ASCO 2015: For Patients With Limited Brain Metastases, Adjuvant Whole-Brain Radiation Therapy Increases Cognitive Decline Without Improving Survival
A federally funded phase III trial found that adding whole-brain radiation therapy to radiosurgery did not significantly extend survival of patients with one to three small metastases of the brain, although it did help to control the growth of brain metastases, as evidenced by imaging studies. Patients who received whole-brain radiation therapy following radiosurgery were more likely to experience cognitive decline than those who received radiosurgery alone.
As a result of the study, the researchers “recommend initial treatment with radiosurgery alone and close monitoring to better preserve cognitive function in patients with newly diagnosed brain metastases amenable to radiosurgery and then reserving whole brain radiation until the time of symptomatic progression,” senior study author Jan C. Buckner, MD, Professor of Oncology at Mayo Clinic, Rochester, Minnesota, stated at a press briefing at the 2015 ASCO Annual Meeting. Detailed study results were presented at Sunday’s Plenary Session (Abstract LBA4).
One to Three Small Metastases
Approximately 250,000 to 400,000 patients are diagnosed with brain cancer in the United States each year, according to Dr. Buckner. He noted that although radiosurgery “is an effective treatment for brain metastases,” with radiosurgery alone there is “a high rate of recurrence of the treated metastases as well as the development of additional brain metastases.” Adding whole-brain radiation therapy to radiosurgery “significantly improves tumor control in the brain” and reduces recurrence.
Both progressive brain metastases and the treatment required can have a negative cognitive impact. “So this is the classic question,” Dr. Bruckner said, “Which is worse: the disease or the treatment?”
To answer that question, the study randomly assigned 213 patients to receive radiosurgery or radiosurgery followed by whole-brain radiation therapy. All patients had one to three small metastases (up to 3 cm in width) in the brain. Dr. Buckner noted that it is not unusual to have one to three brain metastases in patients with some of the more common types of cancer, such as non–small cell lung cancer and breast cancer.
Greater Cognitive Decline
“The primary endpoint of the trial was the cognitive decline at 3 months following the treatment,” Dr. Buckner said. Tools used to assess outcomes included serial magnetic resonance scans, quality-of-life measures, and a battery of cognitive tests.
At 3 months, 91.7% of patients who received whole-brain radiation therapy and radiosurgery experienced cognitive decline, compared with 63.5% receiving radiosurgery alone. Specifically, patients who received whole-brain radiation therapy had a greater decline in immediate recall (30% vs 8%), delayed recall (51% vs 20%), and verbal communication (19% vs 2%). “Patients also reported significantly worse quality-of-life measurement scores with the addition of whole-brain radiation therapy,” Dr. Buckner said.
Whole-brain radiation therapy was associated with fewer progressions in the brain at 3 months. More than 50% of patients receiving radiosurgery alone had progressive disease in the brain, compared with about 25% with radiosurgery plus whole-brain radiation therapy. “In spite of the imaging evidence of disease control, there was no overall impact on survival in these patients, as they died of other causes,” Dr. Buckner noted.
Burden of Proof Switched
“This was a very large, well-done study to quantify both the toxicity or the risks and the benefits of this treatment,” remarked ASCO expert Brian Alexander, MD, MPH. He said “the burden of proof is probably now switched to whether we can prove that whole brain radiation therapy is beneficial in a subset of patients. I have this discussion with my patients, and it takes a long time to go through all the data and frame things so they can make the decision they want to make.” Dr. Alexander is the Disease Center Leader for Radiation Oncology at the Center for Neuro-Oncology at the Dana-Farber Cancer Institute, Boston, and Assistant Professor of Radiation Oncology at Harvard Medical School.
“This federally funded study shows that by limiting what we do upfront, we can decrease toxicity. These findings become more and more relevant as we make progress in systemic treatment of many cancers,” ASCO spokesperson and press briefing moderator Jyoti Patel, MD, remarked. “For example, in 2015, someone with an EGFR-mutated lung cancer can expect to live years, and what we do upfront is so impactful to quality of life and the ability to live full and contributing lives for years. So this method is a new paradigm for us,” he added. Dr. Patel is Associate Professor of Medicine, Division of Hematology/Oncology at Northwestern University Feinberg School of Medicine, Chicago.
This study received funding from the National Institutes of Health. Dr. Buckner reported a consulting or advisory role with Merck Serono and travel, accommodations, and expenses from Genentech/Roche.
Watch The ASCO Post Newsreels for an interview with Dr. Buckner record live at the 2015 ASCO Annual Meeting.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
