Lung Cancer Recurrence, Predictable at Last?

Blood biomarker may tell whether early-stage lung cancer is cured or soon-to-be recurred.
Lung cancer biopsy image.

A biopsy shows an invasive form of lung cancer. 

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Jason Socrates Bardi, Editor

(Inside Science) -- When lung cancer is caught in its earliest stages, before the tumors have spread to other organs, people face the prospect of radiation, chemo, surgery or some combination of the three, and for many, outcomes are good. Through treatment, lung cancer can be cured.

But for far too many others, treatment fails. Sick cells socked away in the bulbous pockets of the lungs survive, and tumors later recur -- one of the reasons why lung cancer is the No. 1 cancer killer in the United States and around the world.

Now, a new blood test may be able to tell doctors which patients still harbor cancer cells in their bodies after initial treatment, which could help address one of the problems with managing early-stage lung cancer: the inability to tell when someone is actually cured.

While successful treatments cause tumors to shrink, tumors also shrink when a treatment is only partially successful, said Max Diehn, a radiation oncologist at Stanford University who led the team that developed the test. When treatment is finished, doctors cannot tell who has been cured and who still harbors microscopic pockets of disease. Modern imaging cannot reveal the difference.

"What we do is we continue to monitor patients over time with usually repeat scans, and we wait and see what happens," Diehn said.

Even for those who are cured, the weeks and months of watchful waiting may be worrisome because of the specter of recurrence. And it's worse for people whose cancer does recur. They face further uncertainty burdened with the knowledge they have already lost precious treatment time.

"At that point, unfortunately, the outcomes for recurrence are worse and these patients do worse," said Aadel Chaudhuri, the chief resident of radiation oncology at Stanford University, who is also a member of the team. If doctors knew earlier who had lingering cancer cells, they could start more aggressive treatment sooner, he said.

A precision medicine approach to lung cancer

At the American Society for Radiation Oncology meeting in San Diego in late September, Chaudhuri presented promising results from a small clinical study of the blood test. The study looked at 41 people with early-stage lung cancer who underwent standard treatment. At the end of treatment, their blood was checked for tumor-derived DNA, a biomarker that Diehn and Chaudhuri hypothesized would indicate persistent cancer that would later recur. The results, which were described in a meeting press conference but are not yet unpublished, supported the idea.

"Patients who have it do worse -- patients who don't have it do better," said Chaudhuri.

Chaudhuri said everyone in the study who still harbored detectable tumor DNA after treatment saw their cancer recur, and the majority of them later died from the disease. In contrast, 95 percent of people who had undetectable levels at the end of treatment did not develop a recurrence, and nearly all of them survived.

"This is very relevant because they were able to find this months before anything showed up on the CT scan or the imaging," said Ben Movsas, who is chair of Radiation Oncology at the Henry Ford Cancer Institute in Michigan and was not involved in the study. "Time is of the essence, especially for a patient with lung cancer."

Because the technique relies on detecting DNA, it may also offer doctors more details about a particular person's cancer, which could help tailor treatment. There are hundreds of known specific DNA signatures associated with lung cancer that have been identified from biopsies taken in recent years. No two tumors have the same genetic profile, and some DNA signatures reveal resistance to treatment or susceptibility to new therapies.

Monitoring those biomarkers could allow doctors to guide treatment for individual patients, starting them earlier on more effective therapies, said Chaudhuri -- an emerging, personalized approach that is generally referred to today as "precision medicine."

"If we can find out that much sooner that a therapy, let's say, is not working -- well then, we have an opportunity -- a window -- to now switch the therapy early on and treat the patient with something else before a lot of time passes," said Movsas. "This is really a paradigm shift in terms of how we would approach managing patients."

The next step, said Diehn, will be to see if using these DNA biomarkers to guide treatment will actually lead to better outcomes for people with lung cancer. That can only be determined by conducting rigorous, large-scale human clinical trials designed to test the ideas and prove that they really do work.

"I'm quite hopeful that they will, but of course one has to actually prove it," Diehn said.

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Jason Socrates Bardi is the former News Director of the American Institute of Physics and a longtime science writer.