Issue: July 10, 2015
Perspective from Andrew B. Lassman, MD
June 02, 2015
5 min read

Risks of adjuvant WBRT may outweigh benefits for limited brain metastases

Issue: July 10, 2015
Perspective from Andrew B. Lassman, MD
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CHICAGO — Whole-brain radiation therapy after stereotactic radiosurgery controlled brain metastases but did not improve OS in patients with one to three small brain metastases, according to phase 3 study results presented at the plenary session of the ASCO Annual Meeting.

Patients who received whole-brain radiation therapy (WBRT) also experienced declines in cognitive function, results showed.

“Adding whole brain radiation therapy to stereotactic radiation reduces the number of patients who have recurrence of the tumors that have been treated and reduces the number of new spots that appear in the brain,” Jan C. Buckner, MD, a professor of oncology at the Mayo Clinic in Rochester, Minnesota, said during a press briefing. “We know that new spots that appear in the brain because of recurrence have negative consequences on cognitive function. Also the new spots or recurrent spots may require salvage therapy and those new spots can negatively influence survival.

“The other side of the coin is that whole brain radiation therapy also has its risks. So this is the classic question: ‘Which is worse, the disease or the treatment?’”

Buckner and colleagues conducted this phase 3 study to assess the risk–benefit ratio of WBRT after stereotactic radiosurgery in a cohort of 213 patients (median age, 60 years) with one to three small brain metastases, or those up to 3 cm in width. Most patients had a primary lung cancer (68%).

Patients underwent stereotactic radiosurgery alone or with WBRT with cognitive testing before and after each treatment.

Cognitive progression — defined as a decline of more than 1 standard deviation from baseline to 3 months in any of the six cognitive tests — served as the study’s primary endpoint.

The data indicated that more patients in the WBRT arm experienced cognitive progression at 3 months than patients in the radiosurgery arm (92% vs. 64%). Specifically, the WBRT cohort experienced significantly greater declines in immediate recall (30% vs. 8%; P = .0007), delayed recall (51% vs. 20%; P = .002) and verbal communication (19% vs. 2%; P = .02).

Patients in each arm achieved comparable median OS (radiosurgery, 10.7 months; WBRT, 7.5 months; HR = 1.02).

Researchers are still evaluating quality of life data from the study.

“Is this for everyone?” Buckner said. “I think the concern is that patients who have a better likelihood of survival may in fact benefit from whole brain radiation but at the cost of cognitive decline. This is an area for further investigation going forward.” – by Anthony SanFilippo


Brown, PD, et al. Abstract LBA4. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Buckner reports consultant/advisory roles with Merck Serono and travel expenses and other accommodations from Genentech/Roche.