Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors

Autor: Travis A. Clark, Weijie Ma, Jay Gong, Zilong Yuan, David K. Shelton, Dean Pavlick, Brady Forcier, Elizabeth H Moore, Hong Li, Matthew Cooke, Vincent A. Miller, Michael Molmen, Reggie R. Fan, Garrett M. Frampton, Siraj M. Ali, Ying Li, Angelique Mahavongtrakul, Cathy Zhou, Jin Li, Tianhong Li, Lihong Qi, Jeffrey P. Gregg, Philip J. Stephens
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Cardiorespiratory Medicine and Haematology
Circulating Tumor DNA
Positron emission tomography (PET) scan
Cell-free DNA
Plasma
0302 clinical medicine
Positron Emission Tomography Computed Tomography
Cancer
Whole blood
Hematology
Next-generation sequencing (NGS)
High-Throughput Nucleotide Sequencing
lcsh:Diseases of the blood and blood-forming organs
Genomics
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Genomic alterations (GAs)
030220 oncology & carcinogenesis
Female
Fresh frozen plasma
Circulating tumor DNA (ctDNA)
Adult
Maximum somatic allele frequency
medicine.medical_specialty
Concordance
Oncology and Carcinogenesis
lcsh:RC254-282
Maximum standardized uptake value
03 medical and health sciences
Clinical Research
Cell-free DNA (cfDNA)
Internal medicine
Maximum standardized uptake value (SUVmax)
Genetics
medicine
Humans
In patient
Genetic Testing
Molecular Biology
Allele frequency
Retrospective Studies
Aged
Genomic alterations
lcsh:RC633-647.5
business.industry
Research
Human Genome
Maximum somatic allele frequency (MSAF)
Retrospective cohort study
medicine.disease
Good Health and Well Being
030104 developmental biology
Next-generation sequencing
business
Zdroj: Journal of hematology & oncology, vol 11, iss 1
Journal of Hematology & Oncology, Vol 11, Iss 1, Pp 1-13 (2018)
Journal of Hematology & Oncology
ISSN: 1756-8722
Popis: Background This 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. Method Cell-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. Results FoundationACT 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). Conclusion This study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden.
Databáze: OpenAIRE
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