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Stereotactic radiotherapy for large vestibular schwannomas: Volume change following single fraction versus hypofractionated approaches

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Hypofractionated stereotactic radiotherapy is a treatment option for large vestibular schwannomas supported by an increasing evidence. A single-institution retrospective review of large (>3.5cc) vestibular schwannomas treated with hypofractionated stereotactic radiotherapy and single-session radiosurgery was conducted. Using serial follow up scans, a volumetric analysis of tumor volume change over time was performed. Vestibular schwannomas treated with hypofractionated stereotactic radiotherapy appeared to reduce in volume significantly faster than those treated with single-session radiosurgery. Cystic lesions reduced in volume faster than solid lesions. There was no significant difference in the rates of radiological and symptomatic oedema, nor subsequent dexamethasone requirement between the two treatment modalities.

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Purpose of Review Vestibular schwannomas are WHO grade I tumors of the eighth cranial nerve that lead to hearing loss, tinnitus, vestibular dysfunction, and facial nerve compromise. The management of vestibular schwannomas consists of observation, radiosurgery, or microsurgical resection. In this review, we discuss the various treatment modalities specifically targeting large vestibular schwannomas in addition to their treatment risk profiles. Recent Findings Although there has been a trend towards treatment with radiosurgery for smaller lesions, consensus reports still advocate for surgical debulking in patients with large vestibular schwannomas. There has been a shift in management philosophy towards functional preservation at the cost of more extensive resection, yet subtotal resection of vestibular schwannomas is associated with higher rates of recurrence on follow-up. Some groups have demonstrated new promise for the management of large vestibular schwannomas with stereotactic radiosurgery alone and multimodality therapy involving subtotal surgical resection with planned postoperative radiosurgery to residual tumor. Summary Although most groups would still advocate for microsurgical debulking of large vestibular schwannomas with evidence of brainstem compression, hybrid treatment strategies have become preferable. More work is required to determine which patients are at risk of progression after a subtotal resection to stratify those who should or should not receive postoperative stereotactic radiosurgery.
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Background: The effectiveness of Diffusion Tensor Imaging (DTI) in demonstrating functional changes in the tumor in determining the response to treatment after radiosurgery in patients with vestibular schwannoma (VS) is not clear yet. Objective: The study aimed to determine the change total in tumor volume (TTV) in terms of radiological response in patients who had VS and were treated with radiosurgery and investigate the relationship between the TTV, follow-up times and DTI parameters. Methods: Thirty-one patients were assessed using DTI and MRI. TTV, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were calculated. Patients were divided into tree groups: those who responded to the treatment (group 1) (n=11), who did not (group 0) (n=9) and who remained stable (group 2) (n=11). Results: The mean duration of follow-up was 28.81±14 months. ADC values increased in patients with VS after radiosurgery (p=0.004). There was no statistical difference in the FA values. A significant reduction in TTV after radiosurgery was detected in group 1 (p=0.003). ADC values increased significantly after radiosurgery in group 2 (p=0.04). Although there were no significant differences, ADC values after radiosurgery increased in group 1 and group 0. Conclusions: ADC values continuously increase due to radiation damage in the period before the tumor volume shrinks after radiosurgery. We think that it is not appropriate to diagnose inadequate treatment or progression only when TTV is evaluated in terms of response to treatment in the early period after radiosurgery.
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Objectives: The aim of this systematic review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus guideline statements for vestibular schwannoma. Methods: A systematic review of the literature was performed up to April 2015. Results: A total of 55 full-text articles were included in the analysis. All studies were retrospective, except for 2 prospective quality of life studies. Five-year tumour control rates with Gamma Knife radiosurgery (RS), single fraction linac RS, or fractionated (either hypofractionated or conventional fractionation) stereotactic radiation therapy (FSRT) were similar at 81-100%. The single fraction RS series (linac or Gamma Knife) with tumour marginal doses between 12 and 14 Gy revealed 5-year tumour control rates of 90-99%, hearing preservation rates of 41-79%, facial nerve preservation rates of 95-100% and trigeminal preservation rates of 79-99%.There were 6 non-randomized studies comparing single fraction RS versus FSRT. There was no statistically significant difference in tumour control; HR=1.66 (95% CI 0.81, 3.42), p =0.17, facial nerve function; HR = 0.67 (95% CI 0.30, 1.49), p =0.33, trigeminal nerve function; HR = 0.80 (95% CI 0.41, 1.56), p =0.51, and hearing preservation; HR = 1.10 (95% CI 0.72, 1.68), p =0.65 comparing single fraction RS with FSRT.Nine quality of life reports yielded conflicting results as to which modality (surgery, observation, or radiation) was associated with better quality of life outcomes. Conclusions: There are no randomized trials to help guide management of patients with vestibular schwannoma. Within the limitations of the retrospective series, a number of consensus statements were made.
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Purpose The aim of this study is to evaluate long-term treatment outcome and toxicities among vestibular schwannoma (VS) patients treated with hypofractionated stereotactic radiotherapy (HSRT). Methods 383 patients with unilateral VS treated with HSRT (25 Gy, five fractions) between 1995 and 2007 were retrospectively reviewed. Treatment failure was defined as requiring salvage microsurgery. Posttreatment new/progressive clinical symptoms or increases in baseline tumor volume (BTV) due to treatment effect or progression were noted. Symptom outcomes were reported as baseline and posttreatment ± improvement, respectively. Symptoms were grouped by cranial nerve (CN) VII or CNVIII. Audiometry was assessed baseline and posttreatment hearing. Patients were grouped as having greater than serviceable hearing [Gardner Robertson (GR) score 1–2] or less than non-serviceable hearing (GR score 3–5) by audiometry. Results Median follow-up was 72.0 months. Nine (2.3%) experienced treatment failure. At last follow-up, 74 (19.3%) had new/progressive symptoms and were categorized as radiologic non-responders, whereas 300 (78.3%) had no tumor progression and were grouped as radiologic responders. Average pretreatment BTV for treatment failures, radiologic non-responders, and radiologic responders was 2.11, 0.44, and 1.87 cm³, respectively. Pretreatment CNVII and CNVIII symptoms were present in 9.4 and 93.4% of patients, respectively. Eight (24%) with pre-HSRT CNVII and 37 (10%) with pre-HSRT CNVIII symptoms recovered CN function post-HSRT. Thirty-five (9%) and 36 (9.4%) experienced new CNVII and CNVIII deficit, respectively, after HSRT. Of these, 20 (57%) and 18 (50%) recovered CNVII and CNVIII function, respectively, after HSRT. Evaluable audiograms were available in 199 patients. At baseline and at last follow-up, 65.8 and 36.2% had serviceable hearing, respectively. Fifty-one percent had preservation of serviceable hearing at last follow-up. Conclusion Treatment of VS with HSRT is effective with treatment success in 97.7% and an acceptable toxicity profile. Less than one-third of patients experience any new CNVII or CNVIII deficit posttreatment. Greater than 50% of patients with serviceable hearing at baseline maintained hearing function. Improved methods to differentiate treatment effect and tumor progression are needed.
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Objective: Repeated controlled studies have revealed that stereotactic radiosurgery is better than microsurgery for patients with vestibular schwannoma (VS) <3 cm in need of intervention. In this systematic review we aimed to compare results from single-fraction stereotactic radiosurgery (SRS) to fractionated stereotactic radiotherapy (FSRT) for patients with VS. Data sources and eligibility criteria: We systematically searched MEDLINE, Web of Science, Embase and Cochrane and screened relevant articles for references. Publications from 1995 through 2014 with a minimum of 50 adult (>18 years) patients with unilateral VS, followed for a median of >5 years, were eligible for inclusion. After screening titles and abstracts of the 1094 identified articles and systematically reviewing 98 of these articles, 19 were included. Intervention: Patients with unilateral VS treated with radiosurgery were compared to patients treated with fractionated stereotactic radiotherapy. Results: No randomized controlled trial (RCT) was identified. None of the identified controlled studies comparing SRS with FSRT were eligible according to the inclusion criteria. Nineteen case series on SRS (n = 17) and FSRT (n = 2) were included in the systematic review. Loss of tumor control necessitating a new VS-targeted intervention was found in an average of 5.0% of the patients treated with SRS and in 4.8% treated with FSRT. Mean deterioration ratio for patients with serviceable hearing before treatment was 49% for SRS and 45% for FSRT, respectively. The risk for facial nerve deterioration was 3.6% for SRS and 11.2% for FSRT and for trigeminal nerve deterioration 6.0% for SRS and 8.4% for FSRT. Since these results were obtained from case series, a regular meta-analysis was not attempted. Conclusion: SRS and FSRT are both noninvasive treatment alternatives for patients with VS with low rates of treatment failure in need of rescue therapy. In this selection of patients, the progression-free survival rates were on the order of 92-100% for both treatment options. There is a lack of high-quality studies comparing radiation therapy alternatives for patients with VS. Finally, 19 articles reported long-term tumor control after SRS, while only 2 articles reported long-term FSRT results, making effect estimates more uncertain for FSRT.
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Typically, vestibular schwannomas (VS) react to Gamma Knife radiosurgery (GKRS) with a transient increase of tumor volume owed to tumor swelling at about 6 months followed by a reduction of tumor volume owed to tumor shrinkage at about 18 months. It is important to distinguish this transient tumor expansion (TTE) from tumor growth. We undertook this study to see if there is a typical time interval in the follow-up of VS following GKRS, which may indicate tumor growth rather than TTE. We retrospectively reviewed the patient charts of patients who underwent GKRS for unilateral sporadic VS at the Gamma Knife Center Zurich from 1994-2009 and who were treated by J. Siegfried or one of the authors (TM). Tumor progression was defined as an increase of tumor volume of ≥ 20 % as compared to the initial tumor volume at the earliest 2 years following GKRS. This time interval of ≥ 2 years was chosen in order to distinguish TTE from genuine tumor progression. Whenever tumor enlargement was suspected on follow-up MRI at ≥ 2 years following GKRS, tumor volumes were measured using custom software. From 1994-2009, 235 patients underwent GKRS in Zurich for unilateral sporadic VS. Tumor progression with a volume increase of ≥ 20 % occurred in 21/235 (8.9 %) patients at 3.4 ± 0.9 years following GKRS. Seventeen out of 235 (7 %) patients had a clinically relevant tumor progression requiring microsurgery or repeat radiosurgery. According to our data, time may be a good parameter distinguishing tumor progression due to tumor growth from TTE due to tumor swelling in VS following GKRS. Tumor growth seems to occur at about 3-4 years following GKRS for VS as opposed to TTE, which seems to be present at about 6-18 months following GKRS for VS.
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Unlabelled: The pupose of this study is to assess the long-term outcome and toxicity of fractionated stereotactic radiation therapy (FSRT) and stereotactic radiosurgery (SRS) for 100 vestibular schwannomas treated at a single institution. From 1993 to 2007, 104 patients underwent were treated with radiation therapy for vestibular schwannoma. Forty-eight patients received SRS, with a median prescription dose of 12.5 Gy for SRS (range 9.7-16 Gy). For FSRT, two different fraction schedules were employed: a conventional schedule (ConFSRT) of 1.8 Gy per fraction (Gy/F) for 25 or 28 fractions to a total dose of 45 or 50.4 Gy (n = 19); and a once weekly hypofractionated course (HypoFSRT) consisting of 4 Gy/F for 5 fractions to a total dose of 20 Gy (n = 37). Patients treated with FSRT had better baseline hearing, facial, and trigeminal nerve function, and were more likely to have a diagnosis of NF2. The 5-year progression free rate (PFR) was 97.0 after SRS, 90.5% after HypoFSRT, and 100.0% after ConFSRT (p = NS). Univariate analysis demonstrated that NF2 and larger tumor size (greater than the median) correlated with poorer local control, but prior surgical resection did not. Serviceable hearing was preserved in 60.0% of SRS patients, 63.2% of HypoFSRT patients, and 44.4% of ConFSRT patients (p = 0.6). Similarly, there were no significant differences in 5-year rates of trigeminal toxicity facial nerve toxicity, vestibular dysfunction, or tinnitus. Conclusions: Equivalent 5-year PFR and toxicity rates are shown for patients with vestibular schwanoma selected for SRS, HypoFSRT, and ConFSRT after multidisciplinary evaluation. Factors correlating with tumor progression included NF2 and larger tumor size.
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Purpose: Benign tumors that arise from the meninges can be difficult to treat due to their potentially large size and proximity to critical structures such as cranial nerves and sinuses. Single fraction radiosurgery may increase the risk of symptomatic peritumoral edema. In this study, we report our results on the efficacy and safety of five fraction image-guided radiosurgery for benign meningiomas. Materials/Methods: Clinical and radiographic data from 38 patients treated with five fraction radiosurgery were reviewed retrospectively. Mean tumor volume was 3.83 mm3 (range, 1.08–20.79 mm3). Radiation was delivered using the CyberKnife, a frameless robotic image-guided radiosurgery system with a median total dose of 25 Gy (range, 25–35 Gy). Results: The median follow-up was 20 months. Acute toxicity was minimal with eight patients (21%) requiring a short course of steroids for headache at the end of treatment. Pre-treatment neurological symptoms were present in 24 patients (63.2%). Post treatment, neurological symptoms resolved completely in 14 patients (58.3%), and were persistent in eight patients (33.3%). There were no local failures, 24 tumors remained stable (64%) and 14 regressed (36%). Pre-treatment peritumoral edema was observed in five patients (13.2%). Post-treatment asymptomatic peritumoral edema developed in five additional patients (13.2%). On multivariate analysis, pre-treatment peritumoral edema and location adjacent to a large vein were significant risk factors for radiographic post-treatment edema (p = 0.001 and p = 0.026 respectively). Conclusion: These results suggest that five fraction image-guided radiosurgery is well tolerated with a response rate for neurologic symptoms that is similar to other standard treatment options. Rates of peritumoral edema and new cranial nerve deficits following five fraction radiosurgery were low. Longer follow-up is required to validate the safety and long-term effectiveness of this treatment approach.
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Objective To retrospectively examine the outcomes of hypofractionated stereotactic radiation therapy in three to five fractions for vestibular schwannomas.
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γ knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors. Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm(3) (range 5.3-19.1 cm(3)). The median maximum posterior fossa diameter was 2.8 cm (range 2.5-3.8 cm). The median tumor margin dose was 12 Gy (range 12-14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26-121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection. Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction. Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.
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Single-session stereotactic radiosurgery (SRS) treatment of vestibular schwannomas results in excellent tumor control. It is not known whether functional outcomes can be improved by fractionating the treatment over multiple sessions. To examine tumor control and complication rates after multisession SRS. Three hundred eighty-three patients treated with SRS from 1999 to 2007 at Stanford University Medical Center were retrospectively reviewed. Ninety percent were treated with 18 Gy in 3 sessions, targeting a median tumor volume of 1.1 cm3 (range, 0.02-19.8 cm3). During a median follow-up duration of 3.6 years (range, 1-10 years), 10 tumors required additional treatment, resulting in 3- and 5-year Kaplan-Meier tumor control rates of 99% and 96%, respectively. Five-year tumor control rate was 98% for tumors < 3.4 cm3. Neurofibromatosis type 2-associated tumors were associated with worse tumor control (P = .02). Of the 200 evaluable patients with pre-SRS serviceable hearing (Gardner-Robertson grade 1 and 2), the crude rate of serviceable hearing preservation was 76%. Smaller tumor volume was associated with hearing preservation (P = .001). There was no case of post-SRS facial weakness. Eight patients (2%) developed trigeminal dysfunction, half of which was transient. Multisession SRS treatment of vestibular schwannomas results in an excellent rate of tumor control. The hearing, trigeminal nerve, and facial nerve function preservation rates reported here are promising.
Article
Introduction: There are many treatment options for vestibular schwannomas (VS), including radiosurgery. Previous studies have shown good outcomes for smaller tumours. We report the results of a seven-year cohort of patients with VS who were treated at our centre using a linear accelerator-based stereotactic radiosurgery system. Methods: We retrospectively reviewed the case notes and magnetic resonance (MR) images of patients with VS treated with radiosurgery. Treatment was administered as either a single 13 Gy session or 25 Gy in five sessions. At our centre, only larger or higher Koos grade VS were routinely treated with hypo-fractionated radiosurgery. Tumour response and hearing were assessed using RECIST criteria and Gardner-Robertson Scale, respectively. Other toxicities were assessed using physical examination and history-taking. Freedom from radiological progression was estimated with the Kaplan-Meier method. Results: 46 patients received single-fraction radiosurgery and 31 received hypo-fractionated radiosurgery. Median follow-up was 40.7 months. 29 patients had prior surgery to remove the tumour (median size 1.68 cm³). One patient who had symptomatic increase in tumour size (> 20% in largest diameter) was treated conservatively and subsequent showed stable disease on MR imaging. Progression-free survival was 98.7%. Another patient had symptomatic oedema requiring ventriculoperitoneal shunt insertion. 11 patients had serviceable hearing before radiotherapy and 72.7% of them retained useful hearing (mean decline in pure tone average 20.1 dB). Facial and trigeminal nerve functions and sense of equilibrium were preserved in > 90% of patients. Conclusion: Radiosurgery is effective and safe for small VS or as an adjunct therapy after microsurgery.
Article
Stereotactic radiosurgery (SRS), typically administered in a single session, is widely employed to safely, efficiently, and effectively treat small intracranial lesions. However, for large lesions or those in close proximity to critical structures, it can be difficult to obtain an acceptable balance of tumor control while avoiding damage to normal tissue when single-fraction SRS is utilized. Treating a lesion in 2 to 5 fractions of SRS (termed "hypofractionated SRS" [HF-SRS]) potentially provides the ability to treat a lesion with a total dose of radiation that provides both adequate tumor control and acceptable toxicity. Indeed, studies of HF-SRS in large brain metastases, vestibular schwannomas, meningiomas, and gliomas suggest that a superior balance of tumor control and toxicity is observed compared with single-fraction SRS. Nonetheless, a great deal of effort remains to understand radiobiologic mechanisms for HF-SRS driving the dose-volume response relationship for tumors and normal tissues and to utilize this fundamental knowledge and the results of clinic studies to optimize HF-SRS. In particular, the application of HF-SRS in the setting of immunomodulatory cancer therapies offers special challenges and opportunities. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected]
Article
Objective: Gamma knife radiosurgery (GKS) for the treatment of vestibular schwannoma (VS) introduces risks to the facial nerve and auditory perception, and may involve post-treatment complications such as pseudoprogression, hydrocephalus, and other cranial neuropathies. This study of patients with VS who underwent GKS investigated radiosurgical results, focusing on post-treatment complications and identifying the factors that predict such complications. Methods: We undertook a retrospective review of all VS patients treated with the Perfexion Leksell gamma knife between November 2007 and October 2010 at our institution. Patients who underwent at least 12 months of clinical and radiological assessments before and after GKS were included. Results: All 235 patients were included in the analyses reported here. The 5-year serviceable hearing and facial nerve preservation values were 73.9% and 94.3%, respectively. Following GKS, 43 patients (18.30%) showed pseudoprogression, 15 (6.38%) exhibited hydrocephalus, 22 (9.36%) showed trigeminal neuropathy, 14 (5.96%) showed vertigo, and 25 (10.64%) showed facial myokymia. According to multivariate analysis, solid tumor nature was significantly associated with pseudoprogression and patient age was significantly associated with hydrocephalus. Patients receiving margin dose ≥ 13 Gy had a significantly higher probability of loss of serviceable hearing. Patients with smaller tumors had a trigeminal nerve preservation rate comparable to patients harboring larger tumors. Patients receiving margin dose < 13 Gy or older patients had a significantly higher probability of vestibular nerve dysfunction. Conclusions: Further prospective studies should be designed to provide further insight into the exact relationship between the predictive factors we investigated and post-treatment complications.
Article
Background: Vestibular schwannomas (VS) have a well-documented response to Gamma Knife? (Elekta AB, Stockholm, Sweden) Stereotactic radiosurgery (SRS). However, there are limited data available regarding the volumetric response of cystic tumors. Objective: This report correlates the radiographic appearance of VS before radiosurgery with the delayed volumetric response. Methods: This study reviewed our SRS experience with 219 VS patients between 2003 and 2013. Patients were treatment na?ve and had a significant extracanalicular tumor volume. Magnetic resonance imaging at the time of SRS identified 42 contrast-enhancing macrocystic tumors, 45 contrast-enhancing microcystic tumors, and 132 homogeneously enhancing tumors with no intratumoral cyst formation. The median follow-up was 49.1 months. The median tumor volume was 2.6 cm 3 (0.70-16.1 cm 3 ) and the median dose was 12.5 Gy (11-13 Gy). Results: The actuarial tumor control rate was 99.4% at 2 years and 96.4% at 5 years. A volumetric reduction of >20% occurred in 85.4% of macrocystic tumors, 76.1% of microcystic tumors, and 62.8% of homogeneously enhancing VS. The median volume decrease per year for macrocystic, microcystic, and homogenous tumors was 17.2%, 7.5%, and 7.9% per year respectively ( P < .001). A 2:1 blinded volumetric case match showed a significant size reduction in macrocystic tumors compared to noncystic tumors ( P = .007). Serviceable hearing was maintained in 61.5% of patients that had Gardner-Robertson grade I-II hearing before treatment. Surgical resection or repeat radiosurgery was performed in 8 patients (3.6%) who had sustained tumor progression. Conclusion: SRS provided VS tumor control in >95% of patients, regardless of radiographic characteristics. Tumor volume regression was most evident in patients with cystic tumors.
Article
Background: Stereotactic radiotherapy (RT) has been established as a valid treatment alternative in patients with vestibular schwannoma (VS). There is ongoing controversy regarding the optimal fractionation. Hearing preservation may be the primary goal for patients with VS, followed by maintenance of quality of life (QoL). Methods: From 2002 to 2015, 184 patients with VS were treated with radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT). A survey on current symptoms and QoL was conducted between February and June 2016. Results: Median follow-up after RT was 7.5 years (range 0-14.4 years). Mean overall survival (OS) after RT was 31.1 years, with 94 and 87% survival at 5 and 10 years, respectively. Mean progression-free survival (PFS) was 13.3 years, with 5‑ and 10-year PFS of 92%. Hearing could be preserved in RS patients for a median of 36.3 months (range 2.3-13.7 years). Hearing worsened in 17 (30%) cases. Median hearing preservation for FSRT was 48.7 months (range 0.0-13.8 years); 29 (23%) showed hearing deterioration. The difference in hearing preservation was not significant between RS and FSRT (p = 0.3). A total of 123/162 patients participated in the patient survey (return rate 76%). The results correlate well with the information documented in the patient files for tinnitus and facial and trigeminal nerve toxicity. Significant differences appeared regarding hearing impairment, gait uncertainty, and imbalance. Conclusion: These data confirm that RS and FSRT are comparable in terms of local control for VS. RS should be reserved for smaller lesions, while FSRT can be offered independently of tumor size. Patient self-reported outcome during follow-up is of high value. The established questionnaire could be validated in the independent cohort.
Article
Background: We evaluated and compared the radiographic and clinical outcomes of patients with vestibular schwannomas treated with single fraction stereotactic radiosurgery (SRS), 5 fractions of hypofractionated stereotactic radiation therapy (hSRT), or 25 to 30 fractions of conventionally fractionated stereotactic radiation therapy (cfSRT). Methods and materials: Fifty-six patients treated with LINAC-based SRS (median, 12.5 Gy), hSRT (25 Gy), or cfSRT (median, 54 Gy) were retrospectively reviewed. Fractionation was based on the size of the tumor, proximity to the brainstem, and potential risk of neurological sequelae. Median follow-up time was 55.2 months. Results: The pretreatment median tumor diameter was significantly smaller for SRS (1.14 cm) compared with hSRT (1.7 cm) (P = .03) and cfSRT (2.0 cm) (P < .001). The overall local tumor control was 96.4%: 100% SRS, 100% hSRT, and 90% cfSRT (P = .19). Tumor regression was observed in 53.3% of SRS, 76.2% of hSRT, and 90% of cfSRT (P = .05). There was less transient expansion of tumors treated with cfSRT (5%) than with SRS (53.3%) or hSRT (28.6%) (P = .005). The median time to regression was 13.8 months for SRS, 14.2 months for hSRT, and 5.5 months for cfSRT (P = .34). There was a 3.6% incidence of grade 3 trigeminal neuropathy, but there was no grade 3 facial neuropathy. Conclusions: All 3 regimens demonstrated similar excellent local control with minimal toxicity; however, the ability of hSRT to treat larger tumors with comparable outcomes to SRS and greater patient convenience when compared with cfSRT suggest that hSRT may offer the optimal treatment approach.
Article
Background: Gamma Knife Radiosurgery (GKRS) represents a well-accepted treatment for small-medium vestibular schwannomas (VS), however, its application in larger VS is still controversial. Methods: Among the 523 patients treated at our Institution for VS between 2001 and 2010, we included 59 patients harboring a VS larger than 25 mm, treated by GKRS as primary treatment, not affected by NF2, and with a clinical follow-up (FU) of at least 36 months. Five patients underwent ventriculo-peritoneal shunt (VPS) placement before radiosurgery. Clinical FU (mean 79.4 months) was obtained in all patients. Patients' age ranged from 24 to 85 (mean 63.8 years). Mean tumor volume was 5.98 cc (max 14.3 cc) and median marginal dose was 13 Gy. A statistical analysis was performed to correlate clinical outcome with tumor radiological features, dose planning parameters and patients' characteristics. Results: Tumor control was achieved in 98.3% of cases. At last follow-up 86.4% of VS showed volume reduction. Recorded complications were: 3 cases (5.1%) of new permanent facial nerve deficit, 4 cases (6.8%) of new or worsened trigeminal impairment and 10 new cases (18.5%) of hydrocephalus requiring VPS. Larger tumor size was significantly associated with a subsequent ventricular enlargement. Overall functional hearing preservation rate was 31.3% (66.7% among Gardner-Robertson I patients). Conclusion: Surgical resection remains the primary approach for large VS with symptomatic brainstem compression. GKRS can be considered a safe and effective option in particular in patients who are not good candidates for surgery.
Article
Objectives: Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypo-fractionated SRS for VS > 3 cm. Methods: 587 VS patients treated with SRS between 1998 and 2014 were retrospectively reviewed, identifying 30 Koos Grade IV VS. There were 6 patients with NF2, 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with > 3 cm after prior resection. Patients were treated by a median of 3 fractions at 18 Gy. Results: After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80% respectively, with 20% requiring salvage treatment. For patients who had prior tumor resection rather than primary CK, there were 46% and 5%, respectively with progression, and 3-year control rates of 71% and 94% (p=0.008). Tumor control was also lower among NF2 vs non-NF2 patients (40% vs 95%, p=0.0014). Among patients with good clinical baselines prior to CK, 88% were functionally independent (mRS 0-2), 88% had good facial function (HB I-II), and 38% had serviceable hearing (GR I-II) at last follow-up. Hearing worsening was more likely among patient treated with primary CK (33% vs 90%, p = 0.04). Conclusions: Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favourable functional outcomes.
Article
Purpose: The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. Methods and materials: This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. Results: The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. Conclusions: Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.
Article
Background: Stereotactic radiosurgery (SRS) and, more recently, fractionated stereotactic radiotherapy (SRT) have been recognized as noninvasive alternatives to surgery for the treatment of acoustic schwannomas. We review our experience of acoustic tumor treatments at one institution using a gamma knife for SRS and the first commercial world installation of a dedicated linac for SRT. Methods: Patients were treated with SRS on the gamma knife or SRT on the linac from October 1994 through August 2000. Gamma knife technique involved a fixed-frame multiple shot/high conformality single treatment, whereas linac technique involved daily conventional fraction treatments involving a relocatable frame, fewer isocenters, and high conformality established by noncoplanar arc beam shaping and differential beam weighting. Results: Sixty-nine patients were treated on the gamma knife, and 56 patients were treated on the linac, with 1 NF-2 patient common to both units. Three patients were lost to follow-up, and in the remaining 122 patients, mean follow-up was 119 +/- 67 weeks for SRS patients and 115 +/- 96 weeks for SRT patients. Tumor control rates were high (> or =97%) for sporadic tumors in both groups but lower for NF-2 tumors in the SRT group. Cranial nerve morbidities were comparably low in both groups, with the exception of functional hearing preservation, which was 2.5-fold higher in patients who received conventional fraction SRT. Conclusion: SRS and SRT represent comparable noninvasive treatments for acoustic schwannomas in both sporadic and NF-2 patient groups. At 1-year follow-up, a significantly higher rate of serviceable hearing preservation was achieved in SRT sporadic tumor patients and may therefore be preferable to alternatives including surgery, SRS, or possibly observation in patients with serviceable hearing.
Article
The purpose of this study was to evaluate the control rate of vestibular schwannomas (VS) after treatment with linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) or radiotherapy (SRT) by using a validated volumetric measuring tool. Volume-based studies on prognosis after LINAC-based SRS or SRT for VS are reported scarcely. In addition, growth patterns and risk factors predicting treatment failure were analyzed. Retrospectively, 37 VS patients treated with LINAC based SRS or SRT were analyzed. Baseline and follow-up magnetic resonance imaging scans were analyzed with volume measurements on contrast enhanced T1-weighted magnetic resonance imaging. Absence of intervention after radiotherapy was defined as "no additional intervention group, " absence of radiological growth was defined as "radiological control group. " Significant growth was defined as a volume change of 19.7% or more, as calculated in a previous study. The cumulative 4-year probability of no additional intervention was 96.4% ± 0.03; the 4-year radiological control probability was 85.4% ± 0.1). The median follow-up was 40 months. Overall, shrinkage was seen in 65%, stable VS in 22%, and growth in 13%. In 54% of all patients, transient swelling was observed. No prognostic factors were found regarding VS growth. Previous treatment and SRS were associated with transient swelling significantly. Good control rates are reported for LINAC based SRS or SRT in VS, in which the lower rate of radiological growth control is attributed to the use of the more sensitive volume measurements. Transient swelling after radiosurgery is a common phenomenon and should not be mistaken for treatment failure. Previous treatment and SRS were significantly associated with transient swelling.
Article
To evaluate and compare outcomes for patients with vestibular schwannoma (VS) treated in a single institution with linac-based stereotactic radiosurgery (SRS) or by fractionated stereotactic radiotherapy (SRT). One hundred and nineteen patients (SRS = 78, SRT = 41) were treated. For both SRS and SRT, beam shaping is performed by a mini-multileaf collimator. For SRS, a median single dose of 12.5 Gy (range, 11-14 Gy), prescribed to the 80% isodose line encompassing the target, was applied. Of the 42 SRT treatments, 32 treatments consisted of 10 fractions of 3-4 Gy, and 10 patients received 25 sessions of 2 Gy, prescribed to the 100% with the 95% isodose line encompassing the planning target volume. Mean largest tumor diameter was 16.6 mm in the SRS and 24.6 mm in the SRT group. Local tumor control, cranial nerve toxicity, and preservation of useful hearing were recorded. Any new treatment-induced cranial nerve neuropathy was scored as a complication. Median follow-up was 62 months (range, 6-136 months), 5 patients progressed, resulting in an overall 5-year local tumor control of 95%. The overall 5-year facial nerve preservation probability was 88% and facial nerve neuropathy was statistically significantly higher after SRS, after prior surgery, for larger tumors, and in Koos Grade ≥3. The overall 5-year trigeminal nerve preservation probability was 96%, not significantly influenced by any of the risk factors. The overall 4-year probability of preservation of useful hearing (Gardner-Robertson score 1 or 2) was 68%, not significantly different between SRS or SRT (59% vs. 82%, p = 0.089, log rank). Linac-based RT results in good local control and acceptable clinical outcome in small to medium-sized vestibular schwannomas (VSs). Radiosurgery for large VSs (Koos Grade ≥3) remains a challenge because of increased facial nerve neuropathy.
Article
To evaluate tumor control and side effects associated with radiosurgery (RS) and stereotactic fractionated radiotherapy (SFR) for vestibular schwannomas (VSs) in a group of patients treated at the same institution. Between May 1997 and June 2007, 115 consecutive cases of VS were treated in our department. The SFR group (47 patients), including larger tumors (maximum diameter >1.5 cm), received a total dose of 54 Gy at 1.8 Gy per fraction. The RS group (68 patients, maximum diameter <1.5 cm) received a total dose of 12 Gy at the 100% isodose. Evaluation included serial imaging tests (magnetic resonance imaging) and neurologic and functional hearing examinations. The tumor control rate was 97.9% in the SFR group for a mean follow-up time of 32.1 months and 98.5% in the RS group for a mean follow-up time of 30.1 months. Hearing function was preserved after RS in 85% of the patients and after SFR in 79%. Facial and trigeminal nerve function remained mostly unaffected after SFR. After RS, new trigeminal neuropathy occurred in 9 of 68 patients (13%). A high tumor control rate and low number of side effects are registered after SFR and RS of VS. These results confirm that considering tumor diameter, both RS and SFR are good treatment modalities for VS.
Article
Stereotactic radiosurgery (SRS) and also fractionated stereotactic radiotherapy (SRT) offer high local control (LC) rates (> 90%). This study aimed to evaluate three-dimensional (3-D) tumor volume (TV) shrinkage and to assess quality of life (QoL) after SRS/SRT. From 1999 to 2005, 35/74 patients were treated with SRS, and 39/74 with SRT. Median age was 60 years. Treatment was delivered by a linear accelerator. Median single dose was 13 Gy (SRS) or 54 Gy (SRT). Patients were followed up > or = 12 months after SRS/SRT. LC and toxicity were evaluated by clinical examinations and magnetic resonance imaging. 3-D TV shrinkage was evaluated with the planning system. QoL was assessed using the questionnaire Short Form-36. Median follow-up was 50/36 months (SRS/SRT). Actuarial 5-year freedom from progression/overall survival was 88.1%/100% (SRS), and 87.5%/87.2% (SRT). TV shrinkage was 15.1%/40.7% (SRS/SRT; p = 0.01). Single dose (< 13 Gy) was the only determinant factor for TV shrinkage after SRS (p = 0.001). Age, gender, initial TV, and previous operations did not affect TV shrinkage. Acute or late toxicity (> or = grade 3) was never seen. Concerning QoL, no significant differences were observed after SRS/SRT. Previous operations and gender did not affect QoL (p > 0.05). Compared with the German normal population, patients had worse values for all domains except for mental health. TV shrinkage was significantly higher after SRT than after SRS. Main symptoms were not affected by SRS/SRT. Retrospectively, QoL was neither affected by SRS nor by SRT.
Article
To compare the effectiveness and complications of fractionated stereotactic radiotherapy (SRT) for cystic-type vestibular schwannoma (VS) with those of solid-type VS. In 65 patients treated with fractionated SRT between 1991 and 1999, 20 were diagnosed with cystic VS, in which at least one-third of the tumor volume was a cystic component on magnetic resonance imaging (MRI), and 45 were diagnosed with solid VS. Thirty-six Gy to 50 Gy in 20-25 fractions was administered to the isocenter and approximately 80% of the periphery of the tumor. All cystic and solid components were included in the gross tumor volume. The mean follow-up period was 37 months, ranging from 6 to 97 months. The actuarial 3-year rate of no episode of enlargement greater than 2.0 mm was 55% for cystic-type and 75% for solid-type VS; the difference was statistically significant (p = 0.023). The actuarial 3-year tumor-reduction (reduction in tumor size greater than 2.0 mm) rates were 93% and 31%, respectively (p = 0.0006). The overall actuarial tumor control rate (no tumor growth greater than 2. 0 mm after 2 years or no requirement of salvage surgery) was 92% at 5 years in 44 patients with a follow-up period of 2 or more years. There was no difference in the class hearing preservation rate between cystic VS and solid VS. No permanent trigeminal or facial nerve palsy was observed in either group. Transient tumor enlargement occurs in cystic VS more frequently than in solid-type VS, but the subsequent tumor-reduction rate in cystic VS is better.
Article
In this single-institution trial, we investigated whether fractionated stereotactic radiation therapy is superior to single-fraction linac-based radiosurgery with respect to treatment-related toxicity and local control in patients with vestibular schwannoma. All 129 vestibular schwannoma patients treated between 1992 and June 2000 at our linac-based radiosurgery facility were analyzed with respect to treatment schedule. Dentate patients were prospectively selected for a fractionated schedule of 5 x 4 Gy and later on 5 x 5 Gy at the 80% isodose in 1 week with a relocatable stereotactic frame. Edentate patients were prospectively selected for a nonfractionated treatment of 1 x 10 Gy and later on 1 x 12.5 Gy at 80% isodose with an invasive stereotactic frame. Both MRI and CT scans were made in all 129 patients within 1 week before treatment. All patients were followed yearly with MRI and physical examination. A fractionated schedule was given to 80 patients and a single fraction to 49 patients. Mean follow-up time was 33 months (range: 12-107 months). There was no statistically significant difference between the single-fraction group and the fractionated group with respect to mean tumor diameter (2.6 vs. 2.5 cm) or mean follow-up time (both 33 months). Only mean age (63 years vs. 49 years) was statistically significantly different (p = 0.001). Outcome differences between the single-fraction treatment group and the fractionated treatment group with respect to 5-year local control probability (100% vs. 94%), 5-year facial nerve preservation probability (93% vs. 97%), and 5-year hearing preservation probability (75% vs. 61%) were not statistically significant. The difference in 5-year trigeminal nerve preservation (92% vs. 98%) reached statistical significance (p = 0.048). Linac-based single-fraction radiosurgery seems to be as good as linac-based fractionated stereotactic radiation therapy in vestibular schwannoma patients, except for a small difference in trigeminal nerve preservation rate in favor of a fractionated schedule.
Article
A few important concepts in radiobiology are illustred. The cell survival, the concept of the biologically effective dose, the basis of fractionation in radiotherapy are considered. Slow tumor regression after irradiation is not an indication of treatment failure, and the rate of regression is not , in general, prognostic. Dose volume histograms provide many data for predicting tumor control and side effects. The magnitude of a dose reduction in the tumor is the major determinant of decline in tumor control probability. Escalation of dose to hypoxic foci may be beneficial. Basic knowledge of these concepts is essential for daily radiotherapy practice and for all radiation oncologists.