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Effect of Radiosurgery Alone vs With Whole-Brain Radiotherapy on Cognitive Function in Patients With Brain Metastases


Physicians from Carolinas HealthCare System’s Neurosciences Institute and Levine Cancer Institute are among the authors of a recent study published by Brown et al in JAMA.1 The study showed how among patients with one to three brain metastases, the use of stereotactic radiosurgery alone, compared with stereotactic radiosurgery combined with whole-brain radiotherapy, resulted in less cognitive deterioration at 3 months. These results will allow tens of thousands of patients to experience a better quality of life while maintaining the same length of life.

Anthony L. Asher, MD, FACS

Anthony L. Asher, MD, FACS

Stuart H. Burri, MD

Stuart H. Burri, MD

Paul Brown, MD

Paul Brown, MD

Anthony L. Asher, MD, FACS, Medical Director at Carolinas HealthCare System’s Neurosciences Institute and the senior author on the report, as well as Stuart H. Burri, MD, Chairman of the Department of Radiation Oncology at Levine Cancer Institute, began their research on this subject over 10 years ago. Along with Paul Brown, MD, at Mayo Clinic, they spearheaded an international, multi-institutional, randomized trial.

Typical therapies for brain metastases include surgery, whole-brain radiation therapy, and focused radiation, also known as stereotactic radiosurgery. “We discovered that whole-brain radiation added to focused radiation in the treatment of brain metastases reduces the number of new [metastases] over time; however, patients receiving the whole-brain radiation had significantly more difficulties with memory and complex thinking than patients who only had the focused radiation,” said Dr. Asher.

“Whole-brain radiation patients also reported worse quality of life compared with patients who only received the focused radiation,” added Dr. Burri. “Interestingly, the data showed that the addition of whole-brain radiation produced no improvement in survival.”

Study Findings

A total of 213 patients with 1 to 3 brain metastases were randomly assigned to receive stereotactic radiosurgery alone (n = 111) or stereotactic radiosurgery plus whole-brain radiotherapy (n = 102). The study was conducted at 34 institutions in North America; average patient age was 61 years. The primary outcome measured for the study was cognitive deterioration among patients who completed assessments at study entry and at 3 months. Other measured outcomes included quality of life, functional independence, long-term cognitive status, and overall survival.

The data from our study show that clinicians can no longer simply rely on the results of traditional lab tests or scans to assess the value of care; we have to understand the total impact of cancer therapies on our patients.
— Stuart H. Burri, MD

The researchers found that there was less cognitive deterioration at 3 months after stereotactic radiosurgery alone (40/63 patients [64%]) than when combined with whole-brain radiotherapy (44/48 patients [92%]. Quality of life was better at 3 months with stereotactic radiosurgery alone, including overall quality of life. There was no significant difference in functional independence at 3 months between the treatment groups. Median overall survival was 10.4 months with stereotactic radiosurgery alone and 7.4 months with stereotactic radiosurgery plus whole-brain radiotherapy. For long-term survivors, the incidence of cognitive deterioration was less after stereotactic radiosurgery alone at 3 months and at 12 months.

Although whole-brain radiotherapy decreased the number of new brain metastases over time, its addition to focused radiation interestingly did not result in a survival benefit over focused radiation alone.

Anthony L. Asher, MD, FACS (right), Medical Director at Carolinas HealthCare System’s Neurosciences Institute and the senior author on the report, and Stuart H. Burri, MD (left), Chairman of the Department of Radiation Oncology at Levine Cancer Institute.

“In the past, clinicians who treated patients with brain tumors seldom used sophisticated techniques like neurocognitive tests to evaluate patients’ daily function in response to various therapies,” said Dr. Burri. “Without those tests, we might have incorrectly concluded that whole-brain radiation was a better option for patients because it made their scans look better, at least in the short term. However, the data from our study show that clinicians can no longer simply rely on the results of traditional lab tests or scans to assess the value of care; we have to understand the total impact of cancer therapies on our patients.”

The trial authors concluded that the benefit of adding whole-brain radiotherapy was outweighed by its risks in patients with one to three newly diagnosed brain metastases. This is a relevant finding, as over 200,000 patients still receive whole-brain radiotherapy in the United States each year, and the majority of patients with brain metastases have a limited number of brain lesions (typically three or fewer). Drs. Asher and Burri, along with their co-investigators, now recommend that patients with one to three brain metastases should no longer receive routine whole-brain radiotherapy and should be treated with focused therapy alone to better preserve cognitive function and quality of life.

Drs. Asher and Burri are working on a new method of focused therapy for tumors that have spread to the brain that combines radiation and surgery. ■

Disclosure: For full disclosures of the study authors, visit jama.jamanetwork.com.

Reference

1. Brown PD, Jaeckle K, Ballman KV, et al: Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases. JAMA 4:401-409, 2016.



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