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Caroline Apra, Karima Mokhtari, Philippe Cornu, Matthieu Peyre and Michel Kalamarides

OBJECTIVE

Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion.

METHODS

The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations.

RESULTS

Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3–13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors.

CONCLUSIONS

Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors.

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Michel Kalamarides, Eddy Dewolf, Anne Couvelard, Arash Shahidi, Didier Bouccara, Francoise Cyna-Gorse, Alain Rey and Olivier Sterkers

✓ Extraaxial cerebellopontine angle (CPA) medulloblastomas and other primitive neuroectodermal tumors (PNETs) are rare tumors. The authors report on two patients with PNETs who presented with progressive audiovestibular symptoms. In each case magnetic resonance (MR) imaging revealed an extraaxial lesion that filled the internal auditory meatus and exhibited the neuroimaging features of a vestibular schwannoma (VS). No high signal intensity was apparent in either the brainstem or adjacent cerebellum on T2-weighted MR images. Surgery with maximum resection (total in one case and subtotal in the other) was performed, followed by craniospinal radiotherapy. One year postoperatively, both patients were free from tumor.

A CPA PNET mimicking a VS is a rare entity, the diagnosis of which is important because its treatment differs dramatically from that of VS, including prescribed surgery followed by conventional craniospinal radiotherapy.

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Michel Kalamarides, Alexis Bozorg Grayeli, Didier Bouccara, Emmanuelle Ambert Dahan, Wolf Peter Sollmann, Olivier Sterkers and Alain Rey

✓ The auditory brainstem implant (ABI) is designed to restore useful auditory sensations in patients with neurofibromatosis Type 2 (NF2). The implantation is usually performed at the time of tumor removal in patients who do not undergo radiation treatment. The authors evaluated the performance of ABIs in three patients with NF2 in whom vestibular schwannoma continued to grow after radiation treatment. These three patients with NF2 received a 21-channel ABI; a translabyrinthine approach was used for both the tumor removal and the ABI placement. The interval between radiosurgery and the tumor removal plus device implantation ranged from 2 to 11 years. In all cases, the tumor was growing and the patients presented with total deafness. The mean number of active electrodes in these three patients was equivalent to the average results reported in other patients who received ABIs. The patients in this study used the ABI regularly for everyday life and obtained useful levels of environmental sound recognition. It is concluded that hearing function can be rehabilitated using ABIs in patients with NF2, even if radiosurgery fails to control the tumor growth.

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Aymeric Amelot, Remy van Effenterre, Michel Kalamarides, Philippe Cornu and Anne-Laure Boch

OBJECTIVE

Meningiomas confined to the cavernous sinus (MCSs) are benign tumors. Due to the high risk of severe complications, the intracavernous surgical procedure was abandoned in favor of radiotherapy. However, the choice of treatment remains complicated due to the fact that the natural history of this lesion has not yet been described.

METHODS

The authors studied the natural history of this lesion using a prospective series of 53 consecutive patients suffering from MCSs. The median follow-up duration was 10.2 years (range 2–25 years), from 1990 to 2016.

RESULTS

Patients ranged in age from 30 to 72 years (mean 53 years). The meningiomas were diagnosed by major symptoms (mainly oculomotor palsy and neuralgia experienced in 28 patients), minor symptoms (headache, intermittent diplopia in 15 patients), or incidental findings (10 patients). Simple symptomatic treatment (short courses of corticosteroids and carbamazepine) allowed patients to become asymptomatic in 19 (67.9%) of 28 cases experiencing major symptoms, and for 12 (80%) of 15 patients with initial minor symptoms (p < 0.0001). All patients with incidental findings remained asymptomatic. Forty four (83%) of 53 MCSs did not show any significant growth and 42 (80%) of 53 patients were not symptomatic at the end of follow-up (p < 0.001). The radiographic progression-free survival rates (± SD) at 5, 10, and 20 years were 90% ± 4.2%, 82% ± 5.7%, and 70% ± 10.2%, respectively. Five patients (9.4%) with no evidence of any effect of the initial medical treatment desired additional conventional radiation therapy.

CONCLUSIONS

Because of the capricious, unpredictable, and slow growth of MCSs, together with high growth variability from one patient to the next, the symptomatic medical treatment of these tumors is a highly effective method. This series shows that these lesions are naturally, clinically, and radiologically indolent.

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Samiya Abi Jaoude, Matthieu Peyre, Vincent Degos, Stéphane Goutagny, Béatrice Parfait and Michel Kalamarides

OBJECTIVE

Intracranial meningiomas occur in about half of neurofibromatosis type 2 (NF2) patients and are very frequently multiple. Thus, estimating individual meningiomas’ growth rates is of great interest to tailor therapeutic interventions. The Asan Intracranial Meningioma Scoring System (AIMSS) has recently been published to estimate the risk of tumor growth in sporadic meningiomas. The current study aimed to determine predictors of rapid meningioma growth in NF2 patients and to evaluate the AIMSS score in a specific NF2 cohort.

METHODS

The authors performed a retrospective analysis of 92 NF2 patients with 358 measured intracranial meningiomas that had been observed prospectively between 2012 and 2018. Tumor volumes were measured at diagnosis and at each follow-up visit. The growth rates were determined and evaluated with respect to the clinicoradiological parameters. Predictors of rapid tumor growth (defined as growth ≥ 2 cm3/yr) were analyzed using univariate followed by multivariate logistic regression to build a dedicated predicting model. Receiver operating characteristic (ROC) curves to predict the risk of rapid tumor growth with the AIMSS versus the authors’ multivariate model were compared.

RESULTS

Sixty tumors (16.76%) showed rapid growth. After multivariate analysis, a larger tumor volume at diagnosis (p < 0.0001), presence of peritumoral edema (p = 0.022), absence of calcifications (p < 0.0001), and hyperintense or isointense signal on T2-weighted MRI (p < 0.005) were statistically significantly associated with rapid tumor growth. It is particularly notable that the genetic severity score did not seem to influence the growth rate of NF2 meningiomas. In comparison with the AIMSS, the authors’ multivariate model’s prediction did not show a statistically significant difference (area under the curve [AUC] 0.82 [95% CI 0.76–0.88] for the AIMSS vs AUC 0.86 [95% CI 0.81–0.91] for the authors’ model, p = 0.1).

CONCLUSIONS

The AIMSS score is valid in the authors’ cohort of NF2-related meningiomas. It adequately predicted risk of rapid meningioma growth and could aid in decision-making in NF2 patients.

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Charles A. Valery, Matthieu Faillot, Ioannis Lamproglou, Jean-Louis Golmard, Catherine Jenny, Matthieu Peyre, Karima Mokhtari, Jean-Jacques Mazeron, Philippe Cornu and Michel Kalamarides

OBJECTIVE

Grade II meningiomas, which currently account for 25% of all meningiomas, are subject to multiple recurrences throughout the course of the disease and represent a challenge for the neurosurgeon. Radiosurgery is increasingly performed for the treatment of Grade II meningiomas and is quite efficient in controlling relapses locally at the site of the lesion, but it cannot prevent margin relapses. The aim of this retrospective study was to analyze the technical parameters involved in producing marginal relapses and to optimize loco-marginal control to improve therapeutic strategy.

METHODS

Eighteen patients presenting 58 lesions were treated by Gamma Knife radiosurgery (GKRS) between 2010 and 2015 in Hopital de la Pitié-Salpêtrière. The median patient age was 68 years (25%−75% interval: 61–72 years), and the sex ratio (M/F) was 13:5. The median delay between surgery and first GKRS was 3 years. Patients were classified as having Grade II meningioma using World Health Organization (WHO) 2007 criteria. The tumor growth rate was computed by comparing 2 volumetric measurements before treatment. After GKRS, iterative MRI, performed every 6 months, detected a relapse if tumor volume increased by more than 20%. Patterns of relapse were defined as being local, marginal, or distal. Survival curves were estimated using the Kaplan-Meier method, and the relationship between criterion and potential risk factors was tested by the log-rank test and univariable Cox model.

RESULTS

The median follow-up was 36 months (range 8–57 months). During this period, 3 patients presented with a local relapse, 5 patients with a marginal relapse, and 7 patients with a distal relapse. Crude local control was 84.5%. The local control actuarial rate was 89% at 1 year and 71% at 3 years. The marginal control actuarial rate was 81% at 1 year and 74% at 2 years. The distal control actuarial rate was 100% at 1 year, 81% at 2 years, and 53% at 3 years. Median distal control was 38 months. Progression-free survival (PFS) was 71% at 1 year, 36% at 2 years, and 23% at 3 years. Median PFS was 18 months. Lesions treated with a minimum radiation dose of ≤ 12 Gy had significantly more local relapses than those treated with a dose > 12 Gy (p = 0.04) in univariate analysis.

Marginal control was significantly influenced by tumor growth rate, with a lower growth rate being highly associated with improved marginal control (p = 0.002). There was a trend toward a relationship between dose and marginal control, but it was not significant (p = 0.09). PFS was significantly associated with delay between first surgery and GKRS (p = 0.03). The authors noticed few complications with no sequelae.

CONCLUSIONS

In order to optimize loco-marginal control, radiosurgical treatment should require a minimum dose of > 12 Gy and an extended target volume along the dural insertion. Ideally, these parameters should correspond to the aggressiveness of the lesion, based on genetic features of the tumor.

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Daniele Bernardeschi, Nadya Pyatigorskaya, Antoine Vanier, Franck Bielle, Mustapha Smail, Georges Lamas, Olivier Sterkers and Michel Kalamarides

OBJECTIVE

In large vestibular schwannoma (VS) surgery, the facial nerve (FN) is at high risk of injury. Near-total resection has been advocated in the case of difficult facial nerve dissection, but the amount of residual tumor that should be left and when dissection should be stopped remain controversial factors. The objective of this study was to report FN outcome and radiological results in patients undergoing near-total VS resection guided by electromyographic supramaximal stimulation of the FN at the brainstem.

METHODS

This study was a retrospective analysis of a prospectively maintained database. Inclusion criteria were surgical treatment of a large VS during 2014, normal preoperative FN function, and an incomplete resection due to the strong adherence of the tumor to the FN and the loss of around 50% of the response of supramaximal stimulation of the proximal FN at 2 mA. Facial nerve function and the amount and evolution of the residual tumor were evaluated by clinical examination and by MRI at a mean of 5 days postoperatively and at 1 year postoperatively.

RESULTS

Twenty-five patients met the inclusion criteria and were included in the study. Good FN function (Grade I or II) was observed in 16 (64%) and 21 (84%) of the 25 patients at Day 8 and at 1 year postoperatively, respectively. At the 1-year follow-up evaluation (n = 23), 15 patients (65%) did not show growth of the residual tumor, 6 patients (26%) had regression of the residual tumor, and only 2 patients (9%) presented with tumor progression.

CONCLUSIONS

Near-total resection guided by electrophysiology represents a safe option in cases of difficult dissection of the facial nerve from the tumor. This seems to offer a good compromise between the goals of preserving facial nerve function and achieving maximum safe resection.

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Mark W. Youngblood, Daniel Duran, Julio D. Montejo, Chang Li, Sacit Bulent Omay, Koray Özduman, Amar H. Sheth, Amy Y. Zhao, Evgeniya Tyrtova, Danielle F. Miyagishima, Elena I. Fomchenko, Christopher S. Hong, Victoria E. Clark, Maximilien Riche, Matthieu Peyre, Julien Boetto, Sadaf Sohrabi, Sarah Koljaka, Jacob F. Baranoski, James Knight, Hongda Zhu, M. Necmettin Pamir, Timuçin Avşar, Türker Kilic, Johannes Schramm, Marco Timmer, Roland Goldbrunner, Ye Gong, Yaşar Bayri, Nduka Amankulor, Ronald L. Hamilton, Kaya Bilguvar, Irina Tikhonova, Patrick R. Tomak, Anita Huttner, Matthias Simon, Boris Krischek, Michel Kalamarides, E. Zeynep Erson-Omay, Jennifer Moliterno and Murat Günel

OBJECTIVE

Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

METHODS

Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher’s exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.

RESULTS

Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among “mutation unknown” samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor’s underlying driver mutation.

CONCLUSIONS

Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.