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How do we assess response to treatments for lung cancer?

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How do we assess response to treatments for lung cancer?

July 9th, 2012 - by Dr. Jack West

http://blog.lungevity.org/2012/07/09/ho ... ng-cancer/

This question of how to evaluate response of the cancer on treatment comes up a lot. There are many different kinds of imaging studies, and sometimes people use blood tests. What’s the best approach?

For most cancers, you can see evidence of it on imaging studies like CT scans that are performed regularly over the course of a person’s treatment. We do an initial, baseline scan, ideally just a short time before treatment is started, and new scans done after some fixed duration of treatment are then compared with the initial scan. The general concept is to see whether the repeat scans demonstrate tumor shrinkage (a partial or, rarely, complete response), an increase in the measurable disease or new lesions (progressive disease), or no change (stable disease). Clinical trials use a more formal definition of complete response, partial response, stable disease, or progression that are incorporated into the RECIST criteria (Response Evaluation Criteria in Solid Tumors), but in routine clinical practice, we’re really most interested in whether the cancer is shrinking, growing, or more or less stable. It’s important to bear in mind that most of the time, we’re quite happy to see any appreciable tumor shrinkage, even if it falls short of meeting a defined threshold for an objective response, and even stable disease is a pretty welcome finding, as long as the treatment is well tolerated.

PET scans are regularly used for initial staging of a cancer, but their role in the routine follow-up of a lung cancer over the course of treatment isn’t clearly standard and is somewhat controversial. Many good doctors use them routinely, but I would say that the majority of experts favor good CT scans of the chest and feel that PET/CT scans are really over-used, either because the doctor and/or patient feel that the newest and most expensive test must be best, or because the doctor may have a financial inventive for ordering PET scans. A CT can provide plenty of helpful information for assessing response to therapy once stage has been established, and CT scans are the well studied and validated metric for assessing interval change for cancers with measurable disease. There may be certain situations in which PET scans are quite helpful, such as if CT findings are very hard to interpret, but there is a real risk of identifying clinically insignificant changes, such as by a minimal increase in the PET uptake of a tumor that remains stable in size, that might lead to an ill-advised change in management. In general, if there isn’t any significant change on a CT scan, the progression is very unlikely to be very clinically significant.

Bone lesions are notoriously difficult to asses in terms of changes over time. It’s worth noting that they aren’t considered measurable disease because it is so challenging to reliably distinguish response from progression of an existing lesion. For this reason, the only response that can be assessed in terms of bone lesions is progression when a new bone lesion appears. We can’t trust an interpretation of an existing bone lesion over time.

Serum tumor markers to track response also share some issues with PET scans. Serum tumor markers are proteins produced by the cancer, and they are checked by some doctors and not others in managing their patients with advanced lung cancer. In the setting of some cancers that often don’t have readily visible evidence of cancer, such as prostate cancer or ovarian cancer, tumor markers are a favored approach to assessing response. In others, such as pancreatic cancer, a serum tumor marker like CA 19-9 is generally accepted as a useful index of disease activity, as CA-125 is for colon cancer. In these cases, the vast majority of these cancers produce the marker, and the level correlates well with the status of the disease. But lung cancer doesn’t have a serum tumor marker that is especially reliable, and none is a standard part of routine management. A leading concern of those who do not favor using them to guide treatment decisions is that, like subtle changes on a PET scan, changes in a serum tumor marker when scans show stable disease (assuming there is visible evidence of disease on imaging) might lead to a decision to change treatments in the setting of clinically insignificant changes. They can also lead to a lot of patient anxiety and oncologist impatience when the scan looks fine but the markers are rising…sometimes leading to a false sense of urgency to “just do something” even when there is no clear value to making changes.

Individual physicians have different perspectives about their reliance on PET scans and serum tumor markers in monitoring the course of a cancer, but for most solid tumors (cancers of solid organs where there is visible evidence of the cancer), changes in the size of known cancer on serial CT scans at regular intervals of follow-up remain the best studied and most validated way to assess response to treatment or monitor for progression off of treatment.

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