Atypical Meningioma Research Articles

Metformin enhances anti-cancer effects of cisplatin in meningioma through AMPK-mTOR signaling pathways

Cisplatin is currently used to treat inoperable recurrent meningiomas, but its side effects and drug resistance limit its use. Metformin has recently been identified as a chemosensitizing agent. However, the combined treatment of cisplatin and metformin in high-grade meningiomas has not been reported. Herein, our findings demonstrate metformin significantly enhanced cisplatin-induced inhibition of proliferation in meningioma cells, which was associated with the induction of G0/G1 cell cycle arrest. Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism. Furthermore, our xenograft murine model confirmed that metformin enhanced cisplatin’s anti-cancer effect by upregulation of AMPK and downregulation of mTOR signaling pathways. In addition, in 63 patients with atypical meningiomas, the activation of AMPK was significantly associated with tumor recurrence and short disease-free survival (DFS). These results demonstrate metformin enhanced the anti-cancer effect of cisplatin in meningioma in vitro and in vivo, an effect mediated through the activation of AMPK and repression of mTOR signaling pathways. Our study suggests the combined treatment of metformin and cisplatin is an effective and safe treatment for high-grade meningiomas.

Letter to the Editor Regarding “Stereotactic Radiosurgery for Atypical and Anaplastic Meningiomas”

Letter to the Editor Regarding “Stereotactic Radiosurgery for Atypical and Anaplastic Meningiomas”

In Reply to the Letter to the Editor Regarding “Stereotactic Radiosurgery for Atypical and Anaplastic Meningiomas”

In Reply to the Letter to the Editor Regarding “Stereotactic Radiosurgery for Atypical and Anaplastic Meningiomas”

NCOG-49. COMBINED NECROSIS AND BRAIN INVASION PREDICT RADIO-RESISTANCE AND TUMOR RECURRENCE IN ATYPICAL MENINGIOMA

Abstract BACKGROUND Meningiomas are the most common tumors in the central nervous system, with variable recurrence rates depending on WHO grading. Atypical (WHO grade II) meningioma has a higher recurrence rate than benign meningioma (WHO grade I). The efficacy of adjuvant radiotherapy (RT) to improve tumor control has been questioned. METHODS This cohort study retrospectively reviewed all patients at St. Michaels Hospital Tumor Patient Database with a diagnosis of atypical meningioma (AM) who underwent surgical resection between 1995 and 2015. Patient and tumor characteristics such as location, neuropathological diagnosis, resection extent, RT and time to reoccurrence or progression were recorded. Resection extent was defined by Simpson Grading Scale as either Gross Total (GTR) or Subtotal (STR) resection. Cox univariate regression and Kaplan-Meier survival analysis were employed to identify risk factors for recurrence and radio-resistance. RESULTS In our cohort of 181 patients, the combination of necrosis and brain invasion was associated with an increased reoccurrence risk (HR= 4.560, P=0.001) and the lowest progression-free survival relative to other histopathological predictors. This trend was maintained after GTR (P=0.001), whereas necrosis alone and combined necrosis and brain invasion were both associated with low progression-free survival in STR (P=0.001). Radiotherapy was associated with decreased progression-free survival (P=0.001), especially in patients who received GTR (P=0.001). This trend was maintained in patients with necrosis alone (P=0.002) but especially in patients with combined necrosis and brain invasion (P=0.001). CONCLUSION Combined necrosis and brain invasion is a strong predictor of tumor recurrence and radio-resistance in AM, regardless of extent of resection or RT.

CTNI-55. PREDICTIVE FACTORS FOR HIGH GRADE TRANSFORMATION IN BENIGN MENINGIOMAS

Abstract OBJECT Meningiomas are generally slow-growing, benign tumors, most of which are classified as WHO Grade I. Rarely, benign meningiomas may recur after surgery with transformation into WHO Grade II atypical meningiomas. As atypical meningiomas are different from benign meningiomas in terms of clinical course, and prognosis, predicting the transformation is important for patient management. The purpose of the study was to investigate the radiological and pathological factors that predict the risk of tumor progression from benign to atypical meningioma. METHOD All patients treated with recurrent meningiomas in whom the tumor showed histopathologically confirmed high grade transformation between 2001 and 2017 were included. To evaluate the predictors for transformation, patients’ medical records for previous benign meningioma before transformation were collected. Each patient was matched with 4 age and sex-matched controls treated with benign meningioma, and were analyzed. RESULTS Fourteen patients with high grade transformation were included. The median time interval of transformation was 63 months (range of 19 – 132). Multivariate analysis indicated that increased mitotic index (OR, 10.409, 95% CI, 1.297–83.549, p=0.027) was significant predictive factor of transformation. And prominent peritumoral edema (OR, 33.822, 95% CI, 0.935–223.688, p=0.054) showed relative risk for transformation. CONCLUSION Increased mitotic index and prominent peritumoral edema may be predictors for high grade transformation of benign meningiomas. Although these tumors do not meet the criteria for atypical meningioma, they may be required more attentive observation and management than other benign meningiomas.

SURG-29. CLINICAL FACTORS ASSOCIATED WITH RECURRENCE IN ATYPICAL MENINGIOMA: RETROSPECTIVE ANALYSIS OF 99 PATIENTS IN TWO INSTITUTES

Abstract OBJECTIVE The objectives of this study were to examine the local control (LC) rate of atypical meningioma after surgical resection with or without adjuvant treatment, to identify risk factors for the recurrence of atypical meningioma, and to compare our results to known factors from the literature. METHODS Clinical and radiological records of patients with atypical meningiomas diagnosed at two institutes from January 2000 to December 2018 were reviewed retrospectively. Histopathological features were also reviewed using formalin-fixed paraffin embedded samples from pathological archives. RESULTS Of the 99 atypical meningiomas eligible for analysis, 36 (36.4%) recurred during the follow-up period (mean 83.3 months, range 12–232 months). The rate of 3-year LC and 5-year LC was 80.8% and 74.7% respectively. The mean time-to-recurrence was 49.4 months (range 12–150 months). Multivariate analysis using Cox proportional-hazard regression model showed that the extent of resection (Hazard ratio [HR] 4.761, p=0.013), Ki67 index (HR 8.541, p=0.004), mitotic index (HR 3.275, p=0.044), tumor size (HR 3.228, p=0.041), and radiotherapy (HR 3.816, p=0.029) were independently associated with 3-year LC. These factors was also statistically associated with recurrence-free survival. In terms of radiotherapy after surgical resection, the recurrence was not prevented by immediate radiotherapy because of the strong effect of proliferative index on recurrence. Three cases of malignant transformation to WHO grade III meningioma were histopathologically confirmed after repeated surgery. Two out of these three patients succumbed to malignant transformation. The mean Ki67 proliferative index increased for recurrent cases in 18 patients (58.1%) from 7.55% (range 4-16) to 11.81% (range 5-24). CONCLUSION The present study suggests that the extent of resection, proliferative index (according to Ki67 expression) and mitotic index, tumor size, and radiotherapy are associated with recurrence of atypical meningiomas. However, our results should be further validated through prospective and randomized clinical trials.

NCOG-56. THE NATURAL COURSE OF ATYPICAL MENINGIOMA AFTER GROSS TOTAL RESECTION WITHOUT ADJUVANT TREATMENT

Abstract Atypical meningioma represent more aggressive clinical behaviors than WHO grade I meningiomas. In this study, We research natural course of atypical meningioma after gross total resection without adjuvant treatment. MATERIAL AND METHODS: We retrospectively reviewed the records of patients with histopathologically diagnosed atypical meningiomas between June 1990 and December 2015 at Asan Medical Center, Korea. Patients treated with Simpson grade I, II resection were included. Patients variably underwent adjuvant radiation therapy according to each surgeon’s preferences. RESULTS: In this study, 117 patients were enrolled and the average follow-up was 43 months (range 3~228 months). In Simpson grade I tumor resection group, recurrence was confirmed in 10 out of 63 patients without adjuvant treatment, and 1 out of 13 patients with adjuvant radiation treatment. There were 12 recurrence cases in Simpson grade II tumor resection and no adjuvant treatment group, of the total 32 cases. There was 4 recurrence case of total 8 cases of Simpson grade II tumor resection with adjuvant radiation treatment group. In groups with no adjuvant treatment, Simpson grade I resection group had a better prognosis on 5-year PFS (82.9% vs 54.9%, p=0.005) compared to Simpson grade II resection group. DISCUSSION: The results of this study show that there is a significant difference in 5-year PFS between the Simpson grade I and II groups without adjuvant treatment, commonly referred to as the gross total resection group. Although this study report adjuvant RT is not superior to observation, more intensive post-operative imaging surveillance protocols would be considered in Simpson grade II resection group without adjuvant treatment. CONCLUSION: The natural course of atypical meningioma after gross total resection without adjuvant treatment signified Simpson grade I and II resection show significant different prognosis.

RADT-41. ASSESSING THE ROLE OF ADJUVANT RADIATION THERAPY AND RISK FACTORS FOR RECURRENCE FOLLOWING GROSS TOTAL RESECTION OF ATYPICAL MENINGIOMAS

Abstract While meningiomas are commonly benign brain tumors, as many as 30% may be classified as atypical, or WHO Grade 2. Patients are at risk of recurrence following resection and often are prescribed adjuvant radiation therapy (RT)-although most data on this treatment is retrospective and has shown mixed RESULTS: In this study we assessed the influence of adjuvant RT following gross total resection (GTR) in patients with newly diagnosed atypical meningiomas at our institution and sought to determine predictors of tumor recurrence. All patients who underwent GTR (Simpson Grade I and II) at their index operation from 1994-2014 were retrospectively reviewed. Patients then either underwent observation or adjuvant RT (Intensity-Modulated Radiation Therapy (IMRT) or stereotactic radiosurgery (SRS)). A total of 145 patients had documented GTR at the time of initial resection, including 88 females (61%) and 57 males (39%), with a mean age of 58 +/- 15.7 years. 118 patients were followed with observation after surgery while 27 (18.6%) patients received adjuvant RT prior to known recurrence (IMRT for 15 patients (55.5%) and SRS in 12 patients (44.4%)). Patients receiving adjuvant RT had significantly larger tumors, as well as a higher incidence of spontaneous necrosis and small cell phenotype on histopathology. Overall 5-year PFS in our cohort was 71.6% (CI 60.6%-84.7%) and was unchanged by adjuvant RT (p = 0.52). 23 patients (15.8%) had a recurrence with a mean follow up of 42.9 months (17.1-53.5 months). Male gender (HR=1.02, p=0.019), tumor size (HR=1.17, p= 0.002) and MIB-1 > 4 (HR=8.50, p=0.04) were associated with increased recurrence risk. There was no association between radiation type (SRS vs. IMRT) and risk of recurrence (p= 0.154). In our patients, adjuvant RT following GTR of atypical meningiomas did not improve PFS. Risk factors for recurrence included male gender, larger tumor size, and MIB-1 > 4.

RADT-36. PROSPECTIVELY ASSESSED TUMOR CONTROL AND TOXICITY OF BENIGN INTRACRANIAL PATHOLOGIES TREATED WITH AUTOMATED VMAT RADIOSURGERY – INITIAL 2 YEAR EXPERIENCE WITH FIRST 100 PATIENTS

Abstract BACKGROUND HyperArc is a treatment planning technology that automates treatment planning and delivery of single-isocenter VMAT radiosurgery (SRS). The technique generates high quality, rapidly deliverable plans. It is unknown whether HyperArc is effective for commonly-encountered, benign, intracranial conditions managed with SRS. Under IRB-approved prospective registry, we collected data on treatment planning/delivery, and clinical outcomes of non-malignant conditions managed with single-fraction or fractionated SRS since deployment in October 2017. METHODS Patients received either single-fraction or fractionated SRS with HyperArc™ (Varian Medical Systems) between October 2017 & October 2019. Patients with < 3 months follow-up were censored. All patients treated received prescription dose to ≥ 99% of gross tumor volume without PTV expansion. All treatments were delivered on Varian Edge linac with 10MV flattening-filter free beam at 2400 MU/min with high-definition (2.5mm) multi-leaf collimator. Standard pathology-specific outcomes and toxicities were assessed. Significant CNS toxicity was defined as Grade 3 or higher event by CTCAE. RESULTS Total of 100 targets (min=0.13cc, max=58.9cc) were treated. 55 received single-fraction SRS (12-22Gy), two received 2-fraction fSRS boost (12Gy) following fractionated treatment, and 43 received 5-fraction fSRS (25-30Gy). The most common pathology was meningioma (n=55), followed by AVM (n=18), non-secretory pituitary adenoma (n=12), acoustic schwannoma (n=9), secretory pituitary adenoma (n=3), glomus tumor (n=2), pineocytoma (n=1), and paraganglioma (n=1). Follow-up ranged from 1.2 to 19.5 months (median 7.2). There were three local failures, all in atypical meningiomas. One patient in the cohort experienced ≥Gr3 toxicity. Each radiosurgery session used median of 3 arcs, with median treatment and beam-on time of 12.03 and 2.3 minutes. Plan quality was excellent; median RTOG conformity was 1.15, and median Paddick GI was 3.52. CONCLUSION Although HyperArc was developed for automated multiple-metastasis radiosurgery, we found it effective and efficient for benign intracranial indications too. Early clinical outcomes appear congruent with historical controls.

TAMI-60. EXPLORING METABOLIC DIFFERENCES IN VARYING GRADES OF MENINGIOMAS THROUGH NONTARGETED MASS SPECTROMETRY

Abstract Emerging molecular data demonstrates the importance of genomic and epigenetic factors in pathogenesis of meningioma. Understanding the metabolic landscape using mass spectrometry is needed to overcome significant uncertainty in predicting tumor behavior and the risk of recurrence. Current technologies lack sensitivity and selectivity, which hinders the discovery of potential novel diagnostic and prognostic features. Here, we present a nontargeted metabolomics approach applied to meningiomas for biomarker discovery and identification of potential therapeutic targets. Fresh frozen tissue from 36 patients (57% women, 43% men; mean age: 48) who underwent surgical resection for newly diagnosed meningiomas and 9 patient samples with non-neoplastic dura were used for case/control comparison. Additionally, 16 patient-derived meningioma cell lines (Grade I-III), 2 immortalized human cell lines (IOMM-Lee and Ch157MN) and immortalized arachnoid cells were used to further explore metabolic changes in meningiomas. Metabolites were extracted from tissue and cells for GC-TOF (primary metabolism), RPLC ESI (±) (lipidomics) and HILIC ESI (±) (biogenic amines) coupled to high-resolution mass spectrometry for analysis. Metabolites were identified using authentic standards, retention time, and MS2 fragmentation. Over one thousand known metabolites were identified and annotated as well as over 300 unknown metabolites. Metabolites were grouped into one of fifteen classes based on chemical ontology and function. Bis(monoacylglycero)phosphates were over 2-fold increase in atypical (Grade II) meningiomas versus Grade I, indicating lysosomal activation. One carbon metabolism pathway showed significant upregulation in neoplastic tissue vs. tumor involved dura, as well as neoplastic cells compared to arachnoid cells, indicating folate-dependent pathways as a potential therapeutic target. Using novel combined untargeted metabolomics, we found multiple classes of metabolites that were either enriched or suppressed in neoplastic tissue and cells compared to non-neoplastic cells. Further studies are warranted for a better understanding of possible oncogenic signaling pathways and to detect potential biomarkers useful for diagnosis and treatment.

NCOG-52. TUMOR TREATING FIELDS IN MENINGIOMA

Abstract BACKGROUND High-grade meningioma are aggressive intracranial tumors and currently only limited treatment options exist. Therefore, there is a need for further studies in search of new therapies. Tumor Treating TTFields (TTFields) therapy serves as an effective treatment against glioblastoma (GBM). Phase 3 clinical trials investigate the use of TTFields in other intracranial tumors, i.e. brain metastases of the non-small cell lung cancer. We here provide an overview of the currently available data regarding the use of TTFields in meningioma. MATERIALS AND METHODS We performed a literature search using the term “Tumor treating fields” “NovoTTF”, “TTFields” and “Optune” in combination with “Meningioma”. A brief overview of TTFields in meningioma is provided here. RESULTS In vitro studies using patient-derived anaplastic grade III meningioma cell lines showed that TTFields treatment at a frequency of 200 kHz causes a significant reduction of cell proliferation and clonogenicity as well as altering cell morphology. In a case report of a 44-year-old woman suffering from a right anterior temporal tumor as well as a distant right parietal extra-axial convexity meningioma TTFields and Temozolomide treatment was initiated. Brain MRI scans 8, 16 and 20 weeks later showed a reduction in the meningioma tumor size of 42%, 58% & 60%, respectively. Currently, two ongoing trials test the efficacy and safety of the use of TTFields in meningioma patients: a phase II single arm trial (n=27), investigating the combination of TTFields and Bevacizumab in recurrent or progressive meningioma (NCT02847559); and a pilot trial, investigating the effects of TTFields as monotherapy on recurrent atypical and anaplastic meningioma (NCT01892397). CONCLUSIONS First data indicate that TTFields might be an option in future high-grade meningioma treatment. Clinical trials need to show safety and efficacy for the TTFields treatment in meningioma patients.

CTNI-69. PRECISION NEURO-ONCOLOGY TREATMENT GUIDED BY NEXT GENERATION SEQUENCING (NGS)-BASED COMPREHENSIVE GENOMIC PROFILING: REAL WORLD EXPERIENCE IN HONG KONG

Abstract BACKGROUND The development of next generation sequencing (NGS) based comprehensive genomic profiling (CGP) has enabled identification of druggable somatic mutations in brain tumours. This cohort reviewed the efficacy of CGP-guided precision treatment in a tertiary neuro-oncology centre. METHODOLOGY From May 2017 to May 2020, CGP were arranged for 43 patients. All patients had exhausted conventional treatments or received CGP for clinical trial screening. Targeted deep NGS was used to assess the mutational status, single nucleotide variant, small insertions and deletions and copy number variant of 440 cancer-related genes. RESULTS The diagnoses of the 43 patients were GBM (n=23), high grade glioma (n=11), brain metastases (n=4), chordoma (n=3), atypical choroid plexus papilloma (n=1) and meningioma (n=1). In most of the patients (42/43, 97.7%), CGP identified at least one druggable targets with a median of 3. Based on the CGP, 27 patients received precision treatment (62.7%). Among these, 14 were GBM and 6 were other high grade glioma. Treatment given included PARP inhibitors, immunotherapy, multi-kinase inhibitor, selective CDK4/6 inhibitor and mTOR inhibitor. Clinical benefit was achieved in 20 patients out of 27 (74%), including 2 complete response (7.4%), 9 partial response (33.3%) and 9 stable disease (33.3%). The median progression free survival (PFS) were 183 days [95% confident intervals (CI): 81–302 days]. For GBM/high grade glioma patients, median PFS was 125 days [95% CI: 52–215] and six-month PFS was 32.7%. Treatment toxicity was mild except two patients developed grade 3 complications and one grade 5 complication (fatal neutropenic fever). For the 16 patients who did not receive precision treatment, one had no druggable target identified, nine were still stable on standard therapies, 6 were too weak when CGP was available. CONCLUSION CGP guided precision treatment for selected, advanced neuro-oncological patients yielded modest clinical efficacy and satisfactory safety profile in real world setting.

Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

Introduction: SOX9, a members of SOX family, plays a significant roles in developmental processes during embryogenesis, including brain tissue. Few studies have shown that SOX9 has been involved in tumourigenesis of several types of cancer including brain tumour. However, such studies are still lacking in the Malaysian population. The aim of this study was to determine SOX9 expression level in several types of brain tumours in East Coast Malaysia. Materials and Methods: Five formalin-fixed pariffin-embedded brain tumour samples of Malay descendants were sectioned by using microtome. RNA extraction was performed with slight modification by adding Trizol during tissue lysis. The RNA was converted to cDNA using reverse transcription technique before SOX9 expression was detected using RT q-PCR assay in brain tumours normalized to non-neoplastic brain tissues. Results: Overall results displayed that SOX9 gene in all samples were up-regulated. SOX9 overexpression was found in both high and low grade glioma (anaplastic and pilocytic astrocytoma respectively). This is consistence with both low grade (benign) and atypical meningioma. Secondary brain tumour also showed up-regulation when compared to normal brain tissue. Conclusion: Up-regulation in SOX9 expression in selected brain tumours in Malay patients revealed its significant roles in brain tumourigenesis. Functional studies should be carried out to observe the SOX9 functions and mechanism whether they should reflect their diverse roles in Malaysia population.

Timing of Adjuvant Radiotherapy in Atypical Meningiomas

The optimal timing of adjuvant radiotherapy (RT) in the management of atypical meningiomas remains controversial. We sought to compare the outcomes of surgically resected atypical meningiomas managed with upfront adjuvant RT vs. initial surveillance. Patients with World Health Organization (WHO) Grade II (atypical) meningiomas who underwent surgical resection between 2000-2015 and were followed at our institution were identified. Clinical, histopathological, and treatment-related variables were compared between patients who received adjuvant RT, defined as RT received within the first year of surgery before tumor progression/recurrence (P/R), vs. those who initially underwent surveillance. The primary endpoints were radiographic evidence of progression/recurrence (P/R) and time to P/R. The secondary endpoint was overall survival (OS). Cox proportional hazards modeling was used to analyze time to tumor P/R and OS. Kaplan-Meier analysis was used to calculate the actuarial rates of P/R and death. The log-rank test was used to compare the Kaplan-Meier curves. A total of 230 patients with atypical meningiomas were identified. Median follow-up was 6.9 years. Median age was 57. Sixty percent were female and 94% had a Karnofsky performance status (KPS) ≥70. Five percent had a remote history of cranial irradiation. Median tumor size was 4.7 cm. Tumor locations were convexity (46%), skull base (32%), parafalcine (21%), and intraventricular (1%). Surgical outcome was gross total resection (GTR) in 151 (66%) and subtotal resection (STR) in 79 (34%) patients. Postoperatively, 51 (22%) patients received upfront adjuvant RT while 179 (78%) initially underwent surveillance alone. Compared to the surveillance group, patients who received adjuvant RT had larger tumors (5.2 cm vs. 4.6 cm; p = 0.04), were more likely to have undergone STR vs. GTR (65% vs. 26%; p<0.01), and more often had bone invasion (18% vs. 7%; p = 0.02). On multivariable analysis adjusted for sex, prior cranial irradiation, tumor size, extent of resection (EOR), mitotic activity, and brain invasion, receipt of adjuvant RT was independently associated with a lower risk of P/R compared to surveillance (HR = 0.21 [95% CI 0.11-0.41]; p<0.01). Patients who initially underwent surveillance and then received salvage RT at time of P/R had a shorter median time to local progression after RT compared to patients who developed local P/R following upfront adjuvant RT (19 vs. 64 months, respectively; p<0.01). There was no difference in overall survival (OS) with adjuvant RT vs. initial surveillance (5-year OS 91% [95% CI 0.78-0.97] vs. 94% [95% CI 0.89-0.97], respectively; log-rank p = 0.95). Upfront adjuvant RT was associated with improved local control in atypical meningiomas irrespective of EOR as compared to initial surveillance. Early adjuvant RT should be considered in certain patients with atypical meningiomas regardless of EOR.

The Impact of Postoperative Radiation Therapy (PORT) on Clinical Outcomes of Resected Atypical Meningioma: A Meta-Analysis

The Impact of Postoperative Radiation Therapy (PORT) on Clinical Outcomes of Resected Atypical Meningioma: A Meta-Analysis

68Ga-DOTATATE PET/MRI as an Adjunct Imaging Modality For Radiation Treatment Planning Of Meningiomas

Meningiomas express somatostatin receptor 2 (SSTR2). PET imaging with [68Ga]-DOTATATE, which targets SSTR2, has demonstrated clinical utility in delineating meningioma versus reactive dural thickening, particularly in the postoperative setting. Our study provides comparative volumetric and dosimetric analyses validating DOTATATE PET/MRI-assisted target delineation for radiotherapeutic planning of meningiomas. As a secondary aim, adverse events and 6-month progression-free survival rates are reported. We identified 9 residual / recurrent meningiomas in 8 patients who underwent 68Ga-DOTATATE PET/MRI prior to fractionated stereotactic radiosurgery (SRS) from 1/1-12/31/19. Demographic and clinical data were collected. CT simulation scans were fused with DOTATATE PET/MRI. Gross target volumes (GTV) were derived from the MRI and DOTATATE PET (acquired simultaneously). All GTV were given a 3.0 mm isometric expansion to generate the planning target volume (PTV). Patients received SRS to a nominal dose of 35 Gy in 5 fractions. Ascribing an α/β = 6 for atypical meningiomas produced a biologically equivalent dose (BED) of 75.83 Gy. Each patient was retrospectively recontoured per the RTOG 0539 intermediate-risk group cohort and received 54 Gy in 30 fractions (BED = 70.2 Gy). Planning volumes from DOTATATE PET/MRI-assisted and SOC plans were compared. All treatment related data were converted to EQD2 for dosimetric analysis. Mean and maximum equivalent doses were generated for target volumes, and OARs within 1 cm of the PTV, and compared using Wilcoxon matched pairs signed rank test. The cohort comprised 8 recurrent / residual WHO grade II meningiomas and 1 recurrent WHO grade I meningioma. BED max and mean were higher among DOTATATE-PET/MRI-guided plans (table). While PET/MRI-guided planning did not significantly reduce mean GTV, it significantly reduced mean PTV, and mean and max dose to the whole brain, optic nerves and scalp. While underpowered to reach significance, DOTATATE-guided plans reduced mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi by at least 50%. Acute side effects were limited to focal alopecia in 1 patient. No recurrences were detected among 3 patients who underwent 6-month post-treatment imaging. [68Ga]-DOTATATE-PET/MRI improves post-operative target delineation for radiotherapy in patients with intracranial meningiomas, often resulting in PTV reduction and decreased OAR dose, compared with plans generated from SOC (MRI-based) planning. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of meningiomas.Abstract 3552; TableParameterDOTATATE- unassisted planDOTATATE - planpGTV mean (cc)16.44.1>0.05PTV mean (cc)71.411.1<0.05BED mean (Gy)55.262.9<0.05BED max (Gy)62.674.9<0.05Whole brain mean dose (Gy)6.581.61<0.05Whole brain max dose (Gy)60.971.4<0.05Scalp max dose (Gy)54.318.8<0.05Optic nerve max (Gy)41.317.3<0.05 Open table in a new tab

Resected atypical meningioma relapsed to anaplastic meningioma during luteinizing hormone-releasing hormone agonist therapy

A 55-year old man with a history of meningioma treated with LHRH-agonist plus radiotherapy for prostate cancer (PCa) experienced a meningioma growth during hormone therapy (HT). Meningioma was radically resected revealing an atypical meningioma and HT was continued due to the high risk of PCa relapse until symptomatic meningioma relapse occurred after further 10 months. Gross lesions were radically removed and histology revealed anaplastic meningioma. This is the first case of rapid meningioma evolution to an anaplastic histology during LHRH-agonist.

Identification of High-Risk Atypical Meningiomas According to Semantic and Radiomic Features.

Up to 60% of atypical meningiomas (World Health Organization (WHO) grade II) reoccur within 5 years after resection. However, no clear radiological criteria exist to identify tumors with higher risk of relapse. In this study, we aimed to assess the association of certain radiomic and semantic features of atypical meningiomas in MRI with tumor recurrence. We identified patients operated on primary atypical meningiomas in our department from 2007 to 2017. An analysis of 13 quantitatively defined radiomic and 11 qualitatively defined semantic criteria was performed based on preoperative MRI scans. Imaging characteristics were assessed along with clinical and survival data. The analysis included 76 patients (59% women, mean age 59 years). Complete tumor resection was achieved in 65 (86%) cases, and tumor relapse occurred in 17 (22%) cases. Mean follow-up time was 41.6 (range 3-168) months. Cystic component was significantly associated with tumor recurrence (odds ratio (OR) 21.7, 95% confidence interval (CI) 3.8-124.5) and shorter progression-free survival (33.2 vs. 80.7 months, p < 0.001), whereas radiomic characteristics had no predictive value in univariate analysis. However, multivariate analysis demonstrated significant predictive value of high cluster prominence (hazard ratio (HR) 5.89 (1.03-33.73) and cystic component (HR 20.21 (2.46-166.02)) for tumor recurrence. The combination of radiomic and semantic features might be an effective tool for identifying patients with high-risk atypical meningiomas. The presence of a cystic component in these tumors is associated with a high risk of tumor recurrence.

MRI predictors for brain invasion in meningiomas.

In the 2016 revision of the World Health Organization classification of central nervous system tumours, brain invasion was added as an independent histological criterion for the diagnosis of a World Health Organization grade II atypical meningioma. The aim of this study was to assess whether magnetic resonance imaging characteristics can predict brain invasion for meningiomas. We conducted a retrospective review of all meningiomas resected at our institution between 2005 and 2016 which had preoperative magnetic resonance imaging and included brain tissue within the pathology specimen. One hundred meningiomas were included in the study, 60 of which had histopathological brain invasion, 40 of which did not. Magnetic resonance imaging characteristics of tumours were evaluated for potential predictors of brain invasion. Tumour location, size, perilesional oedema, contour, cerebrospinal fluid cleft, peritumoral cyst, dural venous sinus invasion, bone invasion, hyperostosis and the presence of enlarged pial arteries and veins were evaluated. Data were analysed using conventional chi-square, Fisher's exact test and logistic regression. The volume of peritumoral oedema was significantly higher in the brain-invasive meningioma group compared to the non-brain-invasive group. The presence of a complete cleft was a rare finding that was only found in non-brain-invasive meningiomas. The presence of enlarged pial feeding arteries was a rare finding that was only found in brain-invasive meningiomas. An increased volume of perilesional oedema is associated with the likelihood of brain invasion for meningiomas.

A Novel Scoring System Based on Preoperative Routine Blood Test in Predicting Prognosis of Atypical Meningioma.

PurposeThe aim of this study was to explore the correlation and clinical significance of preoperative fibrinogen and neutrophil-lymphocyte ratio (F-NLR) scoring system with 3-year progression-free survival (PFS) of patients with atypical meningioma.Materials and MethodsClinical, pathological, radiological, and laboratory variables were collected to analyze their correlation with 3-year PFS in the training set with 163 patients. Patients were classified by different F-NLR scores (0, 1, or 2). External validation for the predictive value of F-NLR scoring system was performed in the validation set with 105 patients.ResultsOverall, 37.3% (100 of 268) of the enrolled patients were male. The scoring system showed good performance in predicting 3-year PFS (AUC = 0.872, 95%CI = 0.811–0.919, sensitivity = 66.1%, specificity = 93.3%, and Youden index = 0.594). DeLong’s test indicated that the AUC of F-NLR scoring system was significantly greater than that of fibrinogen level and NLR (Z = 2.929, P = 0.003; Z = 3.376, P < 0.001). Multivariate Cox analysis revealed that tumor size (HR = 1.39, 95%CI = 1.10–1.76, P = 0.007), tumor location (HR = 3.11, 95%CI = 1.60–6.95, P = 0.001), and F-NLR score (score of 1: HR = 12.78, 95%CI = 3.78–43.08, P < 0.001; score of 2: HR = 44.58, 95%CI = 13.02–152.65, P < 0.001) remained significantly associated with 3-year PFS. The good predictive performance of F-NLR scoring system was also demonstrated in the validation set (AUC = 0.824, 95%CI = 0.738–0.891, sensitivity = 62.5%, specificity = 87.9%, and Youden index = 0.504).ConclusionOur study confirmed the correlation and clinical significance of preoperative F-NLR scoring system with 3-year PFS of patients with atypical meningioma. A prospective and large-scale study is required to validate our findings.