Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients. Trattamento chirurgico degli schwannomi vestibolari: risultati su una serie di 1006 pazienti

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare l’evoluzione negli esiti chirurgici dell’exeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente l’asportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dell’ultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado HouseBrackmann), con una variazione tra il primo e l’ultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione dell’udito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). L’udito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nell’ultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dell’asportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione dell’udito, le perdite di liquido cefalorachidiano, principalmente grazie all’esperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall’ esperienza maturata sulle lesioni di piccole dimensioniThe management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team's experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

Neurofibromatosis 2011: a report of the Children's Tumor Foundation annual meeting.

The 2011 annual meeting of the Children's Tumor Foundation, the annual gathering of the neurofibromatosis (NF) research and clinical communities, was attended by 330 participants who discussed integration of new signaling pathways into NF research, the appreciation for NF mutations in sporadic cancers, and an expanding pre-clinical and clinical agenda. NF1, NF2, and schwannomatosis collectively affect approximately 100,000 persons in US, and result from mutations in different genes. Benign tumors of NF1 (neurofibroma and optic pathway glioma) and NF2 (schwannoma, ependymoma, and meningioma) and schwannomatosis (schwannoma) can cause significant morbidity, and there are no proven drug treatments for any form of NF. Each disorder is associated with additional manifestations causing morbidity. The research presentations described in this review covered basic science, preclinical testing, and results from clinical trials, and demonstrate the remarkable strides being taken toward understanding of and progress toward treatments for these disorders based on the close interaction among scientists and clinicians

Surgical treatment of sporadic vestibular schwannoma in a series of 1006 patients = Trattamento chirurgico degli schwannomi vestibolari: Risultati su una serie di 1006 pazienti

The management of sporadic vestibular schwannoma (VS) has evolved in the last decades. The aim of this study was to analyse the evolution in surgical outcomes of VSs operated by a neurotological team between 1990 and 2006 by different approaches. A monocentric retrospective review of medical charts of 1006 patients was performed. In order to assess eventual changes and progress, the 17-years period was divided in three periods, each one comprehending 268 VS (1990-1996), 299 VS (1997-2001), and 439 VS (2002-2006). Mean follow-up was 5.9 ± 2.4 years. Overall, complete VS removal was achieved in 99.4% of cases. Mortality rate was 0.3%, meningitis and CSF leaks were observed in 1.2 % and 9 % of the cases, respectively. CSF leakage decreased from 11.6% to 7.1% between the first and last period (p < 0.01) as well as revision surgery from 3.4 % to 0.9 % (p < 0.05). Facial nerve was anatomically preserved in 97.7% of cases. At one year, a good facial nerve function was observed in 85.1% of patients (grade I and II of House-Brackmann grading scale), which ranged between the first and last period from 78.4% to 87.6% (p <0.05). At one year, hearing preservation was obtained in 61.6% of patients, which increased from the first period to the last one from 50.9% to 69.0% (p < 0.05) (class A+B+C from the AAO-HNS classification). Useful hearing (class A+B) was observed in 33.5% of cases overall, with 21.8% and 42% in the first and last period, respectively (p < 0.01). Surgical outcomes of sporadic vestibular schwannoma have improved concerning facial nerve function outcomes, hearing preservation and cerebrospinal fluid (CSF) leaks, mainly due to the neuro-otological team’s experience. Functional results after complete microsurgical removal of large VS depend on experience gained on small VS removal

Spinal ependymomas in NF2: a surgical disease?

The management of spinal cord ependymomas in Neurofibromatosis Type 2(NF2) has traditionally been conservative, in contrast to the management ofsporadic cases; the assumption being that, in the context of NF2, they did notcause morbidity. With modern management and improved outcome of otherNF2 tumours, this assumption, and therefore the lack of role for surgery, hasbeen questioned. To compare the outcome of conservative treatment of spinalependymomas in NF2 with surgical intervention in selected patients.Retrospective review at two NF2 centers, Manchester, UK and Paris/Lille,France. In Manchester patients were managed conservatively. In Francesurgery was a treatment option. Inclusion in the study was based on tumorlength of greater than 1.5 cm. The primary parameter assessed was acquired neurological deficit measured by the Modified McCormick Outcome Score.24 patients from Manchester and 46 patients from France were analyzed.From Manchester, 27% of these patients deteriorated during the course offollow-up. This effectively represents the natural history of ependymomas inNF2. Of the surgical cases, 23% deteriorated postoperatively, but only 2/18(11%) of those operated on in the NF2 specialist centers. Comparison of thetwo specialist centers Manchester/France showed a significantly improvedoutcome (P = 0.012, χ test) in the actively surgical center. Spinalependymomas produce morbidity. Surgery can prevent or improve this inselected cases but can itself can produce morbidity. Surgery should beconsidered in growing/symptomatic ependymomas, particularly in theabsence of overwhelming tumor load where bevacizumab is the preferredoption

ACTA OTORHINOLARYNGOLOGICA ITALICA

La gestione dello schwannoma vestibolare (SV) sporadico si è gradualmente evoluta negli ultimi decenni. Lo scopo di questo studio è di analizzare levoluzione negli esiti chirurgici dellexeresi di queste lesioni, realizzata da un team neurotologico tra il 1990 e il 2006, attraverso differenti approcci. È stata eseguita una revisione retrospettica monocentrica dei dati clinici di 1006 pazienti. Al fine di valutare eventuali modifiche e progressi, il periodo di 17 anni è stato diviso in tre periodi, ciascuno comprendente rispettivamente 268 SV (1990- 1996), 299 SV (1997-2001), e 439 SV (2002-2006). Il follow-up medio è stato di 5,9 ± 2,4 anni. Complessivamente lasportazione totale è stata ottenuta nel 99,4% dei casi. Il tasso di mortalità è stato dello 0,3%, la meningite e la perdita di liquido cefalo rachidiano (LCR) sono stati osservati nel 1,2% e il 9% dei casi, rispettivamente. La frequenza della perdita di LCR è diminuita dal 11,6% al 7,1% tra il primo e dellultimo periodo (p < 0,01) e la revisione chirurgica dal 3,4% al 0,9% (p < 0,05). Il nervo facciale è stato anatomicamente conservato nel 97,7% dei casi. Ad un anno, una buona funzione del nervo facciale è stata osservata nel 85,1% dei pazienti (I e II grado House- Brackmann), con una variazione tra il primo e lultimo periodo che andava dal 78,4% al 87,6% (p < 0,05). Ad un anno post-operatorio la conservazione delludito è stata ottenuta nel 61,6% dei pazienti, passando dal 50,9% del primo periodo, al 69,0% del periodo piú recente (p < 0,05) (classe A + B + C dalla classificazione AAO-HNS). Ludito utile (classe A + B) è stato conservato nel 33,5% dei casi complessivamente, con percentuali comprese tra il 21,8% e 42% nel primo e nellultimo periodo rispettivamente (p < 0,01). Gli esiti chirurgici dellasportazion dello schwannoma vestibolare sporadico sono migliorati negli anni per quanto riguarda i risultati funzionali del nervo facciale, la conservazione delludito, le perdite di liquido cefalorachidiano, principalmente grazie allesperienza del team neurotologico. I risultati funzionali dopo la rimozione microchirurgica completa SV di grandi dimensioni dipendono dall esperienza maturata sulle lesioni di piccole dimensioni

European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection

Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4,  ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I (“ready for clinical use”) classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II (“investigational”) classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted. MTG4Molecular tumour pathology - and tumour genetic

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was &gt;20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was &gt;20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to &gt; 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus