distinct facets of tissue morphology, enhancing robustness. Importantly, TTIS can be seamlessly integrated into existing MIL models without retraining or architectural changes, enabling flexible deployment. Extensive evaluations across multiple benchmarks demonstrate that our approach improves or matches baseline MIL performance across a range of classification and subtyping tasks. Our implementation code is available at https://github.com/QuIIL/TTIS

Multi-FRuGaL: Multimodal Flexible Redundancy-aware Decomposed Gated Learning for Cancer Diagnosis and Prognosis

Modern medicine relies on heterogeneous data sources spanning radiology, pathology, text reports, and structured clinical information. However, real-world patient data are frequently incomplete, with missing or sparsely acquired modalities, limiting the effectiveness of standard multimodal fusion approaches. To this end, we propose the Multimodal Flexible Redundancy-aware decomposed GAted Learning (Multi-FRuGaL) framework, a decomposition-aware, adaptive gated intermediate-fusion framework that performs modality-level representation learning under missing data. Multi-FRuGaL integrates per-modality encoders with a signal decomposition layer, an input-conditioned gating network, and an information-aware fusion objective to separate redundant from modality-specific complementary signals, selectively upweighting informative modalities and suppressing redundant or noisy inputs, and remaining well-defined even when multiple modalities are absent. We evaluate Multi-FRuGaL on two multimodal head and neck cancer cohorts: the HANCOCK challenge dataset (N = 763) comprising five modalities and two prognostic endpoints (5-year survival and 2-year recurrence), and the HECKTOR challenge dataset (N = 588) comprising three modalities for human papillomavirus (HPV) status classification. Multi-FRuGaL consistently achieves higher mean performance than the evaluated baselines across multiple tasks, improving AUC from 0.601 to 0.8496 for survival, from 0.672 to 0.8102 for recurrence, and achieving 0.975 AUC for HPV prediction on HECKTOR. For survival analysis, it further achieves a concordance index of 0.6814 for overall survival, 0.7421 for recurrence-free survival, and 0.7143 for progression-free survival on HANCOCK, and 0.7203 for recurrence-free survival on HECKTOR. Qualitative analyses further show that Multi-FRuGaL learns discriminative and robust multimodal representations, even under severe missing-modality conditions.