Interview with Shannon J. McCall of Duke University

As Director of the CAP-accredited BRPC, Dr. McCall serves as principal investigator for Duke’s institutional research biobanking protocol which has gathered the informed consent of over 5,000 patient-participants so far. She co-leads the Precision Cancer Medicine Initiative at Duke which includes maximizing access to anatomic and genomic pathology data for research and facilitating Duke’s participation in the American Association of Cancer Research’s ‘GENIE’ data-sharing project. Dr. McCall is a member of the International Society of Biological and Environmental Repositories (ISBER) Standards Committee and is currently serving as the Vice-chair of the Biorepository Accreditation Program Committee of the College of American Pathologists (CAP). Read her full bio.

Interview with Shannon J. McCall of Duke University

Q: Genomic medicine is entering more hospitals and bringing with it non-invasive technology that can be used to better target and treat diseases. What are some key milestones that contributed to this trend?

A: After several years of the promise of precision medicine and abundant clinical trial work, the recent FDA approval of solid-tumor-agnostic therapies dependent on molecular biomarkers has catapulted genomic/precision medicine into the standard-of-care for late stage cancer.

Q: What technological advancements are driving this change?

A: For patient care, the continued improvement of blood-based assays of cell-free DNA or circulating tumor cells is important to limit the need for invasive tissue acquisition. This is being driven by study of liquid assays against tissue-based assays to understand the representation of heterogenous and evolving tumors in real time. Also, we are starting to look holistically at the costs of biomarker profiling costs across the lifetime of a patient’s cancer. We know we need to design cost-effective, time-efficient and tumor-representative profiling strategies. For early oncogenic drivers, some up-front tumor testing may stand the test of time. Is it worth testing microsatellite instability in early-stage cancer as part of a high-throughput large scale sequencing assay rather than as an isolated test? Work comparing new biomarker testing modalities (e.g., MSI via NGS) to their historical gold standard (e.g., MSI via PCR/IHC) is critical. We need to understand the additional information provided by quantitative genomics (e.g., tumor mutational burden score) and how to best combine this data with accepted biomarkers.

Q: What are some specific examples in how Genomic Medicine is improving healthcare?

A: While our opportunities to treat late-stage cancer patients are currently limited by the frequency of ‘actionable’ variants (which, itself depends on the number of available targeted therapies), selected patients are now experiencing significant and durable responses of their cancers to precision medicine treatments. We are witnessing the earliest stages of the evolution of certain cancers into chronic diseases.

Q: What is required to see a more wide-spread adoption in the clinical sector?

A: Additional research into new frontiers, concordance studies across different testing platforms, additional FDA approvals for targeted therapies, and thoughtful reimbursement strategies for testing and treatment are all needed to advance precision medicine in oncology.

Q: There are some obvious hurdles we need to overcome, which include but are not limited to: a. addressing the reimbursement challenges, b. ensuring access to genetic counseling for everyone, c. having access to technological solutions that support genomic data at scale, d. testing for mainstream medical practice, e. or having access to population biobanks. Can you speak to one or many of the above-mentioned hurdles and how we can best address them as a community within the ecosystem of genomic medicine?

A: The largest challenge I see for precision cancer medicine is informatics. The most advanced next-generation sequencing assays are currently being reported in electronic health records as either PDF documents or long text strings. The required data structures for genomic results, while more complex than the data structures for hemoglobin and sodium measurements, are attainable with the right mix of persons at the table (pathologists, medical, surgical and gynecologic oncologists and clinical informaticians). Electronic health record providers have begun conversations and development of such systems. However, they do not have enough ‘skin in the game’ to motivate the development of rapid and innovative solutions. Common electronic health record systems were developed and adopted in response to Meaningful Use requirements. Currently, the financial benefit to both the adopting health systems and the electronic health record companies is being realized through metrics un-related to genomic data (e.g., demographics, allergies, medication and problem lists, simple laboratory results, imaging reports). As a community, we should investigate ways that our federal regulations could evolve to incentivize the utilization of structured genomic and biomarker data in the electronic health record.

Q: Is there anything else you would like to share - in the context of Genomic Medicine - with the PMWC audience?

A: As a Pathologist, PI of my institutional broad-consent biorepository, and institutional representative for an international genomic data-sharing initiative, I see the gap between clinical care and research activities closing more every day. We need to engage our patients and let them know that we want their role in today’s precision medicine to encompasses both beneficiary and contributor (through their informed consent for responsible research use of their data and leftover biospecimens). We know that over 92% of US patients are willing to participate in this way if asked. We must ensure that we are asking and providing opportunity for all to join, as our datasets and biospecimen cohorts will benefit most the communities and populations they represent.