WBRT Controls Brain Metastases But Does Not Impact Survival

Jan C. Buckner, MD, presenting results of the trial. Photo © ASCO / Scott Morgan 2015.

Whole brain radiation therapy (WBRT) helps control the growth of brain metastases in patients with 1 to 3 small brain metastases, but it does not significantly extend patient survival, according to the results of a phase III trial presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.

What’s more, those who received radiosurgery followed by WBRT were more likely to experience cognitive decline than those who received radiosurgery alone.

“We recommend initial treatment with radiosurgery alone and close monitoring to better preserve cognitive function in patients with newly diagnosed brain metastases amenable to radiosurgery,” senior author Jan C. Buckner, MD, professor of oncology at the Mayo Clinic in Rochester, Minnesota, told a plenary session (abstract LBA4).

In the United States alone about 400,000 patients per year are diagnosed with brain metastases. “Radiosurgery is an effective treatment for brain metastases. However, radiosurgery alone has a high rate of recurrence of the treated metastases, as well as the development of additional brain metastases. WBRT added to radiosurgery significantly improves tumor control in the brain,” said Buckner.

Progressive brain metastases have negative cognitive impact. “Progressive brain metastases require salvage therapy and may negatively impact survival. However, WBRT also has risks. Which is worse, uncontrolled tumor in the brain or WBRT itself?” he asked.

In the study, 213 patients with a median age of 60 years were randomly assigned to receive radiosurgery or radiosurgery followed by WBRT. The patients had 1 to 3 small brain metastases of up to 3 cm in width.

Intracranial tumor control at 6 and 12 months were 66.1% and 50.5% with radiosurgery alone compared to 88.3% and 84.9% with radiosurgery plus WBRT. Median overall survival was 10.7 months for radiosurgery alone compared with 7.5 months for radiosurgery plus WBRT, but the results were not significant (hazard ratio [HR] = 1.02, P = .93).

At 3 months, more patients experienced cognitive decline in the WBRT group (92%) than in the radiosurgery group (64%). Those who received WBRT had a greater decline in immediate recall (30% vs 8%), delayed recall (51% vs 20%), and verbal communication (19% vs 2%).

Brain metastases commonly occur among many cancers, and 1 to 3 metastases is relatively common among patients with non–small-cell lung cancer and breast cancer. 

“We used to offer WBRT early on, but we now know that the toxicities of this therapy are worse for the patient than cancer growth or recurrences in the brain,” Bruckner said. “We expect that practice will shift to reserve the use of WBRT for salvage treatment and end-stage palliative care.”

Brian M. Alexander, MD, assistant professor of radiation oncology at Harvard Medical School, commented: “WBRT does what we want therapeutically, but that does not translate into overall survival.” Progressive disease outside the brain may drive mortality, he said. “Now the burden is to prove that WBRT shows a survival benefit in a subset of patients,” Alexander said. 

He added: “The benefits of adding WBRT must be weighed against the risks and side effects of treatment. This study helps us identify the tradeoffs involved.”