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Whole Brain Radiation for Some Patients with Brain Metastases Worsens Cognitive Decline

, by NCI Staff

A patient scheduled for stereotactic radiosurgery to the brain undergoes CT scanning before treatment to help doctors visualize the tumor.

In some patients with cancer that has spread to the brain, adding radiation to the whole brain following tumor-focused radiosurgery causes more severe cognitive decline and does not improve survival compared with radiosurgery alone, according to findings from a phase III clinical trial.

The results, several experts in neuro-oncology said, should have an impact on clinical practice.

Results of the NCI-funded clinical trial were presented during the plenary session at the American Society of Clinical Oncology annual meeting.

The trial enrolled 213 patients with limited brain metastases, defined as between 1 and 3 metastases that were smaller than 3 cm in diameter. Patients were randomly assigned to receive radiosurgery alone or radiosurgery followed by whole brain radiation (WBRT). All patients underwent cognitive testing before treatment and 3 months after treatment.

At the 3-month cognitive testing, 92 percent of the patients who received the combination of radiosurgery and WBRT experienced cognitive decline, compared with 64 percent of those who received radiosurgery alone, reported a senior author on the study, Jan Buckner, M.D., professor of oncology at the Mayo Clinic in Rochester, MN. Specifically, patients who received both therapies had worse cognitive testing scores on immediate recall (30 percent versus 8 percent), delayed recall/memory (51 percent versus 20 percent), and verbal communication (19 percent versus 2 percent).

Patients who received both therapies also had substantially worse quality of life measures, Dr. Buckner explained during a press briefing.

At 6 and 12 months after treatment, control of tumor growth in the brain was better in patients who received radiosurgery and WBRT (88.3 percent and 84.9 percent) than in those who received radiosurgery alone (66.1 percent and 50.5 percent). However, tumor control did not translate into improved survival.

Approximately 400,000 cancer patients in the U.S. develop brain metastases each year, Dr. Buckner said, a substantial proportion of whom will have limited brain metastases. Multiple limited brain metastases are commonly seen in some cancers, such as lung cancer, melanoma, and breast cancer, he continued. “So it’s not a small subset” of patients, he said.

Based on data from previous studies that suggested WBRT after radiosurgery did not improve survival, use of the combination of radiosurgery and WBRT “has been diminishing in frequency over time,” Dr. Buckner explained.

Nevertheless, the decision about radiation treatments for brain metastases can be very complicated, explained Brian Michael Alexander, M.D., M.P.H., of the Center for Neuro-Oncology at the Dana Farber Cancer Institute. Multiple factors have to be considered, he noted, including the risk posed by patients’ primary systemic cancers, which are more often the cause of their death than their brain metastases. “It’s why this is something I take a lot of time talking with my patients about,” he said.

Although other studies have looked at the impact of radiosurgey and WBRT on survival, this is the first with such robust data on cognitive decline and quality of life, Dr. Alexander stressed. “This study really shows the impact that using both therapies is having on patients."

Based on these findings, Dr. Buckner said, the expectation is that radiosurgery should be used as initial treatment of patients with a limited number of brain metastases, with WBRT typically reserved for recurrence of metastases or for patients with a larger number of metastases.

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