Monitoring Patients With Cancer Using ctDNA Analysis

When taking care of your cancer patients, you, as their healthcare provider, want actionable information to make treatment decisions and to know if your treatment plan is effective.

For your early-stage patients who have had curative treatment, you are likely seeking to understand which patients are at lower risk of disease and which ones may be at higher risk where additional therapy would be a consideration. For your late-stage patients starting on a new therapy, you may want to track whether they are responding. When implementing today’s standard of care, monitoring treatment response may mean ordering imaging or measuring blood serum markers, such as CEA, which may have limited sensitivity. [1,2]

Monitoring circulating tumor DNA can complement traditional imaging and support you in finding the answers you need. [3]

Divider: How ctDNA monitoring works

Through a simple blood test, you can track treatment response and assess risk of cancer recurrence using ctDNA. [3,4]

ctDNA is DNA shed into the bloodstream by the patient’s tumor. It can be detected in the blood and enables monitoring at several timepoints throughout the course of treatment. By measuring the change in ctDNA levels, you and your patients can make more informed treatment decisions. [5]

There are several benefits to ctDNA monitoring. Combining ctDNA monitoring with standard-of-care imaging may be more sensitive for predicting tumor progression than imaging alone [6] and may be more reliable than serum biomarkers like CEA, which are less sensitive and where false positive results are common. [7,8] By using ctDNA monitoring to complement imaging, you may get an earlier indication if treatment is working – allowing you to stop treatment with toxic side effects or unnecessary costs, if not effective – or consider withholding treatment for patients with no detectable disease. [5] And if a patient does have detectable disease, then you can more confidently recommend a new treatment. [4]

Divider: Types of ctDNA monitoring assays

There are several types of ctDNA monitoring assays, some that use tissue to inform the blood test and others that do not use tissue. Both are novel tests that use ctDNA in blood for monitoring. Tests that don’t use tissue often include a large panel of commonly altered genes. [3] Tissue-informed tests use a tissue biopsy to make a personalized small panel of genes unique to the patient’s tumor for the subsequent blood testing, allowing for increased sensitivity. [3]

Based on the results from a ctDNA monitoring test, you can stratify patients into two groups. Patients with a negative ctDNA result may have a lower risk of relapse and better prognosis. Patients with a positive ctDNA result are at high risk of recurrence or may not be responding to therapy, according to several studies, [7,9,10] and may benefit from a new treatment approach. [5]

ctDNA monitoring offers you another tool to support your treatment planning and help track your patients’ response to treatment.

1. Nishino M. Tumor Response Assessment for Precision Cancer Therapy: Response Evaluation Criteria in Solid Tumors and Beyond. Am Soc Clin Oncol Educ Book. May 23 2018;38:1019-1029. doi:10.1200/EDBK_201441

2. Verbanac D, Ceri A, Hlapcic I, et al. Profiling Colorectal Cancer in the Landscape Personalized Testing-Advantages of Liquid Biopsy. Int J Mol Sci. Apr 21 2021;22(9)doi:10.3390/ijms22094327

3. Parikh AR. NCCN. presented at: NCCN 2021 Virtual Congress: Biomarkers in Solid Tumors; 2021; Session What is on the horizon.

4. Dasari A, Morris VK, Allegra CJ, et al. ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal-Anal Task Forces whitepaper. Nat Rev Clin Oncol. Dec 2020;17(12):757-770. doi:10.1038/s41571-020-0392-0

5. Sanz-Garcia E, Zhao E, Bratman SV, Siu LL. Monitoring and adapting cancer treatment using circulating tumor DNA kinetics: Current research, opportunities, and challenges. Sci Adv. Jan 28 2022;8(4):eabi8618. doi:10.1126/sciadv.abi8618

6. Magbanua MJM, Li W, Wolf DM, et al. Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk. NPJ breast cancer. Mar 25 2021;7(1):32. doi:10.1038/s41523-021-00239-3

7. Reinert T, Henriksen TV, Christensen E, et al. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA oncology. May 9 2019;doi:10.1001/jamaoncol.2019.0528

8. Litvak A, Cercek A, Segal N, et al. False-positive elevations of carcinoembryonic antigen in patients with a history of resected colorectal cancer. Journal of the National Comprehensive Cancer Network : JNCCN. Jun 2014;12(6):907-13. doi:10.6004/jnccn.2014.0085

9. Christensen E, Birkenkamp-Demtroder K, Sethi H, et al. Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Jun 20 2019;37(18):1547-1557. doi:10.1200/JCO.18.02052

10. Bratman SV, Yang SYC, Iafolla MAJ, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nature Cancer. 2020/09/01 2020;1(9):873-881. doi:10.1038/s43018-020-0096-5