An Interview with Andrew Seidman, MD, Memorial Sloan-Kettering Cancer Center
Part 4: Radiation Therapy
Musa Mayer: Turning to the subject of whole brain radiation and radiosurgery (stereotactic radiation), I know there are differences of opinion about this in the field, about when each is appropriate, and when it is not appropriate. I know you canâ€™t speak for all physicians, obviously, but when is there no question in your mind that whole brain radiation is the right approach?
Andrew Seidman: The word, â€śinnumerableâ€ť is often used to describe that scenario. When would I think that doing stereotactic radiation on multiple lesions is probably not going to be useful? It would be a scenario where patients would have five or ten or more lesions. The scenario where one would consider stereotactic radiation involves a limited number, and that exact number is even a matter of debate and controversy.
MM: Size of the lesions is an issue with stereotactic radiation, isnâ€™t it?
AS: I would defer more to a radiation oncologist to give the answer to that question, because I honestly donâ€™t know what the limitation would be on size for the lesion to be amenable to stereotactic radiation, but large, bulky lesions would probably not be well treated in this manner.
MM: How does the presence of extracranial disease (metastases outside the brain) figure into that choice, for you?
AS: Sometimes, the approach to management of brain metastases should be informed by whatâ€™s happening elsewhere. But if the patient has other non-central nervous system metastasesâ€”the more common sites being bone, lungs and liverâ€”and they are relatively well controlled, in other words, not rapidly progressing, then they really shouldnâ€™t significantly influence the management of the brain. However, if the problems with the patientâ€™s other organ systemsâ€”for example, having liver involvement with liver failure, or pulmonary involvement with respiratory failure requiring supplemental oxygenâ€”are so severe that the expectation is that their life expectancy could be measured in a short duration, perhaps several weeks to several months at most, then that extracranial disease can inform what might be the appropriate management of the brain metastases.
One example is that the patient who is expected to survive for many years, rather than many weeks or months, may have a greater concern about long term effects of whole brain radiation on cognitive function. For the patient who canâ€™t at the moment be as optimistic about her outcome because of the status of extracranial disease progression, then that really isnâ€™t a significant consideration. One wouldnâ€™t want to avoid whole brain radiation because unfortunately, the patient may not live long enough to actually experience the cognitive dysfunction that whole brain radiation can cause in some patients.
MM: So letâ€™s talk a little about neurotoxicity and cognitive dysfunction as a result of radiation. How convinced are you, based on what the research shows, about shorter and longer term toxicity and cognitive problems? Have you seen it in your practice? Have you read reports that you think are persuasive?
AS: Iâ€™ve certainly seen cognitive dysfunction from whole brain radiation in my practice. I see it in patients who are fortunate enough to not have progression of cancer in the brain, that leads to their being well enough for it to become evident. It is progressive over time. Certainly in the acute setting, depending upon the nature of the disease burden in the brain, the metastases themselves can affect cognitive function, depending upon the position and the number of lesions in the brain itself.
While we all would like to avoid cognitive dysfunction, we mustnâ€™t lose sight of the fact that radiation and whole brain radiation plays a critical role in controlling this disease, and I would not want someone to turn away from potentially useful radiotherapy solely because of the fear of cognitive dysfunction. The flip side of the coin is that uncontrolled metastatic disease in the brain can do its own devastation. Radiation to the brain doesnâ€™t result in death, but progressive brain metastasis does.
Having said that, if there are scenarios where one can avoid radiating the whole brain, where patientsâ€™ lesions are amenable to more localized therapies, like stereotactic radiation, which is associated with a lower change of cognitive dysfunction, then by all means those should be entertained.
MM: That leads to the question of follow-up whole brain radiation, which in some centers is standard-of-care after stereotactic radiation, because of its known ability to reduce recurrence.
AS: There are patients who will have stereotactic radiation and simply be observed, without whole brain radiation. That tends to be the approach that we take at Memorial and that others take. An analogyâ€”perhaps unfortunateâ€”is of weeds growing in the lawn. The use of SRS (stereotactic radiosurgery) is a weed-picking approach, where youâ€™re focusing your attention on just the lesions you can see. When we pull these weeds out of the lawn, weâ€™re very happy that the lawn looks just fine, but often, with time, additional weeds pop up that werenâ€™t apparent before. This is not that far off as an analogy from what happens in the brain. If you do SRS, patients will have very good long term control just from weed-picking alone. However, with further monitoring, many of these patients will develop new lesions. Certainly, if theyâ€™re multiple, and if thereâ€™s a short interval from the time that the previous lesions were detected, most often the approach then is to employ whole brain radiation.
Having said that, I have seen patients treated elsewhere who have been multiply treated with stereotactic radiation for three, four and five different episodes of progressive brain metastases. I donâ€™t know if we have adequate studies to say that this approach of continuous weed-picking of solitary lesions offers an advantage or a disadvantage over whole brain radiation. I certainly think thereâ€™s an impact in terms of cost of care with the serial stereotactic radiation approach costing the healthcare system significantly more than whole brain radiation. Thatâ€™s just my gut sense.
A good message to get across to patients, since many of us are mobile, is that when you have radiation therapy, itâ€™s very important to have accurate records of radiotherapy, in terms of the dose and field, in terms of the area which has been radiated. Without the radiation oncologistâ€™s records, when you end up in another hospital, in another state, in an urgent situation, it can often lead to a delay in initiating appropriate therapy. This is because radiation oncologists are very reluctant to expose parts of the brain to an excess dose of radiation. There is a certain level of radiation that you donâ€™t want to exceed because of the very real potential of causing necrosis, that is death to normal brain tissue.
Sometimes, someone who has already had whole brain radiation and progressed despite itâ€”I know radiation oncologist will consider re-irradiating. Typically the scenario is when youâ€™re between a rock and a hard place, and you donâ€™t have any other good options available.
Interview continues in Part 5...