NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases.

Central Nervous System Tumors
Session Type and Session Title: 
Plenary Session, Plenary Session Including the Science of Oncology Award and Lecture
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA4)
Paul D. Brown, Anthony L. Asher, Karla V. Ballman, Elana Farace, Jane H Cerhan, S. Keith Anderson, Xiomara W. Carrero, Frederick G. Barker, Richard L. Deming, Stuart Burri, Cynthia Menard, Caroline Chung, Volker W. Stieber, Bruce E. Pollock, Evanthia Galanis, Jan C. Buckner, Kurt A. Jaeckle; The University of Texas MD Anderson Cancer Center, Houston, TX; Carolinas Healthcare System-Neuroscience Institute, Charlotte, NC; Mayo Clinic, Rochester, MN; Penn State Hershey Medical Center, Hershey, PA; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN; Massachusetts General Hospital, Boston, MA; Mercy Cancer Ctr, Des Moines, IA; Levine Cancer Institute-Radiation Oncology, Charlotte, NC; Princess Maraget Hospital, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Novant Health Forsyth Medical Center, Winston Salem, NC; Mayo Clinic Florida, Jacksonville, FL

Abstract Disclosures


Background: WBRT significantly improves tumor control in the brain after SRS, yet the role of adjuvant WBRT remains undefined due to concerns regarding neurocognitive risks. Methods: Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, were randomized to SRS alone or SRS + WBRT and underwent cognitive testing before and after treatment. The primary endpoint was cognitive progression (CP) defined as decline > 1 SD from baseline in any of the 6 cognitive tests at 3 months. Time to CP was estimated using cumulative incidence adjusting for survival as a competing risk. Results: 213 patients were enrolled with 2 ineligible and 3 cancels prior to receiving treatment. Baseline characteristics were well-balanced between study arms. The median age was 60 and lung primary the most common (68%). CP at 3 months was more frequent after WBRT + SRS vs. SRS alone (88.0% vs. 61.9% respectively, p = 0.002). There was more deterioration in the WBRT + SRS arm in immediate recall (31% vs. 8%, p = 0.007), delayed recall (51% vs. 20%, p = 0.002), and verbal fluency (19% vs. 2%, p = 0.02). Intracranial tumor control at 6 and 12 months were 66.1% and 50.5% with SRS alone vs. 88.3% and 84.9% with SRS+WBRT (p < 0.001). Median OS was 10.7 for SRS alone vs. 7.5 months for SRS+WBRT respectively (HR = 1.02, p = 0.93). Conclusions: Decline in cognitive function, specifically immediate recall, memory and verbal fluency, was more frequent with the addition of WBRT to SRS. Adjuvant WBRT did not improve OS despite better brain control. Initial treatment with SRS and close monitoring is recommended to better preserve cognitive function in patients with newly diagnosed brain metastases that are amenable to SRS. Clinical trial information: NCT00377156