LBA 02 - NRG-CC009: A Phase III Trial of Stereotactic Radiosurgery (SRS) vs. Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for Brain Metastases from Small Cell Lung Cancer (SCLC)

02:21pm - 02:30pm ET

Grand Ballroom

Presenter(s)

Chad Rusthoven, MD - University of Colorado School of Medicine, Aurora, COLORADO

C. G. Rusthoven^1,2, R. Paulus³, V. Gondi⁴, P. D. Brown⁵, D. R. Camidge⁶, J. A. Bovi⁷, J. D. Palmer⁸, J. S. Wefel⁹, A. Loughan¹⁰, D. R. Grosshans¹¹, M. V. Mishra¹², S. A. Shah¹³, W. A. Tome¹⁴, J. Wenzel¹⁵, S. Zhu¹⁶, C. K. Cramer¹⁷, A. J. Huang¹⁸, I. Thibault¹⁹, S. Pugh²⁰, and L. A. Kachnic²¹; ¹University of Colorado, Aurora, CO, ²University of North Carolina at Chapel Hill, Chapel Hill, NC, ³The American College of Radiology, Philidelphia, PA, ⁴Northwestern University Feinberg School of Medicine, Chicago, IL, ⁵Department of Neurologic Surgery,, Rochester, MN, ⁶Department of Medical Oncology, University of Colorado School of Medicine, Auora, CO, ⁷Thedacare, Appleton, WI, ⁸Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, ⁹Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ¹⁰Virginia Commonwealth University, Richmond, VA, ¹¹Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ¹²Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, ¹³Christiana Care Health Services, Newark, DE, ¹⁴Department of Radiation Oncology, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, ¹⁵Johns Hopkins, Baltimore, MD, ¹⁶University of Florida, Gainesville, FL, ¹⁷Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, ¹⁸California Pacific Medical Center, San Francisco, CA, ¹⁹University of Laval, Quebec, QC, Canada, ²⁰NRG Oncology Statistics and Data Management Center, Philadelphia, PA, ²¹Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY

Purpose/Objective(s):

SRS is the preferred treatment for brain metastases (BM) from most tumor histologies due to superior neurocognitive preservation and quality of life compared to WBRT. However, patients with SCLC BM were excluded from historical SRS trials, and WBRT has remained the standard of care in this population. In patients receiving WBRT, HA-WBRT and memantine offer superior neurocognitive preservation compared to conventional WBRT. NRG-CC009 compared SRS to HA-WBRT + memantine for patients with SCLC BM.

Materials/Methods:

This phase III trial enrolled patients with SCLC BM, with all BM =5 mm outside the hippocampi, =4 cm in largest diameter, and total BM volume =30 cm³, without an upper limit on BM number (initially =10, subsequently amended). Patients were stratified by disease-specific graded prognostic assessment (DS-GPA) score and number of BM and randomized 1:1 to SRS or HA-WBRT + memantine. Cumulative incidence and Gray’s test were used to estimate and compare arms for the primary endpoint, time to neurocognitive failure. Assessment was conducted using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association, and Trail Making Test, with a competing risk of death without failure. Cox proportional models were used to estimate hazard ratios (HR) with adjustment for DS-GPA and patient-specific factors. Secondary endpoints included overall survival (OS), intracranial disease progression, neurological death, salvage therapies, and adverse events (AEs). With 91 events, the study had 85% power to detect a 17% absolute reduction in neurocognitive failure between arms using a two-sided type I error of 0.05, assuming a rate of death without failure of 29.8% in both arms.

Results:

From February 2021 to June 2026, 151 patients were randomly assigned. Baseline characteristics were well balanced between the arms. The median number of BM was 2 (range, 1-26; interquartile range, 1-5). Median follow-up for surviving patients was 9.5 months. There was no significant difference in neurocognitive failure between the arms (Gray’s test, p=0.66; adjusted HR for SRS arm = 0.83; 95% CI, 0.53–1.28; p=0.39). OS was superior in the SRS arm (median 17.4 vs. 8.6 months; adjusted HR for SRS arm = 0.60; 95% CI, 0.39–0.91; p=0.016). No significant differences were observed in adjusted analyses of intracranial failure, neurological mortality, salvage therapy, or treatment-related grade 3-5 AEs.

Conclusion:

Although no difference in neurocognitive failure was observed, SRS was associated with superior OS and comparable CNS control outcomes to HA-WBRT plus memantine. These results support SRS as a standard of care option for SCLC BM.