Reporter: Aviva Lev-Ari, PhD, RN
In researching Intracanalicular Meningiomas, Vestibular Schwannomas — we presented on 10/15/2012 the following article:
Facial Nerve, Intracanalicular Meningiomas, Vestibular Schwannomas: Surgical Planning
Our research continues by tracing all Clinical Trials – active for Schwannoma
| 1 | Recruiting | Intraarterial Cerebral Infusion of Avastin for Vestibular Schwannoma (Acoustic Neuroma)
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| 2 | Active, not recruiting | Bevacizumab for Symptomatic Vestibular Schwannoma in Neurofibromatosis Type 2 (NF2)
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| 3 | Active, not recruiting | Stereotactic Radiation in Vestibular Schwannoma
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| 4 | Not yet recruiting | Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma
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| 5 | Active, not recruiting | Efficacy and Safety Study of RAD001 in the Growth of the Vestibular Schwannoma(s) in Neurofibromatosis 2 (NF2) Patients
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| 6 | Recruiting | Concentration and Activity of Lapatinib in Vestibular Schwannomas
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| 7 | Recruiting | Hearing Outcomes Using Fractionated Proton Radiation Therapy for Vestibular Schwannoma
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| 8 | Recruiting | A Study of Nilotinib in Growing Vestibular Schwannomas
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| 9 | Active, not recruiting | Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
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| 10 | Recruiting | Stereotactic Body Radiotherapy for Spine Tumors
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| 11 | Recruiting | Natural History Study of Patients With Neurofibromatosis Type 2
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| 12 | Recruiting | Using Positron Emission Tomography to Predict Intracranial Tumor Growth in Neurofibromatosis Type II Patients
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| 13 | Unknown † | Hippocampal Radiation Exposure and Memory
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| 14 | Completed | Recovery of Visual Acuity in People With Vestibular Deficits
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| 15 | Recruiting | Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas
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| 16 | Unknown † | NF2 Natural History Consortium
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| 17 | Completed | Analysis of NF2 Mutations in Radiation-Related Neural Tumors
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| 18 | Completed | Corticosteroids in Prevention of Facial Palsy After Cranial Base Surgery
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| 19 | Recruiting | Phase II Study of Everolimus (RAD001) in Children and Adults With Neurofibromatosis Type 2
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| 20 | Completed | Phase II Study of Imatinib Mesylate in Patients With Life Threatening Malignant Rare Diseases
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| 21 | Recruiting | Taste Disorders in Middle Ear Disease and After Middle Ear Surgery
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| 22 | Completed | Vasopressin and V2 Receptor in Meniere’s Disease
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| 23 | Recruiting | Gemcitabine and Docetaxel in Combination With Pazopanib (Gem/Doce/Pzb) for the Neoadjuvant Treatment of Soft Tissue Sarcoma (STS)
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| 24 | Recruiting | Pazopanib Hydrochloride Followed By Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma
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| 25 | Active, not recruiting | Trial of Dasatinib in Advanced Sarcomas
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| 26 | Active, not recruiting | Sorafenib and Dacarbazine in Soft Tissue Sarcoma
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| 27 | Recruiting | Safety Study of PLX108-01 in Patients With Solid Tumors
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| 28 | Active, not recruiting | Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma
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| 29 | Completed | S0330 Erlotinib in Treating Patients With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumor
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| 30 | Recruiting | IMC-A12 and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma
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| 31 | Active, not recruiting | Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors
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| 32 | Terminated | Imatinib Mesylate Treatment of Patients With Malignant Peripheral Nerve Sheath Tumors
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| 33 | Recruiting | Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors
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| 34 | Recruiting | Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma
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| 35 | Recruiting | Proton Therapy for Spinal Tumors
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| 36 | Recruiting | Natural History Study of Patients With Neurofibromatosis Type I
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| 37 | Completed | Phase II Study of the Multichannel Auditory Brain Stem Implant for Deafness Following Surgery for Neurofibromatosis 2
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| 38 | Completed | An Implant for Hearing Loss Due to Removal of Neurofibromatosis 2 Tumors
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| 39 | Suspended | PTC299 for Treatment of Neurofibromatosis Type 2
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| 40 | Unknown † | Sunitinib in Treating Patients With Recurrent or Unresectable Meningioma, Intracranial Hemangiopericytoma, or Intracranial Hemangioblastoma
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SOURCE:
http://clinicaltrials.gov/ct2/results?term=schwannoma&pg=1
http://clinicaltrials.gov/ct2/results?term=schwannoma&pg=2
Benign Intracranial Tumors Radiosurgery Treatment
Points to remember
- Radiosurgery is focused delivery of radiation to an image-defined target performed in 1 to 5 sessions.
- When used as an alternative to or in conjunction with open neurosurgical techniques, radiosurgery is an effective, less invasive option for treating many benign intracranial tumors, including meningiomas, vestibular schwannomas, and pituitary adenomas.
The challenge
Benign intracranial tumors occur about as often as primary malignant brain tumors. Most benign tumors are noninvasive, well defined and well visualized on MRI, and have a slow rate of progression. Each of these features makes them good candidates for radiosurgery.
Radiosurgery can deliver a destructive dose of radiation to the target with little or no radiation effects on adjacent structures. Proper patient selection for this procedure is critical.
Defining selection criteria
With 2 decades of experience performing radiosurgery, Mayo Clinic neurosurgeons have accumulated a depth of expertise and a vast database that includes patient characteristics, radiosurgical dosimetry, and outcomes.
After reviewing more than 1,400 cases of meningiomas, vestibular schwannomas, and pituitary adenomas, Mayo clinicians observe that radiosurgery is an excellent choice when these types of benign tumors are small, occur in critical locations, or have recurred following previous surgery.
Radiosurgery is also well tolerated and of particular utility in elderly patients with medical conditions that put them at risk for an open procedure. Additionally, radiosurgery does not preclude an open procedure, should that be necessary at a later time.
Radiosurgery for meningiomas
The rate of recurrence for a surgically removed meningioma is about 18% to 25% at 10 years. For this reason, Mayo neurosurgeons recommend maintaining extended surveillance of meningiomas. In contrast, radiosurgery has been found to reduce the risk of recurrence or progression.
Tumor progression outside the field of radiation and tumor histology can affect both long- and short-term outcomes. Tumors that can be clearly imaged and those that are benign and without atypical histology have a far greater rate of 5-year progression-free survival.
Radiosurgery is also an effective therapy for cavernous sinus meningiomas, except when there is symptomatic mass effect, an unusual clinical presentation, or nontypical features on imaging.
Radiosurgery is typically not recommended for convexity and parasagittal meningiomas.
Radiosurgery for vestibular schwannomas
Several studies report that radiosurgery for small to moderate-sized vestibular schwannomas is associated with higher rates of hearing preservation and improved facial nerve outcomes when compared to surgical removal. This conclusion was supported by a Mayo Clinic study comparing surgical resection and radiosurgery for vestibular schwannomas with an average diameter of less than 3 cm. These Mayo investigators also found that the radiosurgical patients experienced less postprocedure dizziness.
MRI of patient’s brain with parathyroid carcinoma before radiosurgery
MRI of patient’s brain with parathyroid carcinoma 12 years after radiosurgery
Radiosurgery for pituitary adenomas
Radiosurgery is considered safe and effective for hormone-secreting pituitary adenomas. When compared with radiotherapy, radiosurgery appears to shorten by more than half the time required to achieve biochemical remission and normal hormone levels.
Controversy remains over whether pituitary-suppressive medications at the time of surgery have a negative impact on tumor control. Several studies, however, including a series of 46 acromegaly cases at Mayo Clinic, found that patients were more than 4 times as likely to reach normal hormone levels if they were taken off such medications before surgery.
At Mayo Clinic, patients with oversecretion of growth hormone or adrenocorticotropic hormone and patients who experience new or progressing visual field deficits are referred for surgical resection. Patients with tumors that extend into the cavernous sinuses and patients with recurrent tumors after prior surgery, however, are generally treated with radiosurgery if the tumor does not directly involve the optic nerves and chiasm.
Across Mayo Clinic’s 3 sites in Arizona, Florida, and Minnesota, patients are seen by neurosurgeons with expertise in both open procedures and radiosurgery. When used as an alternative to or in conjunction with traditional neurosurgery, radiosurgery is an effective, noninvasive option for treating benign intracranial tumors.
Source:
http://www.mayoclinic.org/medicalprofs/radiosurgery-for-benign-intracranial-tumors.html
http://www.mayoclinic.org/mcitems/mc2000-mc2099/mc2024-0410.pdf
Radiosurgery Treatment is Radiotherapy in following versions:
- single-session stereotactic radiosurgery,
- fractionated conventional radiotherapy,
- fractionated stereotactic radiotherapy, and
- proton beam therapy.
Radiotherapy for vestibular schwannomas: a critical review.
Source
Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA. murphye3@ccf.org
Abstract
Vestibular schwannomas are slow-growing tumors of the myelin-forming cells that cover cranial nerve VIII. The treatment options for patients with vestibular schwannoma include active observation, surgical management, and radiotherapy. However, the optimal treatment choice remains controversial. We have reviewed the available data and summarized the radiotherapeutic options, including single-session stereotactic radiosurgery, fractionated conventional radiotherapy, fractionated stereotactic radiotherapy, and proton beam therapy. The comparisons of the various radiotherapy modalities have been based on single-institution experiences, which have shown excellent tumor control rates of 91-100%. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy have successfully improved cranial nerve V and VII preservation to >95%. The mixed data regarding the ideal hearing preservation therapy, inherent biases in patient selection, and differences in outcome analysis have made the comparison across radiotherapeutic modalities difficult. Early experience using proton therapy for vestibular schwannoma treatment demonstrated local control rates of 84-100% but disappointing hearing preservation rates of 33-42%. Efforts to improve radiotherapy delivery will focus on refined dosimetry with the goal of reducing the dose to the critical structures. As future randomized trials are unlikely, we suggest regimented pre- and post-treatment assessments, including validated evaluations of cranial nerves V, VII, and VIII, and quality of life assessments with long-term prospective follow-up. The results from such trials will enhance the understanding of therapy outcomes and improve our ability to inform patients.
Below, seminal papers on the subject
Meningioma of the internal auditory canal.
Laudadio P, Canani FB, Cunsolo E.
Source
Department of Otolaryngology–Head and Neck Surgery, Maggiore Hospital, Bologna, Italy.
Abstract
A comprehensive literature search identified only 14 well-documented cases of intracanalicular meningioma. A case is presented of meningioma confined to the internal auditory canal which was excised using a sub-occipital retrosigmoid approach. Preoperative MRI and CT scans were suggestive of intracanalicular vestibular schwannoma. Only the intraoperative findings, which were confirmed by the histological data, revealed that the tumor was a meningioma. We review the literature and discuss the diagnostic and therapeuticissues relating to these tumors.
Facial nerve paralysis and meningioma of the internal auditory canal.
Hilton MP, Kaplan DM, Ang L, Chen JM.
Source
Department of Otorhinolaryngology, Sunnybrook and Women’s College Health Science Centre, University of Toronto, Canada. malcolmhilton@hotmail.com
Abstract
Pathological lesions confined to the internal auditory canal (IAC) commonly present with cochleovestibular symptoms; sensorineural hearing loss, tinnitus and balance disturbance. The commonest lesion of the IAC is vestibular schwannoma. Other lesions include meningioma, facial neuroma, cavernous haemangioma, lipoma and arachnoid cyst. Presentation with facial palsy and an intracanalicular lesion is suggestive of pathology other than acoustic neuroma. Magnetic resonance imaging (MRI) cannot reliably distinguish intracanalicular vestibular schwannomas from meningiomas. Particular care is required for surgery of these lesions: the facial nerve typically does not lie in a protected anterior position within the IAC.
Meningiomas of the internal auditory canal.
Nakamura M, Roser F, Mirzai S, Matthies C, Vorkapic P, Samii M.
Source
Department of Neurosurgery, Nordstadt Hospital, Teaching Hospital Hannover Medical School, Hannover, Germany. mnakamura@web.de
Abstract
OBJECTIVE:
Meningiomas arising primarily within the internal auditory canal (IAC) are notably rare. By far the most common tumors that are encountered in this region are neuromas. We report a series of eight patients with meningiomas of the IAC, analyzing the clinical presentations, surgical management strategies, and clinical outcomes.
METHODS:
The charts of the patients, including histories and audiograms, imaging studies, surgical records, discharge letters, histological records, and follow-up records, were reviewed.
RESULTS:
One thousand eight hundred meningiomas were operated on between 1978 and 2002 at the Neurosurgical Department of Nordstadt Hospital. Among them, there were 421 cerebellopontine angle meningiomas; 7 of these (1.7% of cerebellopontine angle meningiomas) were limited to the IAC. One additional patient underwent surgery at the Neurosurgical Department of the International Neuroscience Institute, where a total of 21 cerebellopontine angle meningiomas were treated surgically from 2001 to 2003. As a comparison, the incidence of intrameatal vestibular schwannomas during the same period, 1978 to 2002, was 168 of 2400 (7%). There were five women and three men, and the mean age was 49.3 years (range, 27-59 yr). Most patients had signs and symptoms of vestibulocochlear nerve disturbance at presentation. One patient had sought treatment previously for total hearing loss before surgery. No patient had a facial paresis at presentation. The neuroradiological workup revealed a homogeneously contrast-enhancing tumor on magnetic resonance imaging in all patients with hypointense or isointense signal intensity on T1- and T2-weighted images. Some intrameatal meningiomas showed broad attachment, and some showed a dural tail at the porus. In all patients, the tumor was removed through the lateral suboccipital retrosigmoid approach with drilling of the posterior wall of the IAC. Total removal was achieved in all cases. Severe infiltration of the facial and vestibulocochlear nerve was encountered in two patients. There was no operative mortality. Hearing was preserved in five of seven patients; one patient was deaf before surgery. Postoperative facial weakness was encountered temporarily in one patient.
CONCLUSION:
Although intrameatal meningiomas are quite rare, they must be considered in the differential diagnosis of intrameatal mass lesions. The clinical symptoms are very similar to those of vestibular schwannomas. A radiological differentiation from vestibular schwannomas is not always possible. Surgical removal of intrameatal meningiomas should aim at wide excision, including involved dura and bone, to prevent recurrences. The variation in the anatomy of the faciocochlear nerve bundle in relation to the tumor has to be kept in mind, and preservation of these structures should be the goal in every case.
Surgical management of jugular foramen schwannomas with hearing and facial nerve function preservation: a series of 23 cases and review of the literature.
Sanna M, Bacciu A, Falcioni M, Taibah A.
Source
Gruppo Otologico, Piacenza-Rome, Rome, Italy. mario.sanna@gruppotologico.it
Abstract
OBJECTIVE:
Schwannomas of the jugular foramen are rare lesions and controversy regarding their management still exists. The objective of this retrospective study was to analyze the management and outcome in a series of 23 cases collected at a single center.
SETTING:
This study was conducted at a quaternary private otology and skull base center.
METHODS:
Charts belonging to patients with a diagnosis of jugular foramen schwannoma attending our center between May 1988 and April 2006 were examined retrospectively.
RESULTS:
The study group consisted of 23 patients. One patient (a 73-year-old woman) with normal lower cranial nerves function was managed with watchful expectancy and regular clinical and radiologic follow ups. The infratemporal fossa approach-type A (IFTA-A) was performed in 3 cases. One patient underwent a transcochlear-transjugular approach. Of the 22 patients surgically treated, 12 patients were operated on by the petrooccipital transsigmoid approach (POTS). In one patient with a preoperative dead ear, a combined POTS-translabyrinthine approach was adopted. Two patients were operated on through the POTS approach combined with the transotic approach. In another case (a 67-year-old woman), a subtotal tumor removal through a transcervical approach was planned to resect a 10-cm mass in the neck. One patient underwent a first-stage combined transcervical-subtotal petrosectomy approach to remove a huge tumor in the neck; the second-stage intradural removal of the tumor was accomplished through a translabyrinthine-transsigmoid-transjugular approach. The last patient underwent a first-stage combined transcervical-subtotal petrosectomy approach to remove the neck tumor component; this patient is now waiting for the second-stage intradural removal of the tumor. Complete tumor removal was accomplished in 21 cases and in one case, a residual schwannoma was left in place in the area of the jugular foramen. The 3 patients who were operated on by IFTA-A underwent permanent anterior transposition of the facial nerve. At 1-year follow up, 2 of these patients had House-Brackmann grade I and 1 reached grade IV. The patient who underwent a transcochlear-transjugular approach had a permanent posterior transposition of the facial nerve. At 1-year follow up, he had grade III facial nerve function. Postoperative facial nerve function was normal (House-Brackmann grade I) in all patients operated on by the POTS approach. Twelve patients had hearing-preserving surgery using the POTS approach. Good hearing was preserved in 10 cases (83.3%), the majority of whom (58.3%) maintained their preoperative hearing level. There was no perioperative mortality. One patient (4.5%) experienced a postoperative cerebrospinal fluid leak. After surgery, all patients did not recover the function of the preoperatively paralyzed lower cranial nerves. A new deficit of one or more of the lower cranial nerves was recorded in 50% of cases. So far, no patient has experienced recurrence during the follow-up period as ascertained by computed tomography or magnetic resonance imaging.
CONCLUSIONS:
Surgical resection is the treatment of choice for jugular foramen schwannomas. The POTS approach allowed single-stage, total tumor removal with preservation of the facial nerve and of the middle and inner ear functions in the majority of cases. Despite the advances in skull base surgery, new postoperative lower cranial nerve deficits still represent a challenge.
Meningiomas and schwannomas: molecular subgroup classification found by expression arrays.
Martinez-Glez V, Franco-Hernandez C, Alvarez L, De Campos JM, Isla A, Vaquero J, Lassaletta L, Casartelli C, Rey JA.
Source
Unidad de Investigación, Hospital Universitario La Paz, 28046 Madrid, Spain. vmartinezg.hulp@salud.madrid.org
Abstract
Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.
Histological classification and molecular genetics of meningiomas.
Riemenschneider MJ, Perry A, Reifenberger G.
Source
Department of Neuropathology, Heinrich-Heine-University, Duesseldorf, Germany.
Erratum in
Abstract
Meningiomas account for up to 30% of all primary intracranial tumours. They are histologically classified according to the World Health Organization (WHO) classification of tumours of the nervous system. Most meningiomas are benign lesions of WHO grade I, whereas some meningioma variants correspond with WHO grades II and III and are associated with a higher risk of recurrence and shorter survival times. Mutations in the NF2 gene and loss of chromosome 22q are the most common genetic alterations associated with the initiation of meningiomas. With increase in tumour grade, additional progression-associated molecular aberrations can be found; however, most of the relevant genes are yet to be identified. High-throughput techniques of global genome and transcriptome analyses and new meningioma models provide increasing insight into meningioma biology and will help to identify common pathogenic pathways that may be targeted by new therapeutic approaches.
The neurofibromatosis type 2 gene is inactivated in schwannomas.
Twist EC, Ruttledge MH, Rousseau M, Sanson M, Papi L, Merel P, Delattre O, Thomas G, Rouleau GA.
Source
Centre for Research in Neuroscience, McGill University, Montreal, Canada.
Abstract
Schwannomas are tumors arising from schwann cells surrounding peripheral nerves. Although most schwannomas are sporadic, they are seen in approximately 90% of individuals with neurofibromatosis type 2 (NF2), an autosomal dominantly inherited disease with an incidence of 1:40000 live births. The NF2 gene has recently been isolated on chromosome 22 and encodes a putative membrane organizing protein named schwannomin. It is believed to act as a tumor suppressor gene based on the high frequency of loss of heterozygosity (LOH) on this autosome in both sporadic and NF2 associated schwannomas and meningiomas and the identification of inactivating mutation in NF2 patients. In this study we examined 61 schwannomas including 48 sporadic schwannomas (46 of which are vestibular schwannomas) and 12 schwannomas obtained from NF2 patients, for mutations in 10 of the 16 coding exons of the NF2 gene. Twelve inactivating mutations were identified, 8 in sporadic tumours and 4 in tumors from people with NF2. These results support the hypothesis that loss of function of schwannomin is a frequent and fundamental event in the genesis of schwannomas.
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