Molecular panels are here to stay – and the GI community will in some shape or form be impacted, be it in performing diagnostic procedures on test-positive patients, or risk-stratifying patients prior to testing.
The conceptual challenge is that it is not about what any given test measures – various panels use separate combination of markers from epigenetics to DNA mutations as well as whole or truncated proteins – but how well a specific test with its somewhat arbitrarily chosen components and cutoffs performs. And, more importantly, what the clinical implications of positive or negative test results are. And no one knows that. At least for now.
A recent report in Science from a group from the Ludwig Center for Cancer Genetics at Johns Hopkins proposes a new cancer blood test based on a very systematic and thoughtful approach to include select mutations in cell-free DNA and circulating proteins associated with various solid organ tumors. For validation, they used healthy and advanced but nonmetastatic cancer cohorts. Through stringent controls and a series of validations, the authors present a range of sensitivities for the various cancer types with an impressive specificity. This is a technically very strong approach with many nifty and thoughtful additions to give this test a very promising first foray – did anybody watch CNN?
While not ready for prime time, which is a tall order for a first report, the authors dutifully point out the need for a prospective real life cohort validation. In the meantime, regardless of the outcome of this particular test, it is a repeated reminder that we need to stay abreast of the advances and the details of each molecular test, especially with a likely very diverse and distinct group of tests to choose from.
Many of us will be part of interpreting results and determining further management. Just as with hereditary cancer genetic panel testing, our technical ability may have stretched beyond our ability to fully understand the implications. Many questions will arise: What about true false positives? False negatives? Intervals? Can such tests replace other screening? How to choose any given test over the other? Should tests be combined or alternated? The tests will be technically refined and are here to stay – we need to get to work on finding answers to the clinically relevant questions.
Barbara Jung, MD, AGAF, is the Thomas J. Layden Endowed Professor and chief of the division of gastroenterology and hepatology, University of Chicago.
