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Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data

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Abstract

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked “very low.” Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.

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Acknowledgements

We thank the Statistical Advisory Board at the University of Copenhagen for their supervision of this project

Funding

Unrelated to this work, Christian Mirian is funded by The Novo Nordisk Foundation Grant No. 0052813.

Unrelated to this work, Mathias Preusser has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, and Gan & Lee Pharmaceuticals.

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Authors and Affiliations

  1. Department of Neurosurgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Lasse Rehné Jensen, Andrea Daniela Maier, Jane Skjøth-Rasmussen, Morten Ziebell, Tina Nørgaard Munch, Kåre Fugleholm, Tiit Mathiesen & Christian Mirian

  2. Department of Pathology, Center of Diagnostic Investigation, Copenhagen University Hospital, Copenhagen, Denmark

    Andrea Daniela Maier, David Scheie & Helle Broholm

  3. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark

    Atle Lomstein

  4. Department of Neurosurgery, Hospital La Timone, Aix Marseille University, APHM, INSERM, MMG, Marseille, France

    Thomas Graillon

  5. Department of Neurosurgery, University of Oklahoma Health Science Center, Oklahoma, OK, USA

    Maya Hrachova

  6. Department of Neurology, UC Irvine Medical Center, Orange, CA, USA

    Daniela Bota

  7. Department of Neurological Surgery, UC Irvine Medical Center, Orange, CA, USA

    Daniela Bota

  8. Foundation for Clinical and Applied Cancer Research–FICMAC, Bogotá, Colombia

    Alejandro Ruiz-Patiño & Andrés Felipe Cardona

  9. Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCaN), Mexico City, México

    Oscar Arrieta

  10. Department of Neurology, Castelfranco Veneto/Treviso, Treviso, Italy

    Roberta Rudà

  11. Department of Neuro-Oncology, City of Health and Science Hospital and University of Turin, Turin, Italy

    Roberta Rudà

  12. Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria

    Julia Furtner

  13. Department of Neurology and Brain Tumor Center, Cantonal Hospital Aarau, Aarau, Switzerland

    Ulrich Roeckle

  14. Department of Oncology, Leuven Cancer Institute, KU Leuven, Louvain, Belgium

    Paul Clement

  15. Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria

    Matthias Preusser

  16. Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden

    Bjarne Winther Kristensen

  17. Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark

    Bjarne Winther Kristensen

  18. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Tina Nørgaard Munch

  19. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    Tina Nørgaard Munch

  20. Department of Nuclear Medicine, University Hospital of Geneva, Geneva, Switzerland

    Martin A. Walter

  21. Gesundheitswissenschaften Und Medizin EN, University of Lucerne, Lucerne, Switzerland

    Martin A. Walter

  22. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Tiit Mathiesen

  23. Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Tiit Mathiesen

Authors
  1. Lasse Rehné Jensen
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  2. Andrea Daniela Maier
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  24. Christian Mirian
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Contributions

Lasse Rehné Jensen, Tiit Mathiesen, and Christian Mirian conceived and designed the study. Lasse Rehné Jensen and Christian Mirian reviewed articles independently and extracted the data jointly. Tiit Mathiesen, Maya Hrachova, Daniela Bota, Alejandro Ruiz-Patiño, Oscar Arrieta, Andrés Felipe Cardona, Roberta Rudà, Julia Furtner, Ulrich Roeckle, Paul Clement, and Matthias Preusser provided data from original articles. Analyzed and interpreted: Lasse Rehné Jensen, Christian Mirian, and the Statistical Advisory Board at the University of Copenhagen analyzed and interpreted the data. Writing: Lasse Rehné Jensen, Tiit Mathiesen, and Christian Mirian. Critical revision: All authors. All authors agreed with the results and conclusions and approved the final draft.

Corresponding author

Correspondence to Christian Mirian.

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Included data was untraceable, anonymized patient data that already has been published previously, thus not requiring Institutional Review Board approval by Danish law.

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Jensen, L.R., Maier, A.D., Lomstein, A. et al. Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data. Neurosurg Rev 45, 3067–3081 (2022). https://doi.org/10.1007/s10143-022-01849-6

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