Whole-Brain Radiation Doesn't Boost Brain Metastases Survival

SAPPORO, Japan, June 7 - Adding whole-brain irradiation to stereotactic radiosurgery does not improve survival of patients with metastatic brain cancer, researchers here reported.

But whole-brain irradiation may reduce recurrence of the metastases, added Hidefumi Aoyama, M.D., Ph.D., of Hokkaido University Graduate Medical School here, and colleagues in other Japanese centers, in the June 7 issue of the Journal of the American Medical Association.

"With respect to patient survival, the control of systemic cancer might outweigh the frequent recurrence of brain tumors," they wrote. "Therefore, stereotactic radiosurgery alone could be a treatment option, provided that frequent monitoring of brain tumor status is conducted."

In a study of 132 cancer patients with one to four metastatic brain tumors there were no significant differences in median survival or one-year actuarial survival between patients treated with stereotactic radiosurgery alone or radiosurgery plus whole-brain irradiation.

However, the 12-month brain tumor recurrence rate was significantly higher among the patients treated with radiosurgery alone that for those who also received whole brain irradiation.

Taken into consideration with other evidence from the literature, the findings from Dr. Aoyama and colleagues suggested that whole-brain irradiation should be continued in patients who have more than four brain metastases, and may be appropriate in other select instances, said Jeffrey Raizer, M.D., of Northwestern University in Chicago, in an accompanying editorial.

"For patients with four or fewer brain metastases, the combination of stereotactic radiosurgery and whole-brain radiation therapy improves local brain control but does not affect survival," Dr. Raizer wrote. "Therefore, either mode is a reasonable first choice; the exception is for patients with a single brain metastasis, non-small cell lung cancer, or RPA [recursive partitioning analysis] class 1 patients, for whom stereotactic radiosurgery should be added to whole-brain radiation therapy."

The latter is preferable for these subsets as several previous studies showed improved survival when treated with combination therapy.

The Japanese investigators evaluated improvements in survival, brain tumor control, and functional preservation rate, and in a lower frequency of neurologic death. The one to four metastases in the 132 patients measured less than 3 cm in diameter; patients were randomly assigned to receive whole-brain radiation therapy plus stereotactic radiosurgery (65 patients) or stereotactic radiosurgery alone (67 patients).

The primary study endpoint was overall survival, with secondary endpoints including brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.

They found that the median survival time and the one-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) for patients in the combined therapy group, compare with 8.0 months and 28.4% (95% CI, 17.6%-39.2%) for those in radiosurgery alone group. The differences were not statistically significant (P=0.42).

The rate of brain tumor recurrence over one year was 46.8% among patients treated with both modalities, vs. 76.4%for those treated only with stereotactic radiosurgery (P<0.001).

Fewer patients treated with the combined therapies needed salvage treatment (29 vs. 10, P<0.001). Deaths from neurologic causes, however, did not differ between the two groups (22.8% of patients in the combined-modality group, vs. 19.3% in the radiosurgery only group, P=0.64). In addition, there were no significant differences in systemic and neurologic functional preservation or toxic effects of radiation between the groups.

"Aoyama et al have prospectively shown that withholding stereotactic radiosurgery does not affect survival for patients who have four or fewer brain metastases; these patients have a higher rate of local brain failure, but apparently withholding stereotactic radiosurgery does not influence how patients die of their disease," Dr. Raizer wrote in his editorial.

"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 radiation therapy could avoid long-term neurotoxic effects," he concluded.