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  • Gamma Knife Stereotactic Radiosurgery and Bevacizumab can be Safely Used to Prolong Survival for Focally Recurrent Glioblastoma

    Final Number:

    Saint-Aaron Morris MD; Mayank Rao; Ping Zhu; Leomar Ballester; jay-jiguang zhu MD, PhD; Sigmund Hsu; Dong H. Kim MD; Nitin Tandon MD FAANS; Scott R Shepard; Angel Blanco; Yoshua Esquenazi MD

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting

    Introduction: There has been promising retrospective data, which suggests a survival benefit with the use radiosurgery and bevacizumab in the treatment of glioblastoma (GBM) recurrences. The existing data is derived from small cohorts, which has limited analysis of the concomitant therapies efficacy.

    Methods: We retrospectively reviewed our experience with GK in combination with bevacizumab for the treatment of focally recurrent glioblastoma (GBM) from 2009 – 2015. Statistical analysis was performed using a Cox regression model. Progression-free and overall survival (OS) were estimated using the Kaplan–Meier method.

    Results: Within a median of 13.7 months after initial diagnosis, a total of 45 GBM patients underwent initial GK in combination with bevacizumab treatment. Median age was 57 years and 63.3% of subjects were female. The median KPS at recurrence was 80 (range: 40 – 100). Sixty-four percent of patients had one treatment target (range: 1 – 4) and median target volume and dosage were 2.2 cm3 (range: 0.1 – 25.2 cm3) and 17.0 Gy (range: 13 – 24 Gy), respectively. Median PFS and OS were 9.3 and 31 months following diagnosis, and 5.2 and 13.3 months after initial radiosurgery, respectively. Factors associated with poor outcomes in this study are use of > 3 chemotherapies and > 3 radiosurgical targets at initial recurrence. No adverse events of radiation were identified in our cohort.

    Conclusions: Stereotactic radiosurgery and bevacizumab can be effectively used to treat focal recurrences of GBM. Increased number of chemotherapy agents and radiosurgical targets correlate with poorer outcomes, likely reflective of a larger tumor burden. Concurrent bevacizumab use resulted in a low incidence of radionecrosis and toxicity compared to published studies, and confers clinically relevant radioprotection in the setting of SRS re-irradiation.

    Patient Care: Our study supports data from prior smaller series that suggest the combined use of bevacizumab and radiosurgery may improve survival for those with focal GBM recurrences. In addition, out data shows that it is a well-tolerated treatment approach.

    Learning Objectives: 1. Understand the natural history of recurrent glioblastoma. 2. Describe the mechanism of radiation injury and bevacizumab's role in suppressing its manifestations. 3. Understand the role of radiosurgery and bevacizumab in focally recurrent glioblastoma.

    References: 1. Ostrom QT GH, Farah P, et al. . CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15(2):ii1-ii56. 2. Stupp R MW, van den Bent MJ, et al. European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-96. 3. Elliott RE, Parker EC, Rush SC, Kalhorn SP, Moshel YA, Narayana A, Donahue B, Golfinos JG: Efficacy of gamma knife radiosurgery for smallvolume recurrent malignant gliomas after initial radical resection. World Neurosurg 76:128-140, 2011 4. Niyazi M, Siefert A, Schwarz SB, Ganswindt U, Kreth FW, Tonn JC, Belka C: Therapeutic options for recurrent malignant glioma. Radiother Oncol 98:1-14, 2011. 5. Stupp R, Hegi ME, Mason WP, et al. Mirimanoff RO: European Organisation for R, Treatment of Cancer Brain T, Radiation Oncology G, National Cancer Institute of Canada Clinical Trials G: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTCNCIC trial. Lancet Oncol 10:459-466, 2009. 6. Stupp R, Mason WP, van den Bent MJ, et al. European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352: 987-996, 2005. 7. Sneed PK, Gutin PH, Larson DA, et al. Patterns of recurrence of glioblastoma multiforme after external irradiation followed by implant boost. Int J Radiat Oncol Biol Phys 1994;29:719–727. 8. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009;27:740-745. 9. Veninga T, Langendijk HA, Slotman BJ. Reirradiation of primary brain tumours: survival, clinical response and prognostic factors. Radiother Oncol. 2001 May;59(2):127-37. 10. Souhami L, Seiferheld W, Brachman D, et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys. 2004;60(3):853-860. 11. Imber BS, Kanungo I, Braunstein S, et al. Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience. Neurosurgery. 2016 Jul 13. 12. Larson EW, Peterson HE, Lamoreaux WT, et al. Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma. World J Clin Oncol. 2014 May 10;5(2):142-8. 13. Giglio P, Gilbert MR. Cerebral radiation necrosis. Neurologist. 2003;9(4):180-188. 14. Kong DS, Lee JI, Park K, et al. Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer. 2008;112(9):2046-2051. 15. Abbassy M, Missios S, Barnet GH, et al. Phase I Trial of Radiosurgery Dose Escalation Plus Bevacizumab in Patients with Recurrent/Progressive Glioblastoma. 2017;0(0)1-8. 16. Schmidt B, Lee HJ, Ryeom S, Yoon SS. Combining bevacizumab with radiation or chemoradiation for solid tumors: a review of the scientific rationale, and clinical trials. Curr Angiogenes. 2012;1(3):169-179. 17. Nahum AE. The radiobiology of hypofractionation. Clin Oncol (R Coll Radiol) 2015;27:260–9. 18. Fetcko K, Lukas RV, Watson GA, et al. Survival and complications of stereotactic radiosurgery: a systematic review of stereotactic radiosurgery for newly diagnosed and recurrent high-grade gliomas. Medicine. 2017;96(43):1-15. 19. Ferrara N (2005) VEGF as a therapeutic target in cancer. Oncology 69(Suppl 3):11–16 20. Salmaggi A, Eoli M, Frigerio S, et al. Intracavitary VEGF, bFGF, IL-8, IL-12 levels in primary and recurrent malignant glioma. J Neurooncol 2003;62:297–303. 21. Lamszus K, Ulbricht U, Matschke J, et al. Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF-A. Clin Cancer Res 2003;9:1399–1405. 22. Gorski DH, Beckett MA, Jaskowiak NT, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 1999;59:3374–3378. 23. Moeller BJ, Cao Y, Li CY, et al. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: Role of reoxygenation, free radicals, and stress granules. Cancer Cell 2004;5:429–441. 24. Heath VL, Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol 2009;6:395–404. 25. Lubelski D, Abdullah KG, Weil RJ, Marko NF. Bevacizumab for radiation necrosis following treatment of high grade glioma: a systematic review of the literature. J Neurooncol. 2013;115(3):317-322 26. Gonzalez J, Kumar AJ, Conrad CA, et al. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 2007;67:323–326. 27. Clarke J, Neil E, Terziev R, et al. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy with Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma. Int J Radiat Oncol Biol Phys 2017;99(4):797–804. 28. Kozin SV, Boucher Y, Hicklin DJ, et al. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res 2001;61:39–44.

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