Ki-67 labeling index predicts tumor progression patterns and survival in patients with atypical meningiomas following stereotactic radiosurgery.

PURPOSE: This study investigated whether Ki-67 labeling index (LI) correlated with clinical outcomes after SRS for atypical meningiomas. METHODS: This retrospective study examined 39 patients with atypical meningiomas who underwent SRS over a 10-year study period. Ki-67 LI was categorized into 3 groups: low (< 5%), intermediate (5%-10%), and high (> 10%). Local tumor control rates (LCRs), progression-free rates (PFRs), disease-specific survival (DSS) rates, and adverse radiation-induced events (AREs) were evaluated. RESULTS: The median follow-up periods were 26 months. SRS was performed at a median prescription dose of 18 Gy for tumors with a median Ki-67 LI of 9.6%. The 3-year LCRs were 100%, 74%, and 25% in the low, intermediate, and high LI groups, respectively (p = 0.011). The 3-year PFRs were 100%, 40%, and 0% in the low, intermediate, and high LI groups (p = 0.003). The 5-year DSS rates were 100%, 89%, and 50% in the low, intermediate, and high LI groups (p = 0.019). Multivariable Cox proportional hazard analysis showed a significant correlation of high LI with lower LCR (hazard ratio [HR], 3.92; 95% confidence interval [CI] 1.18-13.04, p = 0.026), lower PFR (HR 3.80; 95% CI 1.46-9.88, p = 0.006), and shorter DSS (HR 6.55; 95% CI 1.19-35.95, p = 0.031) compared with intermediate LI. The ARE rates were minimal (8%) in the entire group. CONCLUSION: Patients with high Ki-67 LI showed significantly more tumor progression and tumor-related death. Ki-67 LI might offer valuable predictive insights for the post-SRS management of atypical meningiomas.

The role of GammaTile in the treatment of brain tumors: a technical and clinical overview.

Malignant and benign brain tumors with a propensity to recur continue to be a clinical challenge despite decades-long efforts to develop systemic and more advanced local therapies. GammaTile (GT Medical Technologies Inc., Tempe AZ) has emerged as a novel brain brachytherapy device placed during surgery, which starts adjuvant radiotherapy immediately after resection. GammaTile received FDA clearance in 2018 for any recurrent brain tumor and expanded clearance in 2020 to include upfront use in any malignant brain tumor. More than 1,000 patients have been treated with GammaTile to date, and several publications have described technical aspects of the device, workflow, and clinical outcome data. Herein, we review the technical aspects of this brachytherapy treatment, including practical physics principles, discuss the available literature with an emphasis on clinical outcome data in the setting of brain metastases, glioblastoma, and meningioma, and provide an overview of the open and pending clinical trials that are further defining the efficacy and safety of GammaTile.

Peptide radionuclide radiation therapy with Lutathera in multirecurrent nonanaplastic meningiomas: antitumoral activity study by growth rate analysis.

PURPOSE: Several retrospective studies and meta-analyses of Peptide Radionuclide Radiation Therapy in meningiomas suggest six-month progression-free survival improvement for WHO grade 1 and 2 meningiomas. In the present study, we aimed to evaluate the impact of such treatment on three-dimensional volume growth rate (3DVGR) in nonanaplastic meningiomas. METHODS: The authors performed a retrospective study including eight patients treated with Lutathera®. Millimetric 3D T1-weighted with gadolinium enhancement magnetic resonance imaging sequences were requested for volume measurement. Then, tumor growth rate was classified following a previously described 3DVGR classification (Graillon et al.). RESULTS: Patients harbored seven WHO grade 2 meningiomas and one aggressive WHO grade 1. All patients, except one, underwent four treatment cycles. 3DVGR significantly decreased at 3, 6, and 12 months after treatment initiation analyzing each lesion separately. Mean and median 3DVGR from all patients were respectively at 29.5% and 44.5%/6 months before treatment initiation, then at 16.5% and 25%/6 months at three months post-treatment initiation, 9.5% and 4.5%/6 months after 6 months, as well as 9.5% and 10.5%/6 months after 12 months. At 3, 6, and 12 months after treatment initiation, 4/8, 6/7, and 5/6 patients were class 2 (stabilization or severe 3DVGR slowdown), respectively. No patient was class 1 at 6 and 12 months, suggesting a lack of drug response. CONCLUSION: In nonanaplastic meningiomas, Lutathera®'s antitumoral activity appeared delayed and more likely observed at six months, while no major response was observed under treatment. Moreover, its antitumoral activity persisted for 12-18 months following treatment initiation.

Factors Influencing Long-Term Outcomes of Single-Session Gamma Knife Radiosurgery in Large-Volume Meningiomas >10 cc.

INTRODUCTION: Meningiomas are the most common primary intracranial tumour. Gamma knife radiosurgery (GKRS) is a frequently employed non-invasive method of treatment, with good remission rates and low morbidity in literature. However, the role of GKRS in the management of "large" meningiomas is unclear, with reported outcomes that vary by centre. We aimed to assess the factors that influence long-term outcomes following GKRS in meningiomas >10 cc in volume. METHODS: A retrospectively analysed all patients with meningiomas exceeding 10 cc in volume who underwent GKRS between January 2006 and December 2021 at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. Demographic, clinical, radiological, and follow-up data were acquired, and factors associated with progression following GKRS were assessed. RESULTS: The cohort comprised 76 patients 29 males (38.2%) and 47 females (61.8%) with a mean age of 46.3 ± 11.02 years. Thirty-nine patients had been previously operated (51.3%). Meningiomas were most frequently located in the parasagittal region (26 tumours, 34.2%) and sphenopetroclival region (23 tumours, 30.3%), with mean lesion volume of 12.55 ± 5.22 cc, ranging 10.3 cc-25 cc. The mean dose administered to the tumour margin was 12.5 Gy ± 1.2 Gy (range 6-15 Gy). The median duration of clinical follow-up was 48 months, over which period radiological progression occurred in 14 cases (20%), with unchanged tumour volume in 20 cases (28.6%) and reduction in size of the tumour in 36 cases (51.4%). Progression-free survival after GKRS was 72% at 5 years, was significantly poorer among meningiomas with tumour volume >14 cc (log-rank test p = 0.045), tumours presenting with limb motor deficits (log-rank test p = 0.012), and tumours that underwent prior Simpson grade 3 or 4 excision (log-rank test p = 0.032). CONCLUSIONS: Meningiomas >10 cc in volume appear to display a high rate of progression and subsequent need for surgery following GKRS. Primary surgical resection, when not contraindicated, may be considered with GKRS serving an adjuvant role, especially in tumours exceeding 14 cc in volume, and presenting with limb motor deficits. Long-term clinical and radiological follow-up is essential following GKRS as the response of large meningiomas may be unpredictable.

Upfront stereotactic radiosurgery versus adjuvant radiosurgery for parasagittal and parafalcine meningiomas: a systematic review and meta-analysis.

Parafalcine and parasagittal (PFPS) are common locations for meningiomas. Surgical resection for these tumors, the first-line treatment, poses challenges due to their proximity to critical structures. This systematic review investigates the use of stereotactic radiosurgery (SRS) as a treatment for PFPS meningiomas, aiming to elucidate its safety and efficacy. The review adhered to PRISMA guidelines. Searches were conducted on MEDLINE, Embase, and Cochrane. Inclusion criteria involved studies on SRS for PFPS meningiomas, reporting procedure outcomes and complications. Tumors were presumed or confirmed to be WHO grade 1. Data was systematically extracted. Meta-analysis was performed where applicable. The review included data from eight studies, 821 patients with 878 lesions. Tumor control was achieved in greater than 80% of cases. Adverse radiation effects were reported in 7.3% of them. Recurrence and further surgical approach were observed in 17.1% and 9.2% of cases, respectively. Symptom improvement was noted in 33.2% of patients. Edema occurred in approximately 25.1% of patients. A subgroup of 283 patients had upfront SRS, achieving tumor control in approximately 97% of such cases. SRS is a safe and effective treatment for PFPS meningiomas, both as an adjuvant therapy and as an upfront treatment for often smaller tumors. Post-SRS edema can typically be managed medically and usually does not require further surgical intervention. Further studies should provide more specific data on PFPS meningiomas. The use of single and hypofractionated SRS for larger volume PFPS meningiomas should be more explored to better define the risks and benefits.

Intra-operative extracorporeal irradiation of tumour-invaded craniotomy bone flap in meningioma: a case series.

BACKGROUND: Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought to examine the rate of tumour recurrence and other selected outcomes in patients undergoing meningioma resection and EITC. METHODS: Retrospective single-centre study of adult patients undergoing meningioma resection and EITC between January 2015 and November 2022 at a tertiary neurosurgical centre. Patient demographics, surgery data, tumour data, use of adjuvant therapy, surgical complications, and tumour recurrences were collected. RESULTS: Eighteen patients with 11 (61%) CNS WHO grade 1, 6 (33%) grade 2, and 1 (6%) grade 3 meningiomas were included. Median follow-up was 42 months (range 3-88). Five (28%) patients had a recurrence, but none were associated with the bone flap. Two (11%) wound infections requiring explant surgery occurred. Six (33%) patients required a further operation. Two operations were for recurrences, one was for infection, one was a washout and wound exploration but no evidence of infection was found, one patient requested the removal of a small titanium implant, and one patient required a ventriculoperitoneal shunt for a persistent CSF collection. There were no cases of bone flap resorption and cosmetic outcome was not routinely recorded. CONCLUSION: EITC is feasible and fast to perform with good outcomes and cost-effectiveness compared to other reconstructive methods. We observed similar recurrence rates and lower infection rates requiring explant compared to the largest series of cranioplasty in meningioma. Cosmetic outcome is universally under-reported and should be reported in future studies.

Meningioma WHO I with involvement of the optical structures-does proton therapy lead to changes in quality of life with regard to subjective visual performance?

BACKGROUND: In addition to local tumor control, the aim of any curative radio-oncological treatment is to maintain quality of life. In the treatment of patients with meningioma with a close relationship to optical structures, the preservation of visual performance is a particular challenge. Use of proton therapy can reduce the dose burden to organs at risk immediately adjacent to the tumor. The aim of this study was to score the subjective assessment of visual performance in patients with meningioma involving the optical structures before and after proton therapy. METHODS: All proton-treated patients with meningioma WHO I whose planning target volumes (PTV) included parts of the optic nerve and/or chiasm were included in this study. Subjective assessment of visual performance was evaluated using the Visual Disorder Scale (VDS) of the EORTC QLQ-BN20 questionnaire. This scale includes values from 0 to 100, whereby high values reflect a high degree of subjective symptom burden and thus subjective visual impairment. The visual acuity in externally performed eye tests at baseline and follow-ups (FU) was also evaluated. The timepoints for testing were before the start of radiotherapy, at the end of treatment, and 3, 6, 12, and 24 months in FU (times t1-t6). All patients with at least the first annual postradiation FU at the time of the evaluation were included. The correlation between VDS changes and potential influencing factors such as previous therapies, dosimetric data, initial tumor volume, and tumor shrinkage 1 year after treatment was assessed. RESULTS: A total of 56 patients (45 female/11 male) aged 24-82 years (mean ± SD = 53.9 ± 13.3) treated between March 2017 and September 2019 were included in the analysis. The prescription dose was 54.0 Gy (RBE) with active scanned proton therapy. The mean/D2% dose ± SD for the optic chiasm and ipsilateral optic nerve was 43.4 ± 8.9 Gy (RBE)/49.9 ± 7.1 Gy (RBE) and 35.6 ± 11.7 Gy (RBE)/51.7 ± 4.8 Gy (RBE); the mean/D2% dose ± SD of the contralateral optic nerve was 18.8 ± 12.1 Gy (RBE)/42.4 ± 14.6 Gy (RBE), respectively. A total of 302 data collections were available (t1/t2/t3/t4/t5/t6: n = 56/56/48/56/52/34). Median observation time was 23.6 months. Mean symptom burden decreased over time (mean VDS: t1 29.8 ± 27.9; t2 25.0 ± 27.9; t3 21.8 ± 26.0; t4 22.2 ± 26.0; t5 21.4 ± 26.2; t6 17.3 ± 23.6) with statistically significant improvement at 3­ and 6­month FU as well as 1 year after proton therapy (p = 0.0205; p = 0.0187; p = 0.0054). Objective eye tests available in 41/52 patients confirm the trend towards improved visual acuity (97.5% stable/improved until 24-month FU). However, no potential predictor for VDS changes was revealed. CONCLUSION: Proton treatment of patients with meningioma WHO I with involvement of optical structures does not impair subjective visual performance. After treatment, there is a significant improvement in perceived visual performance.

The trends and significance of SSTR PET/CT added to MRI in follow-up imaging of low-grade meningioma treated with fractionated proton therapy.

PURPOSE: Overexpression of the somatostatin receptor (SSTR) has led to adoption of SSTR PET/CT for diagnosis and radiotherapy planning in meningioma, but data on SSTR expression during follow-up remain scarce. We investigated PET/CT quantifiers of SSTR tracers in WHO grade I meningioma following fractionated proton beam therapy (PBT) compared to standard response assessment with MRI. METHODS: Twenty-two patients diagnosed with low-grade meningioma treated by PBT were included. Follow-up included clinical visits, MRI, and [68Ga]Ga-DOTATOC PET/CT scans. Radiologic tumor response, MRI and PET volume (VMRI and VPET), maximum and mean standardied uptake value (SUVmax/SUVmean), total lesion activity (TLA), and heterogeneity index (HI) were evaluated. RESULTS: Median follow-up was 35.3 months (range: 6.4-47.9). Nineteen patients (86.4%, p = 0.0009) showed a decrease of SUVmax between baseline and first follow-up PET/CT (median: -24%, range: -53% to +89%) and in 81.8% of all cases, the SUVmax, SUVmean, and TLA at last follow-up were eventually lower than at baseline (p = 0.0043). Ambiguous trends without significance between the timepoints analyzed were observed for VPET. HI increased between baseline and last follow-up in 75% of cases (p = 0.024). All patients remained radiologically and clinically stable. Median VMRI decreased by -9.3% (range 0-32.5%, p < 0.0001) between baseline and last follow-up. CONCLUSION: PET/CT in follow-up of irradiated meningioma showed an early trend towards decreased binding of SSTR-specific tracers following radiation and MRI demonstrated consistently stable or decreasing tumor volume. Translational research is needed to clarify the underlying biology of the subsequent increase in SSTR PET quantifiers.

Efficacy and safety of peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE in 15 patients with progressive treatment-refractory meningioma.

PURPOSE: There is no evidence-based systemic therapy for patients with progressive meningiomas for whom surgery or external radiotherapy is no longer an option. In this study, the efficacy and safety of peptide receptor radionuclide therapy (PRRT) in patients with progressive, treatment-refractory meningiomas were evaluated. METHODS: Retrospective analysis of all meningioma patients treated with [177Lu]Lu-DOTA-TATE from 2000 to 2020 in our centre. Primary outcomes were response according to RANO bidimensional and volumetric criteria and progression-free survival (PFS). Overall survival (OS) and tumour growth rate (TGR) were secondary endpoints. TGR was calculated as the percentage change in surface or volume per month. RESULTS: Fifteen meningioma patients received [177Lu]Lu-DOTA-TATE (7.5-29.6 GBq). Prior to PRRT, all patients had received external radiotherapy, and 14 patients had undergone surgery. All WHO grades were included WHO 1 (n=3), WHO 2 (n=5), and WHO 3 (n=6). After PRRT, stable disease was observed in six (40%) patients. The median PFS was 7.8 months with a 6-month PFS rate of 60%. The median OS was 13.6 months with a 12-month OS rate of 60%. All patients had progressive disease prior to PRRT, with an average TGR of 4.6% increase in surface and 14.8% increase in volume per month. After PRRT, TGR declined to 3.1% in surface (p=0.016) and 5.0% in volume (p=0.013) per month. CONCLUSION: In this cohort of meningioma patients with exhaustion of surgical and radiotherapeutic options and progressive disease, it was shown that PRRT plays a role in controlling tumour growth.

Neurocognitive considerations in the treatment of meningioma with radiation therapy: applications for quantitative neuroimaging and precision radiation medicine.

This article focuses on the role of radiotherapy in the management of meningioma, in the definitive and adjuvant setting and across the spectrum of meningioma grade. Treatment paradigms, informed by clinical evidence, are discussed. Notably, we focus on the impact of radiotherapy on normal brain tissues and neurocognitive function, particularly the dose-dependent changes in white matter and cerebral cortex thickness. Novel imaging techniques have allowed the identification of microstructural changes to eloquent white matter, cortex, and subcortical regions as biomarkers for understanding RT-induced changes in cognitive functioning. Deficits in multiple domains including attention, memory, language and executive function can become more pronounced following radiation. Longitudinal assessment with imaging and neurocognitive testing pre- and post-radiation have allowed correlation between dose to specific regions of the brain and decline in associated domains of neurocognitive function. These findings suggest incorporation of areas at higher risk for neurocognitive sequelae into precision radiation planning. Volumetric arc therapy, advanced planning with cortical sparing, proton therapy and stereotactic radiosurgery are reviewed as options for delivering therapeutic dose to target volumes while minimizing risk to adjacent sensitive regions. The treatment of meningioma is an evolving area, with improving outcomes for higher grade disease in modern trials, where care must be taken to maximize both disease control as well as quality of life for patients.

Long-term outcomes of fractionated proton beam therapy for benign or radiographic intracranial meningioma.

PURPOSE: Benign intracranial meningioma is one of the most common primary brain neoplasms. Proton therapy has been increasingly utilized for nonoperative management of this neoplasm, yet few long-term outcomes studies exist. METHODS: The medical records of a total of 59 patients with 64 lesions were reviewed under a prospective outcomes tracking protocol for histologically proven or radiographically benign meningioma. The patients were treated with proton therapy at the University of Florida Proton Therapy Institute between 2007 and 2019 and given a median dose of 50.4 GyRBE at 1.8 GyRBE (relative biological effectiveness) (range 48.6-61.2 GyRBE) in once-daily treatments. RESULTS: With a median clinical and imaging follow-up of 6.3 and 4.7 years, the rates of 5-year actuarial local progression and cumulative incidence of grade 3 or greater toxicity were 6% (95% confidence interval [CI] 1%-14%), and 2% (95% CI < 1%-15%), respectively. Two patients experienced local progression after 5 years. The 5-year actuarial overall survival rate was 87% (95% CI 74-94%). CONCLUSION: Fractionated PBT up to 50.4 GyRBE is a safe and highly effective therapy for treating benign intracranial meningioma.

NF2 mutations are associated with resistance to radiation therapy for grade 2 and grade 3 recurrent meningiomas.

PURPOSE: High grade meningiomas have a prognosis characterized by elevated recurrence rates and radiation resistance. Recent work has highlighted the importance of genomics in meningioma prognostication. This study aimed to assess the relationship between the most common meningioma genomic alteration (NF2) and response to postoperative radiation therapy (RT). METHODS: From an institutional tissue bank, grade 2 and 3 recurrent meningiomas with both > 30 days of post-surgical follow-up and linked targeted next-generation sequencing were identified. Time to radiographic recurrence was determined with retrospective review. The adjusted hazard of recurrence was estimated using Cox-regression for patients treated with postoperative RT stratified by NF2 mutational status. RESULTS: Of 53 atypical and anaplastic meningiomas (29 NF2 wild-type, 24 NF2 mutant), 19 patients underwent postoperative RT. When stratified by NF2 wild-type, postoperative RT in NF2 wild-type patients was associated with a 78% reduction in the risk of recurrence (HR 0.216; 95%CI 0.068-0.682; p = 0.009). When stratified by NF2 mutation, there was a non-significant increase in the risk of recurrence for NF2 mutant patients who received postoperative RT compared to those who did not (HR 2.43; 95%CI 0.88-6.73, p = 0.087). CONCLUSION: This study demonstrated a protective effect of postoperative RT in NF2 wild-type patients with recurrent high grade meningiomas. Further, postoperative RT may be associated with no improvement and perhaps an accelerated time to recurrence in NF2 mutant tumors. These differences in recurrence rates provide evidence that NF2 may be a valuable prognostic marker in treatment decisions regarding postoperative RT. Further prospective studies are needed to validate this relationship.

Outcomes of radiation-induced meningiomas treated with stereotactic radiosurgery.

PURPOSE: Data on the efficacy and safety of stereotactic radiosurgery (SRS) for treatment of radiation-induced meningiomas (RIMs) are limited. METHODS: A single institution database of Cobalt-60 SRS cases from 08/1999 to 10/2020 was reviewed. Radiation-induced meningiomas were identified using Cahan's criteria. Endpoints included overall survival (OS), progression free survival (PFS), local control (LC), treatment failure, and treatment toxicity. Univariate and multivariate analyses were performed using cox proportional hazard models. RESULTS: A total of 29 patients with 86 RIM lesions were identified. Median follow-up after SRS was 59 months. The median dose prescribed to the 50% isodose line was 14 Gy (range 12-20 Gy). The actuarial 5-yr OS and PFS were 96% and 68%, respectively. Patients treated for recurrent RIMs had a significantly lower PFS (45% vs 94% at 3 yr, p < 0.005) than patients treated in the upfront setting. Patients with presumed or WHO grade I RIMs had a significantly greater PFS (3-year PFS 96% vs 20%) than patients with WHO grade II RIMs (p < 0.005). On a per-lesion basis, local control (LC) at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. On multivariate analysis, female gender was associated with improved LC (p < 0.001), while marginal doses > 14 Gy were associated with worse local control (p < 0.001). Grade I-III toxicity following treatment was 9.0%. CONCLUSIONS: Stereotactic radiosurgery is a safe and effective treatment option for radiographic RIMs, WHO grade I RIMs, or lesions treated in the upfront setting. WHO grade II lesions and recurrent lesions are at increased risk for disease progression.

Emerging systemic treatment options in meningioma.

PURPOSE: Meningiomas are the most frequently diagnosed intracranial neoplasms. Usually, they are treated by surgical resection in curative intent. Radiotherapy and stereotactic radiosurgery are commonly applied in the adjuvant setting in newly diagnosed atypical (CNS WHO grade 2), and anaplastic (CNS WHO grade 3) meningioma, especially if gross total resection is not feasible, and in recurrent cases. Conversely, the evidence for pharmacotherapy in meningioma is scarce. METHODS: The available literature of systemic treatment in meningioma was screened using PubMed, and ongoing clinical trials were explored using ClinicalTrials.gov. RESULTS: Classical cytotoxic agents, somatostatin analogs, and antihormone treatments have shown only limited efficacy. In contrast, tyrosine kinase inhibitors and monoclonal antibodies, especially those targeting angiogenic signaling such as sunitinib and bevacizumab, have shown promising antitumoral activity in small phase 2 trials. Moreover, results of recent landmark studies on (epi-)genetic alterations in meningioma revealed potential therapeutic targets which are currently under investigation. These include inhibitors of mammalian target of rapamycin (mTOR), focal adhesion kinase (FAK), cyclin-dependent kinases (CDK), phosphoinositide-3-kinase (PI3K), sonic hedgehog signaling, and histone deacetylases. In addition, clinical trials evaluating immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab and avelumab are currently being conducted and early results suggest clinically meaningful responses in a subset of patients. CONCLUSIONS: There is a paucity of high-level evidence on systemic treatment options in meningioma. However, interesting novel treatment targets have been identified in the last decade. Positive signals of anti-angiogenic agents, genomically targeted agents and immunotherapy in early phase trials should be confirmed in large prospective controlled trials.

The "Combo" radiotherapy treatment for high-risk grade 2 meningiomas: dose escalation and initial safety and efficacy analysis.

PURPOSE: The subgroup "high-risk" WHO grade 2 (hRG2) meningiomas may benefit from adjuvant radiation therapy (RT), but results are still suboptimal with high rates of local progression. A dose escalation using high-conformal RT techniques needs to be evaluated in terms of efficacy and safety. We report the results of a dose-escalation study, named "Combo-RT", combining Intensity Modulated Radiotherapy (IMRT) or Volumetric Arc Therapy (VMAT) with Hypofractionated Stereotactic Radiotherapy (hSRT) boost. PATIENTS AND METHODS: From November 2015 to January 2019, we prospectively enrolled 16 patients with hRG2. Seven patients had subtotal resection (STR) and 9 patients had a recurrent tumor. All patients received Combo-RT: LINAC-IMRT/ VMAT on the surgical bed and CyberKnife-hSRT boost on residual/recurrent meningioma Toxicity and initial efficacy were evaluated. RESULTS: The median age was 62 years (range, 31-80 years). The median cumulative dose delivered was 46 Gy For IMRT or VMAT and 15 Gy in 3 fractions at a median isodose line of 77% for hSRT. The median cumulative BED and EQD2 were 108.75 Gy and 72.5 Gy respectively. 3-year-PFS was 75% for the whole cohort,100% for patients with STR, and 55.5% for recurrent patients. Negligible toxicities, and stable or improved symptoms during long-term follow-up were observed. Salvage treatment for recurrence was an independent predictor of treatment failure (P = 0.025). CONCLUSIONS: With the limitation of a small series of patients, our results suggest that a dose escalation for hRG2 meningiomas, using a Combo-RT approach, is safe and particularly effective in the subgroup of patients with STR. Further studies are warranted.

Improvement in visual outcomes of patients with base of skull meningioma as a result of evolution in the treatment techniques in the last three decades: a systematic review.

PURPOSE: We systematically reviewed visual outcomes over the last three decades in patients undergoing treatment for base of skull (BOS) meningiomas and provide recommendations to preserve vision. METHODS: In accordance with the PRISMA guidelines for systematic reviews, a search was conducted from 6/1/2022-9/1/2022 using PubMed and Web of Science. Inclusion criteria included (1) patients treated for BOS meningiomas (2) treatment modality specified (3) specifics of surgical techniques and/or dose/fractions of radiotherapy (4) individual patient outcomes of treatment. Each study was assessed for bias based on study design and heterogeneity of results. RESULTS: A total of 50 studies were included (N = 2911). When comparing improved vision versus unchanged or worsened vision, studies investigating surgery alone published from 2006 and onward had significantly better visual outcomes compared to pre-2006 studies (p = 0.02). When comparing improved vision versus unchanged or worsened vision, studies investigating combined therapy with surgery and radiation published from 2008 and onward had significantly better visual outcomes compared to pre-2008 studies (p < 0.01). Combined modality therapy was less likely to worsen vision compared to either surgery or radiation monotherapy (p < 0.01). However, surgery and radiation monotherapy were more likely to actually improve outcomes compared to combination therapy (p < 0.01). CONCLUSION: For over a decade we have observed improvement in visual outcomes in patients managed for meningioma of BOS, likely attributing the innovation in microsurgical and more targeted and conformal radiation techniques. Combination therapy may be the safest option for preventing worsening of vision, but the highest rates of improving visual function are achieved through monotherapy when indicated.

Gamma Knife radiosurgery for meningiomas of the confluence of the falx and tentorium.

PURPOSE: Meningiomas arising from the confluence of the falx and tentorium (CFT) are a rare and challenging subset of meningiomas. Gamma Knife radiosurgery (GKRS) is well-established as a safe and effective management strategy for intracranial meningiomas, but its role in treating CFT meningiomas is not well-described. This paper reports the largest series focused exclusively on the outcomes of GKRS for CFT meningiomas. METHODS: We retrospectively identified 20 CFT meningiomas out of 2031 meningioma patients who underwent GKRS at our institution between 1987 and 2021. Tumor control, overall survival (OS), and complications were recorded and analyzed. The median tumor margin dose was 13 Gy at the 50% isodose line. The median tumor volume treated was 4.4 cc (IQR 3.5-7.7). The median patient age was 58 years (range 33-83), the median MRI surveillance duration was 59 months (IQR 34-92), and the median overall follow-up duration was 92 months (IQR 42-201). RESULTS: The local tumor control rate (PFS) at 5 and 10-years were 100% (N=10) and 83% (N=4), respectively. Eight patients had stable tumor volumes and 11 patients had regression. One patient with a twice-operated tumor had delayed progression at 7.5 years and was retreated with GKRS. No patient had adverse radiation effects during the period of MRI surveillance. The 5 and 10-year OS were 100% (N=13) and 100% (N=7), respectively. CONCLUSIONS: GKRS is a valuable therapeutic strategy for patients with newly diagnosed CFT meningiomas or progressive residual tumors after surgical resection.

Can Apparent Diffusion Coefficient (ADC) maps replace Diffusion Tensor Imaging (DTI) maps to predict the volumetric response of meningiomas to Gamma Knife Radiosurgery?

PURPOSE: Noninvasive methods are desired to predict the treatment response to Stereotactic Radiosurgery (SRS) to improve individual tumor management. In a previous study, we demonstrated that Diffusion Tensor Imaging (DTI)-derived parameter maps significantly correlate to SRS response. This study aimed to analyze and compare the predictive value of intratumoral ADC and DTI parameters in patients with meningiomas undergoing radiosurgery. METHODS: MR images of 70 patients treated with Gamma Knife SRS for WHO grade I meningiomas were retrospectively reviewed. MR acquisition included pre- and post-treatment DWI and DTI sequences, and subtractions were calculated to assess for radiation-induced changes in the parameter values. RESULTS: After a mean follow-up period (FUP) of 52.7 months, 69 of 70 meningiomas were controlled, with a mean volume reduction of 34.9%. Whereas fractional anisotropy (FA) values of the initial exam showed the highest correlation to tumor volume change at the last FU (CC = - 0.607), followed by the differences between first and second FU values of FA (CC = - 0.404) and the first longitudinal diffusivity (LD) value (CC = - 0.375), the correlation coefficients of all ADC values were comparably low. Nevertheless, all these correlations, except for ADC measured at the first follow-up, reached significance. CONCLUSION: For the first time, the prognostic value of ADC maps measured in meningiomas before and at first follow-up after Gamma Knife SRS, was compared to simultaneously acquired DTI parameter maps. Quantities assessed from ADC maps present significant correlations to the volumetric meningioma response but are less effective than correlations with DTI parameters.

Evaluation of the growth rates and related prognostic factors in radiation-induced meningiomas.

PURPOSE: Literature dedicated to growth patterns and growth rate influencing factors of radiation-induced meningiomas (RIMs) is limited. To deliver new insights into the topic, a volumetric growth analysis of RIMs was performed. METHODS: This single-center, retrospective cohort study included patients diagnosed with intracranial meningioma who received radiation treatment at least > 5 years before the RIM diagnosis. Volumetric analysis of individual RIMs was performed using 3D volumetry at the time of RIM diagnosis and during follow-up. RIM growth was determined by calculating absolute (AGR), and relative (RGR) growth rates. Prognostic factors associated with RIM growth were evaluated. RESULTS: A total of 26 patients with 33 meningiomas were enrolled in the study and radiologically/clinically followed up during a median duration of 5.6 years (IQR 3.9-8.8 years). Median AGR was 0.19 cm3 per year and the median RGR was 34.5% per year. Surgically managed RIMs were more likely fast-growing compared to observed ones based on the AGR (p < 0.002). The recurrence rate after total resection was 14.3%. Younger age at RIM diagnosis was associated with higher tumor growth (RGR ≥ 30%, p = 0.040). A significant correlation was found between the length of latency period and the RGR (p = 0.005). CONCLUSION: To diagnose RIM as early as possible comprehensive MRI surveillance is required. Younger patients with shorter latency periods may profit from shortened MRI intervals, with further management being dependent on the growth rate and eventual symptomatology.

Single session versus multisession stereotactic radiosurgery for the management of intracranial meningiomas: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy, outcomes, and complications of single session (SS-SRS) and multisession (MS-SRS) stereotactic radiosurgery in the treatment of intracranial meningiomas. METHODS: Relevant articles were retrieved from PubMed, Scopus, Web of Science, and Cochrane. A systematic review and meta-analysis of treatment protocols and outcomes were conducted. After the selection process, 20 articles describing 1483 cases were included. RESULTS: A total of 1303 patients who underwent SS-SRS and 180 patients who underwent MS-SRS for the management of their intracranial meningioma were reported in the included studies. SS-SRS and MS-SRS had comparable one-year (SS-SRS: 98% vs. MS-SRS: 100%, p > 0.99) and five-year (SS-SRS: 94% vs. MS-SRS: 93%, p = 0.71) tumor control rates. The groups also had comparable tumor volume reduction/tumor regression rates (SS-SRS: 44% vs. MS-SRS: 25%, p = 0.25), tumor volume stability rates (SS-SRS: 51% vs. MS-SRS: 75%, p = 0.12), and tumor progression rates (SS-SRS: 4% vs. MS-SRS: 4%, p = 0.89). SS-SRS and MS-SRS yielded similar complication rates (10.4% vs. 11.4%, p = 0.68) and comparable functional improvement rates (MS-SRS: 44% vs. SS-SRS: 36%, p = 0.57). However, MS-SRS was used for significantly larger tumor volumes (MS-SRS: 23.8 cm3 vs. SS-SRS: 6.1 cm3, p = 0.02). CONCLUSION: SS-SRS and MS-SRS resulted in comparable tumor control, tumor volumetric change, and functional outcomes despite significant biases in selecting patients for SS- or MS-SRS.