Meningioma

Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

No abstract available

Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease.

Therefore, the benefit of treatment with 177Lu-DOTATATE in the current indication is questionable. In the absence of a validated systemic treatment, and considering a few case reports, treatment with 177Lu-PSMA could be investigated as an additional vectorized internal radiotherapy option.

MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

The study highlights PSH and perifocal oedema's significant effect on olfactory function in OGM patients but finds no link between olfactory impairment and tumour mutations, possibly due to the small sample size. This suggests that age and gender affect olfactory impairment. Additional research with a larger group of participants is needed to explore the impact of OGM driver mutations on olfactory performance.

We also perform a literature review of meningioma cases presenting as a neck mass and evaluated by FNA. Our case highlights the significant diagnostic challenges that can be caused by extracranial meningiomas on FNA and the importance of ancillary studies to avoid diagnostic pitfalls.

P4, N=20, Not yet recruiting, Weill Medical College of Cornell University

Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.

P2, N=200, Not yet recruiting, Emory University | Initiation date: Mar 2024 --> Jul 2024

Bilateral SOMs are usually found in female patients and are strongly associated with hormone replacement therapy. Early surgical management with gross-total resection is the most effective treatment in terms of recurrence and improves visual acuity. Given the slow progressive nature of bSOMs and their time to recurrence, which can be up to 10 years, long-term follow-up of patients is essential.

Deep learning features demonstrated a strong predictive capability for S100 protein expression (AUC = 0.85 ± 0.06) and had reasonable success in identifying NF-2 copy number loss (AUC = 0.74 ± 0.05). In conclusion, SWI showed promise in identifying NF-2 copy number loss and S100 protein expression by revealing neovascularization and microcalcification characteristics in meningiomas.

The lung, bone, liver and cervical lymph nodes are the most common sites of extracranial metastasis. According to the World Health Organization criteria, the most important predictive factor for recurrence and metastasis is the tumor grade.

Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

Preoperative seizures were frequently encountered in about every third patient with meningioma WHO grade 2 or 3. Patients presenting with peritumoral edema on preoperative imaging are at particular risk for developing tumor-related seizures. Tumor resection was highly effective in achieving seizure freedom.

Most meningioma mouse models are based on patient-derived xenografts and only recently have new genetically engineered mouse models of meningioma been developed that will aid in the systematic evaluation of specific mutations found in meningioma and their impact on tumor behavior. In this article, we review recent advances in the understanding of meningioma biology and classification and highlight the most common genetic mutations, as well as discuss new genetically engineered mouse models of meningioma.

P=N/A, N=186, Completed, Giselle Sholler | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Jan 2024 | Trial primary completion date: Jun 2025 --> Jan 2024

The DNA-methylation profile, using a t-distributed stochastic neighbor embedding analysis, evidenced that MAM (pure or associated with meningiomas) clustered in a separate group from pediatric meningiomas. The present results seem to suggest that MAM represents a neoplastic lesion and encourage the further study of similar additional series so that it may be included in a future WHO classification.

Female sex and spinal location predominance were statistically significant in PMs. NF2 mutation was an independent predictor for worse PFS of PMs. Of note, NF2 mutation was detected in all SPMs but in only 38.46% of CPMs, revealing a significant difference.

Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors.

P1, N=48, Active, not recruiting, Nader Sanai | Trial completion date: Jan 2024 --> Jan 2025

P=N/A, N=60, Recruiting, Massachusetts General Hospital | Phase classification: P1/2 --> P=N/A

In summary, our findings highlighted the intricate role of hsa_circ_0004872 in meningioma, shedding light on the regulatory mechanisms involving circ-RNAs in tumor progression. This positions hsa_circ_0004872 as a potential key regulatory factor in meningioma with implications for future therapeutic interventions.

P2, N=135, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC

P=N/A, N=179, Completed, Xiangya Hospital of Central South University

P1, N=68, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Mar 2025 --> May 2024

To detect pathological biomineralization, the meningioma tissue was studied using the methods of macroscopic description, histology, histochemistry, and immunohistochemistry, scanning electron microscopy with microanalysis, and transmission electron microscopy. A significantly higher level of caspase3 and features of the expression of osteoblastic markers (a lower level of OPG expression and a higher level of the presence of RANKL in group I, the absence of fluctuations in the expression of SPARC) may indicate a dystrophic type of development of biomineral deposits in meningiomas.

The identified metalloproteases may play a key role in the process of gliomagenesis and may represent potential targets for personalized therapy. However, as we have not confirmed the relationship between mRNA expression and protein levels in individual samples, it is therefore natural that the regulation of metalloproteases will be subject to several factors.

Additionally, NF2 is a potential biomarker for predicting the efficacy of immune checkpoint inhibitors therapy. Therefore, NF2 can be a promising diagnostic, prognostic, and immunotherapeutic biomarker for many types of tumors.

Employing human NF2-deficient meningioma lines, we compared mTOR inhibitors rapamycin (first-generation), INK128 (second-generation), and RMC-6272 (third-generation) using in vitro dose-response testing, cell-cycle analysis, and immunoblotting. Furthermore, in vivo studies in mice revealed effective blockage of meningioma growth by RMC-6272, compared with vehicle controls. Our study in preclinical models of NF2 supports possible future clinical evaluation of third-generation, investigational mTORC1 inhibitors, such as RMC-5552, as a potential treatment strategy for NF2.

These findings indicate that PgR antagonist may not be an effective alternative for treatment in patients with inoperable meningiomas. Furthermore, P63 immunopositivity may not be a sufficient grading tool for managing meningiomas in our population.

P1, N=27, Not yet recruiting, University of Nebraska | Trial completion date: Jan 2027 --> Apr 2027 | Initiation date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2026 --> Apr 2026

P1/2, N=38, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P2, N=37, Recruiting, Nancy Ann Oberheim Bush, MD | Trial completion date: Apr 2028 --> Apr 2029 | Trial primary completion date: Apr 2024 --> Apr 2025

The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.

We conclude with presenting case studies that identify both the clinical utility and informatic challenges of variant calling specific to gene panel sequencing e.g., i) the capture of potential targetable rare and novel indels and multivariant mutations in exons 19 and 20 of EGFR, and ii) a unique KIT tandem duplication event in a gastrointestinal stromal tumor (GIST). We demonstrate the value in precision oncology for multiple cancer types and how the capture of unique variants can provide better targeted treatment options to cancer patients.

In conclusion, leukoreduction appeared to offer some immune response protection in term of reducing mechanical ventilation timings and cytokine level changes.

The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [177Lu]Lu-DOTA-JR11 are warranted in meningioma patients.

The extent of resection and the Ki67-MIB1 represent the most important factors predicting shorter recurrence time of intracranial meningiomas. Patients with incomplete (Simpson grades III and IV) resection and high Ki67-MIB1 values, especially at non-skull base localization and with low PR values, need of a closer short-term clinical and radiological follow-up in the first years after surgery.

CLU might be a key brake of meningioma malignance by synchronous modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.

P=N/A, N=180, Enrolling by invitation, Central Hospital, Nancy, France

P2, N=72, Not yet recruiting, Nader Sanai | Initiation date: Oct 2023 --> Jun 2024