A blood test may one day replace invasive tissue biopsies as a pain-free way to confirm lung cancer and guide treatment, new research suggests.
According to investigators, the test is as effective as a tissue biopsy in diagnosing advanced non-small cell lung cancer, by far the leading form of the leading cancer killer.
The so-called "liquid biopsy" can also quickly identify tumor gene mutations that match targeted drug therapies -- potentially boosting patient survival.
The new findings present "a convincing argument for use of the liquid biopsy as a first option for molecular testing in advanced non-small cell lung cancer," said lead researcher Dr. Vassiliki Papadimitrakopoulou. She's professor of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center.
As the Houston team explained, if a CT scan suggests lung cancer, patients are typically asked to undergo a surgical tissue biopsy. It's an expensive, invasive procedure that comes with risks and inconvenience to patients.
Seeking a way around these procedures, numerous companies have been developing blood-based diagnostic tests for lung cancer. The new study focuses on one such test, called Guardant360, developed by Guardant Health, the company that funded the new study.
Blood tests like Guardant360 rely on traces of tumor DNA in blood for clues to the presence of lung cancer and the best way to treat it.
In addition to the higher accuracy found in the new study, the researchers reported that the results of the blood test can be turned around sooner than those of a tissue biopsy.
While results for a standard biopsy took 15 days to process, results of the liquid biopsy took just nine days, on average, the study found.
That means treatment could begin sooner, with potentially better outcomes, the researchers said.
Speedier genetic analysis of the tumor is crucial, the investigators explained, because 30 percent of lung cancers can now be successfully treated with new gene-targeted medicines. These drugs tend to have higher response rates than standard chemotherapy.
For the study, Papadimitrakopoulou and her colleagues used Guardant360 to identify mutant genes in the blood of nearly 300 patients.
Specifically, the tests were focused on seven "biomarkers" in blood samples -- tumor-specific gene mutations that can help identify subtypes of lung cancer.
The Guardant360 test also looked for one biomarker -- called KRAS -- that helps predict a cancer patient's prognosis, the research team said.
The blood test seemed to outperform standard tissue biopsy. While the standard surgical biopsy found at least one marker predictive of lung cancer in 60 patients, the blood test spotted it in 89 patients, the findings showed.
Drugs that target many of these lung tumor gene mutations are already approved by the U.S. Food and Drug Administration, the researchers noted.
Among the more than 190 patients who did not show the presence of one of the seven genetic tumor biomarkers, testing was often still able to spot the KRAS prognostic biomarker, the study team said.
Again, the blood test beat tissue biopsy in this regard: The Guardant360 test spotted the KRAS biomarker in 92 patients, compared with 24 patients who underwent standard biopsy.
Still, the new study was limited in two ways. First, Guardant360 results weren't compared to the results of the very latest gene-based surgical biopsy analyses. And secondly, the results apply only to the Guardant360 test -- not to other liquid biopsies already out there.
One lung cancer specialist was still heartened by the results, however.
"For years, we have been doing surgical biopsies, but over the last few years there's been a recognition that this is more a 'molecular disease,' governed by [gene] mutations," said Dr. Richard Lazzaro, chief of thoracic surgery at Lenox Hill Hospital in New York City.
It's also been known that cancer cells can shed their DNA into the blood, he said.
"If you can make diagnosis and treating decisions and save time, that's outstanding for patient care," Lazzaro said.
Effective treatment, delivered sooner after diagnosis, should improve survival, he added.
Already, liquid biopsies are often being used in tandem with surgical biopsies, Lazzaro noted.
However, "perhaps one day they will replace a surgical biopsy and may become a better therapeutical paradigm," he said.
The results of the study are to be presented March 29 at the American Association for Cancer Research meeting, in Atlanta. Findings presented at medical meetings are typically considered preliminary until
ed in a peer-reviewed journal.
According to the American Cancer Society, lung cancer remains the number one cancer killer in the United States, with nearly 143,000 deaths expected in 2019.
In most patients with metastatic colon cancer, the disease may have begun spreading throughout the body very early on -- when the original tumor was no bigger than a poppy seed, a new study suggests.
ReplyDeleteMetastatic refers to the most advanced stage of cancer, when the original tumor has spread to distant sites in the body.
Traditionally, that's been seen as a "late" event -- the result of a cancer accumulating many mutations that allow it to invade various tissues in the body, said Christina Curtis, lead researcher on the new study.
Her team's findings turn that viewpoint on its head.
Through genetic analysis of tumor samples, researchers traced the origins of metastases in 21 patients with advanced colon cancer. They found that for 80%, those metastases likely occurred very early -- before the cancer was even diagnosed.
Essentially, that means some cancers are "born to be bad," said Curtis, an assistant professor of medicine and genetics at Stanford University in California.
While that might sound demoralizing, she said the results can actually be viewed in a positive light.
One day, Curtis explained, doctors might be able to use tumors' genetic characteristics to figure out which patients with early-stage colon cancer need more aggressive treatment.
That could mean, for example, giving chemotherapy after surgeons have removed the colon tumor -- to try to wipe out tumor cells that have traveled to other sites in the body.
Plus, Curtis said, discovering which genetic "drivers" cause cancer to spread early could allow researchers to develop new drugs that target those mechanisms.
According to Dr. Martin Weiser, a colon cancer specialist at Memorial Sloan Kettering Cancer Center in New York City, "These findings are very important. This is top-notch work."
Many researchers and doctors have suspected metastases often get their start early on, he noted, but this is actual proof from patient tumor samples.
"This is showing there are molecular changes that happen early," Weiser said. That early occurrence, he added, should make it easier to pinpoint the particular genetic culprits.
"Maybe we can figure out which patients need additional treatment early on, and which ones don't," Weiser said.
For the study, published June 17 in Nature Genetics, Curtis and her colleagues started with tumor samples from 21 patients with colon cancer that had spread to the liver or the brain.
For each patient, the researchers compared the pattern of genetic mutations in the original colon tumor with that in the metastases.
The investigators found that in 17 patients, the metastases seemed to originate from just one cell -- or a small group of genetically similar cells -- that had broken away from the original colon tumor early in its development.
Next, researchers combed through data on more than 900 patients with metastatic colon cancer, and 1,800 whose cancer had not spread. All had had their original tumor analyzed to detect changes in genes known to be linked to cancer.
The researchers found that certain combinations of gene mutations were strongly related to the odds of metastases.
"It wasn't any single mutation, but specific combinations of mutations, that seemed to tip the balance," Curtis said.
DeleteFor example, mutations in a gene called PTPRT, in combination with certain other mutations, were found almost exclusively in patients with metastatic cancer. Past research has shown that when PTPRT's function is lost, a "cell survival" protein called STAT3 becomes more active.
Curtis said it's possible that a drug that would inhibit STAT3 could prevent metastases.
More research is needed to better understand what genetic drivers cause early metastases -- and why some cancer patients never develop metastases, Curtis said.
The study authors are also looking at whether this same phenomenon is true of other types of cancer.
Curtis stressed that the findings do not diminish the importance of colon cancer screening to catch the disease early. Treating the disease in its early stages is always critical.
Weiser made another point: Patients newly diagnosed with colon cancer often feel they have to rush into treatment, thinking the risk of it spreading rises with each day. But if that risk has more to do with tumor genetics than with time, patients may feel less pressure to make an immediate decision.
"You can take the time to consider the options and make sure you get the right treatment," Weiser said.