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The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

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Abstract

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

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Author contributions

JMK: Conceptualization, formal analysis, methodology, visualization, writing—original draft, writing—review and editing. JAM: Conceptualization, formal analysis, methodology, visualization, writing—review and editing. RK and STC: Conceptualization, writing—review and editing. RX, AJ, MCW, MSA, AMM, DMP, ESM, JHS, GHB, MAV, LA and GHS: Investigation, writing—review and editing.

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Authors and Affiliations

  1. School of Medicine, Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA

    Joseph M. Kim

  2. Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Jacob A. Miller, Roy Xiao, Manmeet S. Ahluwalia, Alireza M. Mohammadi, David M. Peereboom, Erin S. Murphy, John H. Suh, Gene H. Barnett, Michael A. Vogelbaum, Lilyana Angelov, Glen H. Stevens & Samuel T. Chao

  3. Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue, CA50, Cleveland, OH, 44195, USA

    Rupesh Kotecha, Aditya Juloori, Matthew C. Ward, Erin S. Murphy, John H. Suh & Samuel T. Chao

  4. Department of Medical Oncology, Taussig Cancer Institute, Cleveland, OH, USA

    Manmeet S. Ahluwalia & David M. Peereboom

  5. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, OH, USA

    Manmeet S. Ahluwalia, Alireza M. Mohammadi, David M. Peereboom, Erin S. Murphy, John H. Suh, Gene H. Barnett, Michael A. Vogelbaum, Lilyana Angelov, Glen H. Stevens & Samuel T. Chao

  6. Department of Neurological Surgery, Neurological Institute, Cleveland, OH, USA

    Alireza M. Mohammadi, Gene H. Barnett, Michael A. Vogelbaum & Lilyana Angelov

  7. Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Glen H. Stevens

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  1. Joseph M. Kim
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  2. Jacob A. Miller
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  4. Roy Xiao
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Corresponding author

Correspondence to Samuel T. Chao.

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Conflict of interest

J.M. Kim, J.A. Miller, R. Xiao, A. Juloori, M.C. Ward, A.M. Mohammadi, D.M. Peereboom, E.S. Murphy, L. Angelov and G.H. Stevens have declare that they have no conflict of interest. R. Kotecha: Honorarium and research support from Varian Medical Systems. M.S. Ahluwalia: Consulting and grant from Elekta; Grant support from Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Spectrum Pharmaceuticals, Tracon Pharmaceuticals, Novocure; Consultant for Merck, Genentech/ Roche, Incyte, Caris Lifesciences, Monteris Medical, MRI interventions Inc. J.H. Suh: Travel, Elekta; Honorarium and Research Support, Varian Medical Systems. G.H. Barnett: Consultant for Monteris Medical, Inc.; Royalty interests for Mako Surgical Corp, Roche. M.A. Vogelbaum: Equity and royalty interests, company founder and officer for Infuseon Therapeutics, Inc; Honorarium for scientific advisory meeting from Pharmicokinesis, Inc.; Honorarium for DSMB membership from Neuralstem, Inc. S.T. Chao: Honorarium, Varian Medical Systems.

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Kim, J.M., Miller, J.A., Kotecha, R. et al. The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies. J Neurooncol 133, 357–368 (2017). https://doi.org/10.1007/s11060-017-2442-8

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  • DOI: https://doi.org/10.1007/s11060-017-2442-8

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