Addition of whole-brain radiation to highly-focused radiotherapy does not improve survival for patients with brain metastases, but it may reduce the risk for recurrent metastases, according to an article in the June 7 issue of the Journal of the American Medical Association.

Because of the hypothesis that patients with brain metastases have micrometastases seeded throughout the brain, whole-brain radiation therapy, which has possible adverse effects, has been the dominant treatment. Recently, this assumption has been questioned.

For patients who truly have limited intracranial disease, the potential exists that whole-brain therapy could be replaced by more focused therapeutic options such as resection or stereotactic radiosurgery, which delivers high-dose, focal radiation, with fewer long-term adverse effects than whole-brain radiation. These therapies have been used with increasing frequency. It has been unclear whether adding whole-brain radiotherapy to stereotactic radiosurgery improves survival or neurologic function compared with focused therapy alone.

Hidefumi Aoyama, MD, PhD, of Hokkaido University Graduate School of Medicine, Sapporo, Japan, and colleagues conducted a randomized controlled trial comparing whole-brain radiotherapy plus stereotactic radiosurgery or stereotactic radiosurgery alone for patients with limited (defined as 4 or less) brain metastases.

The study included 132 patients enrolled at 11 hospitals in Japan between October 1999 and December 2003. Patients were randomized assigned to combination therapy (65 patients) or stereotactic radiosurgery alone (67 patients).

The median survival time and one-year survival rates were 7.5 months and 38.5 percent for the combination therapy group and 8.0 months and 28.4 percent for stereotactic surgery alone. The 12-month brain tumor recurrence rate was 46.8 percent in the combination group and 76.4 percent for stereotactic radiosurgery group.

Salvage brain treatment was less frequently required in the combination group (10 patients) than with stereotactic radiosurgery alone (29 patients).

Death was attributed to neurologic causes in 22.8 percent of combination patients and in 19.3 percent of stereotactic radiosurgery patients. There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.

"In conclusion, our findings demonstrated that stereotactic radiosurgery alone without up-front whole-brain radiotherapy was associated with increased brain tumor recurrence; however, it did not result in either worsened neurologic function or increased risk of neurologic death. With respect to patient survival, the control of systemic cancer might outweigh the frequent recurrence of brain tumors. Therefore, stereotactic radiosurgery alone could be a treatment option, provided that frequent monitoring of brain tumor status is conducted," the authors wrote.

In an accompanying editorial, Jeffrey Raizer, MD, of the Feinberg School of Medicine, Northwestern University, Chicago, commented on the study concerning treatment for brain metastases.

"How should clinicians interpret the findings reported by Aoyama et al and the data available in the literature? Patients who have more than 4 brain metastases should continue to be treated with whole-brain radiotherapy. For patients with 4 or fewer brain metastases, the combination of stereotactic radiosurgery and whole-brain radiotherapy improves local brain control but does not affect survival. Therefore, either mode is a reasonable first choice. Whether overall quality of life is positively or negatively affected is unknown, but for patients who might be cured of their cancer, omitting whole-brain radiotherapy could avoid long-term neurotoxic effects."