Welcome and Opening Remarks
Nigel Russell, Senior Director, Events, GenomeWeb
Digital Pathology & Augmented Intelligence are Enablers of Biomarker Testing – A Panel Discussion by the Digital Pathology Association
Moderator: Marilyn M. Bui, MD, PhD, Senior Member and Professor of Pathology, Scientific Director of Analytic Microscopy Core, Section Head of Bone and Soft Tissue Pathology, Program Director of Cytopathology Fellowship, Moffitt Cancer Center, Tampa, FL
Panelists: Mike Montalto, PhD, Chief Scientific Officer, PathAI; Anil Parwani, MD, PhD, Professor of Pathology and Biomedical Informatics, Vice-Chair of Anatomic Pathology, Director of Pathology Informatics, Director, Digital Pathology Shared Resources, Principal Investigator, Cooperative Human Tissue Network (CHTN) Midwestern Division, Wexner Medical Center – Department of Pathology, The Ohio State University
Digital Pathology (DP) and Augmented Intelligence (AI) are gaining momentum in the practice of pathology and laboratory medicine. The FDA has approved multiple whole slide imaging systems for primary diagnosis in recent years and an AI algorithm for prostate cancer diagnosis in 2021. Pathology based biomarkers play an important role along early and late phase biopharmaceutical drug development including mechanism of action, indication selection, enrollment, and harmacodynamics, as well as patient selection and stratification. In the era of precision medicine, traditional microscope-based pathology may fall short of the needed precision, reproducibility and accuracy that are needed to enhance the probability of technical and regulatory success (PTRS) of new drug applications.
The Digital Pathology Association (DPA) is leading the way in advancing DP and AI through education, advocacy, and collaboration. This expert panel will share with the scientific community of precision medicine and the public how DP and AI enable biomarker testing and address some commonly asked questions.
Dr. Parwani, in his presentation entitled “Clinical Implementation of Digital and Computational Pathology: Lessons learnt and the Path Forward”, will provide a practical perspective of an Academic Medical Center’s decision on implementing digital pathology, the lessons learned, and future directions. The objectives are to provide an overview of the current state of Digital Pathology at The Ohio State University, to identify the components for a successful transition into a digital workflow and an integration with the LIS, and to discuss the positive impact of digital pathology on improved pathology workflow and patient care, especially during the pandemic.
Dr. Montalto will address “Applications of AI-powered Pathology in Clinical Stage Drug Development”. His talk will explore the application of machine learning and artificial intelligence in pathology across the entire continuum of the clinical drug development process, with emphasis on translational applications. Examples will be presented in oncology and non-oncology therapeutic areas where AI-based pathology provides superior performance over traditional microscope methods on patient samples from randomized controlled clinical trials. Improved biomarker selected prevalence, hazard ratios between drug and control and enhanced statistical significance of endpoint analysis will demonstrated using AI-powered pathology. Regulatory considerations of using AI-based pathology in drug development will also be discussed.
Aneuploidy on a Brush – The Way to Find Esophageal Cancer?
Joseph Willis, MD, Professor and Vice Chair for Translational Research, Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center
Esophageal adenocarcinoma [EAC] is the fastest growing in incidence cancer in the US over the last 25 years, while also having a 5 year survival of less than 20%. Barrett’s Esophagus [BE] which occurs in up to 5% of the population, is the only known precursor of EAC and caused by gastric reflux. Once identified, patients with BE undergo lifelong endoscopic surveillance with multiple biopsies taken for pathology review– even though their individual lifetime risk of EAC is small. This is an extremely costly and inconvenient process which, among other issues, is also associated with pathology ‘overcalling’ of precancerous changes leading to significant overtreatments.
Aneuploidy has long been proposed as a tool of EAC progression risk assessment in BE patients but due to a number of issues has not been implemented as a clinical test. We recently assessed whether an esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to interrogate ~350,000 genome-spanning regions and identify chromosome arm alterations to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer.
Our results demonstrate the feasibility of combining aneuploidy with chromosomal changes of a limited gene panel to accurately define BE patients with BE-associated cancer and pre-cancerous changes. The clinical implications of this approach are now being proposed for prospective trials.
Precision Medicine in Hematopathology: The Versatility of NGS Testing
Mir Basharath Alikhan, MD, Director, Molecular Oncology; Program Director, Molecular Genetic Pathology Fellowship; Hematopathologist, NorthShore University Health System; Clinical Assistant Professor, Pritzker School of Medicine, University of Chicago
Molecular testing has revolutionized the practice of medicine. Ever since the development of imatinib for chronic myeloid leukemia targeting the BCR-ABL1 kinase fusion protein, there has been a flurry of research to find the ‘holy grail’ for cancer. Targeted therapies have since emerged to help treat tumors that have previously been untreatable for many patients. Aside from these targets, many others have been identified that predict therapy response or disease course, helping to manage cancers beyond first-line treatments.
The multitude of genetic changes identified necessitated the development of technologies that allow for multiplexing of both genetic targets as well as patient samples. Next-generation sequencing (NGS) has fulfilled that role, both in solid tumors and hematopoietic neoplasms. Although many genetic changes have been identified in myeloid diseases, the utility of NGS testing is still much in development in lymphomas. The molecular landscape in lymphoproliferative neoplasms offers many challenges due to its heterogeneity, with the presence of fusions, amplifications, and small variants seen in many tumors. Minimal residual disease testing is also gaining traction as an important indication for clinical management. Despite the challenges, NGS offers the best tools to tackle them.
The Role of Spatialomics and TissueCypher® in Today’s Clinical Management of Barrett’s Esophagus (BE)
Matthew Goldberg, MD, Medical Director, Castle Biosciences; Assistant Clinical Professor, Dermatology, Icahn School of Medicine, Mount Sinai, New York City and Board-Certified Dermatologist and Dermatopathologist
Barrett’s esophagus (BE) is a serious complication of GERD and the only known precursor to the esophageal adenocarcinoma (EAC), a highly lethal form of cancer with a five-year survival of less than 20%. As one of the fastest growing cancers by incidence in the world, determining which BE patients will progress to EAC is often a difficult question for clinicians to address. How can they ensure that high-risk BE patients receive the intervention they need and that the treatment of low-risk BE patients can be downgraded accordingly, saving them from unnecessary surveillance endoscopies and anxiety about developing cancer?
The TissueCypher® Barrett’s Esophagus test offers answers to these critical clinical issues. Through the application of spatial biology and biologically aware AI to tissue diagnostics, the TissueCypher Barrett’s Esophagus test offers prognostic risk assessment from esophageal pinch biopsies, independently from tissue histology and other clinical risk variables. As the world’s first precision medicine test designed to predict future development of esophageal cancer in patients with BE, the TissueCypher Barrett’s Esophagus test provides actionable information about each patient’s risk of disease progression to help ensure more personalized and risk-appropriate management decisions.