Metastatic lesions to the brain occur commonly in oncology patients and portend a very poor outcome, as they often occur in the setting of progressive systemic metastatic disease and can result in neurologic deterioration that may preclude therapy. Therapy of patients with brain metastases requires a combination of measures to achieve local control at the site of metastasis (eg, with surgical resection or radiosurgery) and to reduce the subsequent risk of recurrences elsewhere in the brain (eg, with whole-brain radiation). Successful therapy of extracranial systemic metastases is required for optimal outcomes. Clinical trials are currently underway to define the optimal role of whole-brain radiation and radiosurgery in different subsets of patients. Novel therapies to enhance radiation responsiveness are also under investigation. In the current review, we discuss recent developments in the management of patients with brain metastases.
In this issue of ONCOLOGY, Rao et al provide an up-to-date, concise, and soundly written review of current management strategies for cancer patients who present with brain metastasis. This complication of cancer is a serious problem due to its prevalence and because it portends a poor prognosis.
Unfortunately, the lack of a National Cancer Registry prevents the establishment of an accurate overall incidence for this complication, leading several authors to perhaps overstate its incidence by suggesting that "up to 40% of patients with certain metastatic cancers. . . may develop brain metastases." To shed some better light on this topic, Barnholtz-Sloan et al took advantage of the Metropolitan Detroit Surveillance System data to estimate the incidence proportions of brain metastasis associated with the five most common cancer histologies of such disease spread and found it to be 9.6%.
Regardless of what the precise prevalence might be, it is evident that brain metastases represent, by far, the most common type of brain tumors. Moreover, their incidence continues to rise due to an increasingly aging population and to advances in the management of systemic cancers.
The role of whole-brain radiation therapy (WBRT) in the management of brain metastasis remains dominant and is lucidly discussed in this review. Despite an increasing tendency by many to eliminate or postpone this form of therapy, WBRT remains the most common and the most appropriate form of therapy for brain metastasis. Any attempts at modifying this standard of care must be done on the basis of well-conceived prospective trials.
For the important subset of patients with oligo-brain metastases (defined as less than four), especially those that are in recursive partitioning analysis (RPA) class 1 or 2, focal therapies in addition to WBRT are likely to result in better control of the central nervous system disease. Among these therapies, surgical approaches have been best studied. More recently, stereotactic radiosurgery (SRS) has gained wide popularity, even though its results are much less well scrutinized. The number of prospective trials employing this mode of therapy is appallingly low, and yet, this has not prevented the wide surge in its use to treat brain metastases.
In the absence of a large scale randomized, prospective trial comparing surgery with SRS, we are unfortunately left with a series of opinions that are based on analysis of retrospective data or on individual biases. Regardless of any individual's opinion, there are two important concepts that must be highlighted. For SRS to be optimally effective, the size of the tumor must be small. Although a 3-cm diameter metastasis is universally considered within the accepted range for SRS therapy, it is highly unlikely that tumors of such a dimension will be adequately controlled by SRS. Much superior results are seen when treating metastases that are 1.5 cm or less in diameter.
The second concept relates to the anatomic and functional location of the tumor in the brain. It is commonly stated that SRS is preferable to surgery for the treatment of brain metastases that are located in eloquent brain. Such statements might seem intuitively appropriate until the literature is reviewed and the surprising notice that such a relationship has never been studied except for tumors located in the brainstem. Ongoing analyses of data from our own institution indicate that SRS for tumors in or near the motor cortex, for instance, is significantly more associated with neurologic morbidity than for similarly located tumors treated with surgery.
Regardless of these arguments, it is evident from this and other reviews of the management of brain metastases that it is a complication requiring the most advanced team of multispecialists, whose individual members each bring their own expertise to provide the most appropriate and the most effective form(s) of therapy. To this end, it is unfortunate that a neurosurgeon was not included among the otherwise stellar group of neuro-oncology specialists who authored this review. This observation does not reflect only an academic perspective, but is rather meant to stress a greater attention to a topic already suffering from the lack of an integrated approach on the national level.
-Raymond Sawaya, MD
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Rao RD, Brown PD, Buckner JC: Innovation in the management of brain metastases. Oncology (Williston Park) 21:473-489 (incl discussion), 2007.
2. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al: Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 22:2865-2872, 2004.
3. Omuro AMP, Kris MG, Miller VA, et al: High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 103:2344-2348, 2005.
4. Chang EL, Hassenbusch SJ, Shiu AS, et al: The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases. Neurosurgery 53:272-281, 2003.