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Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients

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Abstract

Purpose

Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently.

Methods

A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN).

Results

The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95).

Conclusion

The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

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Data availability

The data associated with this project are stored on an institutional repository. Data requests should be sent to the corresponding author.

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Acknowledgements

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Funding

None.

Author information

Author notes

  1. Eric J. Lehrer, Atulya A. Khosla, and Ahmad Ozair have contributed equally as first authors.

Authors and Affiliations

  1. Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA

    Eric J. Lehrer

  2. Department of Medical Oncology, Miami Cancer Institute, Miami, FL, USA

    Atulya A. Khosla, Ahmad Ozair & Manmeet S. Ahluwalia

  3. Department of Radiation Oncology, NYU Langone Medical Center, New York, NY, USA

    Jason Gurewitz & Kenneth Bernstein

  4. Department of Neurosurgery, NYU Langone Medical Center, New York, NY, USA

    Douglas Kondziolka

  5. Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Ajay Niranjan, Zhishuo Wei & L. Dade Lunsford

  6. Department of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, QC, Canada

    David Mathieu

  7. Department of Medicine, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, QC, Canada

    Claire Trudel

  8. Department of Neurological Surgery, Emory University, Atlanta, GA, USA

    Christopher P. Deibert

  9. Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA

    Timothy D. Malouff, Henry Ruiz-Garcia, Jennifer L. Peterson & Daniel M. Trifiletti

  10. Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB, Canada

    Samir Patel

  11. Department of Neurosurgery, University of Southern California, Los Angeles, CA, USA

    Phillip Bonney, Cheng Yu & Gabriel Zada

  12. Department of Radiation Oncology, University of Southern California, Los Angeles, CA, USA

    Lindsay Hwang

  13. Department of Neurosurgery, IRCCS Humanitas Research Hospital, Rozzano (Mi), Italy

    Piero Picozzi, Andrea Franzini & Luca Attuati

  14. Department of Radiation Oncology, Ohio State University Wexner Medical Center, Columbus, OH, USA

    Rahul N. Prasad, Raju R. Raval & Joshua D. Palmer

  15. Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan

    Cheng-chia Lee & Huai-che Yang

  16. Department of Radiation Oncology, University of Colorado, Denver, CO, USA

    Kareem R. Fakhoury & Chad G. Rusthoven

  17. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Eric J. Lehrer & Daniel R. Dickstein

  18. Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA

    Jason P. Sheehan

Authors
  1. Eric J. Lehrer
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  2. Atulya A. Khosla
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  3. Ahmad Ozair
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  4. Jason Gurewitz
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  5. Kenneth Bernstein
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  7. Ajay Niranjan
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  9. L. Dade Lunsford
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  34. Manmeet S. Ahluwalia
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Contributions

Conceptualization: EJL, MSA, AAK, AO, DMT, JPS. Data Curation: JG, KB, DK, AN, ZW, LDL, TDM, HR-G, SP, PB, LH, CY, GZ, DM, CT, RP, JDP, KRF, CGR, CPD, PP, AF, LA, CL, HY, DMT. Formal Analysis: EJL. Funding Acquisition: N/A. Investigation: EJL. Methodology: EJL, MSA. Project administration: MSA. Resources: MSA. Software: EJL. Supervision: MSA. Validation: EJL. Visualization: EJL. Writing – original draft: EJL, AAK, AO. Writing – review and editing: All authors.

Corresponding author

Correspondence to Eric J. Lehrer.

Ethics declarations

Conflict of interest

Dr. Lunsford is a stockholder in Elekta AB, Stockholm, Sweden; Dr. Trifiletti reports institutional support from Novocure Ltd and consulting for Boston Scientific Corporation for unrelated research. Dr. Palmer reports personal fees from Varian Medical System, Consulting for Huron Consulting group, Advisory board for Novocure, research grant funding from Kroger, NIH R702 grant, outside submitted work. Dr. Kondziolka holds research grants from Brainlab that are not related to this work. Dr. Ahluwalia is a consultant for AnHeart therapeutics, Bayer, Novocure, Kiyatec, Insightec, GSK, Xoft, Nuvation, Cellularity, SDP Oncology, Apollomics, Prelude, Janssen, Tocagen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Varian Medical Systems, and Carin Therapeutics. Dr. Ahluwalia is on the scientific advisory board for Cairn Therapautics, Pyramid Biosciences.  Dr. Ahluwalia has research grants from Seagen. He is a consultant for Bayer, Novocure, Kiyatec, Insightec, GSK, Xoft, Nuvation, Cellularity, SDP Oncology, Apollomics, Prelude, Janssen, Tocagen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Varian Medical Systems, Cairn Therapeutics, Anheart Therapeutics, Theraguix, Menarini Ricerche, Sumitomo Pharma Oncology, Autem therapeutics, GT Medical Technologies. He serves on the scientific advisory board for Cairn Therapeutics, Pyramid Biosciences, Modifi biosciences., Bugworks. He is a shareholder in Mimivax, Cytodyn, MedInnovate Advisors LLC, Trisalus Lifesciences.

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Lehrer, E.J., Khosla, A.A., Ozair, A. et al. Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients. J Neurooncol 165, 63–77 (2023). https://doi.org/10.1007/s11060-023-04413-4

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