In a new study, researchers found that a new method of analyzing cancer patients’ blood for evidence of the disease could be up to ten times more sensitive than previous methods.
This method and others based on this approach could lead to tests that more accurately determine if a patient is likely to relapse after treatment and could pave the way for the development of pinprick home blood tests to monitor patients.
The research was done by a team at the University of Cambridge and elsewhere.
The technique uses personalized genetic testing of a patient’s tumor to search blood samples for hundreds of different genetic mutations in circulating tumor DNA (ctDNA); DNA released by cancer cells into the bloodstream.
Combined with new methods to analyze this data to remove background noise and enhance the signal, the team was able to reach a level of sensitivity that in some cases could find one mutant DNA molecule among a million pieces of DNA—approximately ten times more sensitive than previous methods.
Detecting ctDNA in blood samples is what is known as a liquid biopsy. It allows doctors to find out more about a patient’s cancer without the need for invasive surgery.
The technique is important for monitoring cancer patients, particularly after they’ve received treatment, as it can be an indicator of whether the treatment was successful and if the patient might relapse.
In some situations, other types of tests can be used to detect some cancers before they display any symptoms or show up on a scan.
Currently, the sensitivity of the methods depends on having a high enough number of mutant pieces of DNA, either relative to background DNA or in absolute numbers.
When the amount of ctDNA is low, a test can produce a negative result even if a patient has residual cancer in their body that could lead to relapse.
A single tumor will contain many different mutations that caused cancer to form.
While some of them are commonly known across certain cancer types, such as EGFR in lung cancer, the overall set of mutations for a tumor varies from person to person.
By analyzing the genetic makeup of an individual’s tumor and targeting a set of mutations in a personalized way, liquid biopsies to monitor cancer can become much more sensitive.
Until recently, these personalized liquid biopsies have searched for around 10 to 20 mutations in the blood and up to around 100 at most.
In the material from a tube of blood, these would be able to detect ctDNA to levels on the range of one mutant molecule among 30,000 pieces of DNA.
This new technique looks for hundreds and sometimes thousands of mutations in each blood sample, routinely achieving a sensitivity of one mutant molecule per 100,000, and under optimal conditions can reach a level measured in parts per million.
This new approach searches for many different mutations rather than just one, increase the number of ‘needles’ that can be found, making chances of success more likely.
Eventually, this could lead to tests that would require only a pinprick of blood—a procedure that patients could perform at home—that would then be sent to a lab for analysis.
This would not only mean fewer visits to the hospital but would also allow the patient to be more frequently monitored.
In the study, the researchers analyzed samples from 105 cancer patients, testing the method on small sets of patients with five different cancer types, with both early and late-stage disease.
The method showed promising results and was able to detect ctDNA at high sensitivity in patients with advanced breast and melanoma cancer, and in patients with glioblastoma, which is notoriously difficult to detect in the blood.
The test was also able to detect ctDNA in patients with earlier-stage disease, where the level of ctDNA in the blood is much lower and difficult to find.
This included patients with lung or breast cancer, as well as patients with early-stage melanoma who had already had surgery, which makes detection even more difficult.
In the future, the team plans to use this method to measure ctDNA levels in individuals who are at high risk of developing cancer to help refine future tests for cancer early detection.
One author of the study is Dr. Nitzan Rosenfeld, senior group leader at the Cancer Research UK Cambridge Institute.
The study is published in the journal Science Translational Medicine.
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