Liquid Biopsies for Lymphoma

Very cool research out of Stanford university School of Medicine -- liquid biopsies that can help doctors tell if a treatment is working or not, weeks or even months earlier than we've previously been able to tell.

The research was published in the Journal of Clinical Oncology, in an article called "Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma."

So, first off, the research was done on patients with Diffuse Large B-Cell Lymphoma (DLBCL), which is not Follicular Lymphoma. It's more like a meaner, more aggressive cousin. And it's the type of lymphoma that FL most often turns into when it Transforms.

Like Follicular Lymphoma, DLBCL comes in lots of different forms, so it's hard to predict which way it will go, and which treatment might work best. The liquid biopsy described in the article might help with that. (A press release from Stanford was a big help to me in understanding all of this.)

What's a "liquid biopsy"? Well, most of us have had solid biopsies -- maybe a fine needle aspiration, where a few cells are taken from a lymph node. Maybe a full lymph node removal (like I had), and maybe even a bone marrow biopsy (me again!). Cells are removed and examined to determine if they are cancerous.

A liquid biopsy involves the same process -- looking at cells to determine if they are cancerous -- but the liquid is blood. They have always been hard to do. There is a lot moving around in the blood, and a cancerous cell in the blood might be on its way out, so it doesn't say much about the cancer that's happening elsewhere.

For this study, the researchers looked at something called "Circulating Tumor DNA," or ctDNA. Basically, when a cancer cell is dying, it releases ctDNA. The researchers were able to find the particular DNA sequence they were looking for in the blood (there were possibly millions to search through).  [And don't ask me how they picked them out. I'm almost certain they didn't do it by hand.]

They looked at 271 DLBCL patients in six cancer centers (three in the U.S. and three in Europe). They measured the amount of ctDNA in the blood before they began treatment, and then after the first round of chemo, and again after the second round.(Chemotherapy is still the most common first treatment for DLBCL.)

About 98% of patients had ctDNA in their blood before treatment. A drop in ctDNA after a treatment is a good sign. They found that patients who had a 100-fold drop in ctDNA after the first treatment, and a 300-fold drop after the second treatment, had superior outcomes after 24 months -- they were more likely to have lived without the disease coming back in that time.

The implications here are very important. Right now, a patient might have 6 rounds of chemo, to make sure the cancer is all gone. If a liquid biopsy shows a huge drop in ctDNA after only two rounds (over three weeks), that might show that the two round of chemo was enough, and the other 4 rounds weren't necessary. That's a huge Quality of Life issue -- fewer side effects, less cost.

At the same time, a patient might have an increase in ctDNA after 2 rounds. that would show the chemo isn't working, and would allow doctors to stop it and choose a different treatment right away, one that is more aggressive. That could possibly save a life.

The researchers have already done successful research on this process with lung cancer. Maybe similar tests for other cancers -- including FL? -- are in the future?


Maybe so. We can keep hoping. We have lots of treatments available to us -- and more on the way -- but knowing whether or not they are actually working would be an excellent next step.