Well, I'm finished writing about Follicular Lymphoma presentations at ASCO. (You can read the posts from the last month, but here's my quick review: not a whole lot of exciting new stuff to report, but lots of small bits of progress, which is usually how cancer research goes.)
So now I'm going through all of the links that I've been saving for the last month to find all of the really interesting Follicualr Lymphoma research that wasn't reported at ASCO. There are a few very cool articles from medical journals that I want to share over the next few weeks.
The first is from the journal Leukemia, and the article is called "Circulating tumor DNA in B-cell lymphoma: technical advances, clinical applications, and perspectives for translational research."
This is a review article, so it's more of a "here's everything we know about a topic" piece than one that's reporting on original research. But it's fascinating, and could have some very important information for lymphoma patients, with stuff that could happen very soon (unlike lots of the research we see).
The article is about Circulating Tumor DNA, how to find it, and how to use it. It describes "liquid biopsies," which have been around for a while, but are finally getting accurate enough to be helpful.
So here's how they work:
All of us had a biopsy to help in our diagnosis. It was most likely a lymph node biopsy. For me, that meant a surgeon cut out one of the many swollen lymph nodes near my hip (the surgeon told my wife, "There were about 15 of them in there, I just picked the biggest one.") That tissue sample went to a lab, where a diagnosis specialist looked at it under a microscope. He saw the pattern and shape of the cells and knew right away it was Follicular Lymphoma. (When I say "he," I'm not making assumptions about the doctor being male -- it turns out the Diagnosis specialist at the hospital I was at is the father of a kid who was in the school band with my son. Small world.)
This is how most biopsies have happened for a long time. A doctor looks under a microscope and makes a diagnosis based on what he (or she) sees.
The problem is, there is a lot happening in that cell that can't be seen with the eye, even with a very powerful microscope. Two cancer cells can look the same on the surface, but there are enough genetic differences between them -- mutations in their DNA -- that they are really two different types of cancer. This is why I hate it when someone says they have Non-Hodgkin's Lymphoma. Which type? Because there are as many as 80 different kinds of NHL, and lots of them look similar under a microscope but behave very differently because of differences in their DNA.
That's where a "liquid biopsy" comes in. After a traditional biopsy is done (a "solid biopsy"), a liquid biopsy can use a blood sample to determine if there are any of those DNA mutations floating around a patient's body.
Much of the article looks at different methods for collecting, storing, and analyzing blood samples to test for circulating tumor DNA. It's not worth getting into all of that -- none of us is going to say to a doctor, "Hey, if you're going to do a liquid biopsy, can we talk about advantages and disadvantages of llele-specific oligonucleotide PCR and digital droplet PCR and NGS-based approaches?" (Even I don't have an opinion of those things, and I'm pretty sure I'm a bigger Cancer Nerd than any of you.)
More importantly, the article talks about why a liquid biopsy could be helpful for a patient with a B Cell Lymphoma like Follicular Lymphoma.
First, at diagnosis, a liquid biopsy can identify if the patient has a specific subtype of Lymphoma. Follicular Lymphoma doesn't have a lot of subtypes -- at least not really any that can be identified with a genetic analysis. But it's possible that, in the near future, enough genetic analysis is done that we can start to see some of those subtypes. Right now, patients don't really know if, for example, they are POD24 (their FL is aggressive enough to come back within 24 months after immuno-chemotherapy) until the lymphoma comes back. It's possible that a liquid biopsy could identify POD24 patients right at diagnosis so a more aggressive and appropriate treatment can start immediately. (I say "possible" because researchers still haven't identified a biomarker that can do that.)
Second, a liquid biopsy could be helpful during surveillance, such as during watch and wait, or in the years after treatment. For example, a liquid biopsy could help confirm transformation. As most of you know, Follicular Lymphoma can sometimes transform from a slow-growing cancer into a different, more aggressive one. A solid biopsy can confirm this -- pick a node and remove it through surgery and biopsy it. A microscope can show that the cells are different. Two problems with this, though. The first is, transformation doesn't happen all at once, so there are both Follicular Lymphoma cells and more aggressive transformed cells in the body at the same time. It's possible to get a solid biopsy sample that doesn't have any transformed cells -- the wrong node got picked -- so it doesn't look like there has been a transformation. Also, the biopsy will probably require surgery. Not fun. A liquid biopsy won't require surgery (good for the patient), and can measure DNA circulating in the blood, not hanging around in one spot in a node. Potential for greater accuracy.
Finally, a liquid biopsy can be very helpful after treatment. Right now, a PET scan is used to measure how successful a treatment was. If the scan doesn't light up, the cancer must be all gone. However, small bits of cancer cells might remain -- so small that they don't light up on a scan. But a liquid biopsy may be able to detect some remaining cancer by finding it in the DNA of cells that are moving around in the blood. If that's the case, then salvage treatment (maybe something like Rituxan Maintenance) can be used to clean up anything that's still left over.
As the article points out, this technology has been around for a little while. Like lots of new medical innovations, at first, they are either too expensive or not accurate enough to be useful. But that has changed with liquid biopsies -- they are becoming more refined and accurate (that's another big part of the article that isn't worth getting into).
Liquid biopsies for Lymphoma aren't perfect, and there are a few different ways of doing them that make it hard to have a standard approach. But the authors of the article think these problems will be overcome "in the near future," and we will see a greater use of them soon.
I think this is something worth asking your oncologist about. There may be trials or testing being done at your cancer center, and it probably wouldn't require more than a blood sample to be involved. And it might get us all closer to having fewer scans and fewer biopsies.
[More interesting non-ASCO research coming soon.]
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