Meningioma: International Consortium on Meningiomas (ICOM) Consensus Review on Scientific Advances & Treatment Paradigms for Clinicians, Researchers, and Patients

Meningiomas are the most common primary intracranial tumors in adults, and their incidence is rising with an aging population and the widespread use of neuroimaging examinations. While most meningiomas are benign, a small portion exhibit biological invasiveness, leading to severe neurological complications and death. In recent years, significant progress has been made in understanding the biological mechanisms of these tumors, and molecular biological markers have begun to be incorporated into their grading and prognostic assessment. However, unlike other central nervous system tumors, meningiomas currently lack a unified molecular classification system, and establishing such a system is one of the main goals of the CIMPACT-NOW working group. Additionally, there is some controversy regarding the optimal management strategies for specific cases of meningiomas and patient populations. To address these issues, members of the International Collaborative on Meningiomas (ICOM), including leading experts in the field, have authored a comprehensive consensus review to provide a reference for clinicians, researchers, and patients.

The authors of this review come from renowned medical centers and research institutions around the world, including the Princess Margaret Cancer Center at the University Health Network in Toronto, the University of California, San Francisco, Heidelberg University Hospital in Germany, Duke University, and the University of Cologne. The primary corresponding authors are Dr. Gelareh Zadeh and Dr. Farshad Nassiri from the Princess Margaret Cancer Center at the University Health Network in Toronto, Dr. Matthias Preusser from the Medical University of Vienna, and Dr. Susan Short from the University of Leeds. These authors are highly acclaimed in the field of meningiomas, and the review consolidates the research efforts of multiple leading teams.

The review comprehensively addresses the epidemiology and risk factors of meningiomas, genomics and biology, histopathological classification, biomarkers and molecular classification systems, diagnostic and imaging presentations, surgical management, external beam radiation therapy, stereotactic radiosurgery, peptide receptor radionuclide therapy, clinical trials of new systemic therapies, patient quality of life assessment, and management strategies for special populations (such as newborn screening-positive patients).

Specifically, in the epidemiology section, the authors introduce the incidence of meningiomas, racial and gender differences, as well as identified susceptibility genes and environmental risk factors. In the genomics and biology section, the authors detail the gene mutations and molecular mechanisms associated with the development of meningiomas, such as NF2, TRAF7, SMO, and TERT. The histopathological classification section highlights the revisions to the WHO 2021 grading of meningiomas and the introduction of molecular markers (such as TERT mutations and CDKN2A/B loss) as criteria for WHO grade III.

Regarding biomarkers and molecular classification, the authors systematically review the various molecular classification systems for meningiomas proposed in recent years based on different molecular levels, such as DNA methylation, gene expression profiles, and mutation spectra. These include the MI/IE/HM subtyping by Choudhury et al., the DKFZ subtyping by Sahm et al., and the MG1-4 subtyping by Nassiri et al. The authors also compare and analyze the prognostic value of these classification systems.

In terms of diagnostic and imaging techniques, in addition to conventional CT and MRI, the authors introduce the potential applications of novel SSTR (somatostatin receptor) targeted PET/CT or PET/MR imaging in meningioma diagnosis, surgical and radiation therapy target delineation, and treatment response evaluation.

For treatment, surgical resection remains the primary treatment for meningiomas. The authors systematically describe the grading standards for the extent of surgical resection (such as the Simpson grading) and its evolution, as well as the application of different surgical approaches and assistive techniques in various types of meningiomas. The benefits and risks of different radiation therapy strategies, including intensity-modulated radiation therapy and hypofractionated radiation therapy, in various grades of meningiomas are also discussed in detail. Furthermore, the authors introduce the efficacy and risk of complications of stereotactic radiosurgery in different grades of meningiomas. In addition to traditional surgery and radiation therapy, the review also evaluates the preliminary efficacy of emerging therapies such as peptide receptor radionuclide therapy targeting SSTRs and various new targeted drugs and immunotherapies in recurrent or refractory meningiomas.

Finally, the authors discuss issues related to the quality of life of meningioma patients and its relationship with different molecular subtypes and treatment modalities, the incidence of epilepsy and the management strategies for perioperative antiepileptic drugs, as well as special considerations in the management of meningiomas in patients with NF2-related tumor spectrum.

This review is one of the most comprehensive works on the recent advances in the diagnosis and treatment of meningiomas. It systematically reviews the significant progress made in recent years in various areas, including epidemiology, molecular pathogenesis, molecular subtyping, imaging diagnostics, surgical and radiation therapy treatments, and novel systemic therapies. It also identifies current key issues and deficiencies, providing a blueprint for future research directions.

The review emphasizes the importance and urgency of establishing a unified molecular classification system for meningiomas, which is expected to lay the foundation for personalized molecular targeted therapy and prognostic assessment. It also elucidates the potential role of molecular subtyping in guiding the selection of surgical, radiation therapy, and novel drug treatment modalities for meningioma patients. The review introduces a series of promising new diagnostic and therapeutic technologies, such as SSTR-targeted imaging and radionuclide therapy, novel molecular targeted drugs, and immunotherapies, providing references for clinical practice and new drug development.

Additionally, the review emphasizes the assessment of patients’ quality of life and its relationship with treatment strategies, as well as the individualized management of special populations, reflecting a comprehensive, patient-centered, and humane medical philosophy.