Researchers have developed a new blood test that may change how chemotherapy is used for colon cancer, by identifying the patients that need chemo and those that can safely spare treatment.
More than 450 patients and over 20 hospitals from across Australia were involved in the the clinical trial, which investigated the blood test as a promising aid to cancer treatment decision-making.
The study, co-led by WEHI in Melbourne, Australia and the Johns Hopkins Kimmel Cancer Centre in the U.S., found the test could accurately predict which patients would benefit from chemotherapy after their cancer is surgically removed.
Background: Colon Cancer
Stage II colon cancer is defined as a cancer that has grown through the wall of the colon, but does not extend to the lymph nodes or other organs. Nearly 4,000 Australians are diagnosed with it each year.
While most patients with stage II colon cancer are cured after surgery to remove the cancer from the bowel, the cancer will recur in around 20% of patients. Chemotherapy is currently offered to all stage II colon cancer patients despite a majority not needing it.
WEHI’s Associate Professor Jeanne Tie and Professor Peter Gibbs collaborated with the Johns Hopkins Kimmel Cancer Centre to develop a novel blood test to identify patients who require chemo after surgery.
The test assesses levels of circulating tumor DNA (ctDNA) – genetic material shed from tumors into the bloodstream. The findings from this study, published in The New England Journal of Medicine, could revolutionize chemotherapy treatment for colon cancer patients and fast-track the development of new drug targets.
The goal of chemotherapy when given after colon cancer surgery is to eradicate micrometastases – cancer cells that have travelled from the original cancer in the bowel through the bloodstream to deposit in another site, such as the liver.
These deposits of cancer cells are miniscule and are not seen at surgery or on radiologic images during the initial stages. However, they will gradually increase in size and become large enough to be seen on a standard CT scan if they are not treated with chemotherapy.
The novel blood test, co-developed by WEHI, can detect these invisible cells that release tiny amounts of ctDNA into the bloodstream, enabling researchers to identify which patients should be offered chemotherapy based on whether micrometastases has been detected.
Associate Professor Jeanne Tie, a clinician scientist at WEHI and a medical oncologist at the Peter MacCallum Cancer Centre, says the DYNAMIC study solved a significant health barrier that has been intensely researched for decades: how experts can decide which patients should be recommended for chemotherapy and which patients can safely avoid the treatment.
“Our trial has conclusively shown how the ctDNA blood test can be used to direct post-surgical therapy in stage II colon cancer and substantially reduce the number of patients treated with chemotherapy, without impacting the risk of cancer relapse,” says Tie. “We found that when a patient’s blood test does not reveal ctDNA after colon surgery, the likelihood of micrometastases is very low and chemotherapy can be avoided as there are no tumor fragments left to kill.”
The findings are globally significant as previously there was no way of determining whether all the cancer had been removed through colon surgery.
“While chemotherapy can be essential and lifesaving, many patients are receiving the treatment and its associated toxicities without any benefit,” Tie says. “This ctDNA blood test could be used to spare around 600 Australians and over 100,000 people worldwide from unnecessary chemo treatments each year.”
While previous studies have suggested ctDNA measurements could be used to determine the risk of cancer recurrence, the DYNAMIC study is the first randomized study in the world to provide the clinical evidence required to move this from a promising blood test to one that should be routinely used in clinical practice.
Co-lead author Professor Peter Gibbs says the study would not have been possible without the 23 Australian hospitals that enrolled 455 patients for the multi-center trial since 2015.
“The collaborative efforts from these hospitals were critical for us to complete this trial, the first randomised trial in any solid tumor type worldwide that used a blood test to determine which patients can safely forgo chemotherapy after surgery,” Gibbs says. “Randomised studies like this are needed to deliver meaningful patient outcomes, but they are not possible without the support of our collaborators and philanthropic efforts.”
Victoria’s Western Health hospital contributed the largest number of patients for the trial, while Peter McCallum Cancer Centre was the lead clinical site.
Other hospitals involved were: Barwon Health, Bendigo Health, Border Medical, Cabrini Hospital, Eastern Health, Epworth Freemasons, Flinders Medical Centre, Melbourne Private Hospital, Monash Health, Nepean Cancer Centre, Northern Hospital, Peter MacCallum Cancer Centre, South West Health Care, St Vincent’s Hospital Melbourne, Western Private Hospital (VIC); Border Medical Oncology, Calvary Mater Newcastle Hospital, Chris O’Brien Lifehouse, Newcastle Private Hospital (NSW); Canberra Hospital (ACT), Fiona Stanley Hospital (WA), Royal Hobart Hospital (TAS) and the Royal Brisbane and Women’s Hospital (QLD).
Researchers hope to demonstrate the value of ctDNA-informed treatment in other stages of colon cancer and other cancer types, including pancreas and ovarian cancer, with three additional randomized studies already underway.
“Our ctDNA test can be used to reduce the physical and financial toxicity brought on by unnecessary chemo treatments and believe our findings bring us closer to significantly improving treatment options for many patients across a broad range of cancer types,” Gibbs says.
The research was supported by: NHMRC, Medical Research Future Fund, Marcus Foundation, Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, Conrad R. Hilton Foundation, Sol Goldman Charitable Trust, John Templeton Foundation, National Institutes of Health and Eastern Health Research Foundation.
Featured image: After successful surgery to remove a bowel cancer this new blood test can detect small fragments of cancer DNA in the blood in a small percentage of patients with stage 2 colon cancer, which indicate the presence of otherwise undetectable cancer cells (micrometastases) in the body, which will grow into metastatic cancers if not treated with chemotherapy. Photo: WEHI