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Background Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39–58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. Methods/Design A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. Discussion ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. Trial registration ISRCTN71502099 on 19 May 2014.

Meningioma is the most common intracranial tumor. Sometimes, meningiomas can develop malignant transformation (MT). In this review, we review the incidence of MT of meningiomas. The incidence of MT of grade 2 meningiomas is likely to be higher than benign meningiomas. Approximately 1% to 4% of WHO Grade 1 meningiomas may undergo MT, while about 26% to 33% of Grade 2 meningiomas experience MT. Time to MT of grade 2 meningiomas seemed to be shorter than MT of grade 1 meningiomas. The time for Grade I meningiomas to undergo MT is approximately 5 years, while Grade II meningiomas typically experience MT in about 3 years. Several risk factors may be associated with MT, including non-skull base location, high mitotic Index, a larger primary tumor size, shorter recurrence time interval and male. Potential molecular mechanisms of MT include chromosomal abnormalities (Chromosome 22q deletion, NF2 gene mutation, loss of chromosome 1p), genomic alterations (FOXM1, CDKN2A/B and TERTp), and meningioma cancer stem cells. Secondary meningiomas may have poor tumor control rates and overall survival rates than primary meningiomas. Besides, the role of radiotherapy in MT of meningiomas is unclear. Major concerns are whether radiotherapy can induce MT of meningiomas, and whether radiotherapy can prolong time to MT through long term control of meningiomas. This review summarizes the MT of meningiomas, and may provide the direction for further study of meningiomas.

BackgroundClinical behaviour of atypical meningiomas is not uniform. While, as a group, they exhibit a high recurrence rate, some pursue a more benign course, whereas others progress early. We aim to investigate the imaging and pathological factors that predict risk of early tumour progression and to determine whether early progression is related to outcome.MethodsAdult patients with WHO grade II meningioma treated in three regional referral centres between 2007 and 2014 were included. MRI and pathology characteristics were assessed. Gross total resection (GTR) was defined as Simpson 1–3. Recurrence was classified into early and late (≤ 24 vs. > 24 months).ResultsAmong the 220 cases, 37 (16.8%) patients progressed within 24 months of operation. Independent predictors of early progression were subtotal resection (STR) (p = 0.005), parafalcine/parasagittal location (p = 0.015), peritumoural oedema (p = 0.027) and mitotic index (MI) > 7 (p = 0.007). Adjuvant radiotherapy was negatively associated with early recurrence (p = 0.046). Thirty-two per cent of patients with residual tumour and 26% after GTR received adjuvant radiotherapy. There was a significantly lower proportion of favourable outcomes at last follow-up (mRS 0–1) in patients with early recurrence (p = 0.001).ConclusionsAtypical meningiomas are a heterogeneous group of tumours with 16.8% patients having recurrence within 24 months of surgery. Residual tumour, parafalcine/parasagittal location, peritumoural oedema and a MI > 7 were all independently associated with early recurrence. As administration of adjuvant radiotherapy was not protocolised in this cohort, any conclusions about benefits of irradiation of WHO grade II meningiomas should be viewed with caution. Patients with early recurrence had worse neurological outcome. While histological and imaging characteristics provide some prognostic value, further molecular characterisation of atypical meningiomas is warranted to aid clinical decision making.

Abstract BACKGROUND Meningiomas are the most common tumors occurring in the central nervous system, with variable recurrence rates depending on World Health Organization grading. Atypical (Grade II) meningioma has a higher rate of recurrence than benign (Grade I) meningioma. The efficacy of adjuvant radiotherapy (RT) to improve tumor control has been questioned. OBJECTIVE To investigate clinical and histopathological predictors of tumor recurrence and radio-resistance in atypical meningiomas. METHODS This cohort study retrospectively reviewed all patients in St. Michael's Hospital CNS tumor patient database who underwent surgical resection of a Grade II meningioma from 1995 to 2015. Cases with neurofibromatosis type II, multiple satellite tumors, spinal cord meningioma, radiation-induced meningioma, and perioperative death were excluded. Patient demographics, neuropathological diagnosis, tumor location, extent of resection, radiation therapy, and time to recurrence or progression were recorded. Cox univariate regression and Kaplan-Meier survival analysis were employed to identify risk factors for recurrence and radio-resistance. RESULTS Among 181 patients, the combination of necrosis and brain invasion was associated with an increased recurrence risk (hazard ratio [HR] = 4.560, P = .001) and the lowest progression-free survival (PFS) relative to other pathological predictors. This trend was maintained after gross total resection (GTR, P = .001). RT was associated with decreased PFS (P = .001), even in patients who received GTR (P = .001). CONCLUSION The combination of necrosis and brain invasion is a strong predictor of tumor recurrence and radio-resistance in meningioma, regardless of EOR or adjuvant RT. Our findings question the sensibility of brain invasion as an absolute criterion for Grade II status.

Purpose We assess the efficacy of different surgical resection types, radiotherapy, systemic therapy on overall survival in very elderly patients (age > 80) with intracranial atypical meningioma in contrast with their elderly (65–80) counterparts. Methods Patients > 65 years old with intracranial atypical meningiomas surgically resected and catalogued via the National Cancer Database were included. Cox proportional hazards models were developed to assess the association between surgical resection type, radiotherapy and systemic therapy with OS while controlling for sex, race, ethnicity, facility type, income, tumor size and CDCC score. Results 1747 elderly patients and 382 very elderly patients were included. 61.70% elderly patients and 58.90% very elderly patients received GTR. 26.50% elderly patients and 14.13% very elderly patients received radiotherapy. In multivariate analysis, subtotal resection is associated with worse survival (HR 1.28, p  < 0.01) and radiotherapy is associated with improved survival (HR 0.76, p  < 0.01). Systemic therapy was not associated with changes in survival outcomes (HR 1.17, p  = 0.79). Using subgroup analysis, gross total resection is associated with better survival outcomes in both elderly and very elderly cohorts. Radiotherapy was not associated with improved survival (HR 0.85, p  = 0.11) for patients between 65 and 80 years old, but was associated with improved survival (HR 0.51, p  < 0.01) for patients > 80 years old. Conclusion GTR provides survival advantage in both elderly and very elderly cohorts. Radiotherapy provides survival benefits for very elderly patients even though very elderly patients are less likely to received radiotherapy. Very elderly patients may benefit from more aggressive management in the treatment of atypical meningiomas.

PurposeWe conducted a National Cancer Database (NCDB) study to investigate the epidemiological characteristics and identify predictors of outcomes associated with geriatric meningiomas.MethodsThe NCDB was queried for adults aged 60–89 years diagnosed between 2010 and 2017 with grade 2 and 3 meningiomas. The patients were classified into three age groups based on their age: 60–69 (hexagenarians), 70–79 (septuagenarians), and 80–89 (octogenarians). The log-rank test was utilized to compare the differences in overall survival (OS). Univariate and multivariate Cox proportional hazards regressions were used to evaluate the mortality risk associated with various patient and disease parameters.ResultsA total of 6585 patients were identified. Hexagenerians were the most common age group (49.8%), with the majority of meningiomas being classified as grade 2 (89.5%). The incidence of high-grade meningiomas increased in all age groups during the study period. Advanced age, male sex, black race, lower socioeconomic status, Charlson-Deyo score ≥ 2, and higher tumor grade were independent factors of poor survival. Among the modes of treatment, the extent of surgical resection, adjuvant radiotherapy, and treatment at a noncommunity cancer program were linked with better outcomes.ConclusionIn geriatric patients with high-grade meningiomas, the greater extent of surgical resection and radiotherapy are associated with improved survival. However, the management and outcome of geriatric patients with higher-grade meningiomas are also associated with several socioeconomic factors.

The effect of adjuvant radiotherapy in management for high‐grade meningiomas, especially atypical meningiomas, remains controversial. We aimed to explore the role of adjuvant radiotherapy in this population. A total of 162 adults with high‐grade meningiomas (99 atypical meningiomas and 63 anaplastic meningiomas) were treated from 2003 to 2008 at Huashan Hospital. One hundred and seventeen patients presented with primary and 45 with recurrent disease. One hundred and fifteen patients (70.9%) were treated with adjuvant radiotherapy after surgical resection. The median follow‐up was 76.5 months (range 1‐142 months). Kaplan‐Meier survival curve and Cox proportional hazards modeling were used for analyses. Adjuvant radiotherapy was associated with prolonged progression‐free survival (PFS) and overall survival (OS) in patients with newly diagnosed anaplastic meningiomas irrespective of extent of resection (PFS, P = .001; OS, P = .003). Gross total resection was the only independent prognostic factor for those with newly diagnosed atypical meningiomas (PFS, P < .001; OS, P = .012). A survival benefit for adjuvant radiation was also found in subgroup analysis of patients with high‐grade meningiomas who underwent subtotal resection (PFS, P = .023; OS, P = .013). Among recurrent high‐grade meningiomas, radiotherapy offered no statistically significant improvement in either PFS or OS. Adjuvant radiotherapy is associated with improved survival in patients with newly diagnosed anaplastic meningiomas and those high‐grade meningiomas following subtotal resection. However, there was no significant correlation identified between postoperative radiation and outcome for recurrent high‐grade meningiomas. Future prospective randomized trials may help clarify the optimal tailored treatment for patients with high‐grade meningioma. The article focuses on the prognostic value of postoperative radiation in patients with atypical or anaplastic meningioma. We demonstrate that adjuvant radiotherapy is associated with improved survival in patients with high‐grade meningiomas following subtotal resection. However, postoperative radiation was not associated with significant improvement in outcome for patients with recurrent high‐grade meningiomas. The article focuses on the prognostic value of postoperative radiation in patients with atypical or anaplastic meningioma. We demonstrate that adjuvant radiotherapy is associated with improved survival in patients with high‐grade meningiomas following subtotal resection. However, postoperative radiation was not associated with significant improvement in outcome for patients with recurrent high‐grade meningiomas.

Purpose Atypical meningioma (AM) recurs in up to half of patients after surgical resection and may require adjuvant therapy to improve patient prognosis. Various clinicopathological features have been shown to have prognostic implications in AM, but an integrated prediction model is lacking. Thus, in this study, we aimed to develop and validate an integrated prognostic model for AM. Methods A retrospective cohort of 528 adult AM patients surgically treated at our institution were randomly assigned to a training or validation group in a 7:3 ratio. Sixteen baseline demographic, clinical, and pathological parameters, progression-free survival (PFS), and overall survival (OS) were analysed. Sixty-five combinations of machine learning (ML) algorithms were used for model training and validation to predict tumour recurrence and patient mortality. Results The random survival forest (RSF) model was the best model for predicting recurrence and death. Primary or secondary tumour, Ki-67 index, extent of resection, tumour size, brain involvement, tumour necrosis, and age contributed significantly to the model. The C-index value of the RSF recurrence prediction model reached 0.8080. The AUCs for 1-, 3-, and 5-year PFS were 0.83, 0.82, and 0.86, respectively. The C-index value of the RSF death prediction model reached 0.8890. The AUCs for 3-year and 5-year OS were 0.88 and 0.89, respectively. Conclusion A high-performing integrated RSF predictive model for AM recurrence and patient mortality was proposed that may guide therapeutic decision-making and long-term monitoring.

The object of this study was to analyze treatment outcomes and to identify the prognostic factors, with a focus on the role of adjuvant radiotherapy (ART), predicting disease progression in atypical meningiomas. From 1997 to 2011, 83 patients with meningioma were included in this study. All patients were histologically confirmed as atypical meningioma and were treated with surgical resection with or without ART. As primary therapy, 27 patients received surgical resection followed by ART, and 56 received no adjuvant therapy. Of 83 evaluable patients, 55 (66.3 %) patients underwent complete resection. The median ART dose was 61.2 Gy and their median age was 52 years. The 5- and 10-year actuarial overall survival rates were 90.2 and 62.0 %, and the 5- and 10-year progression-free survival (PFS) rates were both 48.0 %, with a median follow-up of 43.0 months. Addition of ART ( p  = 0.016) and complete tumor resection ( p  = 0.002) were associated with superior PFS. When stratified to four groups according to resection status and ART, the groups of patient with incomplete resection without ART showed significantly worse PFS compared to other three groups ( p  < 0.001). In conclusion, surgical resection followed by ART led to lower local tumor progression in patients with atypical meningioma defined by the updated 2000/2007 WHO classification. Our results may contribute to the routine use of ART, especially after incomplete resection, until the outcomes of ongoing prospective trials are available.

Abstract OBJECTIVE Atypical meningioma (AM) patients often undergo gross total resection (GTR) at the time of presentation, but subsequent prognosis and optimal management remain unclear. We sought to define the long-term recurrence rate of AMs after GTR, along with factors predicting recurrence, including postoperative radiation. METHODS We performed a retrospective review of 108 AMs after GTR at our institution from 1993 to 2004. Recurrence risk factors were analyzed using multivariate Cox regression. RESULTS There were 600 patient-years of imaging follow-up on 48 men and 60 women. Of 108 tumors, 30 (28%) recurred 3 to 144 months after GTR (mean, 36 months). Actuarial tumor recurrence rates were 7% (1 year), 41% (5 years), and 48% (10 years). Of 108 patients, 8 received postoperative radiation without recurrence (P = 0.1). Multivariate analysis including age, sex, postoperative radiation, tumor location, MIB-1 labeling index, and 6 atypical-defining histological features identified recurrence-predicting factors: older age (hazard ratio, 1.6/decade; P = 0.01), sheeting (hazard ratio, 2.2; P = 0.025), and prominent nucleoli (hazard ratio, 2.1; P = 0.034). Recursive partitioning identified a subset, men with mitoses and prominent nucleoli, with 70% recurrence (n = 14). All patients with recurrences received radiation, and 22 of 30 patients underwent craniotomies (average, 2.7 craniotomies per patient with recurrence; range, 1–7 craniotomies). Only 1 of 22 re-resected meningiomas underwent malignant transformation. Of 30 patients with recurrence, 10 experienced tumor-induced mortality an average of 7 years after recurrence (range, 1–14 years). CONCLUSION After GTR without postoperative radiation, AMs have a high recurrence rate. Most recurrences occurred within 5 years after resection. Recurrences caused numerous reoperations per patient and shortened survival. Our finding suggesting lower recurrence rates in patients undergoing immediate postoperative radiation should be investigated in larger, prospective series.