TY - JOUR
T1 - The concept, intention, and evaluation of the term treatment-refractory meningioma
AU - Jensen, Lasse Rehne
AU - Maier, Andrea Daniela
AU - Juratli, Tareq A.
AU - Goutagny, Stephane
AU - Bertero, Luca
AU - Graillon, Thomas
AU - Brokinkel, Benjamin
AU - Gupta, Tejpal
AU - Torp, Sverre Helge
AU - Ruda, Roberta
AU - Clement, Paul M.
AU - van Essen, Martijn
AU - Tabernero, Maria Dolores
AU - Gousias, Konstantinos
AU - Rodriguez, Alvaro Otero
AU - Chang, Jong Hee
AU - Suh, Chang-Ok
AU - Cardona, Andres Felipe
AU - Arrieta, Oscar
AU - Ruiz-Patino, Alejandro
AU - Bota, Daniela A.
AU - Hrachova, Maya
AU - Scheie, David
AU - Kristensen, Bjarne Winther
AU - Munch, Tina Norgaard
AU - Law, Ian
AU - Fugleholm, Kare
AU - Meling, Torstein Ragnar
AU - Furtner, Julia
AU - Preusser, Matthias
AU - Walter, Martin Alexander
AU - Mathiesen, Tiit
AU - Mirian, Christian
PY - 2025
Y1 - 2025
N2 - BackgroundTreatment-refractory meningioma is a widely used term but lacks standardized criteria, impairing research comparability and treatment evaluation. The aim of this study was to assess the heterogeneity of patient populations labeled as treatment-refractory and to explore recommendations for better consistency.MethodsWe systematically reviewed 69 studies published before 2024 and analyzed individual participant data from 15 cohorts (n = 211) that included treatment-refractory patients who underwent experimental therapy with somatostatin receptor (SSTR)-targeted therapies. A reference cohort (n = 102) with newly diagnosed WHO-3 meningiomas was used descriptively for comparison. Progression and death were the primary endpoints. Hazard rate ratios were estimated via Poisson regression, and inter-study heterogeneity was quantified using I-2 statistics.ResultsDefinitions of treatment-refractory varied substantially across previous studies. WHO-1 patients showed high statistical inter-study variability, particularly for the long-acting SSTR-analogues group when assessing progression (I-2 = 81.7%) and death (I-2 =74.8%). Patients with treatment-refractory WHO-2 and WHO-3 meningioma exhibited more consistency across endpoints and SSTR-targeted therapies (I-2 percentages <= 16.0%). Risk of progression and death differed significantly by WHO grade, regardless of SSTR-targeted therapy.ConclusionsOur findings demonstrate an inconsistent use of the term treatment-refractory and substantial variability of effect estimates dependeing on the individual cohorts. Pooling patients across WHO grades is unfeasible for assessing treatment effects. Based on the present study and prior evidence, we outline recommendations to improve consistency in future trial design and enable more meaningful comparisons across studies. The recommendations are grouped into four categories: radiographic evaluation, endpoints, clinical core elements, and molecular classification.
AB - BackgroundTreatment-refractory meningioma is a widely used term but lacks standardized criteria, impairing research comparability and treatment evaluation. The aim of this study was to assess the heterogeneity of patient populations labeled as treatment-refractory and to explore recommendations for better consistency.MethodsWe systematically reviewed 69 studies published before 2024 and analyzed individual participant data from 15 cohorts (n = 211) that included treatment-refractory patients who underwent experimental therapy with somatostatin receptor (SSTR)-targeted therapies. A reference cohort (n = 102) with newly diagnosed WHO-3 meningiomas was used descriptively for comparison. Progression and death were the primary endpoints. Hazard rate ratios were estimated via Poisson regression, and inter-study heterogeneity was quantified using I-2 statistics.ResultsDefinitions of treatment-refractory varied substantially across previous studies. WHO-1 patients showed high statistical inter-study variability, particularly for the long-acting SSTR-analogues group when assessing progression (I-2 = 81.7%) and death (I-2 =74.8%). Patients with treatment-refractory WHO-2 and WHO-3 meningioma exhibited more consistency across endpoints and SSTR-targeted therapies (I-2 percentages <= 16.0%). Risk of progression and death differed significantly by WHO grade, regardless of SSTR-targeted therapy.ConclusionsOur findings demonstrate an inconsistent use of the term treatment-refractory and substantial variability of effect estimates dependeing on the individual cohorts. Pooling patients across WHO grades is unfeasible for assessing treatment effects. Based on the present study and prior evidence, we outline recommendations to improve consistency in future trial design and enable more meaningful comparisons across studies. The recommendations are grouped into four categories: radiographic evaluation, endpoints, clinical core elements, and molecular classification.
KW - Individual participant data
KW - Progressive meningioma
KW - Recommendations
KW - Retrospective cohort
KW - Treatment-refractory
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=starter2208&SrcAuth=WosAPI&KeyUT=WOS:001543262000001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1007/s11060-025-05154-2
DO - 10.1007/s11060-025-05154-2
M3 - Journal article
C2 - 40760312
SN - 0167-594X
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
ER -