A multicentre, prospective study of plasma circulating tumour DNA test for detecting RAS mutation in patients with metastatic colorectal cancer

Br J Cancer. 2019 May;120(10):982-986. doi: 10.1038/s41416-019-0457-y. Epub 2019 Apr 24.

Abstract

Background: OncoBEAMTM RAS CRC kit using BEAMing technology is a circulating tumour DNA (ctDNA) test for detecting plasma RAS mutational status in metastatic colorectal cancer (mCRC). We conducted a multicentre, prospective study to investigate the concordance of the RAS mutational status between plasma ctDNA and tumour tissue DNA.

Methods: mCRC patients without prior anti-EGFR antibodies or regorafenib treatment were enroled. Plasma- and tissue-based RAS mutational status were determined by BEAMing, respectively.

Results: A total of 280 patients from eight institutions were eligible. The overall agreement between plasma- and tissue-based analyses was 86.4%, with a positive percent agreement of 82.1% and negative percent agreement of 90.4%. From logistic regression analysis, lung metastasis alone indicated the most significant factor associated with discordance. The agreement between plasma- and tissue-based analyses was 64.5% in patients with lung metastasis alone (n = 31) indicating lower amount of ctDNA. Among the cases with lung metastasis alone, all plasma- and tissue-based analyses were perfectly concordant in cases with ≥20 mm of maximum lesion diameter or ≥10 lesions.

Conclusion: The clinical validity of OncoBEAMTM RAS CRC kit was confirmed. Careful attention should be paid for mCRC patients with lung metastases alone having fewer metastases or smaller diameter lesions.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Circulating Tumor DNA / blood*
  • Circulating Tumor DNA / genetics
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • ErbB Receptors / genetics
  • Female
  • Gene Frequency
  • Humans
  • Logistic Models
  • Lung Neoplasms / blood*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Phenylurea Compounds / administration & dosage
  • Prospective Studies
  • Pyridines / administration & dosage
  • ras Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • EGFR protein, human
  • ErbB Receptors
  • ras Proteins