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. 2024 May 8;11(5):593-603.
doi: 10.1093/nop/npae043. eCollection 2024 Oct.

Preoperative stereotactic radiosurgery for patients with 1-4 brain metastases: A single-arm phase 2 trial outcome analysis (NCT03398694)

Namita Agrawal  1 , Jack M Shireman  2 , Kevin Shiue  1 , Aaron Kamer  3 , LaKeisha Boyd  4 , Yong Zang  4 , Neel Mukherjee  2 , James Miller  5 , Charles Kulwin  6 , Aaron Cohen-Gadol  5 , Troy Payner  6 , Chih-Ta Lin  5 , Jesse J Savage  5 , Brandon Lane  5 , Bradley Bohnstedt  5 , Tim Lautenschlaeger  1 , Naoyuki Saito  1 , Mitesh Shah  5 , Gordon Watson  1 , Mahua Dey  2
Affiliations

Preoperative stereotactic radiosurgery for patients with 1-4 brain metastases: A single-arm phase 2 trial outcome analysis (NCT03398694)

Namita Agrawal et al. Neurooncol Pract. .

Abstract

Background: Stereotactic radiosurgery (SRS) following surgical resection is the standard of care for patients with symptomatic oligo brain metastasis (BM), however, it is associated with 10-15% local failure. Targeting a resection cavity is imprecise, thus preoperative radiosurgery where the target is well-defined may be superior, however, the efficacy of preoperative SRS has not yet been tested in a clinical trial.

Methods: We conducted a phase 2, single-arm trial of preoperative SRS followed by surgical resection in patients with 1-4 symptomatic oligo BMs (NCT03398694) with the primary objective of measuring 6-month local control (LC). SRS was delivered to all patients utilizing a gamma knife or linear accelerator as per RTOG-9005 dosing criteria [Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291-298] based on tumor diameter with the exception that the largest lesion diameter treated was 5 cm with 15 Gy with all SRS treatment given in single fraction dosing.

Results: The trial screened 50 patients, 48 patients were treated under the protocol and 32 patients completed the entire follow-up period. Of all the patients who completed the follow-up period, the primary endpoint of 6-month LC was 100% (95% CI: 0.891-1.000; P = .005). Secondary endpoints, presented as medians, were overall survival (17.6 months), progression-free survival (5.3 months), distant in-brain failure (40.8% at 1 year), leptomeningeal failure (4.8% at 1 year), and radiation necrosis (7.7% at 1 year).

Conclusions: Our data confirms superior local control in patients who received preoperative SRS when compared to historical controls. Further study with a larger randomized cohort of patients is warranted to fully understand the benefits of preoperative SRS.

Keywords: brain metastases; phase II clinical trial; stereotactic radiosurgery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Flowchart of trial events depicting progression throughout the study period.
Figure 2.
Figure 2.
Consort diagram flowchart and primary study outcomes.
Figure 3.
Figure 3.
Kaplan–Meier graph depicting time to local failure for study treated lesions.
Figure 4.
Figure 4.
Kaplan–Meier graphs depicting progression free survival (A) and overall survival (B) for patients on study.
See this image and copyright information in PMC

References

    1. Maclean J, Fersht N, Singhera M, et al.. Multi-disciplinary management for patients with oligometastasis to the brain: results of a 5 year cohort study. Radiat Oncol. 2013;8(8):156. - PMC - PubMed
    1. Flores BC, Patel AR, Timmerman RD, Barnett SL.. From patchell to brown: an evidence-based evolution of the role of radiotherapy on the management of brain metastases. World Neurosurg. 2016;85(14):10–14. - PubMed
    1. Nayak L, Lee EQ, Wen PY.. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14(1):48–54. - PubMed
    1. Wong J, Hird A, Kirou-Mauro A, Napolskikh J, Chow E.. Quality of life in brain metastases radiation trials: a literature review. Curr Oncol. 2008;15(5):25–45. - PMC - PubMed
    1. Gans JH, Raper DMS, Shah AH, et al.. The role of radiosurgery to the tumor bed after resection of brain metastases. Neurosurgery. 2013;72(3):317–25; discussion 325. - PubMed