LBA 01 - Alliance A071801 Phase III Trial Postoperative Single Fraction Stereotactic Radiosurgery (SRS) vs. Fractionated SRS (fSRS) for Resected Brain Metastasis
Presenter(s)
P. D. Brown1, K. V. Ballman2, A. A. Aizer3, K. E. Dooley4, T. J. C. Wang5, J. D. Palmer6, V. Gondi7, A. Attia8, J. Greenspoon9, T. Kaufmann10, J. L. Peterson8, H. H. M. Yu11, A. Butts12, T. S. Armstrong13, C. Chung14, G. Rao15, P. Brastianos16, and E. Galanis10; 1Department of Neurologic Surgery,, Rochester, MN, 2Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, 3Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 4Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, 5Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, 6Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, 7Northwestern University Feinberg School of Medicine, Chicago, IL, 8Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 9Juravinski Cancer Centre, Hamilton, ON, Canada, 10Mayo Clinic, Rochester, MN, 11H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 12Medical College of Wisconsin, Milwaukee, WI, United States, 13NCI Center for Cancer Research, Bethesda, MD, 14Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 15Baylor College of Medicine, Houston, TX, United States, 16Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA
Purpose/Objective(s):
In patients with brain metastases, post-operative SRS delivered in 1 fraction is a standard of care but local control decreases with increasing target size. To improve tumor control, fractionated SRS (fSRS) is often favored for large surgical cavities. However, there is a lack of high-level data comparing the efficacy of fSRS versus SRS. The primary objective of Alliance A071801 was to ascertain if time to surgical bed failure is increased with fSRS compared to SRS in patients with resected brain metastasis.Materials/Methods:
This multi-institutional cooperative group trial randomized patients with 1 to 4 brain metastases to either SRS (12-20Gy by volume) or fSRS (27Gy/3 <30cc or 30Gy/5 >30cc) after resection of one lesion >2cm. Intact metastases were treated with either SRS or fSRS per study arm. Stratification included age (< 60 years vs. = 60 years), use or planned use of either targeted therapy or immunotherapy within 4 weeks after radiotherapy, and maximal diameter of the resection cavity (=3cm vs. >3cm). The primary endpoint was time to surgical bed failure. Major secondary endpoints included local control of intact brain metastases, overall survival, and radiation necrosis.Results:
Between October 2019 and October 2022, 242 patients were randomized. Baseline characteristics were well-balanced. Median surgical cavity target volumes were 16.5 cm3 for fSRS and 14.8 cm3 for SRS (p=0.41). With a median follow-up of 48 months, surgical bed control was significantly higher in the fSRS arm as compared to the SRS arm (1 year rate 87% versus 81%, p=0.046). Failure of treated, unresected brain metastases occurred in 11% with SRS versus 4% with fSRS (p=0.063). Overall survival (OS) favored fSRS over SRS (median OS 29 versus 20 months; p=0.035; stratified Cox HR=0.69). A stratified multivariable model that included the other baseline variables found a similar association between study arm and OS (HR=0.68; p=0.032). There were no significant differences in adverse event rates between study arms; grade 1+ radiation necrosis and cerebral edema were 14% and 8% in the fSRS arm and 10% and 9% in the SRS arm, respectively.Conclusion:
After resection of larger brain metastasis, fSRS offers superior surgical bed control and should be considered a standard of care. Support: U10CA180821, U10CA180882; NCT04114981; https://acknowledgments.alliancefound.org