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A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases

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Abstract

Introduction

Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT).

Methods

We performed a matched-pair analysis for 128 patients with multiple BM treated with either SRS or WBRT over a 5-year period. Patients were matched pairwise for seven potential prognostic factors. A mixed Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS). Distant intracranial progression-free survival (icPFS) and local control were assessed using a Fine and Gray subdistribution hazard model and considering death as competing event.

Results

Patients undergoing SRS had a median of 4 BM (range 3–16). 1-year local control of individual BM following SRS was 91.7%. Median OS in the SRS subgroup was 15.7 months (IQR 9.7–36.4) versus 8.0 months (interquartile range, IQR 3.8–18.0) in the WBRT subgroup (HR 2.25, 95% CI [1.5; 3.5], p < 0.001). Median icPFS was 8.6 (IQR 3.4–18.0) versus 22.4 (IQR 5.6–28.6) months, respectively (HR for WBRT 0.41, 95% CI [0.24; 0.71], p = 0.001). Following SRS, synchronous BM diagnosis (HR 2.51, 95% CI [1.30; 4.70], p = 0.004), higher initial number of BM (HR 1.21, 95% CI [1.10; 1.40], p = 0.002) and lung cancer histology (HR 2.05, 95% CI [1.10; 3.80], p = 0.024) negatively impacted survival. Excellent clinical performance (KPI 90%) was a positive prognosticator (HR 0.38, 95% CI [0.20; 0.72], p = 0.003), as was extracerebral tumor control (HR 0.48, 95% CI [0.24; 0.97], p = 0.040). Higher initial (HR 1.19, 95% CI [1.00; 1.40], p < 0.013) and total number of BM (HR 1.23, 95% CI [1.10; 1.40], p < 0.001) were prognostic for shorter icPFS.

Conclusion

This is the first matched-pair analysis to compare SRS alone versus WBRT alone for multiple BM. OS was prolonged in the SRS subgroup and generally favorable in the entire cohort. Our results suggest SRS as a feasible and effective treatment for patients with multiple BM.

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Authors and Affiliations

  1. Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Rami A. El Shafie, Aylin Celik, Daniela Schmitt, Kristin Lang, Laila König, Denise Bernhardt, Simon Höne, Tobias Forster, Bastian von Nettelbladt, Sebastian Adeberg, Jürgen Debus & Stefan Rieken

  2. National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Rami A. El Shafie, Aylin Celik, Daniela Schmitt, Kristin Lang, Laila König, Denise Bernhardt, Simon Höne, Tobias Forster, Bastian von Nettelbladt, Sebastian Adeberg, Jürgen Debus & Stefan Rieken

  3. Institute of Medical Biometry and Informatics (IMBI), Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany

    Dorothea Weber

  4. Department of Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Stefan Rieken

  5. Clinical Cooperation Unit Radiation Oncology (E050), German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Jürgen Debus

  6. Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Heidelberg, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Jürgen Debus

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Ethics approval for the study and a waiver of written informed consent was granted by the Heidelberg University ethics committee on April 12th, 2018 (#S-172/2018). Patient confidentiality was maintained by anonymizing patient data to remove any identifying information.

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El Shafie, R.A., Celik, A., Weber, D. et al. A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases. J Neurooncol 147, 607–618 (2020). https://doi.org/10.1007/s11060-020-03447-2

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