Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study.

PURPOSE: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort. METHODS: In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data. RESULTS: We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30). CONCLUSION: This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

PURPOSE: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. METHODS: We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. RESULTS: Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7-639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89-481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. CONCLUSIONS: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

Prognostic impact of clinical and radiological factors on leptomeningeal metastasis from solid cancers.

PURPOSE: The number of leptomeningeal metastasis (LM) patients has increased in recent years, as the cancer survival rates increased. An optimal prediction of prognosis is essential for selecting an appropriate treatment. The European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guidelines for LM proposed a classification based on the cerebrospinal fluid cytological findings and contrast-enhanced magnetic resonance imaging (MRI) pattern. However, few studies have validated the utility of this classification. This study aimed to investigate the prognostic factors of LM, including the radiological and cytological types. METHODS: We retrospectively analyzed the data of 240 adult patients with suspected LM who had undergone lumbar puncture between April 2014 and September 2021. RESULTS: The most common primary cancer types were non-small-cell lung cancer (NSCLC) (143 (60%)) and breast cancer (27 (11%)). Positive cytology results and the presence of leptomeningeal lesions on contrast-enhanced MRI correlated with decreased survival in all patients. Nodular lesions detected on contrast-enhanced magnetic resonance were a poor prognostic factor in cytology-negative patients, while contrast-enhanced patterns had no prognostic significance in cytology-positive patients. Systemic therapy using cytotoxic agents and molecular-targeted therapy after LM diagnosis correlated with prolonged survival, regardless of the cytology results. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment and systemic chemotherapy after LM improved the survival of EGFR-mutated and wild-type NSCLC patients with positive cytology results. CONCLUSIONS: This study validated the efficacy of prognostication according to the EANO-ESMO guidelines for LM. Systemic therapy after LM diagnosis improves the survival of NSCLC patients.

Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma.

Meningioma is the most common intracranial tumor, with generally favorable patient prognosis. However, patients with malignant meningioma typically experience recurrence, undergo multiple surgical resections, and ultimately have a poor prognosis. Thus far, effective chemotherapy for malignant meningiomas has not been established. We recently reported the efficacy of eribulin (Halaven) for glioblastoma with a telomerase reverse transcriptase (TERT) promoter mutation. This study investigated the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines, IOMM-Lee and HKBMM, were used in this study. The strong inhibition of cell proliferation by eribulin via cell cycle arrest was demonstrated through viability assay and flow cytometry. Apoptotic cell death in malignant meningioma cell lines was determined through vital dye assay and immunoblotting. Moreover, a wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. Intraperitoneal administration of eribulin significantly prolonged the survival of orthotopic xenograft mouse models of both malignant meningioma cell lines implanted in the subdural space (P < .0001). Immunohistochemistry confirmed apoptosis in brain tumor tissue treated with eribulin. Overall, these results suggest that eribulin is a potential therapeutic agent for malignant meningiomas.

Survival of brain tumour patients with epilepsy.

Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy; (ii) epilepsy without status epilepticus; and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. The main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus no epilepsy HR 2.30, CI 1.10-4.79, P = 0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy versus no epilepsy HR 2.16, CI 1.60-2.93, P < 0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumours.

Advances in targeted therapy in non-small cell lung cancer with actionable mutations and leptomeningeal metastasis.

WHAT IS KNOWN AND OBJECTIVE?: Leptomeningeal metastasis (LM) is a serious complication of advanced non-small cell lung cancer (NSCLC) that is diagnosed in approximately 3%-5% of patients. LM occurs more frequently in patients with NSCLC harbouring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements and is usually accompanied by a poor prognosis, with a median overall survival (OS) of several months if patients receive conventional treatments. However, tyrosine kinase inhibitor (TKI) therapy after LM diagnosis is an independent predictive factor for extended survival. Here, we aim to summarize the latest advances in targeted therapy for LM and provide patients with better treatment options. METHODS: By reviewing the recent progress of targeted therapy in NSCLC with LM, especially the efficacy of newer generation TKIs, we aim to provide clinicians with a reference to further optimize patient treatment plans. RESULTS AND DISCUSSION: Osimertinib was confirmed to have a several-fold higher CNS permeability than other EGFR-TKIs and was recommended as the preferred choice for patients with EGFR-positive LM whether or not they harboured the T790M mutation. Second-generation ALK-TKIs have a higher rate of intracranial response and can be positioned as front-line drugs in NSCLC with LM. However, the sequence in which ALK-TKIs are administered for effective disease control requires further evaluation. In addition, targeted therapy revealed a potential choice in patients with LM and rare mutations, such as ROS1 and BRAF. WHAT IS NEW AND CONCLUSIONS?: The development of therapeutic agents with greater CNS penetration is vital for the management of CNS metastasis from NSCLC, particularly in the EGFR-mutant and ALK-rearranged subtypes. Systemic therapy with newer generation TKIs is preferred as the initial intervention. This is because newer generation TKIs are designed to penetrate the blood-brain barrier and possess significantly higher intracranial activities. However, their further effectiveness is limited by inadequate blood-brain barrier penetration and acquired drug resistance. Further studies are needed to further understand the mechanisms underlying resistance to treatment.

Neuro-meningeal relapse in anaplastic large-cell lymphoma: incidence, risk factors and prognosis - a report from the European intergroup for childhood non-Hodgkin lymphoma.

Relapses involving the central nervous system (CNS) are rare in children and adolescents with ALK+ anaplastic large cell lymphoma (ALCL) treated with regimens including CNS prophylaxis. Early identification of patients at high-risk for CNS relapse would enable stratification and better adaptation of initial treatment especially in the light of the upcoming targeted therapies with limited CNS penetration. We analyzed clinical and histological data of all ALK+ALCL patients with CNS relapse registered in ALCL99-database with the aim to describe risk factors and outcome. Characteristics of patients with no relapse, relapse without CNS involvement and CNS relapse were compared. At a median follow-up of 8 years (0.05-18 years), a CNS involvement was reported at first or subsequent relapse in 26/618 patients. Median interval between initial diagnosis and first CNS relapse was 8 months (IQR 5.55-10.61/range 1.31-130.69). The 5-year cumulative risk of CNS relapse was 4% (95% CI 2.9-5.5). Bone marrow involvement, peripheral blasts and CNS involvement at diagnosis were more frequent in patients with CNS relapse than in patients with no relapse or with relapse with no CNS involvement. The treatment of CNS relapse was heterogeneous. The median survival after CNS relapse was 23.7 months. Eleven patients were alive at last follow-up. Three-year overall survival after CNS relapse was 48.70% (95% CI 30.52-67.23).

Metabolic alterations in meningioma reflect the clinical course.

BACKGROUND: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses. METHODS: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. RESULTS: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster. CONCLUSION: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.

Clear cell histology portends a worse prognosis than other WHO grade II histologies.

PURPOSE: Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas. METHODS: A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival. RESULTS: We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14-3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97-3.94), though this was not statistically significant. CONCLUSION: This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.

Extent of resection and survival outcomes in World Health Organization grade II meningiomas.

PURPOSE: WHO grade II meningiomas behave aggressively, with recurrence rates as high as 60%. Although complete resection in low-grade meningiomas is associated with a relatively low recurrence rate, the impact of complete resection for WHO grade II meningiomas is less clear. We studied the association of extent of resection with overall and progression-free survivals in patients with WHO grade II meningiomas. METHODS: A retrospective database review was performed to identify all patients who underwent surgical resection for intracranial WHO grade II meningiomas at our institution between 1995 and 2019. Kaplan-Meier analysis was used to compare overall and progression-free survivals between patients who underwent gross total resection (GTR) and those who underwent subtotal resection (STR). Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and mortality. RESULTS: Of 214 patients who underwent surgical resection for WHO grade II meningiomas (median follow-up 53.4 months), 158 had GTR and 56 had STR. In Kaplan-Meier analysis, patients who underwent GTR had significantly longer progression-free (p = 0.002) and overall (p = 0.006) survivals than those who underwent STR. In multivariable Cox proportional-hazards analysis, GTR independently predicted prolonged progression-free (HR 0.57, p = 0.038) and overall (HR 0.44, p = 0.017) survivals when controlling for age, tumor location, and adjuvant radiation. CONCLUSIONS: Extent of resection independently predicts progression-free and overall survivals in patients with WHO grade II meningiomas. In an era of increasing support for adjuvant treatment modalities in the management of meningiomas, our data support maximal safe resection as the primary goal in treatment of these patients.

A review of solitary fibrous tumor/hemangiopericytoma tumor and a comparison of risk factors for recurrence, metastases, and death among patients with spinal and intracranial tumors.

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) had been combined into a single classification until 2016. Recurrence and metastases rates are still understudied, especially for spinal SFT/HPCs. Here, we describe CNS SFT/HPCs and predictors for recurrence, metastases, and death, in spinal and intracranial SFT/HPCs, separately. We collected data from studies with patient-level data available on primary SFT/HPCs from multiple online databases. Clinico-demographic data, surgical outcomes, recurrence, metastases, and death rates were abstracted. We used logistic and Cox regression models to identify predictors for recurrence, metastases, and death for spinal and intracranial SFT/HPCs. Twenty-nine studies (368 patients) were included. Higher histological grade and subtotal resection were associated with recurrence (p values < 0.05), while higher histological grade and recurrence (p values < 0.005) were associated with metastases formation. Time to recurrence (p < 0.005) and metastases (p < 0.001) formation were shorter for spinal SFT/HPCs. Death rates were higher among intracranial SFT/HPC patients (p value = 0.001). Among patients with higher histological grade, rates of metastases formation were different between intracranial and spinal SFT/HPCs. Risk of metastases was higher in the first 5 years from surgery for both intracranial and spinal SFT/HPCs. Meningeal SFT/HPCs patients have high rates of recurrence and metastasis, which occur mostly within the first 5 years after diagnosis. Spinal and intracranial SFT/HPCs show similar behavior, but spinal SFT/HPCs tend to develop metastases and recurrences in a shorter interval of time. Careful follow-up for spinal SFT/HPCs should be considered because spinal cases seem to be slightly more aggressive and require more attention.

Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis.

BACKGROUND: TERT gene alterations (TERT-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought. METHODS: We applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement. We compiled data from eight studies and allocated patients to TERT-alt (n=59) or TERT promoter wild-type (TERTp-wt; n=618). We compared the two groups stratified for WHO grades as: incidence rates, survival probabilities and cumulative recurrences. We estimated the effects of WHO grade, age at diagnosis and sex as HRs. RESULTS: TERT-alt occurred in 4.7%, 7.9% and 15.4% of WHO-I/WHO-II/WHO-III meningiomas, respectively. The median recurrence-free survival was 14 months for all TERT-alt patients versus 101 months for all TERTp-wt patients. The HR for TERT-alt was 3.74 in reference to TERTp-wt. For all TERT-alt patients versus all TERTp-wt patients, the median overall survival was 58 months and 160 months, respectively. The HR for TERT-alt was 2.77 compared with TERTp-wt. TERT-alt affected prognosis independent of WHO grades. Particularly, the recurrence rate was 4.8 times higher in WHO-I/-II TERT-alt patients compared with WHO-III TERTp-wt patients. The mortality rate was 2.7 times higher in the WHO-I and WHO-II TERT-alt patients compared with WHO-III TERTp-wt patients. CONCLUSIONS: TERT-alt is an important biomarker for significantly higher risk of recurrence and death in meningiomas. TERT-alt should be managed and surveilled aggressively. We propose that TERT-alt analysis should be implemented as a routine diagnostic test in meningioma and integrated into the WHO classification. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42018110566.

Craniospinal irradiation(CSI) in patients with leptomeningeal metastases: risk-benefit-profile and development of a prognostic score for decision making in the palliative setting.

BACKGROUND: The aim of our study was to assess the feasibility and oncologic outcomes in patients treated with spinal (SI) or craniospinal irradiation (CSI) in patients with leptomeningeal metastases (LM) and to suggest a prognostic score as to which patients are most likely to benefit from this treatment. METHODS: Nineteen patients treated with CSI at our institution were eligible for the study. Demographic data, primary tumor characteristics, outcome and toxicity were assessed retrospectively. The extent of extra-CNS disease was defined by staging CT-scans before the initiation of CSI. Based on outcome parameters a prognostic score was developed for stratification based on patient performance status and tumor staging. RESULTS: Median follow-up and overall survival (OS) for the whole group was 3.4 months (range 0.5-61.5 months). The median overall survival (OS) for patients with LM from breast cancer was 4.7 months and from NSCLC 3.3 months. The median OS was 7.3 months, 3.3 months and 1.5 months for patients with 0, 1 and 2 risk factors according to the proposed prognostic score (KPS < 70 and the presence of extra-CNS disease) respectively. Nonhematologic toxicities were mild. CONCLUSION: CSI demonstrated clinically meaningful survival that is comparable to the reported outcome of intrathecal chemotherapy. A simple scoring system could be used to better select patients for treatment with CSI in this palliative setting. In our opinion, the feasibility of performing CSI with modern radiotherapy techniques with better sparing of healthy tissue gives a further rationale for its use also in the palliative setting.

Adjuvant radiation for WHO grade II and III intracranial meningiomas: insights on survival and practice patterns from a National Cancer Registry.

INTRODUCTION: WHO grades II (atypical) and III (malignant) meningiomas are associated with significant morbidity and mortality. The role of adjuvant radiotherapy (RT) in management remains controversial. The goal of this study was to evaluate the impact of adjuvant RT on 5-year survival in patients with atypical and malignant meningiomas. We secondarily aimed to assess contemporary practice patterns and the impact of sociodemographic factors on outcome. METHODS: We queried the National Cancer Database for patients ≥ 18 years of age with cranial atypical or malignant meningiomas from 2010 through 2015 who underwent surgical resection with or without adjuvant radiotherapy. Subjects with unknown WHO grade or radiation status and those not receiving any surgical procedure were excluded from analysis. RESULTS: The study includes 7486 patients, 6788 with atypical and 698 with malignant meningiomas. Overall 5-year survival was 76.9% (95% CI 75.5-78.3%) and 43.3% (95% CI 38.8-48.2%) among patients with WHO grades II and III meningiomas, respectively. Adjuvant RT correlated with improved survival in a multivariable model in patients with grade II tumors (HR 0.78; p = 0.029) regardless of the extent of resection. Age (HR 2.33; p < 0.001), male sex (HR 1.27; p < 0.001), Black race (HR 1.27; p = 0.011) and Charlson-Deyo Score ≥ 2 (1.35; p = 0.001) correlated with poorer survival whereas private insurance (HR 0.71; p < 0.001) correlated with improved survival. Adjuvant RT was also associated with improved 5-year survival among those with grade III tumors on univariate analysis (log-rank p = 0.006) but was underpowered for multivariable modeling. Utilization of adjuvant radiotherapy was only 28.4% and correlated with private insurance status. Academic institutions (25.3%) and comprehensive community cancer programs (21.4%) had lower radiotherapy utilization rates compared with integrated network cancer programs (30.5%) and community cancer programs (29.7%). CONCLUSIONS: Adjuvant RT may correlate with improved overall survival in patients with grades II and III intracranial meningiomas regardless of the extent of resection. There is poor utilization of adjuvant RT for patients with grades II and III meningiomas likely due to a paucity of quality data on the subject. These findings will be strengthened with prospective data evaluating the role of adjuvant RT.

Long-term outcomes of multimodality management for parasagittal meningiomas.

PURPOSE: The aim of this study was to systematically analyze the clinical characteristics of a large cohort of parasagittal meningioma (PM) and to evaluate the patients' outcomes and best treatment strategies based on tumor features. METHODS: To minimize selection bias we performed a single-institutional review of PM with restricted criteria. One hundred and ninety-two consecutive patients who met criteria for inclusion were reviewed from 2003 to 2011 in our general hospital. RESULTS: A total of 131 cases (68.2%) were with WHO grade I, while grade II and grade III PMs constituted 40 (20.8%) and 21 cases (10.9%). Higher histological grade was associated with loss of trimethylation of H3K27 (P = 0.000). For WHO grade I PMs, GTR was significantly associated with a better PFS (P = 0.023); however, adjuvant radiotherapy did not benefit patients with STR (P = 0.215). For de novo high-grade (WHO grade II and III) PMs (n = 37), adjuvant radiotherapy was associated with a significantly longer OS (P = 0.013), while no difference was observed between GTR and STR (P = 0.654). In recurrent high-grade PM patients (n = 24), GTR combined with adjuvant radiotherapy increased PFS (P = 0.005). CONCLUSIONS: This study demonstrated that PMs were a heterogeneous group of tumors with a high proportion of high-grade tumors that often displayed aggressive clinical behaviors. Low-grade PM benefited from radical resection, whereas high-grade de novo PM did not. Adjuvant radiotherapy significantly prolonged OS for high-grade primary PM, but did not impact survival of patients with subtotally resected low-grade tumors. Long-term outcome of high-grade recurrent PMs was dismal. We thus show that extent of tumor resection, tumor grade and tumor recurrent status inform therapeutic decisions for PMs.

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

INTRODUCTION: Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM. METHODS: We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS. RESULTS: 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612-1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773-1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886-2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743-0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784-0.835], p < 0.001). CONCLUSION: Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.

Racial and socioeconomic correlates of treatment and survival among patients with meningioma: a population-based study.

BACKGROUND: Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively. RESULTS: 71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients. CONCLUSIONS: This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

Impact of postoperative radiotherapy on recurrence of primary intracranial atypical meningiomas.

BACKGROUND: Atypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas. METHODS: The medical records of all patients who underwent surgery (2007-2017 in 4 neurosurgical departments) for a histologically diagnosed primary atypical meningioma were reviewed to assess progression-free survival (PFS) and prognostic factors. RESULTS: This analysis included 258 patients with a median age of 60 years (54.7% female). The predominant tumor locations were convexity and falx (60.9%) followed by the skull base (37.2%). Simpson grade I-II resection was achieved in 194 (75.2%) patients, Simpson grade III-IV in 53 patients (20.5%). Tumor progressed in 54 cases (20.9%). Postoperative RT was performed in 46 cases (17.8%). RT was more often applied after incomplete resection (37.7% vs. 13.4% Simpson III-IV vs. I-II). A multivariate analysis showed a significantly shorter PFS associated with Simpson III-IV [HR 1.19, (95% CI) 1.09-1.29, p < 0.001] and age > 65 years [HR 2.89, (95% CI) 1.56-5.33, p = 0.001]. A subgroup analysis with a minimal follow-up of 36 months revealed that Simpson III-IV [HR 3.01, 95% CI 1.31-6.931.03-1.24, p = 0.009] and age > 65 years [HR 2.48, 95% CI 1.20-5.13, p = 0.014] reduced PFS. The impact of postoperative RT on PFS remained statistically insignificant, even in a propensity-score matched survival analysis [n = 46; p = 0.438; OR 0.710 (0.299-1.687)]. CONCLUSIONS: In the present study, postoperative RT did not improve PFS. The most important prognostic factors remain the extent of resection and age.

Brachytherapy with surgical resection as salvage treatment for recurrent high-grade meningiomas: a matched cohort study.

PURPOSE: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options. METHODS: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery. RESULTS: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort. CONCLUSION: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.

Effect of seizure timing on long-term survival in patients with brain tumor.

OBJECTIVE: Seizures often occur in patients with primary brain tumor (BT). The aim of this study was to determine if there is an association between the time of occurrence of seizures during the course of BT and survival of these patients. METHODS: This retrospective cohort study at Henry Ford Hospital, an urban tertiary referral center, included all patients who were diagnosed with primary BTs at Henry Ford Health System between January 2006 and December 2014. Timing of seizure occurrence, if occurred at presentation or after the tumor diagnosis during follow-up period, in different grades of BTs, and survival of these patients were analyzed. RESULTS: Of the 901 identified patients, 662 (53% male; mean age: 56 years) were included in final analysis, and seizures occurred in 283 patients (43%). Patients with World Health Organization (WHO) grade III BT with seizures as a presenting symptom only had better survival (adjusted hazard ratio (HR): 0.27; 95% confidence interval (CI), 0.11-0.67; P = 0.004). Seizures that occurred after tumor diagnosis only (adjusted HR: 2.11; 95% CI, 1.59-2.81; P < 0.001) in patients with WHO grade II tumors (adjusted HR: 3.41; 95% CI, 1.05-11.1; P = 0.041) and WHO grade IV tumors (adjusted HR: 2.14; 95% CI, 1.58-2.90; P < 0.001) had higher mortality. Seizures that occurred at presentation and after diagnosis also had higher mortality (adjusted HR: 1.34; 95% CI, 1.00-1.80; P = 0.049), in patients with meningioma (adjusted HR: 6.19; 95% CI, 1.30-29.4; P = 0.021) and grade III tumors (adjusted HR: 6.19; 95% CI, 2.56-15.0; P < 0.001). CONCLUSION: Seizures occurred in almost half of the patients with BTs. The association between seizures in patients with BT and their survival depends on the time of occurrence of seizures, if occurring at presentation or after tumor diagnosis, and the type of tumor. Better survival was noted in patients with WHO grade III BTs who had seizures at presentation at the time of diagnosis, while higher mortality was noted in WHO grade II tumors who had seizure at presentation and after tumor diagnosis, and in grade IV tumors after tumor diagnosis.