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Expert Reflects on Recent Trial Results in CRC and Small Bowel Cancer

Angelica Welch
Published: Thursday, Sep 21, 2017

Heinz-Josef Lenz, MD
Heinz-Josef Lenz, MD
Recent findings from clinical studies on liquid biopsies, Immunoscore®, and primary tumor location have been garnering a lot of interest in the field of colorectal cancer (CRC).

During the 19th World Congress on Gastrointestinal (GI) Cancer, Heinz-Josef Lenz, MD, associate director for Adult Oncology and co-leader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, shared his excitement over these new areas of development in an interview with OncLive.

Additionally, Lenz discussed his study of molecular variations between small bowel adenocarcinomas, right-sided colon cancers, and gastroesophageal cancers.

OncLive: You chaired the colorectal cancer abstract session at this meeting. What studies stood out to you?

Lenz: In the oral session of the CRC part at this conference, there were very interesting abstracts looking at liquid biopsies and Immunoscores®. These new areas will develop into very important research, which will impact clinical practice.

One abstract from Dr Aparna Parikh showed that doing liquid biopsy, which evaluated the monoclonal makeup on the cell-free DNA, was able to detect the mechanism of resistance. She was checking DNA alterations under treatment and was able to show—in most of the cases—the reason that the drug did not work anymore.

This is fascinating because that will determine subsequent treatments depending on way of molecular space. So, when you have an upregulation of c-Met or an upregulation of FGFR inhibitors or HER2, you could target these molecular pathways. However, the most fascinating part of this abstract was that the liquid biopsy detected these mechanisms more effectively than re-biopsying the primary tumor on the metastatic site.

Therefore, the sensitivity of a liquid biopsy is significantly better because when you do a biopsy you only get a little bit of the tumor—which is very heterogeneous. So, you may miss molecular mechanisms of cells that only survive in the blood. Only the surviving resistance cells are found. That is very important because there was so much anxiety that maybe the liquid biopsy will maybe not capture the mechanisms of resistance, as well as the tumor biopsy. 

There are also 2 abstracts looking at Immunoscores®. We are learning more that immunotherapies will become part of our treatment armamentarium for GI cancer, particularly CRC. Last year at the 2016 ASCO Annual Meeting, there was a big presentation in the oral session on Immunoscore®, an independent prognostic marker for outcomes in stage II and stage III disease composed of staining for CD3-positive and CD8-positive T cells.

However, this did not really change the way we are looking at stage II and stage III disease. Therefore, this year we have validation in an American clinical trial, showing that the Immunoscore® is a significant prognostic marker. It validates that the presence of CD3-positive and CD8-positive cells in the tumor, as well as in the invasive margin, are very important. The nice part of this presentation is that the CD3 presence in the invasive margin of the tumor seemed to be the most important information. It is not necessarily the most important regarding CD3 and CD8 ratios, but really CD3 in the invasive margin. This is the first step in using immuno-related markers to better characterize our patients. 

There is another interesting paper looking at the ratio of neutrophils and lymphocytes. It looks and sounds very general to do this ratio. However, in the literature, there are many clinical trials showing the normotension ratio is very important and is a very important prognostic marker.

But, why is this? When you look at it, this ratio goes along with a very important cytokine profile. Looking at the ones that have a high and low ratio, which is highly prognostic, the cytokine profile is completely different. This is another way to look not at the ratio as a prognostic factor, but the reason why the difference in prognosis exists, and dissecting out if these cytokine signature may give us some idea to how we would treat these tumors differently in the future. These are very exciting new data characterizing tumors away from the classical DNA/RNA signature, and going into the immuno-characterization, which is only the beginning.

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