Familial CNS Tumor Syndromes

2017 ◽  
Author(s):  
Jennie W Taylor ◽  
Scott R Plotkin
Keyword(s):  
Standard Treatment ◽  
Retrospective Studies ◽  
De Novo ◽  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Suppressor Gene ◽  
Vestibular Schwannomas ◽  
De Novo Mutations ◽  
Genetic Features

Neurofibromatosis type 2 (NF2) is a genetic disorder caused by constitutional mutations in the NF2 tumor-suppressor gene. Bilateral vestibular schwannomas are the hallmark of the syndrome, though meningiomas, ependymomas, and other peripheral schwannomas are common. Inheritance is autosomal dominant and de novo mutations are found in about 50% of patients. Standard treatment for symptomatic tumors is surgery. Radiation therapy may be considered for progressive tumors that are not surgically accessible, but secondary cancers after radiation have been reported. Retrospective studies suggest that bevacizumab may be active for progressive vestibular schwannomas and trials of chemotherapy for NF2-related tumors are in progress. This chapter reviews the epidemiology, genetic features, clinical characteristics, and current treatments for patients with NF2.

Clinical and molecular genetic features of neurofibromatosis type

2021 ◽  
pp. 3-12
Author(s):  
К.О. Карандашева ◽  
Е.С. Макашова ◽  
А.А. Мартьянова ◽  
К.И. Аношкин ◽  
С.В. Золотова ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Binding Sites ◽  
Genetic Disorder ◽  
Molecular Genetic ◽  
Neurofibromatosis Type ◽  
Suppressor Gene ◽  
Neurofibromatosis Type 2 ◽  
Post Translational Modifications ◽  
Genetic Features

Нейрофиброматоз 2 типа - редкое генетическое заболевание, этиологическим фактором развития которого являются мутации в гене-онкосупрессоре NF2, кодирующем белок мерлин. В обзоре подробно описаны структура, функции и посттрансляционные модификации мерлина, освещены клинические особенности нейрофиброматоза 2 типа, известные клинико-генетические корреляции, а также представлена информация о сайтах связывания мерлина и о функциональном вкладе расположенных в них мутаций, что закладывает базис персонализированной терапии нейрофиброматоза 2 типа. Neurofibromatosis type 2 is a rare genetic disorder caused by pathogenic mutations in the NF2 tumor suppressor gene which encodes a protein called merlin. This review describes the structure, functions, and post-translational modifications of merlin, highlights clinical features and known genotype-phenotype correlations of neurofibromatosis type 2, and provides information on the merlin binding sites and the functional contribution of mutations they harbor, which lays the basis for personalized therapy for neurofibromatosis type 2.

Surgical Management of Vestibular Schwannomas in Neurofibromatosis Type 2

2012 ◽  
Vol 73 (S 02) ◽  
Author(s):  
J. Tysome ◽  
R. MacFarlane ◽  
J. Durie-Gair ◽  
N. Donnelly ◽  
R. Mannion ◽  
...  
Keyword(s):  
Surgical Management ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas

Management of Neurofibromatosis Type 2 Associated Vestibular Schwannomas

2021 ◽  
Vol 9 (2) ◽  
pp. 170-176
Author(s):  
Huan Jia ◽  
Ghizlene Lahlou ◽  
Hao Wu ◽  
Olivier Sterkers ◽  
Michel Kalamarides
Keyword(s):  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas

scholarly journals Disease course of Neurofibromatosis Type 2; a 30-year follow-up study of 353 patients seen at a single institution

2020 ◽  
Author(s):  
Claire Forde ◽  
Andrew T King ◽  
Scott A Rutherford ◽  
Charlotte Hammerbeck-Ward ◽  
Simon K Lloyd ◽  
...  
Keyword(s):  
De Novo ◽  
Radiation Treatment ◽  
Univariate Analysis ◽  
Age At Onset ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Disease Course ◽  
Number Of Patients

Abstract Background Limited data exists on the disease course of Neurofibromatosis Type 2 (NF2) to guide clinical trial design. Methods A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990–2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred and inheritance type. Interventions for NF2-related tumours were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death. Results Three-hundred-and-fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65 respectively per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting <16 and >40 years had poorer overall survival than those presenting at 26-39 years (P=0.03 and P=0.02 respectively) but those presenting between 16-39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P=0.004). Conclusion Understanding disease course improves prognostication, allowing for better informed decisions about care.

scholarly journals NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii419-iii419
Author(s):  
Sheetal Phadnis ◽  
Mari Hagiwara ◽  
Anna Yaffe ◽  
Carole Mitchell ◽  
Theodore Nicolaides ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Volumetric Response

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

scholarly journals Short-Term Clinico-Radiographic Response to Super-Selective Intra-Arterial Cerebral Infusion of Bevacizumab for the Treatment of Vestibular Schwannomas in Neurofibromatosis Type 2

2012 ◽  
Vol 18 (2) ◽  
pp. 127-132 ◽  
Author(s):  
H.A. Riina ◽  
J-K. Burkhardt ◽  
A. Santillan ◽  
L. Bassani ◽  
A. Patsalides ◽  
...  
Keyword(s):  
Bowel Perforation ◽  
Wound Dehiscence ◽  
Neurofibromatosis Type ◽  
Chemotherapeutic Agents ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Blood Brain Barrier Disruption ◽  
Systemic Side Effects ◽  
Brain Barrier Disruption

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a prevalence of approximately 1 in 30,000. NF 2 is characterized by bilateral vestibular schwannomas, as well as meningiomas, ependymomas and gliomas. Currently, surgical resection and radiotherapy represent the mainstay of treatment, although new studies suggest a role for certain chemotherapeutic agents. Intravenous administration of Bevacizumab (Avastin, Genetech Pharmaceuticals) has been shown to be active in the treatment of vestibular schwannomas. The IV route of administration, however, carries a risk of known systemic side-effects such as bowel perforation, wound dehiscence and pulmonary embolism. In addition, the percentage of drug that reaches the tumor site may be restricted by the blood tumor barrier. This report describes the super-selective intra-arterial infusion of Bevacizumab following blood brain barrier disruption for the treatment of vestibular schwannomas in three patients with Neurofibromatosis type 2. It represents the first time such a technique has been performed for this disease. Additionally, this method of drug delivery may have important implications in the treatment of patients with vestibular schwannomas associated with Neurofibromatosis type 2.

Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2

2003 ◽  
Vol 99 (3) ◽  
pp. 480-483 ◽  
Author(s):  
Goro Otsuka ◽  
Kiyoshi Saito ◽  
Tetsuya Nagatani ◽  
Jun Yoshida
Keyword(s):  
Symptom Onset ◽  
Survival Rates ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Content Type ◽  
Fine Print

Object. Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. Methods. From among 283 patients with neurofibromatosis who had been registered in a nationwide study in Japan between 1986 and 1987, 74 patients with bilateral vestibular schwannomas were analyzed. The mean duration of follow up after diagnosis was 121 months (range 2–287 months). Results of a Kaplan—Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis (< 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. Conclusions. This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

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