Not long ago, the diagnosis of one or more metastatic tumors (secondary brain tumors originating from a solid organ cancer elsewhere) was considered a terminal event, with treatment of the tumors limited to palliative whole brain radiotherapy. As central nervous system involvement occurs in about one-fourth of patients with such cancers, brain metastases took a terrible human toll, being the cause of death in just a few months in most affected patients.
Today, aggressive management, aided by a variety of effective treatments, can often lead to indefinite or extended control of even multiple metastatic tumors in patients with controlled or limited systemic disease. At the Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, a multidisciplinary team evaluates such patients and applies one or more individualized treatments to secure control of newly diagnosed or recurrent metastatic brain tumors.
Treatment Options for Metastic Brain Tumors
Surgery, in addition to whole brain radiotherapy, has been shown to be more effective than radiotherapy alone for patients with a single secondary metastatic tumor. Even in patients with multiple brain tumors, surgical resection leads to survival comparable to those patients with single resected lesions. Pioneers in contemporary computer-assisted neurosurgery, Burkhardt Brain Tumor Center (BBTC) neurosurgeons routinely use minimal access techniques to remove one or more metastatic tumors with minimal morbidity and short hospital stays. For patients with recurrent or new metastatic tumors after radiotherapy, surgery in conjunction with placement of carmustine wafers in the tumor cavity may thwart local recurrence. Also, BBTC clinical researchers are investigating the role of intracavitary radiotherapy or liquid brachytherapy after resection with the hope of obviating the need for whole brain radiotherapy.
Today, surgery for brain metastases may be part of a comprehensive brain management plan where other techniques are brought to bear on additional tumors not amenable to radiotherapy. Beyond radiotherapy, staged therapy options include stereotactic radiosurgery, intra-arterial chemotherapy with or without blood brain barrier disruption, and newer systemic chemotherapies.
In many ways, metastatic tumors are ideally suited to treatment with stereotactic radiosurgery such as delivered by Gamma Knife technology. Lesions are typically small (i.e., < 3 cm at presentation), spherical, and displace, rather than infiltrate, the normal brain. Results from radiosurgery appear comparable to those achieved by surgery with radiotherapy, and allow for effective treatment even for surgically inaccessible secondary brain tumors. A recent multi-center randomized trial showed that radiosurgery in addition to whole-brain radiotherapy led to improved survival or enhanced quality of life for patients with one or more metastatic brain tumors, respectively. Also, radiosurgery may reduce the chance of leptomeningeal spread as a result of surgery for certain types of tumors.
So-called “radioresistant” types of tumors (e.g., melanoma, renal cell carcinoma) respond as well to stereotactic radiosurgery as “radiosensitive” tumors. Neurologic morbidity is low when dosing is prescribed to levels set by the Radiation Therapy Oncology Group, of which Cleveland Clinic is an active member. Cognitive side effects are minimal, as the tumor treatment is confined to small regions of the brain.
Cleveland Clinic radiosurgery program is the oldest in Ohio, and has been designated as only one of only a few centers that is certified by the manufacturer of the Gamma Knife to train new users of this “gold standard” of radiosurgery. Further, Cleveland Clinic offers other radiosurgery devices, such as the Novalis system which can be used for unusually large lesions, or for those in intimate contact with critical structures such as the spinal cord.
Once again, radiosurgery may be combined with other brain cancer treatments for comprehensive management of brain metastases, including investigational use of radiosensitizers or chemotherapy.
Systemic cancers that are chemotherapy sensitive often take refuge in the brain, despite systemic control, as most commonly used chemotherapies have poor penetration through the blood brain barrier. Management of such metastatic tumors may take several forms. Patients with metastatic breast cancer to the brain with tumors that are estrogen-receptor positive may respond to high doses of Tamoxifen, thereby compensating for the drug's limited penetration into the brain. Alternatively, temozolomide, an orally administered methylating agent, has excellent penetration into the brain and may be considered in some patients. More intensive treatment includes use of chemotherapy injected directly into the carotid or vertebral arteries, at times using hypertonic manitol to disrupt the blood brain barrier that prevents many active agents from reaching adequate concentrations in brain metastases.
An exciting area of investigation is the use of small, targeted molecules to treat a variety of malignancies. As the molecular characterization of various tumors improves, investigational drugs that target specific molecular pathways may play an increasing role in the management of metastatic tumors and even leptomeningeal disease. The use of these agents and appropriate modes of delivery are and will be a major thrust of BBTC clinical and laboratory research.