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

Lasse Rehné Jensen, Andrea Daniela Maier, Atle Lomstein, Thomas Graillon, Maya Hrachova, Daniela Bota, Alejandro Ruiz-Patiño, Oscar Arrieta, Andrés Felipe Cardona, Roberta Rudà, Julia Furtner, Ulrich Roeckle, Paul Clement, Matthias Preusser, David Scheie, Helle Broholm, Bjarne Winther Kristensen, Jane Skjøth-Rasmussen, Morten Ziebell, Tina Nørgaard MunchKåre Fugleholm, Martin A Walter, Tiit Mathiesen, Christian Mirian*

*Corresponding author for this work
1 Citation (Scopus)

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.

Original languageEnglish
JournalNeurosurgical Review
Volume45
Issue number5
Pages (from-to)3067-3081
Number of pages15
ISSN0344-5607
DOIs
Publication statusPublished - Oct 2022

Keywords

  • Everolimus/therapeutic use
  • Humans
  • Meningeal Neoplasms/drug therapy
  • Meningioma/drug therapy
  • Prospective Studies
  • Receptors, Somatostatin/therapeutic use
  • Somatostatin/therapeutic use
  • Progressive
  • Treatment-refractory
  • Neuro-oncology
  • Meningioma
  • Meta-analysis

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