Gamma Knife Surgery For Vestibular Schwannomas Research Articles

509 Modern Hearing Preservation Outcomes After Vestibular Schwannoma Stereotactic Radiosurgery

INTRODUCTION: For patients with vestibular schwannoma (VS), stereotactic radiosurgery (SRS) has proven effective in controlling tumor growth, while hearing preservation remains a key goal. METHODS: During the years 2013-2018, 353 patients underwent Gamma-knife surgery for VS at our institution. We followed 175 patients with pre-SRS serviceable hearing (Gardner-Robertson Score, GR 1 and 2). Volumetric and dosimetry data were collected, including Biological Effective Dose (BED), integral doses (ID) of total and intra-canalicular (IC) tumor components and hearing outcomes. RESULTS: Mean age was 56 years, 74 (42%) had baseline GR of 2, and mean cochlear dose was 3.5 Gy. Time to serviceable hearing loss (GR 3-4) was 38 months (95% CI, 26-46), with 77% and 62% hearing preservation in the 1st and 2nd years. Patients optimal for best hearing outcomes were younger than 58 with baseline GR of 1, free canal space 0.041cc (diameter of 4.5 mm) and mean cochlear dose <3.1 Gy. For such patients, hearing preservation rates were 92% by 12 months and 81% by 2 years, staying stable for >5 years post-SRS, significantly higher than the rest of the population. CONCLUSIONS: Hearing preservation after SRS for VS patients with serviceable hearing is correlated to the specific baseline GR score (1 or 2), age, cochlear dose and BED. Increased tumor-free canal space correlates with better outcomes. The most durable hearing preservation correlates with factors commonly associated with smaller tumors away from the cochlea.

Modern Hearing Preservation Outcomes After Vestibular Schwannoma Stereotactic Radiosurgery.

For patients with vestibular schwannoma (VS), stereotactic radiosurgery (SRS) has proven effective in controlling tumor growth while hearing preservation remains a key goal. To evaluate hearing outcomes in the modern era of cochlear dose restriction. During the years 2013 to 2018, 353 patients underwent Gamma knife surgery for VS at our institution. We followed 175 patients with pre-SRS serviceable hearing (Gardner-Robertson Score, GR 1 and 2). Volumetric and dosimetry data were collected, including biological effective dose, integral doses of total and intracanalicular tumor components, and hearing outcomes. The mean age was 56 years, 74 patients (42%) had a baseline GR of 2, and the mean cochlear dose was 3.5 Gy. The time to serviceable hearing loss (GR 3-4) was 38 months (95% CI 26-46), with 77% and 62% hearing preservation in the first and second years, respectively. Patients optimal for best hearing outcomes were younger than 58 years with a baseline GR of 1, free canal space ≥0.041 cc (diameter of 4.5 mm), and mean cochlear dose <3.1 Gy. For such patients, hearing preservation rates were 92% by 12 months and 81% by 2 years, staying stable for >5 years post-SRS, significantly higher than the rest of the population. Hearing preservation after SRS for patients with VS with serviceable hearing is correlated to the specific baseline GR score (1 or 2), age, cochlear dose, and biological effective dose. Increased tumor-free canal space correlates with better outcomes. The most durable hearing preservation correlates with factors commonly associated with smaller tumors away from the cochlea.

Vestibular Schwannoma Tumor Size Is Associated With Acute Vestibular Symptoms After Gamma Knife Therapy

To assess how pretreatment vestibular schwannoma (VS) tumor characteristics are associated with vestibular symptoms after gamma knife (GK) surgery. Retrospective chart review of patients undergoing GK treatment for VS at our institution from 2005 to 2018. Academic tertiary referral center. Patients receiving primary GK surgery for vestibular schwannomas with at least 6 months of follow up. Patients with neurofibromatosis 2 or previous surgery were excluded. The presence of posttreatment vestibular symptoms within 6 months after GK. Clinical records were assessed for pretreatment tumor, patient, and treatment characteristics that impacted posttreatment symptoms. All patients received radiation doses between 12 and 13 Gy. Of 115 patients, the average age was 60. Thirty-seven (32%) patients developed vestibular symptoms within 6 months post-GK, and 18 patients were referred for vestibular rehabilitation. Ten of 13 patients undergoing vestibular rehabilitation reported improvement. Overall, 112 patients had tumor measurements. Pretreatment tumors were significantly smaller for patients with acute vestibular symptoms (mean 1.43 cm versus 1.71 cm, p = 0.007). On multivariate analysis, smaller tumor size (p = 0.009, odds ratio [OR] = 0.29, 95% confidence interval [CI] [0.12-0.73]) was significantly associated with vestibular symptoms within 6 months of GK. Patients with tumors less than 1.6 cm were more likely to receive referrals for vestibular rehabilitation within 6 months posttreatment (25% versus 9.4%, p = 0.026, OR = 3.22, 95% CI [1.00, 11.32]). Smaller vestibular schwannomas were significantly associated with higher rates of post-GK vestibular symptoms. Pretreatment tumor size may be used to counsel patients on the likelihood of post-GK vestibular symptoms and vestibular rehabilitation.

Two cases of cystic enlargement of vestibular schwannoma as a late complication following gamma knife surgery

Cyst formation is the most common long-term complication after gamma knife surgery (GKS) for cerebral arteriovenous malformations; however, this rarely occurs after GKS for vestibular schwannoma (VS). We describe two patients that developed aggressive, symptomatic large cysts at more than 4 and 12years after GKS for VS, although the tumor control for these patients had been acceptable at 3 and 11years, respectively. During the surgery, a reddish lesion, which was distinct from the surrounding tumor, was observed. The microscopic examination of the reddish lesion revealed dilated capillary vessels and hemorrhage, which was compatible with late radiation changes; these were usually seen in arteriovenous malformations following radiosurgery. The present patients indicated that cyst formation and enlargement may occur as a late complication following GKS even in extra-axial benign tumors such as VS.

What is the risk of malignant transformation of vestibular schwannoma following radiosurgery?

Since the use of radiosurgery to treat vestibular schwannoma (VS) has only become widespread over the last several decades, we are just now beginning to see the long-term outcomes and side effects of this treatment. One particularly concerning complication is malignant transformation of a benign lesion. Although the malignant-inducing potential of radiation is well documented for traditional radiation therapy, there are limited data available regarding this complication in the context of stereotactic radiosurgery (e.g., Gamma Knife [Elektra, Stockholm, Sweden] and Cyberknife [Accuray, Sunnyvale, CA]) for vestibular schwannoma. Compared to standard radiation therapy, the irradiated volume with radiosurgery is significantly smaller, and the high single doses given to this small target should theoretically lead to cytotoxicity and not mutagenicity. However, there have been several recent case reports in the literature of skull base malignancies following stereotactic radiosurgery. These criteria are problematic for our purposes because the diagnosis of a vestibular schwannoma is based on clinical and radiographic diagnosis and pretreatment biopsy is rarely obtained. Given the rarity of aggressive lesions, biopsying every patient that presents with a VS would add time, morbidity, and cost while providing minimal benefit in terms of management and decision making. A recent review by Demetriades et al. found 14 cases of malignant vestibular schwannoma reported in the literature.2 Only six of the 14 patients actually had prior radiotherapy. Of those six, only three had a pathology-proven benign lesion prior to treatment. Of the five cases of malignant VS in the absence of radiosurgery, two even had initial histology showing benign disease.2 These cases highlight the difficulty of definitively establishing a causal relationship between radiosurgery and malignant transformation. A 2014 review by Patel and Chiang examines not only cases of malignant transformation of VS but also cases of radiation-induced malignancy arising from surrounding normal tissue in the treatment field for VS.3 Of 22 cases treated for VS, 13 transformed into malignant peripheral nerve-sheath tumors, whereas five developed glioblastoma multiforme and four developed sarcomas. Overall, the authors estimated the risk of developing a malignancy after stereotactic radiosurgery to be 0.04% at 15 years posttreatment. This calculation is based on stereotactic radiosurgery for any benign lesion. There are significant differences in treatment dose and volume depending on the initial pathology. As with any treatment decision, patient selection is critical. Age at the time of exposure and certain genetic susceptibilities such as neurofibromatosis type 2 (NF-2) have been identified as increasing the risk of radiation-induced oncogenesis. A review by Hosseini et al. also highlighted a possible association with initial tumor size.4 In their review of 17 cases of malignant transformation of VS, none of the patients had a tumor less than 2.5 cm in size. Thirteen of the 17 cases were in patients with NF-2. Hosseini postulates that radiosurgery serves as the final genetic hit that induces malignant transformation in already mutated cells.4 This theory could also explain the increased risk in younger patients. In this scenario, perhaps radiosurgery serves as an earlier genetic insult. Younger patients, having a longer life ahead, have more opportunity to acquire additional mutations in those cells' DNA, eventually leading to malignant transformation. As the duration of posttreatment follow-up increases for these patients, more specific criteria regarding high-risk patients will be established. Hasegawa et al., in a large study of 440 patients treated with gamma knife surgery for VS and followed for a median of 12.5 years, reported only one case of malignant degeneration.5 The patient did not have a preradiosurgery biopsy. Even with the assumption that this lesion was in fact benign pretreatment, the overall malignant transformation rate was calculated as 0.3%, and the annual incidence of malignant change was 0.02%.5 Radiosurgical treatment of vestibular schwannomas is safe and effective. The risk of malignant degeneration is acceptably low for the majority of patients. Caution is particularly required when counseling young patients, patients with genetic susceptibility, and patients with large tumors. This article references one level I, one level III, and three level IV papers.

Clinical course of vestibular schwannoma in pediatric neurofibromatosis Type 2.

Neurofibromatosis Type 2 (NF2) is an autosomal-dominant inherited disease, characterized by multiple neoplasia syndromes, including meningioma, schwannoma, glioma, and ependymoma. In this report, the authors present their clinical experience with pediatric NF2 patients. In particular, they focused on the clinical course of vestibular schwannoma (VS), including the natural growth rate, tumor control, and functional hearing outcomes. From May 1988 to June 2012, the authors recruited patients who were younger than 18 years and fulfilled the Manchester criteria. In total, 25 patients were enrolled in this study. The authors analyzed the clinical course of these patients. In addition, they measured the natural growth rate of VS before any treatment in these children with NF2. Then, they evaluated the tumor control rate and functional hearing outcomes after the treatment of VS. The mean age at the onset of NF2-related symptoms was 9.9 ± 4.5 years (mean ± SD, range 1-17 years). The mean age at the diagnosis of NF2 was 12.9 ± 2.9 years (range 5-17 years). The mean follow-up period was 89.3 months (range 12-311 months). As initial manifestations, nonvestibular symptoms were frequently observed in pediatric patients with NF2. The mean natural growth rate of VS was 0.33 ± 0.41 cm(3)/year (range 0-1.35 cm(3)/year). The tumor control rate of VS was 35.3% at 3 years after Gamma Knife surgery (GKS). The actuarial rate of useful hearing preservation was 67% in the 1st year and 53% in the 5th year after GKS. Clinical manifestations in children with NF2 were highly variable, compared with their adult counterparts. The natural growth rate of VS in children is slow, and this oncological feature may explain the diverse clinical manifestations besides vestibular symptoms in children with NF2. The treatment outcome of GKS for VS in children with NF2 was not favorable compared with previous reports of affected adults.

Irradiation of cochlear structures during vestibular schwannoma radiosurgery and associated hearing outcome

Object The purpose of this study was to measure the dose of radiation delivered to the cochlea during a Gamma knife surgery (GKS) procedure for treatment of patients with vestibular schwannomas (VSs), and to analyze the relationship between cochlear irradiation and the hearing outcome of these patients. Methods Eighty-two patients with VSs were treated with GKS using a marginal dose of 12 Gy. No patient had neurofibromatosis Type 2 disease, and all had a Gardner–Robertson hearing class of I to IV before treatment, and a radiological and audiological follow-up of at least 1-year after GKS. The dosimetric data of the volume of the cochlea were retrospectively analyzed and were correlated with the auditory outcome of patients. Results The mean radiation dose delivered to the cochlear volume ranged from 1.30 to 10.00 Gy (median 4.15 Gy). The cochlea received significantly higher radiation doses in patients with worsening of hearing after GKS. A highly significant association between the cochlear and the intracanalicular dose of radiation delivered during GKS was found. Conclusions During GKS for VSs, relatively high doses of radiation can be delivered to the cochlea. Worsening of hearing after GKS can be the consequence of either radiation injury to the cochlea or the irradiation dose delivered into the auditory canal, or both.

Acute neurological complications following gamma knife surgery for vestibular schwannoma

The authors describe an acute facial and acoustic neuropathy following gamma knife surgery (GKS) for vestibular schwannoma (VS). This 39-year-old woman presenting with tinnitus underwent GKS for a small right-sided intracanalicular VS, receiving a maximal dose of 26 Gy and a tumor margin dose of 13 Gy to the 50% isodose line. Thirty-six hours following treatment she presented with nausea, vomiting, vertigo, diminished hearing, and a House-Brackmann Grade III facial palsy. She was started on intravenous glucocorticosteroid agents, and over the course of 2 weeks her facial function returned to House-Brackmann Grade I. Unfortunately, her hearing loss persisted. A magnetic resonance (MR) image obtained at the time of initial deterioration demonstrated a significant decrease in tumor enhancement but no change in tumor size or peritumoral edema. Subsequently, the patient experienced severe hemifacial spasms, which persisted for a period of 3 weeks and then progressed to a House-Brackmann Grade V facial palsy. During the next 3 months, the patient was treated with steroids and in time her facial function and hearing returned to baseline levels. Results of MR imaging revealed transient enlargement (3 mm) of the tumor, which subsequently returned to its baseline size. This change corresponded to the tumor volume increase from 270 to 336 mm3. The patient remains radiologically and neurologically stable at 10 months posttreatment. This is the first detailed report of acute facial and vestibulocochlear neurotoxicity following GKS for VS that improved with time. In addition, MR imaging findings were indicative of early neurotoxic changes. A review of possible risk factors and explanations of causative mechanisms is provided.

Radiation exposure of normal temporal bone structures during stereotactically guided gamma knife surgery for vestibular schwannomas.

The dosimetry of radiation exposure of healthy inner, middle, and external ear structures that leads to hearing loss, tinnitus, facial weakness, dizziness, vertigo, and imbalance after gamma knife surgery (GKS) for vestibular schwannomas (VSs) is unknown. The authors quantified the dose of radiation received by these structures after GKS for VS to assess the likelihood that these doses contributed to postradiosurgery complications. A retrospective study was performed using a prospectively acquired database of a consecutive series of 54 patients with VS who were treated with GKS during a 3.5-year period at an "open unit" gamma knife center. Point doses were measured for 18 healthy temporal bone structures in each patient, with the anatomical position of each sampling point confirmed by a fellowship-trained neurootologist. These values were compared against single-dose equivalents for the 5-year tolerance dose for a 5% risk of complications and the 5-year tolerance dose for a 50% risk of complications, which were calculated using known 2-Gy/fraction thresholds for chronic otitis, chondromalacia, and osseous necrosis, as well as the tumor margin dose and typical tumor margin prescription doses for patients in whom hearing preservation was attempted. External and middle ear doses were uniformly low. The intratemporal facial nerve is susceptible to unintentionally high radiation exposure at the fundus of the internal auditory canal, with higher than tumor margin doses detected in 26% of cases. In the cochlea, the basal turn near the modiolus and its inferior portion are most susceptible, with doses greater than 12 Gy detected in 10.8 and 14.8% of cases. In the vestibular labyrinth, the ampulated ends of the lateral and posterior semicircular canals are most susceptible, with doses greater than 12 Gy detected in 7.4 and 5.1% of cases. Doses delivered to middle and external ear structures are unlikely to contribute to post-GKS complications, but unexpectedly high doses may be delivered to sensitive areas of the intratemporal facial nerve and inner ear. Unintentional delivery of high doses to the stria vascularis, the sensory neuroepithelium of the inner ear organs and/or their ganglia, may play a role in the development of post-GKS tinnitus, hearing loss, dizziness, vertigo, and imbalance. Minimizing treatment complications post-GKS for VS requires precise dose planning conformality with the three-dimensional surface of the tumor.