You Can Help Set New Paradigms Involving ctDNA

Welcome to a special issue of ONCOLOGY^® focusing on exciting trials that may set future standards for adjuvant therapy in colon cancer. We are very pleased to highlight these trials, particularly the recently opened phase 2/3 CIRCULATE-US trial (NCT05174169).

What is circulating tumor DNA (ctDNA)? DNA is released into the blood stream by all dying cells, including tumor cells. With advances in DNA amplification and sequencing, it is now possible to identify cell-free DNA, which derives from cancer cells rather than normal cells. Ideally, such a test would be 100% positive in colon cancer preoperatively and would be negative if the tumor was completely resected with no other tumor cells left in the body. If we had a diagnostic test with 100% accuracy, we would be able to treat every patient with microscopic residual disease and avoid treating those who could be cured with surgery alone. In stage III colon cancer, for example, on average we could identify the 35 out of 100 patients destined to recur after “curative” surgery for adjuvant therapy and avoid treating the other 65 patients who actually were cured with surgery.

Some of the preliminary data on the various ctDNA tests look very promising in prospective cohort trials involving patients treated according to standard of care regimens. For example, results of the 1500-patient GALAXY-Japan study (jRCT1031200006), presented at the Gastrointestinal Cancers Symposium in January 2022, showed a highly predictive value for positive ctDNA in risk of relapse and benefit of chemotherapy. The results also suggested no benefit for adjuvant chemotherapy in patients with negative ctDNA. However, such data are contaminated by stage-based treatment and bias in treatment selection. We therefore need prospective randomized trials.

In this issue of ONCOLOGY^®, leaders of these key prospective trials and experts in the area of ctDNA further explain the trials and their goals. For our American readers, I would direct your attention to the National Cancer Institute–sponsored COBRA trial (NCT04068103) for patients with stage IIA disease and the CIRCULATE-US trial for patients with stage II or stage III disease. These are the best opportunities to use this technology for your patients with colon cancer who are eligible for adjuvant treatment. These trials, which will study the outcome of ctDNA-directed treatment with appropriate controls, are needed to demonstrate that by using guidance of ctDNA results, we can do better than our current approach of treating only patients with high-risk pathologic stage II and all pathologic stage III colon cancer with adjuvant chemotherapy.

We need your help and the help of your patients to make this advance in treatment a reality; these are large, randomized trials. Your participation, and that of your colleagues, can help bring this technology into the guidelines and standard of care in the quickest time frame possible.

Please enjoy these state-of-the-art articles and see the Clinical Trials in Progress section for a quick reference guide. We hope this issue will aide your participation in these trials. I would like to express my heartfelt thanks to all the authors of articles in this issue of ONCOLOGY^® and also my coeditor for this special edition, Thomas J. George Jr, MD, FACP.