Metin N. Gurcan

Ziyu Su, Yongxin Guo, Robert Wesolowski et al.

Accurate recurrence risk stratification is crucial for optimizing treatment plans for breast cancer patients. Current prognostic tools like Oncotype DX (ODX) offer valuable genomic insights for HR+/HER2- patients but are limited by cost and accessibility, particularly in underserved populations. In this study, we present Deep-BCR-Auto, a deep learning-based computational pathology approach that predicts breast cancer recurrence risk from routine H&E-stained whole slide images (WSIs). Our methodology was validated on two independent cohorts: the TCGA-BRCA dataset and an in-house dataset from The Ohio State University (OSU). Deep-BCR-Auto demonstrated robust performance in stratifying patients into low- and high-recurrence risk categories. On the TCGA-BRCA dataset, the model achieved an area under the receiver operating characteristic curve (AUROC) of 0.827, significantly outperforming existing weakly supervised models (p=0.041). In the independent OSU dataset, Deep-BCR-Auto maintained strong generalizability, achieving an AUROC of 0.832, along with 82.0% accuracy, 85.0% specificity, and 67.7% sensitivity. These findings highlight the potential of computational pathology as a cost-effective alternative for recurrence risk assessment, broadening access to personalized treatment strategies. This study underscores the clinical utility of integrating deep learning-based computational pathology into routine pathological assessment for breast cancer prognosis across diverse clinical settings.

Hikmat Khan, Usama Sajjad, Metin N. Gurcan et al.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Accurate survival prediction is essential for treatment stratification, yet existing pathology foundation models often overlook organ-specific features critical for CRC prognostication. Methods: We propose MorphDistill, a two-stage framework that distills complementary knowledge from multiple pathology foundation models into a compact CRC-specific encoder. In Stage I, a student encoder is trained using dimension-agnostic multi-teacher relational distillation with supervised contrastive regularization on large-scale colorectal datasets. This preserves inter-sample relationships from ten foundation models without explicit feature alignment. In Stage II, the encoder extracts patch-level features from whole-slide images, which are aggregated via attention-based multiple instance learning to predict five-year survival. Results: On the Alliance/CALGB 89803 cohort (n=424, stage III CRC), MorphDistill achieves an AUC of 0.68 (SD 0.08), an approximately 8% relative improvement over the strongest baseline (AUC 0.63). It also attains a C-index of 0.661 and a hazard ratio of 2.52 (95% CI: 1.73-3.65), outperforming all baselines. On an external TCGA cohort (n=562), it achieves a C-index of 0.628, demonstrating strong generalization across datasets and robustness across clinical subgroups. Conclusion: MorphDistill enables task-specific representation learning by integrating knowledge from multiple foundation models into a unified encoder. This approach provides an efficient strategy for prognostic modeling in computational pathology, with potential for broader oncology applications. Further validation across additional cohorts and disease stages is warranted.

Usama Sajjad, Abdul Rehman Akbar, Ziyu Su et al.

Colorectal cancer (CRC) remains the third most prevalent malignancy globally, with approximately 154,000 new cases and 54,000 projected deaths anticipated for 2025. The recent advancement of foundation models in computational pathology has been largely propelled by task agnostic methodologies that can overlook organ-specific crucial morphological patterns that represent distinct biological processes that can fundamentally influence tumor behavior, therapeutic response, and patient outcomes. The aim of this study is to develop a novel, interpretable AI model, PRISM (Prognostic Representation of Integrated Spatial Morphology), that incorporates a continuous variability spectrum within each distinct morphology to characterize phenotypic diversity and reflecting the principle that malignant transformation occurs through incremental evolutionary processes rather than abrupt phenotypic shifts. PRISM is trained on 8.74 million histological images extracted from surgical resection specimens of 424 patients with stage III CRC. PRISM achieved superior prognostic performance for five-year OS (AUC = 0.70 +- 0.04; accuracy = 68.37% +- 4.75%; HR = 3.34, 95% CI = 2.28-4.90; p < 0.0001), outperforming existing CRC-specific methods by 15% and AI foundation models by ~23% accuracy. It showed sex-agnostic robustness (AUC delta = 0.02; accuracy delta = 0.15%) and stable performance across clinicopathological subgroups, with minimal accuracy fluctuation (delta = 1.44%) between 5FU/LV and CPT-11/5FU/LV regimens, replicating the Alliance cohort finding of no survival difference between treatments.

Qing Lyu, Sanjeev V. Namjoshi, Emory McTyre et al.

Treatment decisions for brain metastatic disease rely on knowledge of the primary organ site, and currently made with biopsy and histology. Here we develop a novel deep learning approach for accurate non-invasive digital histology with whole-brain MRI data. Our IRB-approved single-site retrospective study was comprised of patients (n=1,399) referred for MRI treatment-planning and gamma knife radiosurgery over 21 years. Contrast-enhanced T1-weighted and T2-weighted Fluid-Attenuated Inversion Recovery brain MRI exams (n=1,582) were preprocessed and input to the proposed deep learning workflow for tumor segmentation, modality transfer, and primary site classification into one of five classes. Ten-fold cross-validation generated overall AUC of 0.878 (95%CI:0.873,0.883), lung class AUC of 0.889 (95%CI:0.883,0.895), breast class AUC of 0.873 (95%CI:0.860,0.886), melanoma class AUC of 0.852 (95%CI:0.842,0.862), renal class AUC of 0.830 (95%CI:0.809,0.851), and other class AUC of 0.822 (95%CI:0.805,0.839). These data establish that whole-brain imaging features are discriminative to allow accurate diagnosis of the primary organ site of malignancy. Our end-to-end deep radiomic approach has great potential for classifying metastatic tumor types from whole-brain MRI images. Further refinement may offer an invaluable clinical tool to expedite primary cancer site identification for precision treatment and improved outcomes.

Saima Rathore, Muhammad A. Iftikhar, Metin N. Gurcan et al.

Both radiographic (Rad) imaging, such as multi-parametric magnetic resonance imaging, and digital pathology (Path) images captured from tissue samples are currently acquired as standard clinical practice for glioblastoma tumors. Both these data streams have been separately used for diagnosis and treatment planning, despite the fact that they provide complementary information. In this research work, we aimed to assess the potential of both Rad and Path images in combination and comparison. An extensive set of engineered features was extracted from delineated tumor regions in Rad images, comprising T1, T1-Gd, T2, T2-FLAIR, and 100 random patches extracted from Path images. Specifically, the features comprised descriptors of intensity, histogram, and texture, mainly quantified via gray-level-co-occurrence matrix and gray-level-run-length matrices. Features extracted from images of 107 glioblastoma patients, downloaded from The Cancer Imaging Archive, were run through support vector machine for classification using leave-one-out cross-validation mechanism, and through support vector regression for prediction of continuous survival outcome. The Pearson correlation coefficient was estimated to be 0.75, 0.74, and 0.78 for Rad, Path and RadPath data. The area-under the receiver operating characteristic curve was estimated to be 0.74, 0.76 and 0.80 for Rad, Path and RadPath data, when patients were discretized into long- and short-survival groups based on average survival cutoff. Our results support the notion that synergistically using Rad and Path images may lead to better prognosis at the initial presentation of the disease, thereby facilitating the targeted enrollment of patients into clinical trials.