Revolutionizing Expert Edge Treatment Mary Bronner, MD Division Chief, Anatomic for Cancer Care Pathology and Oncology New Circulating Cell-Free Tumor DNA (ctDNA) Technology

Mary P. Bronner, MD, ARUP Laboratories’ division chief of Anatomic Pathology and Q: What are the advantages of and costly biopsies, surgeries, and circulating cell-free tumor DNA testing CT and MRI scans, to be replaced by Oncology, discusses using over previous method(s) for solid ctDNA blood tests for earlier and more circulating cell-free tumor tumor testing? comprehensive detection of molecular A: ctDNA is far less invasive and alterations in tumors. Improved DNA (ctDNA) for cancer expensive than existing biopsies, treatment will ensue by detection of testing. This break-through surgeries, and imaging modalities. It chemotherapy-resistant mutations to is also more sensitive, allowing earlier redirect therapy. technology is now entering detection. By virtue of blood circulating the clinical realm. In this throughout the body, ctDNA samples Q: What are some future all tumor locations as compared to possibilities involving circulating cell- Q & A, Dr. Bronner explains targeted biopsies and resections. free DNA testing? its application and Current methods of molecular tumor A: The future of ctDNA holds a testing remove only a tiny fraction tremendous amount of clinical trial advantages. for analysis, since whole tumor work. It could help determine the extent testing is cost prohibitive. Because and significance of improved tumor most tumors and their metastases sampling, whether ctDNA can be used Dr. Bronner is the inaugural are highly variable in their genetic for cancer screening, the optimal blood Carl R. Kjeldsberg makeup, important alterations are draw intervals to detect recurrence missed through these multiple forms and resistance, and ultimately whether presidential endowed of sampling error. ctDNA will likely these variables improve survival. professor of pathology at the dramatically improve this because the blood samples essentially all cells Q: Where is this application being University of Utah School of through perfusion and allows for more used now? Medicine. She was awarded comprehensive testing. A: ctDNA tests for the above Finally, ctDNA, as a minimally invasive applications are now in clinical use. the Arthur Purdy Stout and cost-effective test, can be done at ARUP Laboratories’ initial ctDNA test Prize in 2005, recognizing far shorter serial intervals than current targets non-small cell lung cancer radiologic methods to detect not only (NSCLC) by identifying circulating her work as a surgical earlier recurrence but also specific EGFR T790M mutations that confer chemotherapy resistance mutations. resistance to early generation NSCLC pathologist under the age chemotherapy drugs. Virtually of 45 whose research Q: How does circulating tumor DNA all treated patients develop drug (ctDNA) testing differ from circulating resistance, with two-thirds due to publications have had a tumor cell (CTC) testing? the T790M mutation, for which new targeted therapies have been approved. major impact on diagnostic A: ctDNA is over 100 times more ARUP’s test utilizes digital droplet pathology. This is just one of sensitive than CTC testing, permitting much earlier detection. PCR for exquisitely sensitive (<0.5%) many honors recognizing her mutant allele detection. This targeted Q: What does this technology mean test is highly cost effective to enable expertise and commitment for clinicians and their patients? serial testing for early resistance and therapeutic intervention in lung cancer, to anatomic pathology and A: Clinicians and cancer patients the most common and deadly cancer can look forward to fewer invasive molecular oncology. in the world.

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