Multi-Cancer Early Detection Testing for High-Risk Patients

Host Dr. Davide Soldato interviews Dr. Sana Raoof to discuss the JCO article Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures.

TRANSCRIPT

Dr. Davide Soldato: Hello, and welcome to JCO After Hours, the podcast where we sit down with others from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, Medical Oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author Dr. Sana Raoof, Physician at Memorial Sloan Kettering, to talk about her article, “Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures.”  

Thank you for joining us today, Dr. Raoof.

Dr. Sana Raoof: Thank you so much. It's lovely to be here.

Dr. Davide Soldato: So, Dr. Raoof, I just wanted to start a little bit about the theme of your article, which is really centered around multi-cancer early detection tests. And this comes from the results of several studies that showed their reliability and efficacy in identifying cancer in the average risk population. But I just wanted to ask you if you could give us and our readers a brief overview of how these tests work and how they were designed for this specific population.

Dr. Sana Raoof: Of course. Well, there's an interesting story. The origin of multi-cancer early detection tests actually begins with insights that come from the field of obstetrics and gynecology. So about six or seven years ago, in the peripheral blood of pregnant women, we discovered that you can actually find fetal DNA floating around. And that was an early discovery of cell free DNA coming from the baby into the mother's bloodstream. But in some of those young, otherwise healthy women, we also discovered that there's another clonal signal, unfortunately not coming from the fetus, but coming from an undiagnosed tumor. And that led to the entire field of circulating tumor DNA and all of its applications. 

Of course, scientists in the last six or seven years have harnessed the fact that DNA and the methylation patterns on the circulating tumor DNA, as well as other analytes like glycosaminoglycans, proteins, and other analytes, are secreted by tumors into the peripheral blood in order to try and screen for tumors, hopefully at early stages, when there are still curative, definitive interventions that are available. There's several different tests now that are providing the ability to detect cancers at many stages, including early stages. They're in different phases of preclinical to clinical development, and one is even commercialized and available by prescription in the United States.

Dr. Davide Soldato: Okay. So I think that in most of these tests, they really look at the tumor DNA, so they identify mutations or, for example, methylation patterns. But do we also have some tests that integrate some other type of biomarkers that we can identify in the blood? Like, are they integrated all with the others, or are we just relying on circulating tumor DNA?

Dr. Sana Raoof: It's a great question. There's a lot of really fascinating biology that different companies predominantly are using in order to find signs of early cancer. One of the analytes that I find really interesting, other than looking for small variants in circulating tumor DNA and looking at methylation patterns, as you mentioned, is looking at fragment length. So, for example, the company DELFI looks at the different patterns of the length of DNA fragments that are floating around in the peripheral blood. And not only is fragment length tissue specific,