100 - Multicenter, Phase 3 Randomized Trial of Stereotactic Radiation vs. Hippocampal Avoidance Whole Brain Radiation in Patients with 5-20 Brain Metastases: Recurrence, Salvage Therapy, and Mortality Endpoints
Presenter(s)
A. A. Aizer1, S. Tanguturi2, K. Y. Shin3, P. J. Catalano4, M. Johnson5, I. Ricca5, G. Benham6, D. D. Shi7, N. Lamba8, F. E. Chipidza9, M. S. Krishnan10, I. M. Pashtan1, L. C. Peng2, J. Nosker5, M. W. Parsons11, J. T. Hepel12, D. N. Cagney13, P. D. Brown14, B. Alexander15, P. Wen16, D. A. Haas-Kogan17, and R. Rahman18; 1Department of Radiation Oncology, Dana-Farber Brigham Cancer Center, Boston, MA, 2Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, 3Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, 4Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 5Brigham and Women's Hospital / Dana-Farber Cancer Institute, Boston, MA, 6Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 7Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, 8Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, 9Dana-Farber Cancer Institute, Boston, MA, 10Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 11Pappas Center for Neuro-Oncology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 12Alpert Medical School of Brown University, Providence, RI, 13Radiotherapy Department, Mater Private Network, Dublin, MA, Ireland, 14Mayo Clinic Cancer Center, Rochester, MN, 15Brigham and Women's Hospital and Dana-Farber Cancer Institute/ Harvard, Boston, MA, Boston, MA, 16Dana-Farber Cancer Institute, Brigham and Women's Cancer Center, Boston, MA, 17Department of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, 18Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA
Purpose/Objective(s):
Most patients with brain metastases receive brain-directed radiation during their clinical course. Prior randomized trials have demonstrated the superiority of stereotactic radiation (SRS/SRT) over whole brain radiation (WBRT) in patients with =4 brain metastases, but no published randomized studies have compared SRS/SRT and WBRT in patients with >4 brain metastases. In addition, no prior trials have compared SRS/SRT to WBRT with hippocampal avoidance (HA-WBRT), which now comprises the standard of care when WBRT is utilized. We designed a multicenter, phase 3, randomized trial comparing SRS/SRT and HA-WBRT in patients with 5-20 brain metastases.Materials/Methods:
Eligible patients were 18-80 years of age and displayed 5-20 brain metastases. Prior neurosurgical resection and systemic therapy were permitted, but prior brain-directed radiation was not. Underlying small cell lung cancer and leptomeningeal disease (LMD) also represented exclusion criteria. The primary endpoint was patient-reported symptom burden and functional interference. This abstract presents secondary outcomes of recurrence, salvage therapy, and neurologic survival, as assessed via Fine and Gray competing risks-based approaches.Results:
Between 4/2017-5/2024, 196 patients enrolled (98 per arm, completing planned accrual), of whom 25% underwent prior neurosurgical resection. The median number of brain metastases was 14 (IQR 11-18). New brain metastases occurred more commonly in the SRS/SRT vs HA-WBRT arm (12 month cumulative incidence 45.4% vs 23.3%, p<0.001) as did LMD (12 month cumulative incidence 8.2% vs 3.1%, p=0.04), respectively. Fewer lesions treated with SRS/SRT required salvage therapy (p<0.001); 9/98 patients (9.2%) in this arm required salvage WBRT (12 month cumulative incidence, 5.1%). Per patient, no differences were seen in post-baseline salvage SRS, salvage craniotomy, seizures, or systemic disease progression (p > 0.05 in all cases). There were no significant differences in median survival (8.3 vs 8.5 months, p=0.30) or neurologic death (12 month cumulative incidence 9.5% vs 8.5%, p=0.97) between the SRS/SRT and HA-WBRT arms, respectively.Conclusion:
Among patients with 5-20 brain metastases, this phase 3 randomized study indicates better local control of existing tumors with SRS/SRT as opposed to HA-WBRT, without discernable impact on rates of focal brain-directed salvage therapy, systemic progression, overall survival or neurologic death, though with greater risk of new brain metastases and LMD in patients treated with SRS/SRT. These data inform the decision regarding SRS/SRT or HA-WBRT among patients with a larger number of brain metastases and should be taken in the context of other important endpoints including quality of life and neurocognitive function.