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Saeed-Vafa, D.

Publications and source records attributed to Saeed-Vafa, D..

3 recordsLinked to original sources

Deceptive learning in histopathology

Deep learning holds immense potential for histopathology, automating tasks that are simple for expert pathologists, and revealing novel biology for tasks that were previously considered difficult or impossible to solve by eye alone. However, the extent to which the visual strategies learned by deep learning models in histopathological analysis are trustworthy or not has yet to be systematically analyzed. In this work, we address this problem and discover new limits on the histopathological tasks for which deep learning models learn trustworthy versus deceptive solutions. While tasks that have been extensively studied in the field like tumor detection are reliable and trustworthy, recent advances demonstrating the ability to learn molecular profiling from hematoxylin and eosin (H&E) stained slides do not hold up to closer scrutiny. Our analysis framework represents a new approach in understanding the capabilities of deep learning models, which should be incorporated into the computational pathologists toolkit.

pathology↗

Utilizing Digital Pathology to Quantify Stromal Caveolin-1 Expression in Malignant and Benign Ovarian Tumors: Associations with Clinicopathological Parameters and Clinical Outcomes

Loss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expression were quantified in serous OvCa and benign ovarian tissue in two, independent cohorts - one quantified expression using immunohistochemistry (IHC) and the other using multiplex immunofluorescence (IF) with digital image analysis designed to target CAF-specific expression. Cav-1 expression was significantly downregulated in OvCa stroma compared to non-neoplastic stroma using both the IHC (p=0.002) and IF (p=1.8x10-13) assays. OvCa stroma showed Cav-1 downregulation compared to tumor epithelium with IHC (p=1.2x10-24). Conversely, Cav-1 expression was higher in OvCa stroma compared to tumor epithelium with IF (p=0.002). There was moderate correlation between IHC and IF methods for stromal Cav-1 expression (r2= 0.69, p=0.006) whereas there was no correlation for epithelial expression (r2=0.006, p=0.98). Irrespective of the staining assay, neither response to therapy or overall survival correlated with the expression level of Cav-1 in the stroma or tumor epithelium. Our findings demonstrate a loss of stromal Cav-1 expression in ovarian serous carcinomas. Studies are needed to replicate these findings and explore therapeutic implications, particularly for immunotherapy response.

cancer biology↗

Combining radiomics and mathematical modeling to elucidate mechanisms of resistance to immune checkpoint blockade in non-small cell lung cancer

Immune therapies have shown promise in a number of cancers, and clinical trials using the anti-PD-L1/PD-1 checkpoint inhibitor in lung cancer have been successful for a number of patients. However, some patients either do not respond to the treatment or have cancer recurrence after an initial response. It is not clear which patients might fall into these categories or what mechanisms are responsible for treatment failure. To explore the different underlying biological mechanisms of resistance, we created a spatially explicit mathematical model with a modular framework. This construction enables different potential mechanisms to be turned on and off in order to adjust specific tumor and tissue interactions to match a specific patient's disease. In parallel, we developed a software suite to identify significant computed tomography (CT) imaging features correlated with outcome using data from an anti-PDL-1 checkpoint inhibitor clinical trial for lung cancer and a tool that extracts these features from both patient CT images and \"virtual CT\" images created from the cellular density profile of the model. The combination of our two toolkits provides a framework that feeds patient data through an iterative pipeline to identify predictive imaging features associated with outcome, whilst at the same time proposing hypotheses about the underlying resistance mechanisms.

cancer biology↗