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First-Ever Evidence-Based Guidelines on Treatment of Brain Metastases
Zosia Chustecka

November 4, 2009 — The first-ever set of evidence-based guidelines for the treatment of brain metastases is about to be published.
"There have been other documents in the past, but they have not been as multidisciplinary as these are, and they tended to be reviews and consensus statements," said Steven Kalkanis, MD, codirector of the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit, Michigan. "This is the first time that we have treatment guidelines that are based very rigidly on evidence-based medicine."
Dr. Kalkanis headed a panel of 20 experts in various fields, spanning radiation oncology, medical oncology, neuro-oncology, and neurosurgery, who worked together on the document. The panel collaborated closely with the McMaster University Evidence-Based Practice Center to ensure that a strict evidence-based methodology was followed when the guidelines were being developed, he noted.
The guidelines were released last week at the Congress of Neurological Surgeons in New Orleans, Louisiana, and are scheduled to be published in a special issue of the Journal of Neuro-Oncology in December.
Brain Metastases More Common Than Brain Cancer
Brain metastases develop in about 30% to 40% of patients with cancer, and occur commonly with breast and lung cancer. In the United States, there are an estimated 500,000 new cases of brain metastases every year, in contrast to the estimated 17,000 news cases of primary brain cancer seen each year.
There are also differences in biology between the 2, which means that the treatment of brain cancer can differ from that of brain metastases. Primary brain cancers, such as glioma, tend to be "very aggressive and very invasive, and they are part of the brain tissue," Dr. Kalkanis explained, "whereas brain metastases tend to be walled off and rather separate from the brain tissue," but, he added, "they are no less deadly."
The differences between the 2 means that new targeted agents such as bevacizumab (Avastin), which has shown promise in the treatment of glioblastoma multiforme, might not be as useful in the treatment of brain metastases, "but the evidence is not yet definitive."
We are specifically recommending that chemotherapy not be used for brain metastases.
One point that did arise during the literature search is that there is no evidence to support the use of chemotherapy for the treatment of brain metastases. This is not the situation for primary brain cancer, where agents such as temozolomide (Temodar) are a mainstay of treatment, Dr. Kalkanis noted. "As a result, we are specifically recommending that chemotherapy not be used for brain metastases," he added. Of course, there should be chemotherapy as appropriate for the primary tumor, but once that is under control, there is no need for further chemotherapy aimed at secondaries in the brain, he said.
Another difference is in the approach to the prophylactic use of anticonvulsants to prevent seizures. This tends to be standard practice for patients with primary brain cancer, but for patients with brain metastases, current practice is probably split 50/50 for using or not using these drugs, Dr. Kalkanis explained. In this instance, once again the literature search found no evidence to show a benefit, so the guidelines do not recommend it, he said.
One of the reasons for drawing up the guidelines was to place new developments in the field into context. For example, the use of radiosurgery has really taken off over the past decade, and is no longer being carried out by only a few academic institutions, Dr. Kalkanis noted. This approach uses high-intensity radiation that is targeted very specifically (using magnetic resonance imaging) at the brain metastasis, preventing the trauma of open surgery followed by whole brain irradiation, which is the traditional approach. The panel decided that the new approach of radiosurgery offers a "very viable and important option," he said.
Another new development has been the use of radiosensitizers, such as motexafin, which enhance the effects of radiotherapy and appear "to show promise" for brain metastases, he added.
"Because of the growth of these new technologies, there has been wide variation among physicians on how to treat patients. Some centers use X and Y followed by Z, whereas other centers use Z followed by Y and then X," Dr. Kalkanis explained.
"Our primary goal was to identify best treatment practices leading to the best outcomes for patients," he said. "At the same time, we don't want to unduly restrict the physician's practice," he added.
In cases where there was not enough data to suggest a guideline or recommendation for a particular treatment, the report lists all relevant ongoing clinical trials to encourage physicians to enroll patients. In addition, the document highlights areas in which more research is needed.
Dr. Kalkanis has disclosed no relevant financial relationships