Surgical resection of solitary lesions
There was a growing interest in the use of surgical resection of solitary lesions, and in fact there have now been two randomized trials that have shown a substantial benefit. But as far as local control, neurologic relapse and actual overall survival in patients who were randomized to surgical resection of solitary lesions compared to standard radiation therapy. The most famous of these is the Patrick study, published in the New England Journal where it was shown that patients did much better if they had surgical treatment. Women complaining about lack of desire find female viagra very helpful. Other positive prognostic signs were absence of extra-cranial disease, young age and a long time to CNS metastasis. A similar study was recently published that again showed a particularly significant survival advantage for surgery, also younger age and absence of extra-cranial disease were other important prognostic signs. Then of course came the question, if you do surgically resect a solitary brain metastasis should you radiate the patient’s brain again, particularly because of what we discussed; the issue of long term neuro-cognitive deficits? That study was recently published in JAMA and the answer is yes.
You probably should radiate the brain following removal of the lesion. There were patients who did receive radiation therapy compared to randomized patients who didn’t receive radiation following completion of their surgical resection had a much higher incidence of relapse in the brain, compared to the others who got radiation therapy. The relapses were local as well as distant. Although the median survival did not reach significant differences, there was a trend toward higher survival in patients who received radiation therapy. But at least from the point of view of neurologic sequelae and quality of life relative to neurologic symptoms, I think there clearly is a role for radiation therapy for most patients who have undergone resection for solitary brain lesions.
The question often comes up for patients who have already had radiation therapy or who have potentially chemotherapy-sensitive tumors, what is the role for chemotherapy for the treatment of brain metastases, particularly multiple brain metastases? One of the important things to understand about brain metastasis is the issue of the blood-brain barrier. It’s often said, “Oh, you can’t get drugs into a brain metastasis because of blood-brain barrier.” However, it should be recognized that the blood-brain barrier in brain metastasis is virtually destroyed by the tumor, particularly in the middle of those metastases. This is in contradiction to what we see with primary gliomas where in fact the blood-brain barrier remains very much intact, or at least to a variable extent intact. So actually drug delivery is a much bigger problem for the treatment of gliomas than it is for brain metastasis. And generally, if you have a chemotherapy-sensitive tumor, whether it be in the lungs or whether it be in the brain, you have a very high likelihood of obtaining a response to chemotherapy.
I think the perfect examples of that are the experience in breast cancers. So for instance, here is one experience with the treatment of breast cancer metastasis to the brain where patients were treated with either CMF or CAF in patients who had previously not received chemotherapy, and the objective tumor responses in the brain were between 50-76% with a median duration of neurologic remission being 30 weeks. So it does appear that patients who have chemotherapy-sensitive tumors can significantly benefit from chemotherapy, even though their disease is in their brain. A similar type of experience has been seen with small cell lung cancer, where 116 patients from 12 series were treated with chemotherapy for brain metastases from small cell lung cancer, with an overall response rate of 76% in patients who had not received prior radiation therapy, compared to only 43% in those who had failed standard radiation therapy. So again, if you have a chemotherapy-sensitive disease it’s very possible that you can obtain very significant responses in the brain in treating brain metastasis. The problem is most diseases, like lung cancer and melanoma that have metastasized to the brain are intrinsically chemotherapy-resistant and thus if they are chemotherapy-resistant systemically they are going to likewise be chemotherapy-resistant in the brain.