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cell-free (circulating tumor) DNA in plasma (liquid biopsy, cFDNA, ctDNA)

Indications: - identification of fetal genetic disease - detection of early-stage cancers [1] - detection of colorectal adenocarcinoma relapse [6] Procedure: - initial liquid biopsy if abnormal followed by positron-emission tomography- computed tomography (PET-CT) with contrast* * liquid biopsy plus confirmatory imaging sensitivity 27%, specificity 99%, with positive predictive value of 41% [4] Method: - targeted error correction sequencing - DNA methylation pattern of circulating tumor DNA matches the methylation pattern of the primary tumor tissue [3] Notes: - review [7] - for cancer screening, specificity is higher than sensitivity [8]

Specific

CancerSEEK cell-free DNA in plasma for colorectal cancer screening; Shield DNA test Lunar-2 multiplexed maternal plasma DNA sequencing; cell-free DNA aneuploidy screening (cfDNA)

General

molecular diagnostic test

References

  1. Phallen J, Sausen M, Adleff V et al Direct detection of early-stage cancers using circulating tumor DNA. Science Translational Medicine. 16 Aug 2017: 9(403):eaan2415 PMID: 28814544 http://stm.sciencemag.org/content/9/403/eaan2415
  2. Corcoran RB, Chabner BA. Application of Cell-free DNA Analysis to Cancer Treatment. N Engl J Med 2018; 379:1754-1765. Nov 1. PMID: 30380390 https://www.nejm.org/doi/full/10.1056/NEJMra1706174
  3. Shen SY, Singhania R, Fehringer G et al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 2018 Nov 22; 563:579 PMID: 30429608 https://www.nature.com/articles/s41586-018-0703-0
  4. Lennon AM, Buchanan AH, Kinde I et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science 2020 Apr 28; [e-pub] PMID: 32345712 https://science.sciencemag.org/content/early/2020/04/27/science.abb9601
  5. Bradley SH, Barclay ME. "Liquid biopsy" for cancer screening. BMJ. 2021 Jan 4;372:m4933. PMID: 33397684
  6. Bankhead C Liquid Biopsy Predicts Colon Cancer Relapse Months Before CT - Test for ctDNA outperformed existing biomarker, may help guide therapy. MedPage Today January 17, 2021 https://www.medpagetoday.com/meetingcoverage/mgics/90745 - Henriksen TV et al Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients. Gastrointestinal Cancers Symposium (GICS) 2021
  7. Krebs MG, Malapelle U, Andre F et al Practical Considerations for the Use of Circulating Tumor DNA in the Treatment of Patients With Cancer. A Narrative Review. JAMA Oncol. Published online October 20, 2022. PMID: 36264554 https://jamanetwork.com/journals/jamaoncology/fullarticle/2797725
  8. Carr DJ, Welch G Assessing the Clinical Utility of Liquid Biopsies Across 5 Potential Indications From Therapy Selection to Population Screening. A Review. JAMA Intern Med. Published online August 28, 2023 PMID: 37639262 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2808647