The GIST and Sarcoma Journal Interview ������������������������������������������������������������������������������ ���������������������������������������������������������������������� Blood Test Offers a Non-Invasive Alternative to Tissue Biopsy The GIST and Sarcoma Journal ���� A study presented at one of the recent ASCO Scientific Symposia highlights the potential of liquid biopsy to help guide treatment decisions. The fact that genomic mutations vary not only from patient to patient, but also change over time has been a constant challenge in cancer treatment, especially in the precision medicine era, according to Sumanta Kumar Pal, MD, ASCO expert in developmental therapeutics. “Having a good, reliable option beyond a tumor biopsy could have a major impact on our ability to select the right therapy for the right patient. In this interview Philip Mack, PhD, reviews essential information on a blood test that could offer a noninvasive alternative to tissue biopsies. Dr. Mack is Professor and Director of Molecular Pharmacology at the University of California Davis Comprehensive Cancer Center, Sacramento, California. A large-scale genomic analysis has found that patterns of genetic changes detected in blood samples (liquid biopsy) closely mirror those identified in traditional tumor biopsy. With blood samples from more than 15,000 patients and 50 different tumor types, this is one of the largest cancer genomics studies ever conducted. Q. How would you characterize the overall value and applicability of liquid biopsy? Dr Mack: Findings suggest that analysis of shed tumor DNA in patient blood, also known as a liquid biopsy, can be a highly informative, minimally-invasive alternative when a tissue biopsy is insufficient for genotyping or cannot be obtained safely. Moreover, this test, known as Guardant360 - a digital next-generation sequencing panel, provides an unparalleled opportunity to monitor changes in the cancer as it evolves over time, which can be critical when patients and physicians are discussing treatment options for continued tumor control. Q. What are the most widely used applications of liquid biopsy currently? Dr Mack: The clinical use so far has mostly been in nonsmall cell lung cancer, but it also has had application in colorectal cancer, breast cancer and other tumor types. There have been additional applications using it to track biological markers. Q. Do you see a potential application to soft-tissue sarcomas? Dr Mack: Yes. Since there are molecularly targeted agents being used in this disease, it would have potential value in this setting. Perhaps most importantly, there is a good chance that liquid biopsy can be used to detect emergent resistance mechanisms, that could help assign effective therapies. Q.What about speculation that liquid biopsy could ultimately replace tissue biopsy? Will tissue biopsy become obsolete? Dr Mack: ctDNA results will not necessarily replace tissue biopsy but will be an additional tool. I think there is always going to be a role for tissue-based histology. Tumor biopsy will remain the gold standard, as it yields important information about morphology, tumor type, possible site of origin, and somatic mutations. At least in the foreseeable future, that will always be required. Additionally, in about 15% of patients, no tumor DNA can be detected by the ctDNA test. There are simply tumors that do not shed DNA into the circulation at identifiable levels and tissue biopsy will be required to genotype those tumors. More likely, liquid biopsy will be used when tissue is of insufficient quality or quantity to allow a broader array of testing. Probably, the biggest benefit of plasma analysis is its convenient serial collection of samples over time. As the cancer continues to spread and the patients are progressing on therapies, their tumors are evolving, and we will need rapid, convenient ways to monitor genetic changes in those cancers. Q. Can you further delineate the role of liquid biopsy in terms of identifying the genetic changes in a tumor as well as other related advantages that clinicians need to be aware of? Dr Mack: A liquid biopsy can be used periodically to monitor disease progression, response to therapy, and development of treatment resistance. If a repeat test suggests that the cancer is progressing or becoming resistant to treatment, physicians can modify the treatment plan. Periodic liquid biopsy, which requires a simple blood draw, may be preferable to repeat tissue biopsy in terms of patient safety and convenience. In addition, because genetic changes in ctDNA often occur before signs of tumor growth are apparent on a scan, liquid biopsy can help doctors adjust treatment sooner. Philip Mack, MD
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