Recurrent Meningiomas Research Articles

DNA methylation provides diagnostic value for meningioma recurrence in clinical practice.

Meningiomas are the most common intracranial tumors. Recent advancements in the genetic profiling of tumors have allowed information including DNA copy number analysis, mutational analysis, and RNA sequencing to be more frequently reported, in turn allowing better characterization of meningiomas. In recent years, analysis of tumor methylomes that reflects both cell-origin methylation signatures and somatically acquired DNA methylation changes has been utilized to better classify meningiomas with great success. We report DNA methylation profiling on meningiomas from 17 patients. Formalin-fixed paraffin-embedded (FFPE) meningioma tumor samples were processed, loaded onto the Infinium Methylation EPIC array, and scanned using the Illumina IScan system. Raw IDAT files were processed through the the CNS tumor classifier developed by the Molecular Neuropathology group at the German Cancer Research Center (DKFZ). Corresponding genomics were captured using targeted sequencing panels. Among the meningioma samples, 13 samples were classified as "benign," two samples as "intermediate," and the remaining three samples (from two patients) as "malignant," based on previously validated classification algorithms. In addition to tumor methylation profiling, we also present information that includes patient demographics, clinical presentations, tumor characteristics (including size and location), surgical approaches, and mutational analysis. The two patients who provided the samples with "malignant" methylation classifications had tumor recurrence, reflecting a more aggressive disease course. In accordance with prior reports, our case series provides support that tumor DNA methylation profiling adds meaningful classification information and may be beneficial to incorporate in clinical practice. Our report also reveals that DNA methylation combined with WHO histology classification can more accurately predict tumor behavior than WHO classification alone.

Polycystin-2 Associates With Malignancy in Meningiomas.

The involvement of polycystin-2 (PC2) in cell survival pathways raises questions about its role in carcinogenesis. Aberrant expression of PC2 has been associated with malignancy in various tumors. No evidence exists referring to PC2 expression in meningiomas. The aim of this study was to investigate the expression levels of PC2 in meningiomas and compare them with normal brain samples including leptomeninges. PC2 immunohistochemical expression was quantitatively analyzed in archival tissue from 60 patients with benign (WHO grade 1) and 22 patients with high-grade (21: WHO grade 2 and 1: grade 3) meningiomas. Specifically, the labeling index [the percentage of positive (labeled) cells out of the total number of tumor cells counted] was determined. PC2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. PC2 immunostaining was not detected in the leptomeninges. Gene expression analysis revealed increased levels of PC2 in WHO grade 1 ( P = 0.008) and WHO grade 2 ( P = 0.0007) meningiomas compared with that of normal brains. PC2 expression was significantly associated with an ascending grade of malignancy by both immunohistochemistry and quantitative real-time polymerase chain reaction ( P < 0.05). Recurrent meningiomas displayed higher levels of PC2 compared with primary meningiomas ( P = 0.008). Although no significant association of PC2 with the overall survival of the patients was found ( P > 0.05), it was noticed that the patients with WHO grade 2 meningiomas with low expression of PC2 survived longer compared with the patients with WHO grade 1 meningioma with high expression of PC2 (mean survival 49.5 and 28 months, respectively). The above results indicate a possible association of PC2 with malignancy in meningiomas. However, the mechanisms underlying PC2 implication in meningioma pathogenesis should be further elucidated.

Advances in Boron Neutron Capture Therapy (BNCT) for Recurrent Intracranial Meningioma.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

Estrogen and progesterone in meningioma: Bridging the gap of knowledge

Meningiomas are primary central nervous system tumor with the highest prevalence. Meningiomas have a high recurrence rate in the same location. One of the factors thought to be associated with the frequency of meningiomas is hormonal status. However, research on this subject is still controversial. This review aims to discuss the effect of sex hormones on meningiomas. Sex hormones, especially progesterone, have been shown to play a role in tumorigenesis and meningioma recurrence. Progesterone receptors also play a role in meningioma recurrence where a low number of receptors indicates a poor prognosis. However, the molecular relationship between meningiomas at low progesterone receptor expression is still unknown. Further research is still needed to determine the role of sex hormones, especially progesterone, and their receptors, in both tumorigenesis and meningioma progression. This research ensures that new science in the field of endocrinology can be utilized for both primary preventive, secondary preventive, and therapeutic strategies for meningiomas.

Conventionally fully fractionated Gamma Knife Icon re-irradiation of primary recurrent intracranial tumors: the first report indicating feasibility and safety.

With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8-3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors' preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/β ratio of 2 for late normal tissue toxicity and 10 for the tumor. A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator-based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30-63.4) Gy delivered in a median (range) of 28 (10-38) fractions with GKI. The median (range) target volume was 6.58 (0.2-46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9-181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0-111.5) Gy, 58.9 (6.3-102.9) Gy, and 59.9 (36.7-127.3) Gy, respectively. At a median (range) follow-up of 15 (6-42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

Meningiomas and Somatostatin Analogs: A Systematic Scoping Review on Current Insights and Future Perspectives.

Meningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's surgical and radiation-based treatment are not without complications. No drugs specific for meningiomas are hitherto approved and patients with inoperable or recurrent meningioma are left with few treatment options. Somatostatin receptors are previously detected in meningiomas and may inhibit growth when stimulated by somatostatin. Hence, somatostatin analogs could provide a targeted drug therapy. The aim of this study was to compile the current insights of somatostatin analogs for patients with meningioma. This paper adheres to the PRISMA extension for Scoping Reviews. A systematic search was conducted in the search databases PubMed, Embase via Ovid, and Web of Science. Seventeen papers adhered to the inclusion and exclusion criteria, and critical appraisal was conducted. The overall quality of evidence is low, as none of the studies were randomized or controlled. Various efficacy of somatostatin analogs is reported, and adverse effects are sparse. Due to the beneficial effects reported by some studies, somatostatin analogs may offer a novel last-option treatment for severely ill-patients. Nonetheless, only a controlled study, preferably a randomized clinical trial, could clarify the efficacy of somatostatin analogs.

Evaluating risk of recurrence in patients with meningioma.

Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. In this study, the authors aimed to test conventional predictors of meningioma recurrence, histopathology variables for which there exists some controversy (brain invasion), as well as a novel molecular-based location paradigm. This is a retrospective study of a consecutive series of patients with WHO grade I-III meningioma resected at The University of Texas Southwestern Medical Center between 1994 and 2015. Time to meningioma recurrence (i.e., recurrence-free survival [RFS]) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. A total of 703 consecutive patients with meningioma underwent resection at The University of Texas Southwestern Medical Center between the years 1994 and 2015. A total of 158 patients were excluded for insufficient follow-up (< 3 months). The median age of the cohort was 55 years (range 16-88 years) and 69.5% (n = 379) were female. The median follow-up was 48 months (range 3-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade I meningioma (Cox univariate HR 0.92, 95% CI 0.44-1.91, p = 0.82, power 4.4%). Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence (n = 52, Cox univariate HR 0.21, 95% CI 0.03-1.61, p = 0.13, power 71.6%). Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < 0.01, log-rank test). In patients with high-grade meningiomas (WHO grade II or III), location was predictive of RFS (p = 0.03, log-rank test), with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. The data suggest that brain invasion does not increase the risk of recurrence in otherwise WHO grade I meningioma. Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model. Larger studies are needed to confirm these findings.

Specific gene expression signatures of low grade meningiomas.

Meningiomas are the most common primary central nervous system (CNS) tumors in adults, representing approximately one-third of all primary adult CNS tumors. Although several recent publications have proposed alternative grading systems of meningiomas that incorporate genomic and/or epigenomic data to better predict meningioma recurrence and progression-free survival, our understanding of driving forces of meningioma development is still limited. To define gene expression signatures of the most common subtypes of meningiomas to better understand cellular processes and signaling pathways specific for each tumor genotype. We used RNA sequencing (RNA-seq) to determine whole transcriptome profiles of twenty meningiomas with genomic alterations including NF2 inactivation, loss of chr1p, and missense mutations in TRAF7, AKT1 and KLF4. The analysis revealed that meningiomas with NF2 gene inactivation expressed higher levels of BCL2 and GLI1 compared with tumors harboring TRAF7 missense mutations. Moreover, NF2 meningiomas were subdivided into two distinct groups based on additional loss of chr1p. NF2 tumors with intact chr1p were characterized by the high expression of tumor suppressor PTCH2 compared to NF2 tumors with chr1p loss. Taken together with the high expression of BCL2 and GLI1, these results suggest that activation of Sonic Hedgehog pathway may contribute to NF2 meningioma development. In contrast, NF2 tumors with chr1p loss expressed high levels of transcription factor FOXD3 and its antisense RNA FOXD3-AS1. Examination of TRAF7 tumors demonstrated that TRAF7 regulates a number of biomechanically responsive genes (KRT6a, KRT16, IL1RL1, and AQP3 among others). Interestingly, AKT1 and KLF4 meningiomas expressed genes specific for PI3K/AKT signaling pathway, suggesting overlapping gene signatures between the two subtypes. In addition, KLF4 meningiomas had high expression of carcinoembryonic antigen family members CEACAM6 and CEACAM5. Each group of meningiomas displayed a unique gene expression signature suggesting signaling pathways potentially implicated in tumorigenesis. These findings will improve our understanding of meningioma tumorigenesis and prognosis.

An MDT treatment of extremely proptosis caused by the recurrent meningioma

Meningiomas are the most common primary tumors of the central nervous system and are more common in female patients. Most meningiomas are benign, but the tumor infiltration can often lead to recurrence

Even heterozygous loss of CDKN2A/B greatly accelerates recurrence in aggressive meningioma.

Even heterozygous loss of CDKN2A/B greatly accelerates recurrence in aggressive meningioma.

Using 68 Ga-DOTATATE PET for Postoperative Radiosurgery and Radiotherapy Planning in Patients With Meningioma: A Case Series.

For patients with either an incompletely resected meningioma or recurrence after surgery, stereotactic radiosurgery is frequently used. MRI is typically used for stereotactic radiosurgery targeting, but differentiating tumor growth from postoperative change can be challenging. 68 Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2, has been shown to be a reliable meningioma biomarker. To evaluate the impact of 68 Ga-DOTATATE on treatment planning in patients who had previously undergone meningioma resection. We present a consecutive case series of 12 patients with pathology-proven meningioma who received a 68 Ga-DOTATATE PET between April 2019 and April 2021. Treatment planning was performed first using MRI. DOTATATE-PET images were then used to assess accurate tumor identification. Ten patients had WHO Grade 2 meningioma, and 2 patients had Grade 1 tumor. Eight patients had recurrent meningiomas, and 4 patients had newly diagnosed disease. Overall, 68 Ga-DOTATATE PET scans altered previously formulated treatment plans in 5 of 12 patients. In addition, 9 of 12 patients had disease foci not appreciated on MRI. In this series, incorporating 68 Ga-DOTATATE PET imaging had clinical utility for most patients in whom it was used. It proved particularly adept in demonstrating intraosseous meningiomas, differentiating recurrence from postoperative changes, and identifying subcentimeter disease foci. It is an imaging modality that our center will continue to use as a means of improving postoperative treatment plans after the surgical resection of meningiomas.

Recurrent grade III anaplastic meningioma metastasising to the humerus: a case report

Meningiomas are usually slow growing neoplasms that follow a benign clinical course. However, atypical and anaplastic meningiomas can show more aggressive behaviour and have the potential to metastasise. The most common sites for metastases are lung, spine, soft tissue, liver and bone. Bone metastases are exceedingly rare. We report a case of a 70-year-old man with a previous history of recurrent anaplastic meningioma (WHO grade III) with a pathological fracture of the left humerus. Histopathology aided by immunohistochemistry revealed metastatic meningioma.

Malignant intracerebral nerve sheath tumour of the brain presenting as a recurrent meningioma

A malignant intracerebral nerve sheath tumour (MINST) is a variant of MPNST arising inside the brain. They are very rare tumours that are aggressive and have strong metastatic potential. We report a case of a recurrent lesion in the brain in a 39 years male who presented as recurrent meningioma. It was finally reported as MINST with histopathology and immunohistochemistry. Surgical excision is the treatment of choice. The patient is on follow-up after an uneventful surgical excision. To the best of our knowledge, very few cases of malignant intracerebral nerve sheath tumours have been reported so far in the literature. This case is presented not only for its rarity but also to highlight that this aggressive tumour needs to be kept in mind while diagnosing such lesions with these histomorphological findings.

The Role of Pharmacotherapy in Treatment of Meningioma: A Systematic Review.

The safety and efficacy of various pharmacotherapeutic regimens on refractory meningiomas have been the focus of investigations. We present a comprehensive review of the previous efforts and the current state of ongoing clinical trials. A PRISMA-compliant review of the MEDLINE and ClinicalTrial.gov databases of the National Library of Medicine were performed. The primary outcomes of interest for included articles were radiographic response, overall survival, progression-free survival, six-month progression-free survival, and adverse events. Overall, 34 completed trials and 27 ongoing clinical trials were eligible. Six-month progression-free survival was reported in 6-100% of patients in the completed studies. Hematological disorders were the most common adverse events. Of the ongoing clinical trials identified, nine studies are phase I clinical trials, eleven are phase II trials, two are phase I and II trials, one is phase II and III, and two trials do not have a designated phase. Currently, there is no effective chemotherapy for refractory or recurrent meningiomas. Several promising targeted agents have been developed and are currently being investigated in the hope of identifying novel therapeutic strategies for the treatment of this pathology.

Analysis of the common complications and recurrence-related factors of superior parasagittal sinus meningioma.

Parasagittal meningioma resection is prone to postoperative complications and tumor recurrence because the tumor invades the superior sagittal sinus. This study aimed to clarify the incidence of perioperative complications and the recurrence of superior sagittal paranasal meningiomas and explored potential predictors in this context. The study retrospectively reviewed the clinical, imaging, and follow-up data of parasagittal meningiomas among patients who underwent microsurgical resection in the authors' institution from January 2008 to December 2017. Univariate and multivariate logistic regression analyses were conducted to explore independent predictors of perioperative complications and tumor recurrence. A total of 212 parasagittal meningioma patients were included in this study. The incidence of perioperative complications was 23.6% (50/212), and perioperative death occurred in 6 (2.8%) patients. In univariate and multivariate logistic regression analyses of perioperative complications, peritumoral edema ≥1 cm (odds ratio [OR] 2.163, 95% confidence interval [CI] 1.057-4.428, P = 0.035) and the Sindou invasion Class V-VI(OR0.018, 95% CI 1.248-11.064, P = 0.018) were independent predictors. After an average of 83 (39-154) months of clinical follow up among the living 206 patients, 22 (10.7%) patients showed tumor recurrence. In univariate and multivariate logistic regression analyses of tumor recurrence, the Sindou invasion Class III-IV (OR 5.539, 95%CI 1.469-20.884, P = 0.011) and the Sindou invasion Class V-VI (OR 9.144, 95%CI 2.215-37.757, P = 0.002) were independent predictors. Peritumoral edema ≥1 cm and the Sindou invasion Class V-VI were the independent predictors of perioperative complications, and the Sindou invasion Class III-IV and the Sindou invasion Class V-VI were the independent predictors of tumor recurrence. The part of the parasagittal meningioma involving the sinus wall should be actively removed to the largest degree possible to reduce the recurrence rate.

Recent advances in the molecular prognostication of meningiomas.

Meningiomas are the most common primary intracranial neoplasm. While traditionally viewed as benign, meningiomas are associated with significant patient morbidity, and certain meningioma subgroups display more aggressive and malignant behavior with higher rates of recurrence. Historically, the risk stratification of meningioma recurrence has been primarily associated with the World Health Organization histopathological grade and surgical extent of resection. However, a growing body of literature has highlighted the value of utilizing molecular characteristics to assess meningioma aggressiveness and recurrence risk. In this review, we discuss preclinical and clinical evidence surrounding the use of molecular classification schemes for meningioma prognostication. We also highlight how molecular data may inform meningioma treatment strategies and future directions.

In Reply: Transcriptomic Profiling Revealed Lnc-GOLGA6A-1 as a Novel Prognostic Biomarker of Meningioma Recurrence.

To the Editor: We read with great interest the letter to the editor by Dr Wang titled “Letter: Transcriptomic Profiling Revealed Lnc-GOLGA6A-1 as a Novel Prognostic Biomarker of Meningioma Recurrence”1 and are deeply appreciative of his interest in our study.2 The extent of surgical resection is among the most important predictors of meningioma recurrence.3,4 In our retrospective study, the extent of resection was evaluated using the Simpson grade (SG) scale,5 which has been widely used to grade meningioma resection since 1957. Total resection, defined as removal of the whole tumor along with the attached dura mater and potentially affected bone, is unfeasible in many patients because of a high risk of brain injury, disrupting the blood supply to the central nervous system or simply because the lesion's location is inaccessible.6 The SG scale5 was therefore introduced into clinical practice as a parameter describing the extent of meningioma resection, which can be determined either intraoperatively by the surgeon or postoperatively by follow-up imaging. SG I denotes total resection and is associated with the lowest probability of recurrence. SG II-III denote gross total resections with the tumor itself removed completely but dura mater left in place with (SG II) or without (SG III) coagulation. SG IV denotes incomplete resection of the tumor, with a risk of recurrence almost 5 times higher than for SG I. Finally, SG V indicates that only a biopsy and/or decompression of the affected area were performed.7 MRI is used at most centers for accurate preoperative, intraoperative, and postoperative patient management, including assessing the extent of meningioma resection. A recent publication reported high concordance between SG classification and MRI assessment of tumor resection (up to 75%).8 Moreover, in prognostic value, the difference between SG IV and SG I-III is more significant than any other difference between SG categories, and SG IV resections are readily distinguished from those of lower grades through intraoperative assessment by a neurosurgeon. Consequently, despite the clear value of postoperative MRI for assessing the extent of resection, it is clear that clinically useful assessments can be obtained using the SG scale alone. Intraoperative MRI is also a powerful tool but can be problematically time consuming, and its practical utility may be limited by technical and economic factors, especially because it should ideally be applied in conjunction with other imaging methods and molecular analyses.9 However, perhaps the most important point relating to our study and Dr Wang's comments is that the inherent limitations of retrospective studies mean that evaluations based on follow-up MRI imaging are often simply unavailable in studies analyzing the prognostic and predictive value of novel genomic or proteomic biomarkers using archived tumor tissue samples.10-12 It therefore seems that evaluating the extent of tumor resection by MRI will be more viable in prospective studies than in retrospective studies based on follow-up data sets spanning 15 to 20 years.

Recurrence of Solitary Spinal Meningothelial Meningioma in a Dog

Recurrence of Solitary Spinal Meningothelial Meningioma in a Dog

MicroRNA 200a as a histologically independent marker for meningioma recurrence: Results of a four microRNA panel analysis in meningiomas.

Meningiomas are mostly benign neoplasms of the central nervous system. Nevertheless there are recurrences in about 20% after surgical resection. Previous studies could reveal several predictors of meningioma recurrence. Tumor progression often is associated with a specific pattern of chromosome losses. Our study investigated the potential function of selected microRNAs as markers of tumor progression. By real-time polymerase chain reaction the expressions of microRNA 21-3p, 34a-3p, 200a-3p, and 409-3p were analyzed in solid tumor and in blood samples of 51 meningioma patients as well as in blood samples of 20 healthy individuals. Additionally, aberrations of parts of chromosomes 1, 14, 18, and 22 were analyzed by FISH. Tumor and blood samples were statistically analyzed, using Spearman's rank correlation coefficient as well as Mann-Whitney U- and Kruskal-Wallis-Test. MicroRNA 200a showed significantly lower expressions in recurrent meningiomas than in newly diagnosed ones. MicroRNA 409 in meningiomas was correlated significantly with tumor volume and showed a significant negative correlation with patient age. Significance was found between the expression patterns of microRNAs 34a and 200a with the respective aberrations of chromosome 1p and the microRNA 409 with aberration of chromosome 14. In the male cohort the expression of microRNA 200a in blood was significantly upregulated in patients compared to healthy volunteers. By our research the function of microRNA 200a was proved to detect meningioma patients by liquid biopsy. We detected microRNA 200a as a new biomarker to indicate meningioma recurrences. Future transferability to blood could be important for patient follow-up.

Resection of Anaplastic Meningioma via Combined Craniofacial Approach

Introduction: Meningiomas are common and mostly benign intracranial tumors but may show a histological progression to malignancy. The mechanism of malignant transformation remains unclear. Malignant meningiomas usually bear a high recurrence rate and unfavorable prognosis; hence, multiple surgical resections are required for the treatmentCase Presentation: A 41-year-old woman with a prior history of craniotomy at another center six years ago with Meningioma Grade 1 presented to our institution with new neurological symptoms. The magnetic resonance image demonstrated a large frontal base mass that extended to the nasal cavity with diffuse contrast enhancement and extensive surrounding edema. A craniofacial approach combined with a bifrontal approach was performed in multistage tumor resection. The tumor and the infiltrated dura were radically removed. The histopathology demonstrated an Anaplastic Meningioma. The patient also underwent radiation therapy.Conclusion: Treatment of recurrent meningioma with anaplastic histology remains challenging because recurrence rates remain high with a poor prognosis.