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

  • Author(s): Zhou, Cathy
  • Yuan, Zilong
  • Ma, Weijie
  • Qi, Lihong
  • Mahavongtrakul, Angelique
  • Li, Ying
  • Li, Hong
  • Gong, Jay
  • Fan, Reggie R
  • Li, Jin
  • Molmen, Michael
  • Clark, Travis A
  • Pavlick, Dean
  • Frampton, Garrett M
  • Forcier, Brady
  • Moore, Elizabeth H
  • Shelton, David K
  • Cooke, Matthew
  • Ali, Siraj M
  • Miller, Vincent A
  • Gregg, Jeffrey P
  • Stephens, Philip J
  • Li, Tianhong
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219073/pdf/13045_2018_Article_671.pdf
No data is associated with this publication.
Abstract

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.

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