RESUMEN

Background: We sometimes encounter refractory meningioma cases that are difficult to control, even after achieving a high resection rate or following radiation therapy (RT). In such cases, additional surgical resection might be attempted, but reports regarding outcomes of re-do surgery for recurrent meningiomas are scarce. Methods: This study was a retrospective review of patients who underwent re-do surgery for recurrent meningiomas. The risks of re-doing surgery were statistically analyzed. A comparative analysis between the patients who underwent primary surgery for intracranial meningiomas was also performed. Twenty-six patients underwent re-do surgeries for recurrent meningiomas. Results: At first re-do surgery, gross total resection was achieved in 20 patients (77%). The disease-free survival rate after the first re-do surgery was calculated as 73/58/44% at 1, 2, and 5 years, respectively. A significant factor affecting longer disease-free survival was WHO Grade 1 diagnosis at first re-do surgery (p = 0.02). Surgery-related risks were observed in 10 patients presenting a significant risk factor for skull base location (p = 0.04). When comparing with the risk at primary surgery, the risks of surgical site infection (p = 0.04) and significant vessel injury (p < 0.01) were significantly higher for the re-do surgery. Conclusions: Re-do surgery could increase surgery-related risks compared to the primary surgery; however, it could remain a crucial option, while the indication should be carefully examined in each case.

RESUMEN

INTRODUCTION: Meningiomas represent the most common primary neoplasms of the central nervous system (CNS). 20% present with atypical (WHO grade II) or malignant (grade III) meningiomas, which show aggressive biologic behavior and high recurrence. Although surgical resection and radiation therapy are the primary treatment options for these tumors, there is a subgroup of patients who do not respond well to or are poor candidates for these approaches, leading to the exploration of systemic therapies as an alternative. AREAS COVERED: The literature on different therapeutic groups of systemic drugs for recurrent meningiomas is reviewed, with a focus on the different molecular targets. Past and current ongoing clinical trials are also discussed. EXPERT OPINION: To date, there is no recognized treatment that has demonstrated a substantial increase in progression-free or overall survival rates. Nonetheless, therapies targeting anti-VEGF have exhibited more encouraging results in general. The examination of genomic and epigenomic traits of meningiomas, along with the integration of molecular markers into the latest WHO tumor grading system, has provided valuable insights. This has opened avenues for exploring numerous intracellular and extracellular pathways, as well as mutations, that have been targeted in ongoing clinical trials.

Asunto(s)

RESUMEN

Systemic treatment approaches are urgently needed for a subset of meningioma patients who do not achieve local tumor control with surgery and radiotherapy. Classical chemotherapy or anti-angiogenic agents exert only very limited activity in these tumors. Long-term survival of patients with advanced metastatic cancer following treatment with immune checkpoint inhibitors, i.e., monoclonal antibodies designed to unleash suppressed anticancer immune responses, has fostered hopes for benefit from similar approaches in patients with meningiomas that recur after standard local therapy. Moreover, a plethora of immunotherapy approaches beyond these drugs have entered clinical development or clinical practice for other cancer entities, including (i) novel immune checkpoint inhibitors that may act independently of T cell activity, (ii) cancer peptide or dendritic cell vaccines to induce anticancer immunity utilizing cancer-associated antigens, (iii) cellular therapies utilizing genetically modified peripheral blood cells to directly target cancer cells, (iv) T cell engaging recombinant proteins that link tumor antigen-binding sites to effector cell activating or recognition domains, or to immunogenic cytokines, and (v) oncolytic virotherapy utilizing attenuated viral vectors designed to specifically infect cancer cells, seeking to elicit systemic anticancer immunity. This chapter provides an overview of the principles of immunotherapy, summarizes ongoing immunotherapy clinical trials in meningioma patients, and discusses the applicability of established and emerging immunotherapy concepts to meningioma patients.

Asunto(s)

RESUMEN

Meningioma occurs most frequently as a benign tumor central nervous system that is common in old females. Radiation exposure and deletion of the NF2 gene are known risk factors. However, there is no consensus about the role of sex hormones. Meningiomas are usually benign tumors, but 6% can be anaplastic or atypical. Most asymptomatic patients do not require treatment, but complete surgical resection is recommended for symptomatic patients. If a tumor returns after being resected previously, it is recommended to be resected, followed by radiotherapy in some cases. Meningiomas (benign, atypical, and malignant) recurring after standard treatment fails could be treated with hormone therapy, chemotherapy, target therapy, and calcium channel blockers.

RESUMEN

PURPOSE: To determine if loss of H3K27me3 could predict higher risk of re-recurrence in recurrent meningiomas. METHODS: A retrospective, single-center cohort study was performed for patients who underwent resection of recurrent grade 1 (N = 132) &2 (N = 32) meningiomas from 2009 to 2013. Association of H3K27me3 staining and clinical parameters was analyzed. Additionally, H3K27me3 staining was performed from 45 patients whose tumors recurred and were resected during the follow-up, to evaluate H3K27me3 change during tumor progression. Survival analysis was performed as well. RESULTS: Loss of H3K27me3 expression was observed in 83 patients, comprising 63 grade 1 (47.7%) and 20 grade 2 patients (62.5%). Both grade 1 (p < 0.001) and grade 2 recurrent meningiomas (p < 0.001) had a higher frequency of H3K27me3 loss, compared to de novo meningiomas. 8 of 27 tumors with retained H3K27me3 lost H3K27me3 during re-recurrence (29.6%), while no gain of H3K27me3 was observed in progressive disease from 18 tumors with H3K27me3 loss. Loss of H3K27me3 expression was associated with an earlier re-recurrence in recurrent meningiomas grade 1 and 2 (p < 0.001), and was an independent prognostic factor for PFS in recurrent grade 1 meningiomas (p = 0.005). CONCLUSION: Compared to primary meningiomas, recurrent meningiomas more predominantly had loss of H3K27me3 expression, and further loss can occur during the progression of recurrent tumors. Our results further demonstrated that loss of H3K27me3 predicted shorter PFS in recurrent grade 1 and grade 2 meningiomas. Our work thus supports clinical testing of H3K27me3 in recurrent meningiomas WHO grade 1 and 2.

Asunto(s)

RESUMEN

Objectives The study aims to describe surgical management of an invasive cavernous sinus meningioma with a combination of several skull base approaches and bypass surgery. Design This study is an operative video. Results Resection of the recurrent skull base meningioma is still challenging, especially if the tumor involves or encases the carotid artery. Cerebral bypass surgery is an essential adjunct in the armamentarium of skull base surgery when vessel reconstruction is required. In this paper, we describe our experience of successful treatment of an invasive recurrent skull base meningioma, which involved the entire cavernous sinus and the internal carotid artery. A 46-year-old woman presented with a 2-year history of gradually worsening left-sided exophthalmos and visual impairment. The patient had previously undergone two craniotomies for resection of the left-sided spheno-orbital meningioma. Pathological diagnosis was chordoid meningioma, which is classified as an intermediate-grade meningioma. The second surgery had been performed for a rapid tumor regrowth 6 months after the first surgery. The patient lost her left-side vision after the second surgery. Aggressive tumor regrowth was confirmed with extension into the left orbit, infratemporal fossa, and cavernous sinus with engulfment of the carotid artery. A balloon occlusion test revealed intolerance of the left internal carotid artery occlusion. Considering the patient's age, tumor behavior, and intolerance of the carotid artery of the lesion side, we scheduled gross total resection of the tumor with vessel reconstruction. Conclusion Although cerebral bypass surgery is a technically challenging procedure, it plays an important role in the surgical management of the complex vessel-engulfing tumor. The link to the video can be found at https://youtu.be/GCmpxK3hW18 .

RESUMEN

Meningiomas are common intracranial tumors that can be treated successfully in most cases with surgical resection and/or adjuvant radiotherapy. However, approximately 20% of patients show an aggressive clinical course with tumor recurrence or progressive disease, resulting in significant morbidity and increased mortality. Despite several studies that have investigated different cytotoxic agents in aggressive meningiomas in the past several years, limited evidence of efficacy and clinical benefit has been reported thus far. Novel molecular alterations have been linked to a particular clinicopathological phenotype and have been correlated with grading, location, and prognosis of meningiomas. In this regard, SMO, AKT, and PIK3CA mutations are typical of anterior skull base meningiomas, whereas KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD, and BAP1 correlate with poor outcomes. Moreover, some actionable mutations, including SMO, AKT1, and PIK3CA, regulate meningioma growth and are under investigation in clinical trials. PD-L1 and/or M2 macrophage expression in the microenvironment provides evidence for the investigation of immunotherapy in progressive meningiomas.

RESUMEN

INTRODUCTION: Meningiomas that progress despite surgery and radiotherapy represent an unmet medical need. Expression of PD-1 and PDL-1 has been demonstrated in meningiomas and is proportional to tumor grade, suggesting a potential role for anti-PD-1/anti-PDL-1 inhibitor therapy. We explored the potential role of immunotherapy for recurrent meningiomas by describing progression-free survival (PFS) and overall survival (OS) in a single-center patient sample. METHODS: This is a retrospective chart review of patients with meningioma who were treated with PD-1 inhibitors at UPMC Hillman Cancer Center. Any patient over age 18 who received immunotherapy was included in this study. Patients received treatment until development of disease progression, intolerable toxicities or adverse events, death, or oncologist decision. Serial radiographic assessments were made every 3-6 months. RESULTS: Between January 2015 and November 2021, eight patients received anti-PD-1 therapy. All patients underwent tumor resection and radiosurgery, and four patients received prior systemic therapy. Six out of eight patients experienced symptomatic perilesional edema and three patients experienced exacerbation of seizures. Median PFS was 7 months (95% CI 1-24) and median OS was 1.75 years (95% CI 1.5-4.0). In patients with positive PD-1/PD-L1 expression, median PFS was 2 years and median OS was 3 years. CONCLUSION: Anti-PD-1 therapy was associated with a manageable safety profile in patients with recurrent meningiomas. Patients with WHO Grade III tumors and positive PD-1/PD-L1 expression were noted to have increased PFS and OS, suggesting a potential role for immunotherapy in these patients, but further studies are needed to investigate this in a larger patient population.

Asunto(s)

RESUMEN

INTRODUCTION AND IMPORTANCE: En-plaque-meningioma (EPM) is characterized by its flat growth along the bony contour. It accounts for 2-9% of all meningiomas. Very few grade II or III EPM cases were reported. Surgical resection of sphenoid wing EPM is especially challenging as the tumour tends to invade the cavernous sinus, and/or the orbit, and their neurovascular structures. Consequently, tumours in such locations have a higher rate of recurrence. We report the clinical course and management of a patient suffering a second recurrence of grade II EPM. The clinical course of grade II EPM, and the management of multiple recurrences of EPM are scarcely reported in the literature. CASE PRESENTATION: A 53-year-old male with a history of three previous surgeries for EPM presented with decreased vision in the right eye. Brain magnetic resonance imaging (MRI) showed progression of a sphenoid wing meningioma invading the left optic nerve, indicating a second recurrence of the tumour. CLINICAL DISCUSSION: We reviewed the literature discussing the clinical course of grade II EPM, and cases suffering multiple recurrences. Only a few cases were found with varying clinical course and management. In our case, surgical intervention was necessary to save the patient's vision. A modified orbitozygomatic craniotomy was performed. A small residual tumour invading the cavernous sinus was left for treatment with stereotactic radiosurgery. CONCLUSION: Sphenoid wing EPM is challenging pathology to manage, especially grade II tumours which are rarely encountered. Multimodality treatment with surgery and radiotherapy offers EPM patients the best chance of treatment.

RESUMEN

Treatment for recurrent intracranial neoplasms is often difficult and less standardized. Since its approval by the Food & Drug Administration (FDA), GammaTileTM (GT, GT Medical Technologies, Tempe, AZ), a novel collagen tile cesium brachytherapy, has been investigated for use in this population. This study presents the initial experience with the use of GT for patients with recurrent intracranial neoplasms at a tertiary referral center. A retrospective analysis of all patients with GT implantation from November 2019 to July 2021 was performed. Information regarding demographics, clinical history, imaging data, prior tumor treatment, dosing, surgical complications, and outcomes was collected. Twelve patients were included in this study. Pathologies included gliomas (five patients), meningiomas (five patients), and metastatic tumors (two patients). The median tumor volume treated was 24 cc (IQR: 21.2 - 31.3 cc), and patients had a median of 7.5 tiles implanted (IQR: 5.4 - 10.3). One patient had a delayed epidural hematoma requiring reoperation, which was unrelated to GT implantation. Median follow-up was seven months (IQR: 3 -10), with the longest follow-up time of 20 months. Two patients have had local disease recurrence and three patients have had systemic progression of their disease. Three patients are deceased with survivals of 2.9, 4.8, and 5.8 months. Collagen tile brachytherapy is a safe and viable option for patients with recurrent intracranial tumors. Our data are consistent with early results seen at other institutions. Long-term data with larger patient populations are required to assess efficacy, safety, and indications for the use of this novel technology.

RESUMEN

Meningiomas are the most common primary central nervous system tumors, as they can account for up to one-third of all primary brain tumors. Most meningiomas are benign, although up to one-fourth of such tumors are classified as atypical or malignant. Atypical and malignant meningiomas are associated with an increased risk of local recurrence and decreased overall survival. Our patient is a 57-year-old male with a history of recurrent malignant meningioma, with metastasis to the liver. He underwent multiple surgical interventions, radiation treatments, and systemic therapies for a malignant meningioma, ultimately requiring transfer to hospice care. Not only did a positive novel coronavirus (COVID-19) infection delay his ability to receive radiation therapy, the infection in itself may have had an impact on the course of care for this patient. Treatment targeting the patient's COVID-19 infection may have suppressed the immune system, and as a result, caused the progression of metastatic disease. Palliative care was needed in the setting of losing all functional goals for quality of life due to malignant neoplasm.

RESUMEN

Background En plaque meningiomas are a rare subtype of meningiomas that are frequently encountered in the spheno-orbital region. Characterized by a hyperostotic and dural invasive architecture, these tumors present unique diagnostic and treatment considerations. Objective The authors conduct a narrative literature review of clinical reports of en plaque meningiomas to summarize the epidemiology, clinical presentation, diagnostic criteria, and treatment considerations in treating en plaque meningiomas. Additionally, the authors present a case from their own experience to illustrate its complexity and unique features. Methods A literature search was conducted using the MEDLINE database using the following terminology in various combinations: meningioma , meningeal neoplasms, en plaque , skull base , spheno-orbital, and sphenoid wing . Only literature published in English between 1938 and 2018 was reviewed. All case series were specifically reviewed for sufficient data on treatment outcomes, and all literature was analyzed for reports of misdiagnosed cases. Conclusion En plaque meningiomas may present with a variety of symptoms according to their location and degree of bone invasion, requiring a careful diagnostic and treatment approach. While early and aggressive surgical resection is generally accepted as the optimal goal of treatment, these lesions require an individualized approach, with further investigation needed regarding the role of new therapies.

RESUMEN

BACKGROUND:  Over 200 human telomerase reverse transcriptase (hTERT) polymorphism combinations have been implicated in the development of cancer. This study aimed to evaluate hTERT mutations in meningioma tissue and its association with meningioma. MATERIAL AND METHODS: A total of 90 patients who underwent surgery between 2006 and 2015 and were histopathologically diagnosed with meningioma (WHO 2016) were included. RESULTS: Among the 90 participants included herein, 50 (55.5%) and 40 (44.5%) were female and male, respectively, with an average age of 56.2 ± 14 years. Mean Ki-67 values were 10.56% (SD 12.41, range 0-60), while the mean follow-up duration was 39.1 months (SD 26.3). Low- and high-grade patients had a mean Ki-67 score of 4.31% (SD 3.58, range 0-16) and 19.92% (SD 14.91, range 2-60) (p = 0.0001). Our results showed a moderate positive correlation between Ki-67 score and the presence of hTERT mutation (Pearson correlation test, r = 0.5161; p = 0.0001). Patients with an hTERT mutation > 30% had significantly higher risk for reoperation than those with lower levels of mutation (p = 0.016, chi square test). None of the patients requiring reoperation had an hTERT mutation < 10%. Moreover, high-grade patients had a 7.2 times higher risk of reoperation than those with an hTERT mutation > 30%. CONCLUSION: The presence of hTERT mutation, in addition to high Ki-67, indicated a more aggressive meningioma disease course and potentially increased risk of recurrence.

RESUMEN

OBJECTIVE: Meningiomas are among the most frequent intracranial tumors. Although the majority of meningiomas can be cured by surgical resection, up to 20% of the patients develop an aggressive clinical course with tumor recurrence or progressive disease.Cytogenetically, meningiomas frequently harbour a normal karyotype or monosomy of chromosome 22 as the sole anomaly. However, progression of meningiomas is associated with a non-random pattern of secondary losses of the chromosomes and chromosomal regions 1p, 6, 10, 14, 18, and 19. There is evidence, that loss of chromosome 17 might be involved in the clonal cytogenetic evolution of recurrent meningiomas. The aim of this study was to determine the role of deletions in the 17q chromosomal region in patients with recurrent meningiomas. RESULTS: The authors retrospectively reviewed all patients that underwent repeated surgery for recurrent meningiomas between 1999 and 2015 at the Department of Neurosurgery of the Saarland University Hospital. Patients were included in this study if tumor samples from two or more different meningiomas were available.A total of 7 patients underwent repeated surgery for recurrent meningiomas (4 males, 3 females, mean age: 45.4 years at the date of surgery) between 1999 and 2015. Collectively, 22 biopsies were analyzed with FISH (fluorescence-in-situ-hybridization) for the chromosomal region 17q23.3. In 20/22 (90.1%) specimens, the tumor samples harboured a significant deletion in the chromosomal region 17q (range: 10 to 63% of the cells). In 3/3 (100%) cases, deletion in the 17q chromosomal region was detectable in the primary tumor. In the tumor evolution, there was no steady in- or decrease in the percentage of this deletion. CONCLUSION: Deletion in the 17q chromosomal region was present in the patients' primary tumors as well as in late recurrences. Overall, a significant deletion in the 17q chromosomal region was detected in 90.1% of the tumors. Thus, the authors assume that deletion in the 17q chromosomal region displays rather an early event in meningioma progression. Accordingly, deletion in the 17q chromosomal region might clinically serve as a potential early marker for malignancy and a higher risk for recurrence in meningiomas.

RESUMEN

Meningiomas are primary CNS tumors that arise from the arachnoid layer of the meninges. Genomic sequencing has revealed that NF2 mutations are the most common genetic alteration seen in meningiomas. Meningiomas although usually low grade, can sometimes progress to high grade. A patient who had several recurrences of meningiomas since childhood presented with recurrent headaches. Imaging showed that he had another recurrence of a meningioma. He underwent surgery for resection of the meningioma and histopathology showed NF2 mutation. He was started on everolimus and bevacizumab with good effect. Studies have shown that NF-2 mutated meningiomas have a good response to everolimus and bevacizumab with increased progression-free survival time and progression-free survival time at 6 months.

RESUMEN

BACKGROUND: Extracranial metastasis from intracranial meningioma is a very rare condition. A current literature review reveals that only few cases are documented with extensive pulmonary involvement >10 years after initial intracranial meningioma resection. Diagnosis of pulmonary meningioma is often confirmed by computed tomography chest-guided core biopsies. The prognosis of extensive metastatic pulmonary meningioma, however, is unknown and there is no gold standard treatment option. CASE DESCRIPTION: We present a case of multiple pulmonary meningioma metastases developing 13 years after initial resection of left occipital parafalcine World Health Organization Grade I intracranial meningioma. CONCLUSION: There are no established guidelines for the optimal management or surveillance of extensive pulmonary metastatic meningioma. In patients with high-grade meningioma and multiple cannonball pulmonary lesions, metastatic meningioma should be considered as part of the differential diagnosis. Metastatic meningioma may occur even a decade after initial tumour resection.

RESUMEN

OBJECTIVE: We analyzed the applicability of the Simpson grading system to estimate the risk of tumor recurrence after microsurgery for recurrent meningiomas. METHODS: Correlations between the Simpson grade and the extent of resection (EOR) (gross total resection [Simpson grade I and II] vs. subtotal resection [Simpson grade ≥III]) with tumor relapse after microsurgery for meningioma recurrence were investigated compared with the findings in primary diagnosed tumors. Location-specific differences were further elucidated in subgroup analyses. RESULTS: A total of 829 individuals (88% in group A) with primary diagnosed meningioma and 109 patients with first postoperative recurrence (12% in group B) who underwent surgery were included. In group A, both Simpson grade (P = 0.003) and EOR (P < 0.001) correlated strongly with recurrence. In group B, Simpson grade correlated with tumor location (P = 0.030), and the risk of subtotal resection was greater in the posterior fossa (odds ratio, 5.26; P = 0.018) and skull base (odds ratio, 6.16; P = 0.002) meningiomas. Older age at tumor relapse (hazard ratio [HR], 1.05; P = 0.001), male sex (HR, 2.19; P = 0.02), and grade 2/3 histologic findings (HR, 2.18; P = 0.02). However, neither the Simpson grade nor dichotomized EOR correlated with further tumor recurrence. The frequency of postoperative complications was similar in both groups. CONCLUSIONS: Surgery for recurrent meningiomas is not generally associated with an increased risk of postoperative complications compared with resection of primary diagnosed tumors. However, the Simpson grade and EOR in recurrent meningiomas correlated poorly with further tumor relapse. The lower prognostic value of the tumor remnants left behind during microsurgery for recurrent meningiomas should be considered when operating on lesions that can be surgically challenging.

Asunto(s)

RESUMEN

Chordoid meningioma is a rare variant of meningioma, with a higher incidence in the young and a supposed association with Castleman's syndrome. They have an aggressive clinical course, and are assigned as WHO grade II meningiomas. To the best of our knowledge, 284 chordoid meningiomas have been reported in the literature. This series reporting 33 cases is the third largest series in published literature from a single Institution. We reviewed Clinico-pathological characteristics of 33 patients diagnosed with chordoid meningioma between 2001 and 2015 in our institution. Forty-one specimens were available for review of histopathological and immunohistochemical characteristics. There were 15 men and 18 women with mean age of 36.8 years (median 36 years, range 9-62 years) at diagnosis with three cases occurring in pediatric age group. The majority were supratentorial in location with 11 convexity, 1 falcine, 5 parasagittal, 1 intraventricular, skull base involvement in 12 with 4 being petroclival location and 3 had spinal lesions. Lymphoplasmacytic infiltrates were seen in 23 cases with majority being T cells. MIB index varied from 1 to 14%. Five patients received radiotherapy for residual lesion. Two patients died (recurrence-1, post-operative complication-1). Three patients were lost to follow up after surgery. The mean post-operative follow up period for the remaining was 55.3 months. Seven patients had recurrence of which three had it twice. This study adds to the pool of available data for better understanding of this variant of meningioma. These meningiomas occur in middle age; spinal lesions and pediatric cases are not uncommon. We did not find any association between surgery, post-operative radiotherapy and histopathological features with recurrence and survival. Small number of cases may be responsible for this statistical insignificance.

Asunto(s)

RESUMEN

The aim of this study was to evaluate long-term clinical outcome, prognostic factors and quality of life after adjuvant or definitive fractionated stereotactic radiotherapy (SRT) of meningioma WHO grade II and III or at recurrence. 131 patients with 138 meningioma (64 WHO grade II, 16 WHO grade III, 58 without histology) of the skull base, falx and convexity were treated between 01/2002 and 01/2015 at the Erlangen University Hospital by fractionated stereotactic radiotherapy (SRT) as primary treatment (adjuvant or definitive) and at recurrence. 53% (n = 53) lesions of patients with primary tumour received postoperative SRT and 47% (n = 47) as definitive treatment (without surgery). All 38 lesions (100%) of recurrent meningioma underwent surgery followed by SRT. SRT was mostly given in 28, 30 or 25 fractions to a median dose of 54.0 Gy in the reference point. Progression-free-survival at 8 years for patients with meningioma at primary treatment were significantly better with 100% for patients with definitive SRT (p = 0.008) or 85% for patients with adjuvant SRT (p = 0.009) compared to 42% after treatment (surgery + SRT) of recurrence. Progression-free-survival at 8 years for patients with SRT as adjuvant treatment after gross total resection of WHO grade II meningioma were significantly better at 83% (p = 0.016) compared to 46% after adjuvant SRT of recurrence. In 31% of patients after primary treatment and in 38.5% after recurrence treatment an improvement of pain symptoms was achieved. The favourable prognostic factor for better PFS at recurrence treatment was tumor location (skull base or convexity better compared to the falx). Postoperative SRT of WHO grade II meningioma after gross total resection (GTR) can effectively reduce recurrence risk.

Asunto(s)