Study: Liquid biopsies personalize early-stage colon cancer treatment
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STUDY AT A GLANCE
What is this study about?
This study is about whether liquid biopsies can be used to personalize treatment for 2 colon cancer.
Why is this study important?
After a diagnosis of colon cancer, surgery is performed to remove all visible cancerous tissue. Chemotherapy is often used to destroy any remaining cancer cells in the body that can’t be detected through imaging but could cause recurrence.
Current guidelines recommend chemotherapy for 2 colon cancers with features that increase the risk for recurrence and spread. However, this approach is not ideal for predicting who will most likely have a recurrence. Surgery alone can cure up to 80 percent of patients with 2 colon cancers, but some will experience recurrence.
It’s important to better understand which people with 2 colon cancer may benefit from chemotherapy.
Circulating tumor () is fragmented that is released from cancer cells and floats freely in the blood. Blood tests called “liquid biopsies” can detect very small amounts of , which has been linked to a risk for recurrence in some cancers. Notably, tests are not ready for early detection of undiagnosed cancer (see this XRAY review for more information). However, for people diagnosed with cancer, the information provided by tests may help doctors select treatments, predict outcomes or find and treat recurrence earlier.
Researchers wanted to know whether using to detect circulating tumor could reduce the overall use of chemotherapy without compromising recurrence-free survival in people with 2 colon cancer.
The DYNAMIC study enrolled people with 2 colon cancer from healthcare centers in Australia and New Zealand between 2015 and 2019. Participants were randomly assigned to the group (302 people) or the standard of care group (153 people).
The liquid biopsy-guided group was tested for in their blood at four and seven weeks after surgery. People with a positive test underwent up to six months of chemotherapy, and people with negative tests underwent surveillance only.
Participants in the standard care group received chemotherapy only if their cancers were determined to be high-risk based on tumor features (higher T , difficult lymph node retrieval, presence of cancer invasion into blood vessels, bowel obstruction or bowel perforation, and irregular cells when viewed under the microscope) at the time of surgery. They did not have a test. The median follow-up time for participants was about three years.
Can testing identify people with 2 colon cancer who should receive ?
- Using a liquid biopsy-guided strategy roughly halved the use of chemotherapy without affecting recurrence-free survival, with 15% of participants in the group receiving chemotherapy vs 28 percent in the standard management group.
- At 2 years of follow-up, 93.5% of participants in the group had no disease recurrence, compared to 92.4% of participants in the standard management group.
- At 3 years of follow-up, 91% of the participants in the group had no disease recurrence compared to 92.4% of the standard management group.
- Within the group, 3-year recurrence-free survival was 86.4% among ctDNA-positive people who received and 92.5% among ctDNA-negative people who did not. These results were similar for those who received standard of care.
- Previously, researchers observed a high risk for recurrence (more than 80%) in people with 2 colon cancer who tested positive for after surgery but did not undergo . In this study, only 14% of ctDNA-positive people who received treatment had a recurrence within 3 years, suggesting that chemotherapy is beneficial for this group.
Can testing find people who do not need therapy?
This is less clear. Patients whose was negative after surgery had fewer recurrences than individuals whose was positive. However people with no detected and high-risk tumor features had more recurrences than if they had low-risk tumor features. This suggests that tumor features may also be needed to identify those without who would still benefit from .
- People with no detected and low-risk clinical tumor features are less likely to have a recurrence and can likely omit .
- People with no detected and high-risk clinical tumor features may need to consider . More research is needed to clarify this group.
- This type of study, known as a , tends to provide answers that are more conclusive than other kinds of studies. The goal of a is to identify the difference between treatments. In this study, a ctDNA-guided approach to chemotherapy was compared to the standard of care.
- This is the first clinical trial to show that liquid biopsies can guide chemotherapy decisions and benefit people by decreasing the need for chemotherapy without increasing cancer recurrence.
- A longer follow-up time is needed to determine whether chemotherapy prevents or only delays recurrence.
- This research did not specifically look at outcomes of people with inherited mutations linked to colorectal cancer, including people with .
- This trial was smaller than most trials. The number of trial participants was too small to draw conclusions about the best treatment for different subgroups of people. For example, more research is needed to determine which type of chemotherapy works best for ctDNA-positive people and whether ctDNA-negative people with high-risk tumor features could benefit from chemotherapy.
- This study only looked at individuals with resected (cancer removed by surgery) 2 colon cancer. Individuals with other stages of colon cancer and individuals with rectal cancer were not analyzed in this study.
- It remains unclear what the optimal type of chemotherapy is for patients with resected 2 colon cancer patients who are positive after surgery. In this study the positive group received two chemotherapy drugs fluoropyrimidine and oxaliplatin. Typically people with 2 colon cancer are given only one, fluoropyrimidine. This may account for the low rate of recurrence in this group. It is also possible that group was overtreated. Because these drugs can have significant side effects, finding the optimal treatment is important. More research is needed to understand the most beneficial approach for people with 2 colon cancer who are positive for .
- Recurrence-free survival at 3 years in both the group and the standard of care group was higher than typically seen. It suggests that additional research is needed to understand why this is and whether the overall results are repeatable.
- The specific test used in this study was not indicated. There are large differences between the reliability and variability of different types of tests for different cancers and stages. It is not clear how generalizable these findings are.
Circulating tumor testing, or , is a promising tool to improve clinical decision-making, especially for advanced cancers. It also has been shown to predict which people are most likely to have a cancer recurrence. Previous studies have shown a high risk for recurrence (more than 80 percent) in people with 2 colon cancer who test positive for after surgery but do not undergo . However, among people in this study who had a positive test and received therapy, only 14 percent had a recurrence.
It is still important to note that a prior study conducted on people with breast cancer showed that ctDNA-positive people had the highest probability of recurrent disease (see this XRAY review for more information). This confirms that therapy is beneficial when is present. Whether therapy can be omitted for ctDNA-negative patients is less clear.
This study is the first to show that can help guide chemotherapy decisions for people with colon cancer. Yet, questions remain about how to best treat ctDNA-positive people and whether ctDNA-negative people with high-risk tumors might still benefit from chemotherapy. In addition, longer follow-up is needed to determine whether chemotherapy prevents or only delays recurrence in ctDNA-positive people. The results of the DYNAMIC trial provide a basis for additional research that will improve and refine in the context of personalized therapy. Two clinical trials are currently recruiting people with 3 (NCT03803553) and nonmetastatic (NCT03832569) colon cancer to build on the DYNAMIC results. Similar studies are also being conducted in breast cancer.
It is not yet known how the results of this study apply to people with or other inherited mutations that are linked to colorectal cancer.
The results of this study support the emerging body of evidence showing that can be used to predict cancer recurrence. This is also the first study to indicate that can be used to guide chemotherapy decisions without sacrificing recurrence-free survival for people with 2 colon cancer. Using a ctDNA-guided approach resulted in fewer people requiring treatment, sparing many others from the side effects of unnecessary chemotherapy. On the other hand, those with positive findings ended up receiving more aggressive chemotherapy than is typically used for most patients with 2 colon cancers in current practice. The results of the DYNAMIC trial suggest that may be a useful addition to personalize in colon cancer.
Ongoing studies are looking at for treatment decision-making in other settings.
If you have 2 colon cancer, this study suggests that liquid biopsies could help determine if you need chemotherapy. However, it is not yet known how the results of this study apply to people with or other inherited mutations that are linked to colorectal cancer.
Currently, most healthcare providers base their treatment recommendations for people with 2 colon cancer on high-risk tumor features. This study shows that adding tests to make decisions about chemotherapy could prevent unnecessary treatment. Some doctors are beginning to include in their decision-making for people with 2 colon cancer. More research is needed to determine if this is useful for people with all types of 2 colon cancer.
Tie J, Cohen JD, Lahouel K, et al., Circulating tumor analysis guiding therapy in II colon cancer. The New England Journal of Medicine; 2022; 386: Article number 24. Published online June 4, 2022.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
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This article is relevant for:
People with early-stage colorectal cancer
This article is also relevant for:
People newly diagnosed with cancer
People with colorectal cancer
Be part of XRAY:
- Given my of colorectal cancer, what are my chances of recurrence?
- Would be useful for determining my need for chemotherapy and my chance of recurrence? Will my insurance pay for the test?
- What are the risks and benefits of ?
The following research studies are looking at and cancer.
- NCT04962529 Breast cancer trial. This study is looking at whether a test in development is a less invasive alternative to a tissue biopsy in patients with suspected breast cancer.
- NCT04369053 Prevention of colorectal cancer through multiomics blood testing (PREEMPT CRC). This study is testing whether a test for the early detection of colorectal cancer in average-risk participants works as intended.
- NCT03837327 Clinical validation of the InterVenn Ovarian CAncer (VOCAL). This study is testing whether a works as intended to distinguish between benign and cancerous masses in women presenting with pelvic masses.
- NCT04915755: Screening for Cancer in the Blood after Treatment for TNBC and/or a Mutation; Followed by Study Comparing with for People with Cancer found in their Blood (ZEST). The ZEST study has two parts, a screening portion that will look for evidence of cancer cell in the bloodstream, and an intervention portion that is open to people who test positive for cancer cell in their bloodstream.
- NCT03568630 Blood markers of early pancreas cancer. This study is looking for markers of early pancreatic cancer for screening individuals who are at higher-than-average risk.
- Validating a blood test for early ovarian cancer detection in high-risk women and families: microRNA detection study (MiDE). The MiDe study is looking at whether a can accurately detect ovarian cancer in women who are at high risk due to an inherited mutation.
The following organizations offer peer support services for people with or at high risk for colorectal cancer:
- FORCE peer support
- Visit our message boards.
- Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Sign up for our Peer Navigation Program.
- Users are matched with a volunteer who shares your mutation and situation.
- Join our private Facebook group.
- Find a virtual or in-person support meeting.
- Join a Zoom community group meeting.
- American Sign Language
- People of Color
- Visit our message boards.
- Colorectal Cancer Alliance
- AliveAndKickn for people with
Who covered this study?
Johns Hopkins Medicine Newsroom
DNA shed from colon cancers into bloodstream guide chemotherapy This article rates 4.5 out of 5 stars
Circulating tumor DNA-guided approach safely reduces chemotherapy use in colon cancer This article rates 4.5 out of 5 stars