Drs. Wen and Loeffler present a scholarly review of the management of brain metastases. They correctly note the high frequency of the brain as a site of metastasis and the fact that, overall, there are more metastatic than primary brain tumors. I would add one further point to this observation. Although metastasis represents a failure of local control for any primary cancer, brain metastasis can produce a clinically more devastating complication than almost any other form of cancer spread. A brain metastasis, inducing a combination of headache, cognitive disorder, motor or sensory disturbance, and loss of ambulation, converts a patient with “internal” illness to one with overt, visible illness, which now requires the assistance of others, often for the most personal and menial of tasks.
A middle-aged man (or woman, in this age of sexual equality), with a “spot” on a chest x-ray may be subject to a variety of therapies but, to outward appearances, functions at a near-normal, independent level. If that individual has a brain metastasis, he or she is suddenly invalided by a “visible” disease, now requiring nursing by professionals or loved ones.
The appearance of a brain metastasis also suddenly makes death palpable. Now cancer is at its most fearsome.
There are a few positive aspects of this dreadful complication of progressive systemic cancer. One is that the major neurologic catastrophe produced by a brain metastasis can be readily and successfully treated, at least in the short run. For most patients and most cancers, a course of corticosteroids, radiation therapy in its several guises, and, occasionally, neurosurgical intervention returns the patient to an independent state.
Also, for most patients and most cancers, death comes from systemic tumor spread, not from neurologic disease. As a neurologist with more than 3 decades of experience in treating such patients, I think that is the “better” mode of death.
Roles of Whole-Brain Radiation, Resection, and Radiosurgery
As for the details, a few points are worth making. I think that for most patients with metastatic brain tumors, whole-brain radiation therapy (WBRT) is as effective as any of the more complicated combination treatments, including adjunctive surgical resection or radiosurgery. However, whole-brain irradiation damages normal brain tissue; cognitive changes are the rule with such treatment. Although adjunctive resection or radiosurgery may improve immediate neurologic outcome—and prolong survival if the metastasis is single or especially solitary—the real value of these modalities should be in reducing the need for whole-brain irradiation. So far, it is not clear that they do so.
As cited in the paper, most studies indicate a need for WBRT following surgery or radiosurgery. I would hope for a more efficient form of such therapy, for example, with a radiosensitizer, so as to reduce the dose of radiation. I would look for other modalities—chemotherapy, gene therapy, monoclonal antibodies, or whatever—to eliminate WBRT, but that is a topic for further research.
With respect to the specifics, I offer my own view. I seek to have my neurosurgeons remove single or solitary metastatic brain tumors. In my view, the randomized studies demonstrate very persuasively that such treatment is better than WBRT alone. I usually give WBRT afterward, despite my concerns for creating brain damage.
I think that radiosurgery is an effective adjunctive therapeutic tool, although I doubt that if it will replace surgical resection. Take the case of one of my patients, a young businesswoman with melanoma. She developed a single brain metastasis high in the posterior frontal region of her brain, causing a paresis in one leg. I favored resection, but the patient opted for radiosurgery. For the next year, she required continued steroid therapy to permit her to walk; every attempt at reducing the steroid dose caused a return of her leg paralysis. Finally, 1 year after the radiosurgery, the tumor had shrunk enough to allow her to stop taking the steroids. In retrospect, a surgical resection would have accomplished in less than 1 week what it took 1 year to do with radiosurgery.
I agree with Wen and Loeffler that a randomized study comparing resection with radiosurgery is unlikely to happen. I often favor radiosurgery, especially as an adjunct to WBRT and when there is much systemic disease. When it comes to a decision about initial therapy for a single brain metastasis or, occasionally, two or three brain lesions, I favor resection.
Better Medical Therapies Needed
As for the future, I hope for better medical therapies. I strongly advocate that we perform only prospective, randomized trials. Let us not waste patients’ already foreshortened lives by not controlling our studies. Make trials definitive early; if new approaches do not work, discard them. Avoid using the same therapies until we prove by proper studies that they are of no value.
Finally, I like Figure 2 in the article. For physicians who are new to this field, it provides an excellent guide to managing patients with brain metastases. And for those of us who are old-timers, it is a reminder of some of the accomplishments that have improved our patients’ lives, even for a short while.