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  • Two-staged Stereotactic Radiosurgery (2-SSRS) for ≥2cm Brain Metastases

    Final Number:

    L. Angelov M.D. (1,2,4), A. M. Mohammadi M.D. (1,2,4), E. Bennett M.D. (2), M. Abbassy M.D. (5), P. Elson Ph.D. (4), J. Montgomery RN (1), G. Habboub, M.D. (2), S. T. Chao M.D. (1,3), M. Vogelbaum M.D. (1,2,4), J. H. Suh, M.D. (1,3), E. Murphy M.D. (1,3), S. Nagel M.D. (2), G. H. Barnett M.D. (1,2,4)

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting - Late Breaking Science

    Introduction: Radiosurgical treatment of brain metastases (BM) >= 2cm is associated with suboptimal local control (LC) rates. To enhance LC while limiting toxicity in these patients we utilized a 2-staged stereotactic radiosurgery (2-SSRS) approach.

    Methods: An IRB-approved retrospective review evaluated 2-SSRS treatment in 54 patients with 63 BM >= 2cm. Clinical outcomes and volumetric measurements before treatment and subsequent 3 month intervals were determined. Study outcomes were response at 3-month MRI, time to failure (TTF related to either progression or acute radiation effects [ARE]) and overall survival.

    Results: 2-SSRS was performed on 46 (85%) patients with one BM; 7 (13%) with two BMs; 1 (2%) patient with three BMs >= 2cm. Median age was 63 (23-83) yrs. 23 (43%) patients had NSCLC and 14 (26%) had radio-resistant tumors (renal/melanoma). Median 2-SSRS treatment interval was 34 days. Median dose delivered/treatment was 15 Gy (12-18Gy). Median tumor volumes at 1st and 2nd 2-SSRS were 10.5 cm3 (2.4-31.3) and 7.0 cm3 (1.0-29.7) respectively [p<.0001]. 3-month follow-up imaging was available for 43 lesions, median volume 4.0 cm3 (0.1-35.9), median change in volume -54.9% (-98.2–66.1) [p<.0001] with a 95% (n=41) LC rate. Overall, 18 (29%) lesions failed, median 3.4 months; 11 (17%) due to local progression and 7 (11%) demonstrated ARE (8% Grade1/2 toxicity; 3% Grade 3). TTF was associated with greater baseline volume of disease (p=.03, cut-off =9cm3) and smaller relative decreases in tumor volume from baseline to the second SRS (p <.005, cut-off =20%). Estimated cumulative incidence of failure at 6-months was 29%+6%; 12-months was 35%+7%.

    Conclusions: 2-SSRS is an effective treatment modality resulting in a significant response in BM >= 2cm, excellent 3-month (95%) and overall (83%) LC with 11% ARE rate. Prospective studies with larger cohorts and longer follow-up are necessary to further assess the durability and toxicity of 2-SSRS treatments.

    Patient Care: Currently, the management of large brain metastases (LBM), ≥2 cm in maximum diameter with SRS remains controversial with a relatively poor control rate compared to smaller lesions. This study presents the first North American experience (and only one of 4 studies overall) of a novel ‘dose-dense’ treatment approach for LBM achieved using SRS delivered in 2 stages (2-SSRS) approximately 1 month apart. Preliminary results are very encouraging and this effective treatment option can be successfully offered with modest toxicity and minimal disruption to ongoing systemic treatments in these patients.

    Learning Objectives: 1. Discuss radiosurgical management of BM >= 2cm 2. Evaluate efficacy of 2-SSRS 3. Review 2-SSRS toxicity and its management

    References: Higuchi, Y., et al. (2009). Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors. Int J Radiat Oncol Biol Phys 74(5): 1543-1548. Zimmerman, A. L., et al. (2016). Treatment of Large Brain Metastases With Stereotactic Radiosurgery. Technol Cancer Res Treat 15(1): 186-195. Yomo, S., et al. (2012). A prospective pilot study of two-session Gamma Knife surgery for large metastatic brain tumors. J Neurooncol 109(1): 159-165. Vogelbaum, M. A., et al. (2006). Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin. J Neurosurg 104(6): 907-912. Yomo, S. and M. Hayashi (2014). A minimally invasive treatment option for large metastatic brain tumors: long-term results of two-session Gamma Knife stereotactic radiosurgery. Radiat Oncol 9: 132.

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