Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors |
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| Authors: | Cathy Zhou Zilong Yuan Weijie Ma Lihong Qi Angelique Mahavongtrakul Ying Li Hong Li Jay Gong Reggie R Fan Jin Li Michael Molmen Travis A Clark Dean Pavlick Garrett M Frampton Brady Forcier Elizabeth H Moore David K Shelton Matthew Cooke Siraj M Ali Vincent A Miller Jeffrey P Gregg Philip J Stephens Tianhong Li |
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| Institution: | 1.Department of Radiology,University of California Davis School of Medicine,Sacramento,USA;2.University of California Davis Comprehensive Cancer Center,Sacramento,USA;3.Department of Radiology,Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan,China;4.Division of Hematology and Oncology, Department of Internal Medicine University of California Davis School of Medicine,Sacramento,USA;5.Department of Public Health Sciences,University of California,Davis,USA;6.Currently Department of Medical Oncology,Chinese PLA General Hospital,Beijing,China;7.Currently Department of Geriatrics, Peking University First Hospital,Beijing,China;8.Foundation Medicine, Inc.,Cambridge,USA;9.Department of Pathology and Laboratory Medicine and Genomic Shared Resource,University of California Davis School of Medicine,Sacramento,USA;10.Department of Internal Medicine, Veterans Affairs Northern California Health Care System,Mather,USA |
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| Abstract: | BackgroundThis retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay.MethodCell-free DNA (cfDNA) extracted from frozen plasma (N?=?35) or fresh whole blood (N?=?90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT. Concordance was analyzed for 51 matched FoundationACT and FoundationOne (tissue) cases. The maximum somatic allele frequency (MSAF) was used to estimate the amount of tumor fraction of cfDNA in each sample. The detection of GAs was correlated with the amount of cfDNA, MSAF, total tumor anatomic burden (dimensional sum), and total tumor metabolic burden (SUVmax sum) of the largest ten tumor lesions on PET/CT scans.ResultsFoundationACT detected GAs in 69 of 81 (85%) cases with MSAF >?0. Forty-two of 51 (82%) cases had ≥?1 concordance GAs matched with FoundationOne, and 22 (52%) matched to the National Comprehensive Cancer Network (NCCN)-recommended molecular targets. FoundationACT also detected 8 unique molecular targets, which changed the therapy in 7 (88%) patients who did not have tumor rebiopsy or sufficient tumor DNA for genomic profiling assay. In all samples (N?=?81), GAs were detected in plasma cfDNA from cancer patients with high MSAF quantity (P?=?0.0006) or high tumor metabolic burden (P?=?0.0006) regardless of cfDNA quantity (P?=?0.2362).ConclusionThis study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden. |
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