Whole Brain Radiation Therapy (WBRT) is associated with significantly worse cognitive function than radiosurgery, and should no longer be used in the adjuvant setting after radiosurgery to treat cancer patients with brain metastases, according to a large study led by Professor Paul Brown at The University of Texas MD Anderson Cancer Center.

The final results of NCCTG N0574 (Alliance) Phase III randomised trial of whole brain radiation plus SRS versus SRS, was presented at ASCO by Dr. Paul Brown, MD Anderson. Findings included that decline in cognitive function, specifically immediate recall, memory and verbal fluency, was more frequent with the addition of WBRT and that adjuvant WBRT did not improve overall survival despite better brain control.

The North American study enrolled 213 patients of different tumor histologies (the majority of whom had a lung primary diagnosis), from 2002-2013, all with one-to-three brain metastases. Patients were randomized to receive either radiosurgery alone, or radiosurgery followed by WBRT, and underwent cognitive testing before and after treatment. The study’s primary endpoint was cognitive progression (CP), defined as significant decline in any of the seven cognitive tests at three months.

Intracranial tumour control at three and six months were 75 and 65 percent, respectively, with radiosurgery alone, compared to 94 and 88 percent, respectively, with radiosurgery and WBRT. Although intracranial control was significantly better with the addition of WBRT, there was no difference in survival with a median overall survival of 10.7 months in the radiosurgery arm of the clinical trial versus 7.5 months in those who received radiosurgery and WBRT. In addition patients treated with WBRT and radiosurgery had a worse quality of life compared to those treated with radiosurgery alone.

The definitive findings should serve as recognition that the deleterious impact on cognitive function outweighs any benefit associated with WBRT and tumor control, says Dr. Brown.

“Overtime there’s been a general shift in moving away from using whole brain radiation, in favour of stereotactic radiosurgery,” says Brown. “With these results and appropriate concerns for cognitive decline, it will likely will be pushed even further — reserving WBRT for later in a patient’s disease course.”

The ASCO presentation can be accessed here.