Study: Liquid biopsies more effective in some cases than tissue biopsies

Non-invasive liquid biopsies might offer a more effective method to detect clinically relevant mutations and guide clinical treatment in advanced lung cancer patients than traditional tissue biopsies, according to a new study in the journal Clinical Cancer Research.

Researchers from the Perelman School of Medicine at the University of Pennsylvania reported that in patients with non small cell lung cancer (NSCLC) mutations detected from liquid biopsies (cell-free circulating tumor DNA (ctDNA) captured from blood), liquid biopsies yielded clinically relevant mutations not found in tissue biopsies as a patient's disease progressed.

Liquid biopsies also presented an advantage in lung cancer since it's often difficult to obtain tissue samples and new mutations emerge overtime. Sequentially testing mutations with a simple blood test is often easier than performing an additional tissue biopsy.

The work gains particular importance in light of the recent cancer 'moonshot' blue ribbon panel, which recommended greater efforts toward the development of non-invasive tests for markers, to accelerate the ability to detect the emergence of drug resistant disease.

In the study, liquid biopsies were performed in 102 patients but tissue samples could be administered in only 50 patients.

Among the 50 patients, 41 mutations were detected by both methods, while 24 therapeutically targetable drive EGFR mutations – a known driver of lung disease – were detected in tissue samples and 19 in blood samples.

When done currently, blood and tissue results matched almost 100 percent of the time, but showed differences when the blood sample was collected at longer intervals after the tissue sample. A possible explanation is that blood tests can detect new mutations that have evolved to resist treatment that may not have been detectable at time of the initial tissue test, especially if the patient had not yet received a targeted therapy.

We spoke with Erica Carpenter, senior author of the paper and research assistant professor at the Perelman School of Medicine about her findings:

Q. What's the most important takeaway from the study?

A. Our goal was to find mutations that are targets for drugs and we now have a test with improved sensitivity to do just that. Using liquid biopsies, we can improve care and do it with less pain and suffering for patients. Our next step will be to see when and whether it is appropriate to replace invasive biopsies with liquid biopsies, especially when searching for such resistant mutations.

This is not only a change for a physician in how to get information for clinically actionable decisions, but how to do it by using a blood test. And it's much easier for patients. More often than not, patients are having other blood work done when they see a physician. So for most patients it doesn't involve any additional discomfort or inconvenience.

Q. What are the advantages of using liquid biopsies for NCSLC?

A. There are several advantages to liquid biopsies and a number of different reasons that tissue biopsies don't always have the same sensitivity.

During a patient's disease, under the pressure of therapy and particularly targeted therapy, a tumor can evolve a series of drug-resistant mutations. In lung cancer, we use drugs to target these resistant mutations. We can see in the liquid biopsy if the patient is a target for additional drug resistant therapies.

Because we looked at advanced lung cancer patients, almost all of them had cancer in other places, also known as metastatic disease. From a genetic perspective, a tumor in another location, like your liver, may have a different genetic profile than the one that started in your lung. Tissue biopsies mean having to sample from each site, whereas with a liquid biopsy we think we can get information from DNA shed by all of the various cancer locations in the blood.

Another advantage is that a liquid biopsy can be done over and over again: every time a patient comes in for monitoring is an opportunity for us to do another blood test if the physician thinks it is indicated.

Q. What's the next step with this work?

A. Our study was designed as a feasibility study. We wanted to compare the usefulness of tissue biopsies and liquid biopsies to try to understand where a liquid biopsy fit with traditional information.

We were pleasantly surprised by the clinical implications. But the study was of patients who had been previously diagnosed. Our next step is to see if we can add additional value in using liquid biopsies at diagnosis to see if it will provide additional information to physicians and patients.

Q. Will liquid biopsies eventually replace tissue biopsies?

A. I'm hesitant to say that liquid biopsies will replace tissue biopsies. From a genetic point of view, we might decide that the comprehensiveness of a tissue biopsy could be replaced or perhaps supplemented with a liquid biopsy, but we would always seek to obtain a tissue biopsy so our pathology group could identify the type of tumor and its physical characteristics.

I don't see a world without tissue biopsies but do see a world where liquid biopsies will play a larger role.

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