PHILADELPHIA (September 26, 2016) – Whole-brain radiation appears to confer no obvious survival advantage when compared with more targeted radiation for patients whose cancer has metastasized to limited areas of the brain but who otherwise have controlled extracranial disease or a favorable predicted prognosis.
Thomas M. Churilla, MD, a resident physician at Fox Chase Cancer Center, presented the results of a secondary analysis of a prospective randomized trial at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting. Stephanie Weiss, MD, Chief of Neurologic Oncology at Fox Chase, and Brian Alexander, MD, Disease Center Leader, Radiation Oncology, Center for Neuro-Oncology, Dana-Farber Cancer Institute, were senior authors on the study.
Historically, whole-brain radiation therapy (WBRT) has been the standard of care when cancer spreads to the brain. However, because of the short- and long-term side effects of WBRT, including permanent cognitive decline, investigators increasingly offer focal therapies, such as stereotactic radiosurgery (SRS), which focuses high-dose of radiation directly to tumors, sparing normal brain tissue, in lieu of WBRT.
Four gold-standard studies have shown that while the addition of WBRT to SRS for patients with four or fewer brain metastases (or oligometastatseis) helps prevent relapse in the brain, this advantage does not translate to a survival benefit. Investigators have speculated that this finding is due to either cancer outside the brain typically remaining the bigger threat to most patients or salvage treatment options being effective, or both.
To address this question, Fox Chase researchers used the largest of the data-sets to examine the effect of WBRT on patient survival while extracranial disease remained under control. Therefore, only patients at high risk of death from brain metastases were analyzed because the main competing risk of extracranial progression was removed from the equation, according to Churilla. Additionally, to determine if those who might benefit from WBRT could be identified at diagnosis, the researchers evaluated the impact of WBRT on survival in patients with a favorable calculated prognosis.
Results showed that patients who continued to have controlled extracranial disease after receipt of WBRT tended to have a slightly longer survival than those who did not receive WBRT, but the researchers concluded that the possibility it was a chance finding could not be discounted. Given the known side effects of WBRT, Churilla and colleagues concluded that their “analysis supports the use of stereotactic radiosurgery alone for patients with limited brain disease undergoing close, active surveillance.”
“Because this is a secondary analysis, the study design and statistical power limit us from definitive conclusions,” Weiss said. “But in this data set, we were unable to detect a subgroup of patients who received a survival benefit from the improved brain control offered by the addition of whole-brain radiation to targeted therapy. Further work will likely continue to examine the benefits of differing radiotherapeutic strategies and targeted drugs based on the molecular and genetic profiles of a given tumor.”