Since the first reported case in 1971 of a patient with vestibular schwannoma who was treated using radiosurgery by Leksell,34 GKS for the treatment of vestibular schwannoma has rapidly established itself as a viable alternative to microsurgical resection.7,28,29,32,47,53,57,61,77 Because GKS rarely requires hospitalization, is relatively noninvasive, and requires minimal recovery time, it may seem the ideal method of treatment. However, it is not without risk. Radiosurgery for the treatment of vestibular schwannoma introduces risks to the facial nerve and hearing, as well as posttreatment complications such as balance disturbances, hydrocephalus, headaches, tinnitus, and other cranial neuropathies.17,49
A large volume of literature has been published to date describing the postradiation morbidity and mortality in patients with vestibular schwannoma. However, given that most of these studies are small- to modest-sized case series, frequently from single institutions, it may be difficult for the new individual practitioner to use those studies to develop his/her own approach to the management of these tumors.
For this reason, we report a comprehensive review of the English-language literature to evaluate and present results on morbidity and mortality in patients treated via GKS for vestibular schwannoma. Through this, we aim to provide a representation of the effect of dose on the overall rates of morbidity for patients undergoing GKS for vestibular schwannoma.
Methods
Article Selection
A comprehensive review of the literature was conducted on the morbidity and mortality of patients who were treated using GKS for vestibular schwannoma by pooling data from the existing English-language literature. Articles were identified via a PubMed search using Boolean searches with the key words “Gamma Knife,” “vestibular schwannoma radiosurgery AND morbidity,” “vestibular schwannoma radiosurgery AND mortality,” “acoustic neuroma radiosurgery AND morbidity,” and “Gamma Knife surgery AND mortality” alone and in combination. After reviewing these articles, we then reviewed all references in these papers. This search was performed multiple times, most recently on May 31, 2007 (Table 1).
A summary of studies included in our analysis*
| Authors & Year | Pub-Med ID | Sample Size | Dose (Gy) | |||
|---|---|---|---|---|---|---|
| Fractionated | Marginal | Max | ||||
| Hirsch et al., 1979 | 386705 | 9 | no | NA | 50 | |
| Hirsch & Norén, 1988 | 3051887 | 111 | no | 21.5 | 37.5 | |
| Kamerer et al., 1988 | 3059942 | 110 | no | NA | 50 | |
| Thomsen et al., 1990 | 2240175 | 1 | no | NA | 26 | |
| Linskey et al., 1992 | 1436407 | 17 | no | 18 | 33.3 | |
| Oyama et al., 1994 | 7526251 | 13 | no | NA | 28.7 | |
| Foote et al., 1995 | 7607937 | 36 | no | 18 | NA | |
| Ogunrinde et al., 1995 | 7826279 | 31 | no | NA | 32.8 | |
| Pollock et al., 1995 | 7708162 | 78 | no | 16.3 | 31.2 | |
| Hirato et al., 1995 | 8532129 | 28 | no | 12.1 | 25.2 | |
| Kondziolka et al., 1998 | 17112219 | 462 | no | 15 | NA | |
| Miller et al., 1999 | 10030254 | 82 | no | 18 | NA | |
| Niranjan et al., 1999 | 10515468 | 29 | no | 14 | NA | |
| Schulder et al., 1999 | 10337979 | 1 | no | 14 | NA | |
| Spiegelmann et al., 1999 | 11370134 | 44 | no | 14 | NA | |
| Subach et al., 1999 | 10223445 | 40 | no | NA | 29.4 | |
| Unger et al., 1999 | 10672298 | 56 | no | 13 | NA | |
| Ito et al., 2000 | 10924974 | 125 | no | 15.4 | 29.8 | |
| Shirato et al., 2000 | 11121639 | 65 | yes | 36 | 50 | |
| Tago et al., 2000 | 11143268 | 1 | no | 14 | 20 | |
| Roos et al., 2000 | 10849982 | 23 | no | 12 | 20 | |
| Prasad et al., 2000 | 10794287 | 153 | no | 13.3 | 34.3 | |
| Kida et al., 2000 | 10825525 | 20 | no | 13 | 26.8 | |
| Foote et al., 2001 | 11565866 | 149 | no | 14 | NA | |
| Shamisa et al., 2001 | 11354416 | 1 | no | NA | 27.5 | |
| Petit et al., 2001 | 11846928 | 47 | no | 12 | 24 | |
| Flickinger et al., 2001 | 11147876 | 190 | no | 13 | 26 | |
| Bertalanffy et al., 2001 | 11534689 | 40 | no | 12 | NA | |
| Karpinos et al., 2002 | 12459364 | 75 | no | 14.5 | NA | |
| Régis et al., 2002 | 12450031 | 104 | no | 13 | NA | |
| Rowe et al., 2003 | 12933938 | 96 | no | 15.2 | NA | |
| Watanabe et al., 2003 | 14609174 | 1 | no | 24 | NA | |
| Rowe et al., 2003 | 14617712 | 234 | no | 13 | NA | |
| Linskey et al., 2003 | 12691405 | 54 | no | 12 | NA | |
| Iwai et al., 2003 | 12925242 | 51 | no | 12 | NA | |
| Flickinger et al., 2004 | 15337560 | 313 | no | 13 | 26 | |
| Wackym et al., 2004 | 15354007 | 29 | no | NA | 27.4 | |
| Wowra et al., 2004 | 15707030 | 111 | no | 13 | NA | |
| Chung et al., 2004 | 15234046 | 72 | no | 13 | 21.9 | |
| Combs et al., 2005 | 16111574 | 106 | yes | NA 57.6 | ||
| Hasegawa et al., 2005 | 15658090 | 73 | no | 14.6 | 28.4 | |
| Hayhurst et al., 2005 | 16120523 | 2 | no | NA | NA | |
| Poetker et al., 2005 | 16272946 | 23 | no | NA | 27.47 | |
| Wowra et al., 2005 | 15662792 | 111 | no | NA | 31.1 | |
| Wang et al., 2005 | 15697166 | 7 | no | 12 | 25.4 | |
| van Eck et al., 2005 | 15662811 | 78 | no | 13 | 20 | |
| Paek et al., 2005 | 15952200 | 25 | no | 12 | NA | |
| Myrseth et al., 2005 | 15854240 | 103 | no | 12.2 | 35.3 | |
| Lunsford et al., 2005 | 15662809 | 829 | no | 13 | NA | |
| Inoue, 2005 | 15662791 | 18 | no | 12 | NA | |
| Huang et al., 2005 | 16038371 | 45 | no | 11.5 | 23 | |
| Hasegawa et al., 2005 | 16094154 | 317 | no | 13.2 | 26.2 | |
| Chung et al., 2005 | 15662787 | 195 | no | 13 | 21.9 | |
| Pollock, 2006 | 16462477 | 208 | no | 13.5 | 27 | |
| Park et al., 2006 | 16397752 | 8 | no | 12 | NA | |
| Massager et al., 2006 | 16458446 | 82 | no | 12 | NA | |
| Hempel et al., 2006 | 16741754 | 123 | no | 13 | 22.7 | |
| Combs et al., 2006 | 16464537 | 26 | no | 13 | NA | |
| Koh et al., 2007 | 17318817 | 60 | yes | NA | 50 | |
| Mathieu et al., 2007 | 17327790 | 62 | no | 14 | 27.5 | |
| Neuhaus et al., 2007 | 17310028 | 1 | no | NA | 26 | |
| Rutten et al., 2007 | 17182142 | 26 | no | 14 | NA | |
| Franco-Vidal et al., 2007 | 17159493 | 1 | no | 13 | NA | |
* All patients underwent GKS. Abbreviations: ID = identification; NA = not available.
Inclusion criteria for articles were that morbidity and/ or complication rates were reported specifically for GKS without other radiotherapy or radiosurgery modalities mixed in an aggregated fashion. Patients with neurofibromatosis Type 2 were also included. Studies of patients who underwent microsurgery as a definitive treatment or those that described other forms of radiation were excluded.
Data Extraction
Data from individual and aggregated cases were extracted from each paper as follows. For those studies that did not specifically state the morbidity rate, the complication rate was used. Facial nerve and hearing morbidities are not included in this study, but are reported in separate studies in our series.
Data were analyzed as a whole and stratified into 2 cohorts according to the mean marginal dose of radiation delivered: ≤ 13 Gy and > 13 Gy. The morbidities recorded in this review were all new morbidities, appearing after radiation treatment or exacerbations of symptoms present prior to radiosurgery. Short-term morbidities were those that lasted less than 3 months. All other morbidities were considered to be long term. Mortality was defined as death after GKS within 30 days of treatment.
All tumors included in this study were < 25 mm in their largest diameter. The median largest dimension and median tumor volume were not reportable as studies did not consistently report either value.
Statistical Analysis
The Pearson chi-square test was used for statistical evaluation of the data. The p value was considered significant at the 5% (0.05) level, after correcting for multiple comparisons with Bonferroni correction, using the 2-sided reading in each case.
Results
A total of 63 articles2–6,8–12,15–25,27,28,30,31,33,35,37–40,42,44–46,48,50–52,54,56,58–67,69,72–76,78,80–82,85,86 describing 5631 patients provided some useable data and were included in estimates of overall incidence of these complications. A large number of articles represented repeat publications from the same investigators on the same patient cohort discussing other aspects of that cohort. When this conflict arose, we excluded all obviously duplicated cohorts except the largest published cohort from that institution, or the most recent, which we assumed would include all previously published patients from this group. Other excluded articles had to be eliminated from the analysis for reasons of missing data or unusable data presentation.
Of these patients, 3248 received a mean marginal radiation dose ≤ 13 Gy, while 2383 patients (42%) received > 13 Gy. The median follow-up time for the group receiving ≤ 13 Gy was 39.5 months, and the median follow-up time for the group receiving > 13 Gy was 36.5 months.
Cranial Nerve Neuropathy
Following radiosurgery, 135 patients (2.4%) were reported to have developed a new non-CN VII or non-CN VIII cranial neuropathy. The rate of neuropathies of individual CNs are summarized in Table 2. Trigeminal neuropathy, manifested by facial paresthesias or tingling, was by far the most common neuropathy, occurring over 28 times more frequently than the next most common neuropathy. Patients receiving > 13 Gy were significantly more likely to develop trigeminal nerve neuropathy than those receiving < 13 Gy (p < 0.001) (Table 2).
A summary of rates of various CN neuropathies in the reported literature*
| CN | % | p Value | ||
|---|---|---|---|---|
| Overall | >13 Gy | <13 Gy | ||
| I | 0.0 | 0.0 | 0.0 | NS |
| II | 0.0 | 0.0 | 0.0 | NS |
| III | 0.0 | 0.0 | 0.0 | NS |
| IV | 0.0 | 0.0 | 0.0 | NS |
| V | 2.30 | 3.15 | 1.63 | <0.001 |
| VI | 0.03 | 0.08 | 0.0 | NS |
| IX | 0.0 | 0.0 | 0.0 | NS |
| X | 0.0 | 0.0 | 0.0 | NS |
| XI | 0.0 | 0.0 | 0.0 | NS |
| XII | 0.08 | 0.0 | 0.15 | NS |
* NS = not significant.
Hydrocephalus
Hydrocephalus was reported in 48 patients (0.85%). Of these patients 36 (75%) required a shunt as the definitive form of treatment, and 12 patients (25%) were treated conservatively. Hydrocephalus was reported to have occurred in 24 (0.74%) of the 3248 patients receiving ≤ 13 Gy and in 24 (1.0%) of the 2383 patients receiving > 13 Gy. The reported incidence of hydrocephalus was not affected by marginal doses of radiation delivered to these patients (0.6% for both cohorts) (Fig. 1). However, patients with hydrocephalus who were receiving > 13 Gy appeared to have a higher rate of symptomatic hydrocephalus requiring shunt treatment than those receiving lower doses (96% [> 13 Gy] vs 56% [≤ 13 Gy], p < 0.001).
Bar graph showing a comparison of rates of hydrocephalus and symptomatic hydrocephalus between patients receiving > 13 Gy marginal radiation dose and those receiving ≤ 13 Gy. *p > 0.001.
Vertigo and Tinnitus
Eighty-four patients were reported to have experienced vertigo or balance disturbance after their treatment. In the group of 2383 patients that received marginal doses > 13 Gy, vertigo or balance disturbance occurred in 26 (1.1%). Of the 3248 patients in the group that was subjected to ≤ 13 Gy as their marginal dose of radiation, 58 (1.8%) were reported to have developed vertigo or balance disturbance. The rate of vertigo or balance disturbance in the lower-dose cohort was significantly higher than that in the higher-dose cohort (p = 0.001) (Fig. 2).
Bar graph showing a comparison of rates of vertigo and balance disturbance and tinnitus between patients receiving > 13 Gy marginal radiation dose and those receiving ≤ 13 Gy. *p > 0.001.
Twenty-five patients were reported to have tinnitus after treatment. In the group of 2383 patients that received marginal doses > 13 Gy, tinnitus occurred in 2 (0.1%). Of the 3248 patients in the group that was subjected to ≤ 13 Gy as their marginal dose of radiation, 23 patients (0.7%) reported tinnitus. The rate of tinnitus in the lower-dose cohort was significantly higher than that in the higher-dose cohort (0.1% [> 13 Gy] vs ≤ 13 Gy 0.7%, p = 0.001) (Fig. 2).
Discussion
Although the morbidity and mortality rates in patients undergoing radiosurgery for vestibular schwannoma have seen drastic improvements over the years, there has been wide variation in the published literature, with tumor control rates ranging from 60 to 100%.30,36 Due to the rarity of certain morbidities, it has been hard for smaller studies to provide accurate information regarding rates of occurrence. A large number of investigators have published their results previously, but to date there have been few attempts to systematically summarize the literature about this topic. In this study, we performed a comprehensive review of the literature of the morbidity and mortality in a large population of patients with vestibular schwannomas who were treated via single-fraction GKS.
Our analysis revealed that patients treated with an average marginal dose of 13 Gy or less were less likely to develop symptomatic trigeminal neuropathy over the time period of reported follow-up, when compared with those who received higher doses of radiation. Furthermore, while there was no statistically significant difference in the incidence of hydrocephalus between those patients who received a mean marginal radiation dose of 13 Gy or less and those that received a higher dose, patients receiving the higher dose seemed to have more severe hydrocephalus and usually required a CSF diversion procedure.
Interestingly, we found that patients treated with lower marginal doses experienced a small, but significantly increased rate of vertigo and balance problems, as well as an increase in the rate of posttreatment tinnitus. The reason for this is unclear, but we hypothesize that perhaps patients treated with higher doses have more complete dysfunction of this nerve, while those treated with lower doses have enough function left to detect vertigo or tinnitus. This may result from more severe involvement of the vestibular nerve with higher doses. Other reviews of the radiosurgery literature found that increased marginal doses lead to higher rates of posttreatment CN VIII dysfunction.87 Further work is needed to address this complex question.
More recently, fractionated radiosurgery has been used in an attempt to minimize injury to adjacent normal CNs using a linear accelerator or the CyberKnife (Accuray Systems).1,13,14,26,41,55,71,79,83,84 While planning is often similar to GKS, the method of immobilization is different. Rather than a frame-based approach, the position of target structure is replicated daily using customized head molds and/or face masks while obtaining regular radiographs to confirm positioning. While some consider the degree of accuracy less with these methods than that with frame-based techniques, there is evidence that results can be comparable if done properly.43,68,70 Further study is needed to assess whether fractionated radiotherapy has reduced morbidity when compared with radiosurgery.
There are several limitations with our study that should be acknowledged. Most notably, our analysis is inherently limited by the quality and accuracy of the reported literature, and unpublished data, which cannot be included in an analysis of this type, might reveal different results than an analysis limited to published data. Additionally, given the importance of long-term follow-up in studies of radiosurgery, it is not uncommon for investigators to follow up a cohort for a long period of time and to publish serial reports about the outcomes of these same patients. While we made every effort to exclude duplicated patients, it is possible that in our effort to exclude these patients, some of the smaller, earlier reports from some groups included unique patients not included in later cohorts and, thus, were incorrectly excluded from our analysis. Without the primary data sets, we cannot determine if this occurred and correct for it. Similarly, because we do not have the treatment plans for these patients, we can only look at marginal dose and are not able to assess the dose delivered to important structures such as the cochlea and the vestibular apparatus. Thus, the effect of lower dose could, in part, be the result of improved conformality of treatment plans in recent years, when lower doses were used more frequently.
Conclusions
We report our results from a large aggregated review of the English-language literature regarding radiosurgery for vestibular schwannoma. We hope that by using such a large data set, we are able to minimize the effect of individual institutions' bias to determine accurate outcome characteristics, specifically morbidity and mortality, for patients treated with radiosurgery to help physicians and patients determine the best approach for managing these tumors.
Disclosure
Dr. Sughrue was supported in part by a grant from the AANS Neurosurgery Research and Education Foundation (NREF). Dr. Yang was supported in part by the NIH National Research Service Award (NRSA) program. Dr. Kane was supported in part by a grant from the Howard Hughes Medical Institute. Dr. Parsa was supported by the Georgiana and Reza Khatib endowed chair for skull base tumor surgery.
References
- 1↑
Andrews DW, , Silverman CL, , Glass J, , Downes B, , Riley RJ, & Corn BW, et al.: Preservation of cranial nerve function after treatment of acoustic neurinomas with fractionated stereotactic radiotherapy. Preliminary observations in 26 patients. Stereotact Funct Neurosurg 64:165–182, 1995
- 2
Bertalanffy A, , Dietrich W, , Aichholzer M, , Brix R, , Ertl A, & Heimberger K, et al.: Gamma knife radiosurgery of acoustic neurinomas. Acta Neurochir (Wien) 143:689–695, 2001
- 3
Chung HT, , Ma R, , Toyota B, , Clark B, , Robar J, & McKenzie M: Audiologic and treatment outcomes after linear acceleratorbased stereotactic irradiation for acoustic neuroma. Int J Radiat Oncol Biol Phys 59:1116–1121, 2004
- 4
Chung WY, , Liu KD, , Shiau CY, , Wu HM, , Wang LW, & Guo WY, et al.: Gamma knife surgery for vestibular schwannoma: 10-year experience of 195 cases. J Neurosurg 102:Suppl 87–96, 2005
- 5
Combs SE, , Thilmann C, , Debus J, & Schulz-Ertner D: Long-term outcome of stereotactic radiosurgery (SRS) in patients with acoustic neuromas. Int J Radiat Oncol Biol Phys 64:1341–1347, 2006
- 6
Combs SE, , Volk S, , Schulz-Ertner D, , Huber PE, , Thilmann C, & Debus J: Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys 63:75–81, 2005
- 7↑
Delbrouck C, , Hassid S, , Massager N, , Choufani G, , David P, & Devriendt D, et al.: Preservation of hearing in vestibular schwannomas treated by radiosurgery using Leksell Gamma Knife: preliminary report of a prospective Belgian clinical study. Acta Otorhinolaryngol Belg 57:197–204, 2003
- 8
Flickinger JC, , Kondziolka D, , Niranjan A, & Lunsford LD: Results of acoustic neuroma radiosurgery: an analysis of 5 years' experience using current methods. J Neurosurg 94:1–6, 2001
- 9
Flickinger JC, , Kondziolka D, , Niranjan A, , Maitz A, , Voynov G, & Lunsford LD: Acoustic neuroma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int J Radiat Oncol Biol Phys 60:225–230, 2004
- 10
Foote KD, , Friedman WA, , Buatti JM, , Meeks SL, , Bova FJ, & Kubilis PS: Analysis of risk factors associated with radiosurgery for vestibular schwannoma. J Neurosurg 95:440–449, 2001
- 11
Foote RL, , Coffey RJ, , Swanson JW, , Harner SG, , Beatty CW, & Kline RW, et al.: Stereotactic radiosurgery using the gamma knife for acoustic neuromas. Int J Radiat Oncol Biol Phys 32:1153–1160, 1995
- 12
Franco-Vidal V, , Songu M, , Blanchet H, , Barreau X, & Darrouzet V: Intracochlear hemorrhage after gamma knife radiosurgery. Otol Neurotol 28:240–244, 2007
- 13↑
Fuss M, , Debus J, , Lohr F, , Huber P, , Rhein B, & Engenhart-Cabillic R, et al.: Conventionally fractionated stereotactic radiotherapy (FSRT) for acoustic neuromas. Int J Radiat Oncol Biol Phys 48:1381–1387, 2000
- 14↑
Fuss M, , Salter BJ, , Sadeghi A, , Vollmer DG, , Hevezi JM, & Herman TS: Fractionated stereotactic intensity-modulated radiotherapy (FS-IMRT) for small acoustic neuromas. Med Dosim 27:147–154, 2002
- 15
Hasegawa T, , Fujitani S, , Katsumata S, , Kida Y, , Yoshimoto M, & Koike J: Stereotactic radiosurgery for vestibular schwannomas: analysis of 317 patients followed more than 5 years. Neurosurgery 57:257–265, 2005
- 16
Hasegawa T, , Kida Y, , Kobayashi T, , Yoshimoto M, , Mori Y, & Yoshida J: Long-term outcomes in patients with vestibular schwannomas treated using gamma knife surgery: 10-year follow up. J Neurosurg 102:10–16, 2005
- 17↑
Hayhurst C, , Dhir J, & Dias PS: Stereotactic radiosurgery and vestibular schwannoma: hydrocephalus associated with the development of a secondary arachnoid cyst: a report of two cases and review of the literature. Br J Neurosurg 19:178–181, 2005
- 18
Hempel JM, , Hempel E, , Wowra B, , Schichor Ch, , Muacevic A, & Riederer A: Functional outcome after gamma knife treatment in vestibular schwannoma. Eur Arch Otorhinolaryngol 263:714–718, 2006
- 19
Hirato M, , Inoue H, , Nakamura M, , Ohye C, , Hirato J, & Shibazaki T, et al.: Gamma knife radiosurgery for acoustic schwannoma: early effects and preservation of hearing. Neurol Med Chir (Tokyo) 35:737–741, 1995
- 20
Hirsch A, & Norén G: Audiological findings after stereotactic radiosurgery in acoustic neurinomas. Acta Otolaryngol 106:244–251, 1988
- 21
Hirsch A, , Norén G, & Anderson H: Audiologic findings after stereotactic radiosurgery in nine cases of acoustic neurinomas. Acta Otolaryngol 88:155–160, 1979
- 22
Huang CF, , Tu HT, , Lo HK, , Wang KL, & Liu WS: Radiosurgery for vestibular schwannomas. J Chin Med Assoc 68:315–320, 2005
- 23
Inoue HK: Low-dose radiosurgery for large vestibular schwannomas: long-term results of functional preservation. J Neurosurg 102:Suppl 111–113, 2005
- 24
Ito K, , Shin M, , Matsuzaki M, , Sugasawa K, & Sasaki T: Risk factors for neurological complications after acoustic neurinoma radiosurgery: refinement from further experiences. Int J Radiat Oncol Biol Phys 48:75–80, 2000
- 25
Iwai Y, , Yamanaka K, , Shiotani M, & Uyama T: Radiosurgery for acoustic neuromas: results of low-dose treatment. Neurosurgery 53:282–288, 2003
- 26↑
Kalapurakal JA, , Silverman CL, , Akhtar N, , Andrews DW, , Downes B, & Thomas PR: Improved trigeminal and facial nerve tolerance following fractionated stereotactic radiotherapy for large acoustic neuromas. Br J Radiol 72:1202–1207, 1999
- 27↑
Kamerer DB, , Lunsford LD, & Møller M: Gamma knife: an alternative treatment for acoustic neurinomas. Ann Otol Rhinol Laryngol 97:631–635, 1988
- 28↑
Karpinos M, , Teh BS, , Zeck O, , Carpenter LS, , Phan C, & Mai WY, et al.: Treatment of acoustic neuroma: stereotactic radiosurgery vs. microsurgery. Int J Radiat Oncol Biol Phys 54:1410–1421, 2002
- 29↑
Kaylie DM, & McMenomey SO: Microsurgery vs gamma knife radiosurgery for the treatment of vestibular schwannomas. Arch Otolaryngol Head Neck Surg 129:903–906, 2003
- 30↑
Kida Y, , Kobayashi T, , Tanaka T, & Mori Y: Radiosurgery for bilateral neurinomas associated with neurofibromatosis type 2. Surg Neurol 53:383–390, 2000
- 31↑
Koh ES, , Millar BA, , Ménard C, , Michaels H, , Heydarian M, & Ladak S, et al.: Fractionated stereotactic radiotherapy for acoustic neuroma: single-institution experience at The Princess Margaret Hospital. Cancer 109:1203–1210, 2007
- 32↑
Kondziolka D, , Lunsford LD, , McLaughlin MR, & Flickinger JC: Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med 339:1426–1433, 1998
- 33↑
Kondziolka D, , Subach BR, , Lunsford LD, , Bissonette DJ, & Flickinger JC: Outcomes after gamma knife radiosurgery in solitary acoustic tumors and neurofibromatosis Type 2. Neurosurg Focus 5:3 e2, 1998
- 35↑
Linskey ME, , Johnstone PA, , O'Leary M, & Goetsch S: Radiation exposure of normal temporal bone structures during stereotactically guided gamma knife surgery for vestibular schwannomas. J Neurosurg 98:800–806, 2003
- 36↑
Linskey ME, , Lunsford LD, & Flickinger JC: Radiosurgery for acoustic neurinomas: early experience. Neurosurgery 26:736–744, 1990
- 37
Linskey ME, , Lunsford LD, & Flickinger JC: Tumor control after stereotactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors. Neurosurgery 31:829–839, 1992
- 38
Lunsford LD, , Niranjan A, , Flickinger JC, , Maitz A, & Kondziolka D: Radiosurgery of vestibular schwannomas: summary of experience in 829 cases. J Neurosurg 102:Suppl 195–199, 2005
- 39
Massager N, , Nissim O, , Delbrouck C, , Devriendt D, , David P, & Desmedt F, et al.: Role of intracanalicular volumetric and dosimetric parameters on hearing preservation after vestibular schwannoma radiosurgery. Int J Radiat Oncol Biol Phys 64:1331–1340, 2006
- 40
Mathieu D, , Kondziolka D, , Flickinger JC, , Niranjan A, , Williamson R, & Martin JJ, et al.: Stereotactic radiosurgery for vestibular schwannomas in patients with neurofibromatosis type 2: an analysis of tumor control, complications, and hearing preservation rates. Neurosurgery 60:460–470, 2007
- 41↑
Meijer OW, , Wolbers JG, , Baayen JC, & Slotman BJ: Fractionated stereotactic radiation therapy and single high-dose radiosurgery for acoustic neuroma: early results of a prospective clinical study. Int J Radiat Oncol Biol Phys 46:45–49, 2000
- 42↑
Miller RC, , Foote RL, , Coffey RJ, , Sargent DJ, , Gorman DA, & Schomberg PJ, et al.: Decrease in cranial nerve complications after radiosurgery for acoustic neuromas: a prospective study of dose and volume. Int J Radiat Oncol Biol Phys 43:305–311, 1999
- 43↑
Murphy MJ, , Chang SD, , Gibbs IC, , Le QT, , Hai J, & Kim D, et al.: Patterns of patient movement during frameless image-guided radiosurgery. Int J Radiat Oncol Biol Phys 55:1400–1408, 2003
- 44
Myrseth E, , Møller P, , Pedersen PH, , Vassbotn FS, , Wentzel-Larsen T, & Lund-Johansen M: Vestibular schwannomas: clinical results and quality of life after microsurgery or gamma knife radiosurgery. Neurosurgery 56:927–935, 2005
- 45
Neuhaus O, , Saleh A, , van Oosterhout A, & Siebler M: Cerebellar infarction after gamma knife radiosurgery of a vestibular schwannoma. Neurology 68:590, 2007
- 46
Niranjan A, , Lunsford LD, , Flickinger JC, , Maitz A, & Kondziolka D: Dose reduction improves hearing preservation rates after intracanalicular acoustic tumor radiosurgery. Neurosurgery 45:753–765, 1999
- 47↑
Norén G: Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg 70:1 Suppl 65–73, 1998
- 48↑
Ogunrinde OK, , Lunsford LD, , Flickinger JC, & Kondziolka DS: Cranial nerve preservation after stereotactic radiosurgery for small acoustic tumors. Arch Neurol 52:73–79, 1995
- 49↑
Okunaga T, , Matsuo T, , Hayashi N, , Hayashi Y, , Shabani HK, & Kaminogo M, et al.: Linear accelerator radiosurgery for vestibular schwannoma: measuring tumor volume changes on serial three-dimensional spoiled gradient-echo magnetic resonance images. J Neurosurg 103:53–58, 2005
- 50
Oyama H, , Kobayashi T, , Kida Y, , Tanaka T, , Mori Y, & Iwakoshi T, et al.: Early changes in volume and non-enhanced volume of acoustic neurinoma after stereotactic gamma-radiosurgery. Neurol Med Chir (Tokyo) 34:607–611, 1994
- 51
Paek SH, , Chung HT, , Jeong SS, , Park CK, , Kim CY, & Kim JE, et al.: Hearing preservation after gamma knife stereotactic radiosurgery of vestibular schwannoma. Cancer 104:580–590, 2005
- 52
Park CK, , Jung HW, , Kim JE, , Son YJ, , Paek SH, & Kim DG: Therapeutic strategy for large vestibular schwannomas. J Neurooncol 77:167–171, 2006
- 53↑
Pellet W, , Regis J, , Roche PH, & Delsanti C: Relative indications for radiosurgery and microsurgery for acoustic schwannoma. Adv Tech Stand Neurosurg 28:227–284, 2003
- 54↑
Petit JH, , Hudes RS, , Chen TT, , Eisenberg HM, , Simard JM, & Chin LS: Reduced-dose radiosurgery for vestibular schwannomas. Neurosurgery 49:1299–1307, 2001
- 55↑
Poen JC, , Golby AJ, , Forster KM, , Martin DP, , Chinn DM, & Hancock SL, et al.: Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: a preliminary report. Neurosurgery 45:1299–1307, 1999
- 56↑
Poetker DM, , Jursinic PA, , Runge-Samuelson CL, & Wackym PA: Distortion of magnetic resonance images used in gamma knife radiosurgery treatment planning: implications for acoustic neuroma outcomes. Otol Neurotol 26:1220–1228, 2005
- 57↑
Pogodzinski MS, , Harner SG, & Link MJ: Patient choice in treatment of vestibular schwannoma. Otolaryngol Head Neck Surg 130:611–616, 2004
- 58
Pollock BE: Management of vestibular schwannomas that enlarge after stereotactic radiosurgery: treatment recommendations based on a 15 year experience. Neurosurgery 58:241–248, 2006
- 59
Pollock BE, , Lunsford LD, , Kondziolka D, , Flickinger JC, , Bissonette DJ, & Kelsey SF, et al.: Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 36:215–229, 1995
- 60
Prasad D, , Steiner M, & Steiner L: Gamma surgery for vestibular schwannoma. J Neurosurg 92:745–759, 2000
- 61↑
Régis J, , Pellet W, , Delsanti C, , Dufour H, , Roche PH, & Thomassin JM, et al.: Functional outcome after gamma knife surgery or microsurgery for vestibular schwannomas. J Neurosurg 97:1091–1100, 2002
- 62
Roos DE, , Brophy BP, , Zavgorodni SF, & Francis JW: Radiosurgery at the Royal Adelaide Hospital: the first 4 1/2 years' clinical experience. Australas Radiol 44:185–192, 2000
- 63
Rowe JG, , Radatz MW, , Walton L, , Hampshire A, , Seaman S, & Kemeny AA: Gamma knife stereotactic radiosurgery for unilateral acoustic neuromas. J Neurol Neurosurg Psychiatry 74:1536–1542, 2003
- 64
Rowe JG, , Radatz MW, , Walton L, , Soanes T, , Rodgers J, & Kemeny AA: Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis. J Neurol Neurosurg Psychiatry 74:1288–1293, 2003
- 65
Rutten I, , Baumert BG, , Seidel L, , Kotolenko S, , Collignon J, & Kaschten B, et al.: Long-term follow-up reveals low toxicity of radiosurgery for vestibular schwannoma. Radiother Oncol 82:83–89, 2007
- 66
Schulder M, , Sreepada GS, , Kwartler JA, & Cho ES: Microsurgical removal of a vestibular schwannoma after stereotactic radiosurgery: surgical and pathologic findings. Am J Otol 20:364–368, 1999
- 67
Shamisa A, , Bance M, , Nag S, , Tator C, , Wong S, & Norén G, et al.: Glioblastoma multiforme occurring in a patient treated with gamma knife surgery. Case report and review of the literature. J Neurosurg 94:816–821, 2001
- 69↑
Shirato H, , Sakamoto T, , Takeichi N, , Aoyama H, , Suzuki K, & Kagei K, et al.: Fractionated stereotactic radiotherapy for vestibular schwannoma (VS): comparison between cystic-type and solid-type VS. Int J Radiat Oncol Biol Phys 48:1395–1401, 2000
- 70↑
Solberg TD, , Medin PM, , Mullins J, & Li S: Quality assurance of immobilization and target localization systems for frameless stereotactic cranial and extracranial hypofractionated radiotherapy. Int J Radiat Oncol Biol Phys 71:1 Suppl S131–S135, 2008
- 71↑
Song DY, & Williams JA: Fractionated stereotactic radiosurgery for treatment of acoustic neuromas. Stereotact Funct Neurosurg 73:45–49, 1999
- 72
Spiegelmann R, , Gofman J, , Alezra D, & Pfeffer R: Radiosurgery for acoustic neurinomas (vestibular schwannomas). Isr Med Assoc J 1:8–13, 1999
- 73
Subach BR, , Kondziolka D, , Lunsford LD, , Bissonette DJ, , Flickinger JC, & Maitz AH: Stereotactic radiosurgery in the management of acoustic neuromas associated with neurofibromatosis Type 2. J Neurosurg 90:815–822, 1999
- 74
Tago M, , Terahara A, , Nakagawa K, , Aoki Y, , Ohtomo K, & Shin M, et al.: Immediate neurological deterioration after gamma knife radiosurgery for acoustic neuroma. Case report. J Neurosurg 93:3 Suppl 78–81, 2000
- 75
Thomsen J, , Tos M, & Børgesen SE: Gamma knife: hydrocephalus as a complication of stereotactic radiosurgical treatment of an acoustic neuroma. Am J Otol 11:330–333, 1990
- 76
Unger F, , Walch C, , Haselsberger K, , Papaefthymiou G, , Trummer M, & Eustacchio S, et al.: Radiosurgery of vestibular schwannomas: a minimally invasive alternative to microsurgery. Acta Neurochir (Wien) 141:1281–1286, 1999
- 77↑
Unger F, , Walch C, , Schrottner O, , Eustacchio S, , Sutter B, & Pendl G: Cranial nerve preservation after radiosurgery of vestibular schwannomas. Acta Neurochir Suppl 84:77–83, 2002
- 78↑
van Eck AT, & Horstmann GA: Increased preservation of functional hearing after gamma knife surgery for vestibular schwannoma. J Neurosurg 102:Suppl 204–206, 2005
- 79↑
Varlotto JM, , Shrieve DC, , Alexander E III, , Kooy HM, , Black PM, & Loeffler JS: Fractionated stereotactic radiotherapy for the treatment of acoustic neuromas: preliminary results. Int J Radiat Oncol Biol Phys 36:141–145, 1996
- 80
Wackym PA, , Runge-Samuelson CL, , Poetker DM, , Michel MA, , Alkaf FM, & Burg LS, et al.: Gamma knife radiosurgery for acoustic neuromas performed by a neurotologist: early experiences and outcomes. Otol Neurotol 25:752–761, 2004
- 81
Wang CP, , Hsu WC, & Young YH: Vestibular evoked myogenic potentials in neurofibromatosis 2. Ann Otol Rhinol Laryngol 114:69–73, 2005
- 82
Watanabe T, , Saito N, , Hirato J, , Shimaguchi H, , Fujimaki H, & Sasaki T: Facial neuropathy due to axonal degeneration and microvasculitis following gamma knife surgery for vestibular schwannoma: a histological analysis. Case report. J Neurosurg 99:916–920, 2003
- 83↑
Williams JA: Fractionated stereotactic radiotherapy for acoustic neuromas. Int J Radiat Oncol Biol Phys 54:500–504, 2002
- 84↑
Williams JA: Fractionated stereotactic radiotherapy for acoustic neuromas: preservation of function versus size. J Clin Neurosci 10:48–52, 2003
- 85↑
Wowra B, , Muacevic A, , Jess-Hempen A, , Hempel JM, , Müller-Schunk S, & Tonn JC: Outpatient gamma knife surgery for vestibular schwannoma: definition of the therapeutic profile based on a 10-year experience. J Neurosurg 102:Suppl 114–118, 2005
- 86↑
Wowra B, , Muacevic A, , Muller-Schunk S, & Tonn JC: Special indications in gamma knife surgery. Acta Neurochir Suppl (Wien) 91:89–102, 2004
- 87↑
Yang I, , Aranda D, , Han SJ, , Chennupati S, , Sughrue ME, & Cheung SW, et al.: Hearing preservation after stereotactic radiosurgery for vestibular schwannoma: a systematic review. J Clin Neurosci 16:742–747, 2009
