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Original Investigation
October 15, 2020

Multi-institutional Analysis of Prognostic Factors and Outcomes After Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients With Brain Metastases

Author Affiliations
  • 1Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany
  • 2Institute for Radiation Medicine (IRM), Helmholtz Zentrum München, Neuherberg, Germany
  • 3Department of Radiation Oncology, University of Washington, Seattle
  • 4Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada
  • 5Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  • 6Department of Radiation Oncology, University of Queensland, Brisbane, Queensland, Australia
  • 7Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania
  • 8Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 9Radiation Oncology Service, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
  • 10Department of Radiation Oncology, University Hospital Cleveland Medical Center, Cleveland, Ohio
  • 11Department of Neurosurgery, Technical University of Munich (TUM), Munich, Germany
JAMA Oncol. Published online October 15, 2020. doi:10.1001/jamaoncol.2020.4630
Key Points

Question  What are the outcomes and prognostic factors after hypofractionated stereotactic radiotherapy to the resection cavity of patients with brain metastases?

Findings  In this cohort study of 558 patients, overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, and local control was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Prognostic factors associated with overall survival were a Karnofsky Performance Status score of 80% or greater, 22 to 33 days between resection and radiotherapy, and a controlled primary tumor, whereas prognostic factors associated with local control were a target volume of 23 mL or less, a single brain metastasis, and a controlled primary tumor.

Meaning  The results of this study suggest that hypofractionated stereotactic radiotherapy has a favorable risk-benefit profile and, compared with whole-brain radiotherapy, a low risk of treatment-related adverse effects.

Abstract

Importance  For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking.

Objective  To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases.

Design, Setting, and Participants  An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment.

Exposures  A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied.

Main Outcomes and Measures  The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity.

Results  A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis.

Conclusions and Relevance  To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.

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    1 Comment for this article
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    Deniz Yalman, Prof. Dr. | Ege University Faculty of Medicine Dept. of Radiation Oncology
    The manuscript is about brain metastasis but the authors wrote "bone matastasis" instead of "brain metastasis" insistently. This error should be corrected.
    CONFLICT OF INTEREST: None Reported
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