Abstract PO4-26-01: Computational pathology: Revolutionizing diagnostics and clearing the way for precision medicine

Abstract While targeted cancer therapies often rely on subjective and semi-quantitative visual assessment of protein biomarkers by pathologists through immunohistochemically stained tissue, the transformative force of computational pathology is reshaping healthcare by unleashing unprecedented diagnostic accuracy and unlocking personalized treatments. In recent years, we have established a large integrated computational pathology unit to foster collaboration between interdisciplinary teams of computer scientists, pathologists, molecular biologists, and data scientists. This integration of cutting-edge technologies enabled us to develop a computational pathology approach called Quantitative Continuous Scoring (QCS). QCS deploys the power of Deep Learning (DL) to provide objective and continuous expression data of biomarkers in digitized IHC whole slide images (WSI), particularly of proteins expressed at low levels. While manual scoring of IHC WSIs is limited by subjectivity and semi-quantitative assessment of protein expression, QCS overcomes these limitations with an unprecedented accuracy. QCS utilizes two DL-based algorithms, which we developed fully supervised by using pathologist input as the reference standard. These algorithms identify invasive tumour areas and segment each tumour cell across the WSI into cell nuclei, cytoplasm and membrane. Based on an accurate subcellular segmentation, we can compute biomarker expression, on a continuous scale, as mean Optical Density (OD) in each subcellular compartment based on the Hue-Saturation-Density (HSD) model. Therefore, this approach enables precise detection of the low biomarker expression range with single-cell resolution. Importantly, it also allows the computation of the spatial distribution of tumour cells across the WSI. We have successfully used QCS to drive the selection of antibody clones for IHC assays and to delineate the mode of action and PK/PD mechanisms. Of note, the combination of assessing continuous target expression and capturing the spatial distribution of tumor cells has provided surrogate markers to predict potential bystander activity of antibody drug conjugates (ADCs). This approach outperformed traditional pathologist scoring in identifying patient populations having maximum treatment benefit through retrospective analysis of multiple clinical trials. At present, all computational pathology approaches are developed based on conventional IHC assays that have been optimized for manual scoring. Importantly, we draw a vision in which the assay serves as a critical catalyst for unleashing the full potential of computational pathology by providing high-quality, standardized data inputs. We suggest an approach utilizing orthogonal methods as a reference standard to develop highly sensitive IHC assays, capable of detecting even subtle molecular and cellular changes with precision and exhibiting exceptional specificity for accurately identifying and distinguishing target biomarkers from background noise. In summary, we here describe and discuss a computational pathology-based approach for precise biomarker quantification and superior patient selection with broad applicability and the potential to transform the very fabric of how we diagnose and treat cancer. Citation Format: Mark Gustavson, Markus Schick, Ansh Kapil, Anatoliy Shumilov, Carl Barrett, Hadassah Sade. Computational pathology: Revolutionizing diagnostics and clearing the way for precision medicine [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-01.