Guiding Colorectal Cancer Treatment Decisions by Using ctDNA With Jeanne Tie, MD, MBChB, FRACP

At the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Dr. Jeanne Tie spoke with Oncology Data Advisor to share more about her presentation regarding the clinical utility of circulating tumor DNA (ctDNA) analysis to guide treatment decision making for patients with colorectal cancer.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. I am here with Dr. Jeannie Tie from the Peter MacCallum Cancer Centre at the University of Melbourne and Walter and Eliza Hall Institute. She presented the results of the randomized DYNAMIC trial on adjuvant chemotherapy guided by circulating tumor DNA analysis in stage II colon cancer. This work was also just published in the New England Journal of Medicine. Thank you for joining us, Dr. Tie.

Jeanne Tie, MD, MBChB, FRACP: You’re welcome.

Oncology Data Advisor: What is the importance of circulating DNA analysis in stage II colon cancer?

Dr. Tie: So ctDNA, which is circulating tumor DNA, detects DNA that is shed by cancer cells. In stage II disease, after surgery, often a computed tomography (CT) scan cannot pick up this micrometastatic disease. The use of ctDNA can pick up these residual micros, or what we call invisible cells, in the circulation.

Our previous work has demonstrated that if you have a detectable ctDNA or positive ctDNA result after surgery, and if you don’t receive any further treatment, you have a very high risk of cancer recurrence—over an 80% risk of cancer recurrence. The purpose of this study is really to use this test to decide who needs chemotherapy or not. In stage II colon cancer at the moment, the huge clinical dilemma in the clinic is who should be offered adjuvant chemotherapy or not, because surgery alone cures over 80% of patients.

Oncology Data Advisor: Based on the results, do you think ctDNA should be used as a tool to determine which patients should receive adjuvant chemotherapy?

Dr. Tie: I definitely think ctDNA should be incorporated into clinical practice with pathological risk features in stage II colon cancer to help decide whether a patient will need chemotherapy or not. What we’ve found is that if you have clinical low-risk disease and your ctDNA is negative, your long-term outcome is very, very good. The recurrence-free survival is around 96%. Those patients are very unlikely to benefit from chemotherapy, so they should be avoiding chemotherapy.

However, if you have a positive result, the outcome normally will be very unfavorable. The patients included in our study had an outcome after chemotherapy that was very good compared with untreated patient previously. For that group of patients, I would definitely be recommending chemotherapy. It is a tool that I think will be increasingly incorporated into clinical care.

Oncology Data Advisor: I also noticed in your presentation, you mentioned that there was some difference in the chemotherapy that was given to the patients with ctDNA-positive colon cancer. Do you think it will be possible at some point to use the ctDNA to determine which treatment is better?

Dr. Tie: I don’t know that the ctDNA per se—in terms of yes or no, detectable or not detectable—is going to be predictive of the benefit of chemotherapy or the type of chemotherapy. We do know that FOLFOX chemotherapy (leucovorin/fluorouracil/oxaliplatin) works better because there are more agents, whereas single agents are less effective, even in the metastatic setting. I think that there may be different outcomes between the FOLFOX chemotherapy and single-agent chemotherapy, purely because of the efficacy of the treatment. I don’t think that using ctDNA could predict that at this stage.

Oncology Data Advisor: Do you have anything else that you would like to add?

Dr. Tie: Not really, no.

Oncology Data Advisor: Well, thank you very much.

Dr. Tie: No problem.

About Dr. Tie

Associate Professor Jeanne Tie, MD, MBChB, FRACP is the Lower Gastrointestinal Medical Oncology and Trials Lead at the Peter MacCallum Cancer Center and a Senior Research Fellow in the Personalized Oncology Division of the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia. She performs translational research focusing on using prognostic and predictive biomarkers to personalize treatments for patients with colorectal cancer. Dr. Tie is currently leading several randomized trials assessing the clinical utility of ctDNA in guiding adjuvant treatment selection in colon cancer.

For More Information

Tie J, Cohen J, Lahouel K, et al (2022). Adjuvant chemotherapy guided by circulating tumor DNA analysis in stage II colon cancer: the randomized DYNAMIC trial. J Clin Oncol (ASCO Annual Meeting Abstracts), 40 (suppl_17). Abstract LBA100. DOI:10.1200/JCO.2022.40.17_suppl.LBA100

Tie J, Cohen JD, Lahouel K, et al (2022). Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med, 386(24):2261-2272. DOI:10.1056/NEJMoa2200075

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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