Open research questions in Meningioma and schwannoma management

What the literature leaves open

• The mixed results of this study—modest improvement in OS but shorter PFS—highlight the need for further research to fully elucidate the role of trabectedin in meningioma treatment. Larger, multicenter trials are essential to validate the preliminary findings and ensure the results are generalizable across diverse patient popu- lations. Implementing double-blind, placebo-controlled designs can reduce bias and provide a clearer assessment of trabectedin’s true efficacy and safety. Given the limited efficacy of trabectedin as a monotherapy, exploring its use in combination with other agents, such as immune inhibitors or targeted therapies, could checkpoint enhance its therapeutic potential [16–19]. Research into predictive biomarkers for response to trabectedin could help tailor treatment to those most likely to benefit, opti- mizing therapeutic outcomes and minimizing unneces- sary toxicity [20, 21].

  Effect of trabectedin on the survival of meningioma patients: a systematic review · 2026 · DOI

• This review has several important limitations. First, all included studies are case reports or small case series with inherently high risk of bias. Second, quantitative meta-analysis was not possible given study heterogene- ity. Third, outcome definitions were not standardized across studies. Fourth, no comparator group of untreated patients was available, precluding causal conclusions about SRS-attributable hemorrhage risk. Future prospec- tive registries with standardized outcome reporting are needed. The overall certainty of evidence for all outcomes in this review is rated as Very Low under the GRADE framework. This reflects exclusive reliance on case reports and series without comparator groups, high risk of selection bias, absence of standardized outcome defi- nitions, inconsistent follow-up duration, and a small total sample (n = 47). All reported frequencies and outcome rates represent descriptive summaries only and should not be interpreted as epidemiological estimates.

  Intratumoral hemorrhage in vestibular schwannomas post-radiosurgery: a systematic review · 2026 · DOI

• A limitation of the current work is that the Delphi ques- tionnaire will be distributed only within the United King- dom (UK) and Europe. However, a broader international perspective is incorporated through the identification of international studies published in English within the global literature. While the core measurement set is designed with practical relevance to NHS and European practice, it is acknowledged that stakeholders beyond this geographical region may prioritise different indicators. 1 3Neuroradiology Impact and dissemination By actively involving a multidisciplinary stakeholder steer- ing group in the development of the Delphi study ques- tions, and ensuring broad engagement from relevant clinical stakeholders throughout the questionnaire process, this study aims to enhance the future adoption of the resulting consensus recommendations and AI-driven clinical pipe- line. Additionally, we will publish the Delphi study and guidelines in a peer-reviewed journal and present the results at relevant clinical and academic meetings.

  Consensus on the use of artificial intelligence in the management and measurement of vestibular schwannomas: A protocol for a modified delphi consensus · 2026 · DOI

• Despite multiple described techniques, no consensus exists on the optimal surgical approach, with the supracerebellar infratentorial (SCIT) and occipital interhemispheric transtentorial (OITA) approaches representing the most adopted corridors.

  What is the best surgical approach for Pineal Region Tumors? A systematic literature review and anatomical comparative study · 2026 · DOI

• The main strength of this report relies on detailed, stepwise description of surgical strategy. The integration of preoperative 3D CT planning, intraoperative neuronavigation, and custom implant technology represents a reproducible approach for the management of similar lesions. These techniques reflect advancements in neurosurgical technology and highlight the importance of tailored surgical planning. The main limitation is represented by the single case report like almost all the literature concerning pediatric patients. Secondly, while the 1-year follow-up is reassuring with respect to early recurrence, it is insufficient to draw definitive conclusions regarding long-term tumor behavior, given the characteristically indolent growth of meningiomas and the possibility of late recurrence. Moreover, no molecular or genetic profiling, including NF2 mutation analysis or DNA methylation profiling, was performed in the present case, limiting mechanistic insight into tumor pathogenesis in this age group. Lastly, the long-term impact of a titanium cranioplasty on cranial growth and remodelling in a 9-year-old patient remains unknown and warrants longitudinal monitoring. The potential need for implant revision in the context of progressive skull growth should be anticipated and discussed with the family during follow-up.

  Primary intraosseous meningioma in a child: an unusual case report and literature review · 2026 · DOI

• Future research should focus on molecular and genetic investigation of PIOMs, particularly in pediatric cases, to identify potential therapeutic targets. Multicenter studies are needed to compile larger cohorts of pediatric PIOMs, given the rarity of PIOMs in order to improve their management. Additionally, long-term follow-up data are essential to assess recurrence rates and the impact of cranial prosthesis on development of the skull in children.

  Primary intraosseous meningioma in a child: an unusual case report and literature review · 2026 · DOI

• Our study’s limitations reflect the current state of evidence in this field. Although we restricted analysis to skull base 1 3Neurosurgical Review (2026) 49:403 403 Page 10 of 11 lesions to improve methodological consistency, the inclusion of multiple pathologies still introduces clinical and statisti- cal heterogeneity. Most included studies are observational, with single-arm proportions, short and variable follow- up, and non-uniform definitions for EOR and ophthalmic outcomes, limiting interpretability of pooled complication rates. Specific oculomotor outcomes were inconsistently reported, precluding dedicated analysis despite their ana- tomical relevance. Even with leave-one-out and Baujat analyses, residual heterogeneity persists, and pooled GTR estimates should be interpreted as context-dependent rather than approach-defining. Reporting bias toward favorable cases and inconsistent documentation of complications (temporary vs. permanent) further limit cross-study com- parability. These constraints support cautious interpreta- tion of cytoreductive outcomes and reinforce the value of evaluating ETOA primarily through consistent safety end- points (CSF leak, infection, visual preservation). Publica- tion bias was assessed using funnel plots for outcomes with sufficient studies. However, the small number of included studies (n = 11) limits funnel plot reliability and precludes formal asymmetry testing (e.g., Egger’s test). Although visual inspection did not suggest significant asymmetry for most outcomes, publication bias cannot be excluded, par- ticularly given the predominance of studies reporting favor- able outcomes. Future work should consolidate pathology-specific core outcome sets for skull base transorbital surgery, including standardized BCVA and perimetry, as well as harmonized definitions of complications (temporary vs. permanent). These should be embedded in prospective registries with long-term follow-up (≥ 5 years). Comparative studies by indication should integrate volumetric EOR with patient- reported outcomes, including vision-related quality of life. Additionally, learning-curve analyses and cost-effectiveness studies may help define how surgical experience, corridor optimization, and reconstruction techniques influence com- plication rates and long-term outcomes.

  Safety profile and surgical outcomes of the endoscopic transorbital approach as a skull base surgical corridor: a systematic review and meta-analysis · 2026 · DOI

• Future work should prioritize multicenter, prospective cohorts with standardized reporting of clinical, dosimetric, and surgical variables. Harmonized definitions of local con- trol, prospectively collected late toxicity graded with con- temporary systems (e.g., CTCAE), and routine reporting of grade ≥ 3 events would substantially reduce measurement bias and strengthen future meta-analytic inferences. Larger, more granular datasets would also enable adequately pow- ered meta-regression to test candidate moderators such as total dose, WHO grade, treatment year (technology era), and fractionation type. In parallel, collaborative registries and, where feasible, randomized or pragmatic comparative trials against modern photon IMRT and stereotactic radio- surgery could validate the survival and toxicity advantages suggested by this review and inform cost-effectiveness across different healthcare settings.

  Effectiveness and safety of proton therapy in intracranial meningioma treatment: a systematic review and meta-analysis · 2026 · DOI

• Multi-center collaborations and meta-analytic efforts across independent datasets are needed to strengthen the generalizability and reproducibility of VLSM findings in meningioma research.

  Extending voxel-based lesion mapping to neurosurgical oncology: applications in intracranial meningiomas · 2026 · DOI

• VLSM may miss network-level dysfunction, which is increasingly recognized as critical in understanding brain-tumor interactions; complementary approaches such as lesion-network mapping should be considered in future research.

  Extending voxel-based lesion mapping to neurosurgical oncology: applications in intracranial meningiomas · 2026 · DOI

• None of the VLSM studies on meningiomas have applied the concept of DAZ (Damage-Associated Zone) in their analysis, despite its anatomical specificity and biological meaningfulness.

  Extending voxel-based lesion mapping to neurosurgical oncology: applications in intracranial meningiomas · 2026 · DOI

• Conclusion: There was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy.

  Repeat single-fraction stereotactic radiosurgery for recurrent vestibular schwannoma · 2022 · DOI

• WHO grade classification criteria (reference 40) have not been systematically applied to distinguish WHO grade I benign meningiomas with hepatic metastases (documented in references 21, 30) from atypical (grade II) and anaplastic (grade III) variants. A standardized histopathological reclassification of existing case reports using current WHO criteria is needed to clarify whether metastatic potential correlates with tumor grade.

  The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy · 2022 · DOI

• Treatment outcomes for hepatic metastatic meningioma have been reported only through individual case reports (surgical resection, selective hepatic arterial chemo-embolization). No comparative effectiveness analysis exists evaluating hepatectomy versus radiotherapy versus systemic chemotherapy versus combined multimodal approaches specifically in atypical and anaplastic hepatic meningioma metastases.

  The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy · 2022 · DOI

• The pathobiological mechanisms underlying hepatic tropism in metastatic meningioma remain unexplored. While cerebrospinal fluid dissemination pathways and multivisceral spread patterns are described (references 11, 14), no molecular profiling or gene expression studies have identified the specific cellular adhesion molecules, growth factors, or liver microenvironment interactions that facilitate meningioma colonization of hepatic tissue.

  The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy · 2022 · DOI

• The diagnostic utility of 68Ga-DOTATATE PET/CT and somatostatin receptor scintigraphy for detecting metastatic meningioma to the liver has been reported in only scattered cases (references 24, 26, 28). A comparative diagnostic accuracy study evaluating these nuclear imaging modalities against conventional imaging (CT/MRI) and histopathological confirmation in a prospective cohort is needed to establish standardized staging protocols for metastatic meningioma.

  The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy · 2022 · DOI

• The temporal dynamics of hepatic metastasis development in meningioma patients require systematic investigation. Current literature presents isolated case reports spanning decades (from 1974 to 2020), but no longitudinal cohort study has characterized the interval between initial cranial meningioma resection and hepatic metastasis detection, or the progression patterns of liver involvement in atypical versus anaplastic meningiomas.

  The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy · 2022 · DOI

• BACKGROUND Spontaneous regression of meningiomas is rare, and the association between tumor growth dynamics and progressive calcification remains not well elucidated.

  Biphasic growth and subsequent spontaneous regression of posterior fossa meningioma with progressive calcification: illustrative case · 2026 · DOI

• The optimal cranial approach for giant olfactory groove meningiomas (OGMs) remains controversial, particularly when tumors distort the anterior skull base or extend across compartments.

  GIANT OLFACTORY GROOVE MENINGIOMAS: A RETROSPECTIVE SINGLE-CENTER COMPARISON OF PTERIONAL AND BICORONAL SURGICAL APPROACHES · 2026 · DOI

• Variability in tumor size, the extent of peritumoral edema, and postoperative changes can introduce noise into lesion maps, and rigorous statistical approaches are essential to ensure validity.

  Extending voxel-based lesion mapping to neurosurgical oncology: applications in intracranial meningiomas · 2026 · DOI

• Comparing the distribution pattern of meningiomas with radiogenomic mutation maps could yield powerful multidimensional models of tumor behavior, but this integration has not yet been systematically explored.

  Extending voxel-based lesion mapping to neurosurgical oncology: applications in intracranial meningiomas · 2026 · DOI

• The epidemiological link between hormone use and development of meningioma remains inconclusive; however, case reports suggest that exogenous hormones influence the in vivo behavior of meningioma.

  Recurrence and Progression of Meningioma in Male-to-Female Transgender Individuals During Exogenous Hormone Use · 2013 · DOI

Most-cited papers in Meningioma and schwannoma management

• Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma · Nature Medicine · 2024 · 74 citations
• Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base · Reports of Practical Oncology & Radiotherapy · 2017 · 14 citations
• Secondary brain tumors after cranial radiation therapy: A single-institution study · Reports of Practical Oncology & Radiotherapy · 2020 · 13 citations
• Recurrence and Progression of Meningioma in Male-to-Female Transgender Individuals During Exogenous Hormone Use · International Journal of Transgenderism · 2013 · 12 citations
• Microsurgery for Vestibular Schwannoma via Retrosigmoid Transmeatal Approach with Intraoperative Monitoring Techniques · Balkan Medical Journal · 2021 · 8 citations
• The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy · Romanian Journal of Morphology and Embryology · 2022 · 5 citations
• Adults brain tumor in Cipto Mangunkusumo General Hospital: A descriptive epidemiology · Romanian Journal of Neurology · 2021 · 2 citations
• Comment on Chen et al. Vestibulo-Ocular Reflex Results in Patients with Intralabyrinthine Schwannomas: Case Series with a Literature Review. Diagnostics 2025, 15, 2093 · Diagnostics · 2026 · 1 citations
• Probabilistic MRI Maps for the Presentation and Management of Intracranial Meningiomas · Radiology Imaging Cancer · 2026 · 1 citations
• Is a “floater” always a floater? Case report and short review of sphenoid meningiomas’ ocular manifestation · Klinika Oczna · 2024 · 1 citations

Most recent work

• Comment on Chen et al. Vestibulo-Ocular Reflex Results in Patients with Intralabyrinthine Schwannomas: Case Series with a Literature Review. Diagnostics 2025, 15, 2093 · Diagnostics · 2026
• Probabilistic MRI Maps for the Presentation and Management of Intracranial Meningiomas · Radiology Imaging Cancer · 2026
• Extending voxel-based lesion mapping to neurosurgical oncology: applications in intracranial meningiomas · Frontiers in Oncology · 2026
• Effectiveness and safety of proton therapy in intracranial meningioma treatment: a systematic review and meta-analysis · Neurosurgical Review · 2026
• Safety profile and surgical outcomes of the endoscopic transorbital approach as a skull base surgical corridor: a systematic review and meta-analysis · Neurosurgical Review · 2026
• Feasibility of Deep Learning-Based Segmentation of the Facial and Vestibulocochlear Nerves on High-Resolution Magnetic Resonance Imaging · Cureus · 2026
• Prior surgical resection is a predictor of facial nerve function decrement after radiosurgery for vestibular schwannomas · Clinical Neurology and Neurosurgery · 2026
• Outcomes of Gamma Knife radiosurgery for meningiomas overlying the motor cortex · Journal of Clinical Neuroscience · 2026
• INTRA-OSSEOUS MENINGIOMA – A RARE ENTITY · Zenodo (CERN European Organization for Nuclear Research) · 2026
• Deep Learning for Automated Meningioma Segmentation: Toward Clinical Integration and Workflow Efficiency · medRxiv · 2026

Related topics in Medicine