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Immunotherapy and the Concept of “Pseudo-Progression”


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June 28th, 2013 - by Dr. Jack West

Immunotherapy was again an exciting area in the field of cancer care in general, and lung cancer in particular, at ASCO this year. But it’s a different kind of treatment from standard chemo, and as we begin to gain experience with it, we continue to learn about some issues that are very specific to immunotherapy. One of those is the concept of “pseudo-progression”. As the name implies, it looks like progression, but it actually isn’t — in fact, it may precede a good and prolonged response to the immunotherapy. But because it looks just like progression on scans, it’s important to know about it and avoid discontinuing a potentially very effective treatment based on a misinterpretation of what the scans are telling us. What does that mean?

Historically, we judge the efficacy of treatments for cancers that are visible on scans by looking at whether the visible areas of disease have grown, shrunk, or stayed the same in size, and whether any new lesions appeared after a period of time on the cancer treatment. We’re happy if it shrinks, not happy if it grows or new areas of disease appear, and we may have more mixed feelings about the utility of the treatment if a person shows stable findings of neither shrinkage nor progression (a kind of “half empty vs. half full” situation). The size of the cancer is almost always a helpful indicator of the status of the cancer when we’re treating with standard chemo or targeted therapies like Tarceva (erlotinib), Avastin (bevacizumab), etc.

But with immunotherapies, we’re learning that a growing or even new lesion isn’t always progressing cancer. Confusing though it may be, sometimes patients seem to be feeling great, cancer symptoms improving, and perhaps most of the areas of disease are shrinking, but there’s one new or growing lesion. What researchers on these treatments are sometimes finding is that biopsies of the growing area or new lesion doesn’t reveal a collection of viable cancer cells, but rather shows an infiltration of the host’s immune cells (called T cells) that appear to be aggregating to attack the cancer cells there. But the crowd of cells looks like progression even when, as may happen, you later see this area clear away with more time on immunotherapy. The presumption is that when you see a new lung nodule, for instance, that may actually be a collection of mostly immune cells that may have converged on an area that was a small collection of tumor cells so small it wasn’t picked up on a prior scan, so it looks like a new nodule now. And these sometimes just vanish later.

This concept doesn’t apply for the cancer treatments that we have more experience with, so unfortunately we can’t just presume that growing lesions in most people are something other than progressing cancer, but for the growing number of people on clinical trials of treatments mediated by the immune system, it makes sense to do a biopsy if the imaging looks worse than the clinical picture. Many of these trials now allow patients who seem to be doing well clinically to stay on treatment even in the face or a new or growing area of disease, since we can’t necessarily just trust our eyes anymore. It’s confusing, but it’s worth being careful not to cast aside a potentially effective therapy because we misinterpret the scans by applying old rules to new therapies.

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