The use of ctDNA to determine benefit of adjuvant chemotherapy after surgery
The use of ctDNA to determine benefit of adjuvant chemotherapy after surgery
Findings from a recent study on the potential benefit of circulating tumour DNA (ctDNA) testing for patients with colorectal cancer (CRC) were presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium this January.
Currently, understanding whether a patient requires additional treatment after surgery is primarily based on their cancer stage and other key risk factors including whether the cancer has spread to the lymph nodes or other tissues and organs (distant metastasis). While many patients will receive additional chemotherapy and benefit from it, some patients may receive chemotherapy after surgery without any additional benefit. ctDNA is a tool with the potential to personalize cancer treatment so that additional treatments are only given to patients who are more likely to benefit from them.
What is ctDNA?
When cancer cells are present in the body, they release their genetic material (DNA) into the bloodstream. ctDNA testing examines a patient’s blood for the presence of microscopic amounts of circulating tumour DNA (ctDNA). If found, a personalized treatment plan for the patient can be developed. ctDNA testing is non-invasive, requiring a simple blood test to do, and is also able to detect the presence of tumour cells at much lower quantities than what would be detectable through standard imaging tests like a CT scan. ctDNA testing, however, is a relatively new test that is still being investigated through clinical trials.
The study
The study used the Signatera™ personalized ctDNA test that is built using the unique mutations found in each patient’s tumour tissue. For more information about this test, visit their website: https://www.natera.com/oncology/signatera-advanced-cancer-detection/). 2,998 patients were included in the study. The patients had their blood drawn at various intervals – 1,3,6,9,12,18, and 24 months after surgery or until their cancer came back. Patients also underwent CT scans of the chest, abdomen, and pelvis every 6 months.
Patients who were ctDNA-positive (tumour DNA was found in the blood) had significantly worse disease-free survival compared to patients who were ctDNA negative (no tumour DNA was identified in the blood), meaning that their cancer was much more likely to come back or recur.
Patients who remained ctDNA-positive to a 6-month time point were more than five times more likely to experience a cancer recurrence than those who were ctDNA negative.
445 patients in the study were ctDNA-positive, 240 of which received adjuvant chemotherapy (chemotherapy that is given after surgery). For patients who tested ctDNA positive after surgery and became ctDNA negative following adjuvant chemotherapy, 58% maintained their ctDNA negative status while 42% became ctDNA-positive again. For patients who were ctDNA positive and were treated with adjuvant chemotherapy, those that experienced a decrease in ctDNA levels of at least 50% at the 6 months mark were associated with better disease-free survival compared to patients who had less than a 50% decrease or increase in ctDNA levels.
What does this mean?
These findings are important because they show the importance of sustained ctDNA negative status, and the impact of a change in ctDNA levels of more than 50% at 6 months on disease-free survival. These findings point to how patients who are ctDNA-negative could be spared the toxicity of additional chemotherapy without compromising their long-term survival, and patients who are ctDNA-positive can be identified to receive additional chemotherapy. Closely monitoring ctDNA levels after surgery allows for earlier detection of cancer recurrence, which can allow for earlier intervention with treatment, improve the chances for a cure, and/or extend survival.
