Howard (Jack) West, M.D.
Thoracic Oncologist, Swedish Cancer Institute in Seattle, WA
Among the many challenges of managing malignant pleural mesothelioma (MPM) is reliably assessing the response of the disease to our treatment. We don’t want to discard a treatment that is effective, nor do we want to have patients continue on a treatment that isn’t helpful but is causing significant side effects. In oncology, we typically grade our work by comparing an imaging study like a computerized tomography (CT) scan of the chest done after 2-3 cycles of systemic therapy (usually covering a 6-9 week interval) to a baseline scan performed prior to the start of treatment. As you’d suspect, significant tumor shrinkage is good, while growth is bad, and stable disease is somewhere in between. Typically, we want to continue our treatment in the absence of significant progression or prohibitive side effects.
So why is it so difficult to measure response in MPM? Unlike most solid tumors, MPM doesn’t typically appear on scans as a well circumscribed sphere that can be easily measured. Instead, it appears as a rind around the lung, often with irregular contours, sometimes areas of benign plaques from asbestos exposure, and collections of pleural fluid filling the cavity between the outside of the lung and the inner chest wall. Patients who have undergone a palliative pleurodesis, an intervention in which there is deliberate inflammation within the pleural space in order to cause scarring and close off that space (and thereby prevent fluid from filling there), will typically have marked thickening in that area that represents inflammation and scarring (the desired effect of the pleurodesis) that can be remarkably difficult to distinguish from active cancer.
There are various ways to contend with the challenges of measuring response to treatment for MPM. First, metabolic/functional imaging with positron emission tomography (PET) scanning along with fused CT images is often employed, as it can be instructive to see the level of metabolic activity decrease or increase as an indicator of response or progression, respectively, particularly when the thickness of the rind of tissue thought to represent MPM is not obviously increasing or decreasing in thickness. It is worth noting, however, that a pleurodesis is also expected to transiently increase PET activity in the pleural space in the weeks and perhaps even months after this procedure is performed, so it is necessary to be cautious about interpreting changes in PET uptake that have developed following a pleurodesis. Another clue can come from changes in a patient’s symptoms: many patients with MPM will experience chest wall pain from their underlying disease, and changes in a patient’s symptoms are another helpful indicator of the direction that the cancer is moving in when imaging is notoriously ambiguous. Finally, a blood test such as levels of soluble mesothelin-related proteins (MSRP) can potentially serve as a serum-based indicator that the cancer is responding or progressing.
Ideally, we would hope to have a test for assessing treatment response in MPM that is widely available and well validated. We are limited in the relative infrequency of the disease, with patients treated in a wide range of settings with varied levels of expertise in interpreting imaging results that are often ambiguous and complex. In this setting, it is often necessary to accept greater ambiguity, to be pleased to see an absence of convincing progression, and to utilize additional clues such as the trajectory of a patient’s cancer-related symptoms and potentially serum-based testing such as MSRP levels to provide greater direction as we do our best to make good judgments about the value of the treatment being administered.