ATLANTA – Younger adults with one to three brain metastases survive longer when they are treated with stereotactic radiosurgery alone rather than whole-brain radiation therapy or a combination of both modalities, researchers reported at the annual meeting of the American Society for Radiation Oncology.
Among patients aged 35-50 years, stereotactic radiosurgery (SRS) alone was associated with hazard ratios (HR) for death ranging from 0.46 to 0.64, compared with an age-matched cohort treated with a combination of SRS and whole-brain radiation therapy (WBRT), based on a meta-analysis of data on 389 individual patients in three randomized clinical trials.
For local control, however, the data show a benefit for combined SRS and WBRT. For control of distant brain metastases, the data indicate a benefit for the combined therapies, but only among patients aged 55 years and older, reported Dr. Arjun Sahgal, associate professor of radiation oncology at the University of Toronto.
Courtesy ASTRO
Dr. Arjun Sahgal
"Our overall survival results favoring radiosurgery alone in younger patients may be explained by the lack of benefit of whole-brain radiation with respect to distant brain control in this cohort, while still exposing them to the harms of whole-brain radiation with respect to memory function and quality of life," he said.
Dr. Sahgal and his colleagues had previously published an aggregate meta-analysis showing that WBRT and SRS improved distant and local brain control but without overall survival benefit compared with SRS alone.
The current study looked at the raw, individual patient data from the three randomized controlled trials included in the original aggregate analysis. The trials included a 2006 study of 132 patients with an endpoint of brain tumor recurrence, a 2009 trial looking at the effect of SRS/WBRT on neurocognitive function in 58 patients, and a 2011 study examining the effect of adjuvant SRS on World Health Organization performance status scores.
The overall median time to local failure in the trials was 6.6 months for SRS alone, compared with 7.7 months for SRS/WBRT. Time to distant failure was also shorter with SRS alone, at a median of 4.7 vs. 7.7 months, respectively. Median time to death, however, was longer with SRS, at 10 vs. 8.2 months.
In a multivariate model for overall survival, the HR was 0.46 for patients at age 35 years, 0.52 at age 40, 0.58 at age 45, and 0.64 at age 50; all hazard ratios had significant confidence intervals. For patients aged 55 years and older, however, the HR for overall survival was not significant.
Patients with only one metastasis had a significantly lower risk of dying, compared with those who had two or three metastases (HR, 0.72).
The risk of local failure was significantly greater with SRS alone for patients aged 45-70.
The risk of new distant metastases was significant with SRS alone for patients aged 55 years and older, and was significantly lower for patients with one metastasis (HR, 0.63) vs. two or more metastases.
Salvage therapy was performed in 28% of patients who underwent SRS alone and 12% of those who received the combined therapies. Distant brain failures occurred in 54% of those in the SRS alone group, compared with 34% of those in the SRS/WBRT group.
Patients who underwent salvage therapy had significantly greater survival rates than those who did not, and this effect did not vary significantly by age, Dr. Sahgal reported.
The authors did not report specific funding sources. Dr. Sahgal reported having no relevant financial disclosures.