Adding whole-brain radiation therapy to highly-focused radiation therapy does not improve survival for patients with cancer and brain metastases, but it may reduce the likelihood of the recurrence of brain metastases, according to a study in the June 7 issue of JAMA.

Brain metastases (lesions in the brain due to spread of cancers occurring elsewhere) occur in 20 percent to 40 percent of all patients with cancer and are generally associated with a poor prognosis, according to background information in the article. It has been believed that in brain metastases, the entire brain is “seeded” with micrometastatic disease, even when only a single intracranial lesion is detected. Consequently, whole-brain radiation therapy (WBRT), which has possible adverse effects, has been the dominant treatment. Recently, the assumption that the entire brain is seeded with micrometastases has been questioned. For patients who truly have limited intracranial disease, the potential exists that WBRT could be replaced by more focused therapeutic options such as resection (partial surgical removal) or stereotactic radiosurgery (SRS), which delivers high-dose, focal radiation, with less long-term adverse effects than WBRT. These therapies have been used with increasing frequency. It has been unclear whether adding WBRT to SRS improves survival or neurologic function compared with SRS alone.

Hidefumi Aoyama, M.D., Ph.D., of Hokkaido University Graduate School of Medicine, Sapporo, Japan, and colleagues conducted a randomized controlled trial comparing WBRT plus SRS vs. SRS 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 randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).

The researchers found that the median (midpoint) survival time and the 1-year actuarial (calculated) survival rate were 7.5 months and 38.5 percent in the WBRT + SRS group and 8.0 months and 28.4 percent for SRS alone. The 12-month brain tumor recurrence rate was 46.8 percent in the WBRT + SRS group and 76.4 percent for SRS alone group. Salvage (treatment after other measures have been unsuccessful) brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29). Death was attributed to neurologic causes in 22.8 percent of patients in the WBRT + SRS group and in 19.3 percent of those treated with SRS alone. There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.

“In conclusion, our findings demonstrated that SRS alone without up-front WBRT 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, SRS alone could be a treatment option, provided that frequent monitoring of brain tumor status is conducted,” the authors write.

Editorial: Radiosurgery and Whole-Brain Radiation Therapy for Brain Metastases -
Either or Both as the Optimal Treatment

In an accompanying editorial, Jeffrey Raizer, M.D., of the Feinberg School of Medicine, Northwestern University, Chicago, comments 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 WBRT. For patients with 4 or fewer brain metastases, the combination of stereotactic radiosurgery and WBRT 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 WBRT could avoid long-term neurotoxic effects.”

American Medical Association (AMA)