Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

Clin Cancer Res. 2016 Nov 15;22(22):5497-5505. doi: 10.1158/1078-0432.CCR-16-0318. Epub 2016 May 16.

Abstract

Purpose: There is a growing interest in using circulating tumor DNA (ctDNA) testing in patients with cancer.

Experimental design: A total of 168 patients with diverse cancers were analyzed. Patients had digital next-generation sequencing (54 cancer-related gene panel including amplifications in ERBB2, EGFR, and MET) performed on their plasma. Type of genomic alterations, potential actionability, concordance with tissue testing, and patient outcome were examined.

Results: Fifty-eight percent of patients (98/168) had ≥1 ctDNA alteration(s). Of the 98 patients with alterations, 71.4% had ≥ 1 alteration potentially actionable by an FDA-approved drug. The median time interval between the tissue biopsy and the blood draw was 2.7 months for patients with ≥ 1 alteration in common compared with 14.4 months (P = 0.006) for the patients in whom no common alterations were identified in the tissue and plasma. Overall concordance rates for tissue and ctDNA were 70.3% for TP53 and EGFR, 88.1% for PIK3CA, and 93.1% for ERBB2 alterations. There was a significant correlation between the cases with ≥ 1 alteration with ctDNA ≥ 5% and shorter survival (median = 4.03 months vs. not reached at median follow-up of 6.1 months; P < 0.001). Finally, 5 of the 12 evaluable patients (42%) matched to a treatment targeting an alteration(s) detected in their ctDNA test achieved stable disease ≥ 6 months/partial remission compared with 2 of 28 patients (7.1%) for the unmatched patients, P = 0.02.

Conclusions: Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment. Clin Cancer Res; 22(22); 5497-505. ©2016 AACR.

Publication types

  • Clinical Trial

MeSH terms

  • Circulating Tumor DNA / blood*
  • Circulating Tumor DNA / genetics*
  • DNA, Neoplasm / blood*
  • DNA, Neoplasm / genetics
  • ErbB Receptors / genetics
  • Female
  • Genomics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Liquid Biopsy / methods
  • Male
  • Medical Oncology / methods
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / genetics
  • Receptor, ErbB-2 / genetics
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Circulating Tumor DNA
  • DNA, Neoplasm
  • Tumor Suppressor Protein p53
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Receptor, ErbB-2