title: Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay.
abstract: Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent.
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Maria
authors: M
authors: Schwaederle
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Hatim
authors: H
authors: Husain
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Paul T
authors: PT
authors: Fanta
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: David E
authors: DE
authors: Piccioni
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Santosh
authors: S
authors: Kesari
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Richard B
authors: RB
authors: Schwab
authors: Guardant Health, Inc., Redwood City, CA, USA.
authors: Kimberly C
authors: KC
authors: Banks
authors: Guardant Health, Inc., Redwood City, CA, USA.
authors: Richard B
authors: RB
authors: Lanman
authors: Guardant Health, Inc., Redwood City, CA, USA.
authors: AmirAli
authors: A
authors: Talasaz
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Barbara A
authors: BA
authors: Parker
authors: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, CA, USA.
authors: Razelle
authors: R
authors: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001706:Biopsy; D058534:Class I Phosphatidylinositol 3-Kinases; D056915:DNA Copy Number Variations / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: actionable alteration; cancer; ctDNA; liquid biopsy; personalized therapy