Abstract
Background
The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD.
Methods
A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN.
Results
53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24–25 Gy in 3–5 fractions. There were 0 LFs, 3 Grade 2–3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate.
Conclusions
In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49–60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
References
Patchell RA, Tibbs PA, Walsh JW et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500
Patchell R, Tibbs P, Regine W et al (1998) Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280:1485–1489
Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044
Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316:401–409
Brown PD, Ballman KV, Cerhan JH et al (2017) Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1049–1060
Kayama T, Sato S, Sakurada K et al (2018) Effects of surgery with salvage stereotactic radiosurgery versus surgery with whole-brain radiation therapy in patients with one to four brain metastases (JCOG0504): a phase III, noninferiority, randomized controlled trial. J Clin Oncol 36:3282–3289
Prabhu RS, Dhakal R, Vaslow ZK et al (2021) Preoperative Radiosurgery for resected brain metastases: the PROPS-BM Multicenter Cohort Study. Int J Radiat Oncol Biol Phys 111:764–772
Mahajan A, Ahmed S, McAleer MF et al (2017) Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1040–1048
Redmond KJ, De Salles AAF, Fariselli L et al (2021) Stereotactic radiosurgery for postoperative metastatic surgical cavities: a critical review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines. Int J Radiat Oncol Biol Phys 111:68–80
Brennan C, Yang TJ, Hilden P et al (2014) A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys 88:130–136
Lehrer EJ, Peterson JL, Zaorsky NG et al (2019) Single versus multifraction stereotactic radiosurgery for large brain metastases: an international meta-analysis of 24 trials. Int J Radiat Oncol Biol Phys 103:618–630
Patel RK, Burri HS, Asher LA et al (2016) Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis. Neurosurgery 79:279–285
Murphy ES, Yang K, Suh J et al (2019) Early results from a prospective phase ii dose escalation study for neoadjuvant radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 103:E5–E5
Iheagwara UK, Siddiqui Z, Holeva K et al (2021) A phase II study to determine the efficacy of pre-operative stereotactic radiosurgery followed by resection for brain metastasis. Int J Radiat Oncol Biol Phys 111:S25
Asher AL, Burri SH, Wiggins WF et al (2014) A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys 88:899–906
Patel AR, Nedzi L, Lau S et al (2018) Neoadjuvant stereotactic radiosurgery before surgical resection of cerebral metastases. World Neurosurg 120:e480-487
Vetlova E, Golbin DA, Golanov AV et al (2017) Preoperative stereotactic radiosurgery of brain metastases: preliminary results. Cureus 9:e1987
Prabhu RS, Miller KR, Asher AL et al (2018) Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm. J Neurosurg 131:1–8
Funding
No funding was received to assist with the preparation of this manuscript.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by HKP, JDP, JM, CH, BK, and RP. BK: responsible for Statistical Analysis. The first draft of the manuscript was written by HKP, JDP, JM, CH, BK, and RP, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
All authors declare no conflict of interest related to this manuscript.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Since this study is retrospective, informed consent was not obtained in this study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Palmer, J.D., Perlow, H.K., Matsui, J.K. et al. Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis. J Neurooncol 159, 389–395 (2022). https://doi.org/10.1007/s11060-022-04073-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-022-04073-w