Molecular Diagnostics in NSCLC with David Berz, MD, PhD, and Philip Bonomi, MD - Episode 3
What are the benefits of using a liquid biopsy over surgical biopsy for patients with recurrent NSCLC and metastatic disease?
BERZ:Although the somatic mutations leading to secondary resistance to first and second generation tyrosine kinase inhibitors within the EGFR space are understood to happen on the tissue base, tissue diagnostics can be complicated in certain settings. These complications can arise from the tissue acquisition itself, due to patients progressing in difficult to access areas like the bone. The processing can be rather challenging in the pre and post fixation settings as well. Artifacts can occur by virtue of the tissue preparation and conservation of the specimen, and these procedures could be quite uncomfortable at times to the patient.
BONOMI:Some patients are not eager to do another biopsy, as these procedures are associated with some discomfort and risk, though usually not severe. Even though some patients will opt for a biopsy, you will not always get an adequate specimen, meaning a mutational analyses cannot be performed.
The advantage of a liquid biopsy is that you can obtain blood and do genomic analyses on the circulating DNA. The only concern is if a patient has a relatively small tumor burden, there may not be enough circulating DNA to identify it. In patients who have a significant amount of tumor bulk, you can usually find enough DNA to analyze it.
BERZ:Although historically medical professionals feel as though the glomerular filter cannot negotiate molecular sizes beyond 50 kilodalton, we have recently identified sizable DNA fragments between 180 and 360 base pairs that allow us to pursue those molecular diagnostics, not only in the serum but also in the urine.
BONOMI:I think that information will be useful in patients that have a low tumor burden due to those fragments being more concentrated in the urine. The other advantage of liquid biopsies is that you would be able to more easily find a mutation. The circulating DNA in the serum is more likely to give you a more global picture of what is going on in a tumor and it might detect T790M mutations in the serum where you might not detect it with a biopsy of a mass.
BERZ:That is a very important aspect of this type of diagnostic. As we know fora prioriprimary driver mutations, there are subsets detected within primary tumors where a certain molecular heterogeneity is identified.
Naoko T. is a 74-year-old retired high school teacher originally from Nagoya, Japan. She currently lives in San Diego, California and enjoys tennis and traveling with her husband.
In November 2014, after several months of stable disease, the patient returns for follow-up visit with worsening back pain, and her CT scan is consistent with progression of metastatic lesions.
At this point, the patient declined further treatment, and by March 2015, she returned with worsening dyspnea and declining performance status