Postoperative Adjuvant Radiotherapy in Atypical Meningioma Patients: A Meta-Analysis Study

Background and PurposeConsensus regarding the need for adjuvant radiotherapy (RT) in patients with atypical meningiomas (AMs) is lacking. We compared the effects of adjuvant RT after surgery, gross total resection (GTR), and subtotal resection (STR) on progression-free survival (PFS) and overall survival (OS) in patients with AMs, respectively.MethodsWe performed a systematic review and meta-analysis of the literature published in PubMed, Embase, and the Cochrane Library from inception to February 1, 2021, to identify articles comparing the PFS and OS of patients receiving postoperative RT after surgery, GTR and STR.ResultsWe identified 2307 unique studies; 24 articles including 3078 patients met the inclusion criteria. The sensitivity analysis results showed that for patients undergoing undifferentiated surgical resection, adjuvant RT reduced tumor recurrence (HR=0.70, p<0.0001) with no significant effect on survival (HR=0.89, p=0.49). Postoperative RT significantly increased PFS (HR=0.69, p=0.01) and OS (HR=0.55, p=0.007) in patients undergoing GTR. The same improvement was observed in patients undergoing STR plus RT (PFS: HR=0.41, p<0.00001; OS: HR=0.47, p=0.01). A subgroup analysis of RT in patients undergoing GTR showed no change in PFS in patients undergoing Simpson grade I and II resection (HR=1.82, p=0.22) but significant improvement in patients undergoing Simpson grade III resection (HR=0.64, p=0.02).ConclusionRegardless of whether GTR or STR was performed, postoperative RT improved PFS and OS to varying degrees. Especially for patients undergoing Simpson grade III or IV resection, postoperative RT confers the benefits for recurrence and survival.

FDG avid cerebellar atypical meningioma masquerading as solitary brain metastases in a recently diagnosed breast malignancy: a toss between MR and CT

Background SUV Max is a glycolytic index obtained from PET imaging, relates to tumour cell proliferation. FDG uptake (i.e. SUV max) is found to be high in aggressive tumours and is used to identify malignant from benign pathologies. Meningiomas are intracranial tumours which display varying grades of FDG avidity based on its biological aggressiveness. Benign grade I meningiomas are FDG non-avid, while the rest of the typical and atypical meningiomas show varying degrees of FDG avidity. Uptake of FDG can be high in certain infectious and inflammatory brain etiologies and pose a diagnostic challenge in differentiating benign brain lesions from neoplasms. MRI is the preferred modality for accurately identifying meningiomas, providing superior contrast differentiation and its ability to differentiate extra-axial from intra-axial brain lesions. CT is said to be superior in specific types of meningioma where there is calcification and adjacent changes in calvarium. Although typical meningiomas have characteristic MRI features, care must be taken to avoid misleading diagnosis between brain tumours and atypical meningiomas. Case presentation We are presenting a recently diagnosed case of invasive breast carcinoma (Ca) referred for staging by PET/MR imaging. Based on atypical DWI and ADC map findings, MRI falsely reported an atypical meningioma as a brain metastasis. Abnormal intense FDG uptake was noted in a well-defined homogeneously enhancing mass lesion in posterior fossa in left paramedian aspect and broad base to left transverse sinus protruding into left cerebellar hemisphere. Atypical meningioma Grade III, i.e. papillary meningioma was later histologically proven. Conclusions We wish to highlight the inconsistency of DWI and ADC map MR findings in papillary meningioma masquerading as solitary brain metastases in a Ca breast patient on 18F FDG PET/MR imaging. From an imaging standpoint, it is important to recognize the variable and pleomorphic features exhibited by meningiomas in MR based on atypical location, histological subtypes, and biologic behaviours. Further FDG PET was incremental in displaying a high SUV max indicating biologic aggressiveness of lesion and correlating with the CT diagnosis of papillary meningioma.

RADT-28. RECURRENT MENINGIOMA WITH 1p/22q SOMATIC MUTATION OF GNAS: A CASE REPORT

OBJECTIVE Refractory meningioma faces the problems of low total resection rate, high recurrence rate and high disability rate. Here we report a patient with recurrent refractory meningioma who was benefited from precision treatment plan based on molecular diagnosis. METHODS Molecular diagnosis by next generation sequencing (NGS) test was used to test the hybridized captured DNA in the tumor tissue of the patient. RESULTS The 53-year-old female diagnosed with meningioma was admitted to our hospital after tumor progression was observed for 3 weeks. She had received 4 operations for the tumor previously. The first three times of postoperative pathology indicated WHO Ⅰ grade meningioma. The fourth postoperative pathology showed excessive meningioma, with active growth of tumor cells in some areas and small focal necrosis, WHO Ⅰ- fair grade. Somatic mutation GNAS p.F309VFS *25 and deletion of the short arm of chromosome 1 / long arm of chromosome 22 were also found (1P / 22Q) by NGS test. The second recurrent foci showed partial amplification of 17q and 19, except for 1p/22q deletions, compared with the first. Meningiomas with 1p/22q deletion are type C meningiomas (more than half are grade WHO Ⅰ). Meningiomas have been shown to be highly vascularized neoplasms, with a 2-fold increase in VEGF expression in atypical meningiomas and a 10-fold increase in malignant meningiomas. According to the molecular diagnosis results, the precise treatment plan was determined: concurrent chemoradiotherapy, followed by anti-VEGF-targeted drugs combined with temozolomide for 2 months. The residual lesions were significantly reduced after treatment. CONCLUSION This case is the first to report a meningioma with pituitary tumor driver gene GNAS mutation, which is more prone to recurrence due to the combination of 1P / 22Q chromosome mutation. Molecular diagnosis can guide precise treatment to benefit patients.

RADT-31. TREATMENT TRENDS AND SURVIVAL OUTCOMES IN ATYPICAL MENINGIOMA

BACKGROUND WHO grade II (atypical) meningiomas are treated with surgical resection, often followed by adjuvant fractionated radiation therapy (FRT). The increased availability of frameless stereotactic radiosurgery (SRS) presents an opportunity to offer patients a high biological effective dose over fewer fractions. Here we study the patterns of care and outcomes of these two forms of adjuvant RT. METHODS Patients with atypical meningioma were abstracted from the National Cancer Database (NCDB). Descriptive statistics were reported, and differences between treatment groups were assessed using either a chi-square test or ANOVA. Patients were grouped by treatment type and Kaplan Meier (KM) analysis was performed to compare overall survival (OS) using a log rank test. Univariable (UVA) and multivariable (MVA) cox regression analyses were completed. RESULTS Of 10,015 cases diagnosed from 2004-2016, 7,153 received surgery alone, 2,059 received surgery and adjuvant FRT (S+RT), and 362 received adjuvant SRS (S+SRS). The use of adjuvant RT increased by 71.8% for S+RT and 97.8% for S+SRS. In 2004, 15.1% of 443 registered patients received S+RT and 2.26% received S+SRS, while in 2016 these figures were 26.0% and 4.47%, respectively, for the 1051 registered patients (p< 0.001 and 0.022, respectively). For the 8,636 patients with survival data there was no significant difference in median OS between S+RT and S+SRS (130 months vs. 125 months, log rank p=0.935). On UVA, S+RT conferred better survival compared to surgery alone (HR 0.81 [0.72-0.91], p< 0.001) while S+SRS trended towards better survival (HR 0.82 [0.64-1.06], p=0.124). On MVA, no significant OS benefit was seen with S+RT (HR 0.96 [0.85-1.08], p=0.491) or S+SRS (HR 0.90 [0.69-1.16], p=0.413) versus surgery alone. CONCLUSIONS While the use of adjuvant RT for atypical meningioma has increased substantially since 2004, OS is comparable between FRT and SRS. The data presented here support further prospective investigation of adjuvant SRS.

Prognostic Factors For Intermediate-Risk Atypical Meningiomas Determining Early Postoperative Adjuvant Radiotherapy Versus Active Monitoring After Gross Total Resection

Background Atypical meningiomas (AMs) constitute 18% of meningiomas. Predictors of recurrence are still indeterminate, and the timing of RT whether to treat with radiation upfront or at initial recurrence remains controversial, especially after gross total resection (GTR). Methods A retrospective study of AMs with uni-and multivariate analyses was conducted with clinical, surgical, radiological, and histopathological parameters. The prognostic factors associated with increased risk of recurrence were elucidated in the whole series and in the subgroup with GTR only. Results Subtotal resection (STR), skullbase-tentorium localization, no adjuvant RT, and progesterone-negativity caused tumor recurrence in 37 patients with a median follow-up of 48 (2-120) months. Among subgroup of 23 patients GTR only, 30.8% showed recurrence in a median of 39.65 months. AMs with a preoperative volume ≥27.5 cm3 disclosed a significantly higher risk of recurrence (a 9.3 fold increase) than those with <27.5 cm3 (66.7% vs. 14.3%, respectively). Skullbase-tentorium localization and progesterone negativity tend to have higher recurrence rates after GTR. Conclusions Preoperative volume was found to be a prognostic factor for AMs with a cut-off value of 27.5 cm3 for the first time in the literature. Our results disclosed that RT could be delayed with active monitorization after GTR for AMs, which are smaller than 27.5 cm3, not localized in skullbase-tentorium and progesterone-positive. Otherwise, early postop RT would be a safer approach without waiting the recurrence for AMs.

Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression

More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54–0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.

Adjuvant Radiotherapy in Grade II, Atypical Meningioma of the Skull Base

Introduction Atypical meningiomas (AM) are meningiomas that are more aggressive than their grade-I counterparts and have a higher rate of recurrence. The effect of adjuvant radiotherapy (ART) on AM of the skull base is not defined. Methods A retrospective review of all AM's of the skull base primarily resected at our institution from 1996 to 2018 was completed. ART was defined as radiotherapy (RT) that occurred within 6 months of initial resection, regardless of Simpson's grade. Minimum time length of follow-up after resection was 2 years. Statistical analysis was performed using SAS. Results There were a total of 59 skull base–located (SBL) AMs resected at our institution from 1996 to 2018. The average age of our cohort was 53.2 years. Gross total resection, defined as Simpson's grades I to III resection, was achieved in 36 (61%) of cases. Thirty-five of 59 (59%) patients received ART. Recurrence was observed in 14 patients (24%), and mean time to recurrence was 63.8 months. Patients who received ART had a lower observed rate of recurrence (8 vs. 46%); however, time to recurrence was not significantly different between the two populations. Conclusion We observe that AM in the skull base location have higher recurrence rates than we would expect from grade-I meningioma. These data suggest that ART may offer benefit to the overall observed frequency of recurrence of SBL AM; however, the time to recurrence between patients who received ART and those who did not was not statistically significant in survival analysis.

Single-fraction Stereotactic Radiosurgery for Atypical Meningiomas (WHO grade II): Treatment Results Based on a 25-year Experience

PurposeTo clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM).MethodsA retrospective analysis of 68 patients with AM having SRS from 1995 until 2019. Nineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54 Gy). The median follow-up period was 52 months.ResultsEighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6 months), early salvage (7-18 months), or late salvage treatment (> 18 months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals (DSSs) were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n=7). Prior EBRT was associated with reduced PFS (HR = 5.92, P <0.01), reduced DSS (HR = 5.84, P <0.01), and an increased risk of ARE (HR = 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR = 3.17, P = 0.01) or late salvage treatment (HR = 4.39, P <0.01). ConclusionPFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.