European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection

Abstract

Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4,ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I ("ready for clinical use") classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II ("investigational") classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.

Keywords: meningioma; predictive marker; targeted therapy.

Figure 1.

Overview of the frequency and ESCAT score of molecular targets found in meningiomas. Numbers as found in the literature. ARID1A, AT-rich binding domain protein 1A; BAP1, BRCA1-associated protein 1; CDK4/6, cyclin-dependent kinase 4/6; CDKN2A/B, cyclin-dependent kinase inhibitor 2A/B; ESCAT, European Society for Medical Oncology Clinical Actionability of molecular Targets; KLF4, Krüppel-like factor 4; mTOR, mammalian target of rapamycin; NF2, neurofibromin 2/schwannomin; PD-L1, programmed cell death ligand 1; PDGFR, platelet-derived growth factor receptor; PIK3CA, Phosphatidylinositol 3-kinase, catalytic subunit alpha; SMARCE1, SWI/SNF related, matrix associated, actin dependent regulator of chromatin E1; SMO, smoothened; SSTR, somatostatin receptor; SUFU, suppressor of fused homolog; TERT, telomerase reverse transcriptase; TRAF7, TNF receptor-associated factor 7; VEGF(R), vascular endothelial growth factor (receptor).