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Radiation Therapy in the Management of Brain Metastases From Renal Cell Carcinoma

Radiation Therapy in the Management of Brain Metastases From Renal Cell Carcinoma

For some time, the standard of care for patients with metastatic brain disease was whole-brain radiation therapy (WBRT). Despite advances in the detection and treatment of brain metastases, the median survival for patients treated with WBRT alone is approximately 4 to 6 months, and tumor recurrence/progression is common if the patient survives more than 1 year. Nonetheless, it has been recognized that particular subsets of brain metastasis patients will benefit from a more aggressive approach. The most commonly utilized system is the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) system.[1] As outlined by Doh and colleagues in their thorough review on the management of patients with brain metastases from renal cell carcinoma, survival appears to be longer for well selected patients when a more aggressive approach is employed, including surgical resection, stereotactic radiosurgery, or a combination of both techniques.

Role of the Neurosurgeon

The understanding that aggressive intervention is appropriate for many brain metastasis patients has markedly changed the role of neurosurgeons in the management of these patients.[2] Previously, neurosurgeons were typically consulted in one of three situations: First, in patients with presumed metastatic brain disease from an unknown primary site, a biopsy of an intracranial lesion (either stereotactically performed or excisional) was requested. Second, patients with a new diagnosis of metastatic brain disease and one or more large tumors causing symptomatic mass effect might require a neurosurgical consult. In such cases, it was realized that tumor resection was required to improve neurologic deficits and enable a patient to undergo WBRT. Third, following WBRT, if one or more tumors continued to progress and the patient was systemically stable, he or she was referred for consideration of tumor resection.

By these criteria, neurosurgeons were consulted about few patients in this setting. However, with studies showing improved survival times for patients with single metastases undergoing surgical resection in addition to WBRT—as well as the introduction of radiosurgery—the number of brain metastasis patients undergoing neurosurgical care continues to grow exponentially. This is significant if one considers that the total number of gliomas, meningiomas, schwannomas, and pituitary adenomas diagnosed each year in the United States is approximately 40,000, whereas the number of newly diagnosed brain metastasis patients is in the hundreds of thousands.

Treatment Decisions

The decision to recommend surgical resection or radiosurgery for brain metastasis patients is multifactorial. Patients with large tumors and symptomatic mass effect are poor candidates for radiosurgery. For such patients, surgical resection augmented by stereotactic guidance and awake cortical mapping (if the tumor is located in regions of the brain involved with speech and language) is indicated. In some patients with several large tumors, multiple craniotomies are performed in a single setting. The average length of hospital stay is 3 days. To minimize the chance of local tumor recurrence, we typically recommend postoperative WBRT once the patient has recovered from surgery. Another situation that favors surgical resection over radiosurgery is the patient with diabetes mellitus. Tumor removal generally permits the rapid elimination of corticosteroids, which makes blood glucose control much simpler.

Radiosurgery is generally preferred for patients with multiple tumors and for patients with tumors that cannot be safely resected with acceptable risk. Questions that remain unanswered relate to the appropriate roles of WBRT and radiosurgery[3] and the relative indications of surgical resection vs radiosurgery for patients with brain metastases.[4-6]

WBRT With or Without Radiosurgery

Kondziolka et al performed a randomized controlled trial in 27 patients to compare survival and tumor control using WBRT or WBRT and radiosurgery.[7] They found that combined WBRT and stereotactic radiosurgery significantly improved local tumor control for patients with two to four brain metastases compared to patients receiving WBRT alone. No difference was noted in patient survival, although a difference was detected between patients who underwent WBRT alone and those who later had salvage stereotactic radiosurgery or those who had initial WBRT and stereotactic radiosurgery.

Andrews et al recently reported a prospective randomized RTOG trial (RTOG 95-08) of WBRT vs WBRT plus radiosurgery for patients with one to three brain metastases.[8] WBRT plus radiosurgery provided a survival advantage compared to WBRT alone in the following patient groups: (1) patients with a single brain metastasis, (2) patients with two or three metastases and RPA class I, (3) patients with two or three metastases who were under the age of 50 years, (4) patients with two or three metastases and non-small-cell lung cancer or any squamous carcinoma. All subsets of patients in the WBRT-plus-stereotactic radiosurgery group were more likely to have a stable or improved performance status, improved local control, and reduced steroid dependence compared to the WBRT-alone group. Systemic disease remained the primary cause of death in both groups.

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