A new liquid biopsy may give oncologists a tool to let them figure out quickly whether a treatment is working and, if it is, to keep monitoring for resistance.
In the usual cancer biopsy, a surgeon cuts out a piece of the patient’s tumor, but researchers in labs across the country are now testing a potentially transformative innovation.
The liquid biopsy is a blood test that has only recently become feasible with the latest exquisitely sensitive techniques. It is showing promise in finding tiny snippets of cancer DNA in a patient’s blood.
The hope is that a simple blood draw — far less onerous for patients than a traditional biopsy or a CT scan — will enable oncologists to quickly figure out whether a treatment is working and, if it is, to continue monitoring the treatment in case the cancer develops resistance. Failing treatments could be abandoned quickly, sparing patients grueling side effects and allowing doctors to try alternatives.
“This could change forever the way we follow up not only response to treatments but also the emergence of resistance, and down the line could even be used for really early diagnosis,” said Dr. José Baselga, physician in chief and chief medical officer at Memorial Sloan Kettering Cancer Center.
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Researchers caution that more evaluations of the test’s accuracy are needed. So far, there have been only small studies in particular cancers, including lung, colon and blood cancer. But early results are encouraging.
A National Cancer Institute study published this month in The Lancet Oncology, involving 126 patients with the most common form of lymphoma, found the test predicted recurrences more than three months before they were noticeable on CT scans. The liquid biopsies also identified patients unlikely to respond to therapy.
Oncologists who are not using the new test say they are looking on with fascination. “Our lab doesn’t do it, but we are very interested,” said Dr. Levi Garraway of the Dana-Farber Cancer Institute.
Researchers are finding out things about individuals’ cancers that astonish them. MarySusan Sabini, a teacher from Gardiner, N.Y., has lung cancer that resisted two attempts at chemotherapy and a round of radiation. Her doctors at Sloan Kettering saw cancer DNA in her blood when she began taking an experimental drug in October that was her last hope.
Four days later, the cancer DNA shards had vanished, a sign, the doctors hoped, that the treatment was working. But they dared not tell her. The blood test was so new, they were afraid to rely on it.
Within weeks, Sabini began to breathe easier. Months later, she had a CT scan, an X-ray test that uses a computer to assemble detailed images of slices of tumor tissue. It confirmed her tumors were shrinking.
“Every cancer has a mutation that can be followed with this method,” said Dr. David Hyman, the oncologist at Sloan Kettering who is leading the study of the experimental drug Sabini takes. “It is like bar coding the cancer in the blood.”
The idea for the test grew out of a discovery made years ago about fetuses: They shed little pieces of DNA into the bloodstreams of mothers-to-be. It turned out that all growing cells, including tumors, shed tiny DNA fragments.
But finding those minuscule bits of DNA, floating in a sea of other molecules, is not easy. They remain in circulation for just a couple of hours before they are metabolized. And the detection method became useful only when cancer researchers, using advanced methods for DNA sequencing, found hundreds of mutations that could serve as bar codes for cancers and developed the technology for finding a snippet of DNA.
The standard methods of assessing a treatment’s effectiveness have serious drawbacks. Doctors routinely monitor patients for symptoms like pain or shortness of breath, but some people do not have any. In those who do, it can take time for such symptoms to wane; the tumor can die, but the body has to heal.
Patients often have scans to determine if tumors are shrinking, but it can take weeks or months before a tumor looks smaller on a scan, in part because a scan shows not just the cancer but also connective tissue, immune-system cells and scars at the site. Doctors can be fooled into thinking a tumor is present when, in fact, it is gone.
“When you are treating a patient — and we see this many times — your treatment is quite effective but there is some residual lesion on a scan,” Hyman said. “You take the patient to surgery for a biopsy, and all you see is scar tissue. There is no visible cancer there.”
The blood tests also allow frequent monitoring of tumors as they spread and mutate or develop resistance to treatment. The only other way to know is with biopsies.
“I cannot do a weekly liver biopsy and see how things are going,” Baselga said. “But I can do a blood test every week.”
Another possible application — early diagnosis of cancer — is trickier. If a blood test showed cancer DNA, what would that mean? Where is the tumor, and would it help to find and treat it early? Some cancers stop growing and even go away on their own. With others, the outcome is just as good if the cancer is found later.
One early use for DNA blood tests may be helping doctors decide which patients with Stage 2 colon cancer need chemotherapy. Eighty percent of patients with these large tumors that have not spread outside the colon are cured by surgery alone; the rest have recurrences. Six months of intense chemotherapy reduces the risk the cancer will return, but there is no way to predict who needs the treatment.
Two Australian scientists, working with Dr. Bert Vogelstein of Johns Hopkins, wondered if a cancer DNA blood test might be predictive. They began with a study in 250 patients, looking for cancer DNA in blood after surgery. The tumors recurred in 80 percent of those with cancer DNA in their blood, but in only 6 to 8 percent of those whose blood did not have detectable cancer DNA.
Now the Australian researchers, Dr. Jeanne Tie and Dr. Peter Gibbs of the Walter and Eliza Hall Institute of Medical Research, are starting a study of 450 patients randomly assigned to have the blood test or not. Those who have it will get chemotherapy if the test finds cancer DNA. Those who do not have the test will get usual care, as their physician prescribes.
The patients will be told their blood test results although the investigators worry how some will react.
“If you find DNA and tell the patient there is a very high risk of recurrence, that creates a lot of anxiety,” Gibbs said. “And we are not sure chemotherapy will be helpful.”
The blood test, they hope, will answer that question.