Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care

Alireza Mansouri^{1

2

3}, Ahmad Ozair⁴, Debarati Bhanja⁵, Hannah Wilding⁶, Elad Mashiach⁵, Waqas Haque⁷, Nicholas Mikolajewicz⁸, Leonardo de Macedo Filho^{9

6}, Sean S Mahase¹⁰, Mitchell Machtay¹⁰, Philippe Metellus¹¹, Frédéric Dhermain¹², Jason Sheehan¹³, Douglas Kondziolka⁵, L Dade Lunsford¹⁴, Ajay Niranjan¹⁴, Giuseppe Minniti¹⁵, Jing Li¹⁶, Steven N Kalkanis¹⁷, Patrick Y Wen¹⁸, Rupesh Kotecha^{19

20}, Michael W McDermott^{20

21}, Chetan Bettegowda^{22

23}, Graeme F Woodworth^{4

24

25}, Paul D Brown²⁶, Arjun Sahgal²⁷, Manmeet S Ahluwalia^{28

29}

Affiliations

¹ Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. amansouri@pennstatehealth.psu.edu.
² Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. amansouri@pennstatehealth.psu.edu.
³ Department of Neurosurgery, Penn State College of Medicine, Pennsylvania State University, Hershey, PA, USA. amansouri@pennstatehealth.psu.edu.
⁴ Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ Department of Neurological Surgery, NYU Langone Health, New York University, New York, NY, USA.
⁶ Department of Neurosurgery, Penn State College of Medicine, Pennsylvania State University, Hershey, PA, USA.
⁷ Division of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
⁸ Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.
¹⁰ Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA.
¹¹ Department of Neurosurgery, Ramsay Santé, Hôpital Privé Clairval, Marseille, France.
¹² Radiation Therapy Department, Institut Gustave Roussy, Villejuif, France.
¹³ Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
¹⁴ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁵ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza IRCCS Neuromed, Pozzilli, Italy.
¹⁶ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁷ Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA.
¹⁸ Center For Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
¹⁹ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
²⁰ Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
²¹ Department of Neurosurgery, Miami Neuroscience Institute, Baptist Health South Florida, Miami, FL, USA.
²² Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
²⁴ Brain Tumour Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
²⁵ University of Maryland-Medicine Institute for Neuroscience Discovery, Baltimore, MD, USA.
²⁶ Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
²⁷ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
²⁸ Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. manmeeta@baptisthealth.net.
²⁹ Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA. manmeeta@baptisthealth.net.

PMID: 40108412
DOI: 10.1038/s41571-025-01013-1

Review

Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care

Alireza Mansouri et al. Nat Rev Clin Oncol. 2025 May.

. 2025 May;22(5):327-347.

doi: 10.1038/s41571-025-01013-1. Epub 2025 Mar 19.

Authors

Affiliations

¹ Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. amansouri@pennstatehealth.psu.edu.
² Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. amansouri@pennstatehealth.psu.edu.
³ Department of Neurosurgery, Penn State College of Medicine, Pennsylvania State University, Hershey, PA, USA. amansouri@pennstatehealth.psu.edu.
⁴ Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ Department of Neurological Surgery, NYU Langone Health, New York University, New York, NY, USA.
⁶ Department of Neurosurgery, Penn State College of Medicine, Pennsylvania State University, Hershey, PA, USA.
⁷ Division of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
⁸ Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.
¹⁰ Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA.
¹¹ Department of Neurosurgery, Ramsay Santé, Hôpital Privé Clairval, Marseille, France.
¹² Radiation Therapy Department, Institut Gustave Roussy, Villejuif, France.
¹³ Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
¹⁴ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁵ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza IRCCS Neuromed, Pozzilli, Italy.
¹⁶ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁷ Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA.
¹⁸ Center For Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
¹⁹ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
²⁰ Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
²¹ Department of Neurosurgery, Miami Neuroscience Institute, Baptist Health South Florida, Miami, FL, USA.
²² Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
²⁴ Brain Tumour Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
²⁵ University of Maryland-Medicine Institute for Neuroscience Discovery, Baltimore, MD, USA.
²⁶ Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
²⁷ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
²⁸ Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. manmeeta@baptisthealth.net.
²⁹ Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA. manmeeta@baptisthealth.net.

PMID: 40108412
DOI: 10.1038/s41571-025-01013-1

Erratum in

Author Correction: Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care.
Mansouri A, Ozair A, Bhanja D, Wilding H, Mashiach E, Haque W, Mikolajewicz N, de Macedo Filho L, Mahase SS, Machtay M, Metellus P, Dhermain F, Sheehan J, Kondziolka D, Lunsford LD, Niranjan A, Minniti G, Li J, Kalkanis SN, Wen PY, Kotecha R, McDermott MW, Bettegowda C, Woodworth GF, Brown PD, Sahgal A, Ahluwalia MS. Mansouri A, et al. Nat Rev Clin Oncol. 2025 Dec;22(12):996. doi: 10.1038/s41571-025-01083-1. Nat Rev Clin Oncol. 2025. PMID: 41044428 No abstract available.

Abstract

The management of brain metastases is challenging and should ideally be coordinated through a multidisciplinary approach. Stereotactic radiosurgery (SRS) has been the cornerstone of management for most patients with oligometastatic central nervous system involvement (one to four brain metastases), and several technological and therapeutic advances over the past decade have broadened the indications for SRS to include polymetastatic central nervous system involvement (>4 brain metastases), preoperative application and fractionated SRS, as well as combinatorial approaches with targeted therapy and immune-checkpoint inhibitors. For example, improved imaging and frameless head-immobilization technologies have facilitated fractionated SRS for large brain metastases or postsurgical cavities, or lesions in proximity to organs at risk. However, these opportunities come with new challenges and questions, including the implications of tumour histology as well as the role and sequencing of concurrent systemic treatments. In this Review, we discuss these advances and associated challenges in the context of ongoing clinical trials, with insights from a global group of experts, including recommendations for current clinical practice and future investigations. The updates provided herein are meaningful for all practitioners in clinical oncology.

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Conflict of interest statement

Competing interests: D.K. declares institutional grant funding from Neuropoint Alliance; and is named on US Patent 11,253,726: Method to select radiation dosage for tumour treatment based on cellular imaging. L.D.L. has acted as a consultant for Insightec and holds stock in Elekta. G.M. has received honoraria for seminars from Accuray and BrainLAB. J.L. has received funding support for clinical trials from Bristol Myer Squibb. P.Y.W. has received research support from AstraZeneca, Black Diamond, Bristol Myers Squibb, Chimerix, Eli Lily, Erasca, Global Coalition for Adaptive Research, Kazia Therapeutics, MediciNova, Merck, Novartis, Quadriga, Servier and VBI Vaccines; and consultancy fees from Anheart, AstraZeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, GSK, Kintara, Merck, Mundipharma, Novartis, Novocure, Prelude Therapeutics, Sagimet, Sapience, Servier, Symbio, Tango, Telix and VBI Vaccines. R.K. has received honoraria from Accuray, BrainLAB, Castle Biosciences, Elekta, Elsevier, Ion Beam Applications, Kazia Therapeutics, Novocure and ViewRay; and institutional research funding from AstraZeneca, Blue Earth Diagnostics, BrainLAB, Cantex Pharmaceuticals, Exelixis, GT Medical Technologies, Ion Beam Applications, Kazia Therapeutics, Medtronic, Novocure and ViewRay. G.F.W. has received funding support for clinical trials from Insightec and the Keep Punching Foundation. P.D.B. has received honoraria from UpToDate. A.S. has acted as a consultant for Abbvie, BrainLAB, Elekta (Gamma Knife Icon), Merck, Roche and Varian; has received honorarium for educational seminars from Accuray, AstraZeneca, BrainLAB, Elekta, Seagen and Varian; research grants from BrainLAB, Elekta, Seagen and Varian; travel accommodations/expenses from BrainLAB, Elekta and Varian; and is also a Clinical Steering Committee Member of the Elekta MR-Linac Research Consortium and chairs the Elekta Oligometastases Group and the Elekta Gamma Knife Icon Group. M.S.A. has received research grants from AstraZeneca, Bayer, Bristol Myers Squibb, Incyte, Merck, Mimivax, Novocure and Pharmacyclics; consultancy fees from Allovir, Anheart Therapeutics, Apollomics, Autem, Bayer, Cairn Therapeutics, Caris Lifesciences, Celularity, GSK, Insightec, Janssen, Kiyatec, Novocure, Nuvation, Prelude Therapeutics, Pyramid Biosciences, SDP Oncology, Theraguix, Tocagen, Varian Medical Systems, Viewray, Voyager Therapeutics and Xoft; is a scientific advisory board member for Cairn Therapeutics, Modifi Biosciences and Pyramid Biosciences; and holds stock in Cytodyn, MedInnovate Advisors and MimiVax. The other authors declare no competing interests.

References

1. Schnurman, Z. et al. Causes of death in patients with brain metastases. Neurosurgery 93, 986–993 (2023). - PubMed - DOI
1. Lamba, N., Wen, P. Y. & Aizer, A. A. Epidemiology of brain metastases and leptomeningeal disease. Neuro-Oncol. 23, 1447–1456 (2021). - PubMed - PMC - DOI
1. Ladbury, C. et al. Stereotactic radiosurgery in the management of brain metastases: a case-based radiosurgery society practice guideline. Adv. Radiat. Oncol. 9, 101402 (2024). - PubMed - DOI
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Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care

Affiliations

Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

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Medical

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