Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis

AbstractVestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. However, the literature on repeat SRS after previously failed SRS remains scarce and reported in a low number of series with a limited number of cases. Here, we aimed at performing a systematic review and meta-analysis of the literature on repeat SRS for VS. Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed. Tumor control and cranial nerve outcomes were evaluated with separate meta-analyses. Eight studies comprising 194 patients were included. The overall rate of patients treated in repeat SRS series as per overall series with first SRS was 2.2% (range 1.2–3.2%, p < 0.001). The mean time between first and second SRS was 50.7 months (median 51, range 44–64). The median marginal dose prescribed at first SRS was 12 Gy (range 8–24) and at second SRS was 12 Gy (range 9.8–19). After repeat SRS, tumor stability was reported in 61/194 patients, i.e., a rate of 29.6% (range 20.2–39%, I2 = 49.1%, p < 0.001). Tumor decrease was reported in 83/194 patients, i.e., a rate of 54.4% (range 33.7–75.1%, I2 = 89.1%, p < 0.001). Tumor progression was reported in 50/188 patients, i.e., a rate of 16.1% (range 2.5–29.7%, I2 = 87.1%, p = 0.02), rarely managed surgically. New trigeminal numbness was reported in 27/170 patients, i.e., a rate of 9.9% (range 1.4–18.3%, p < 0.02). New facial nerve palsy of worsened of previous was reported in 8/183 patients, i.e., a rate of 4.3% (range 1.4–7.2%, p = 0.004). Hearing loss was reported in 12/22 patients, i.e., a rate of 54.3% (range 24.8–83.8%, I2 = 70.7%, p < 0.001). Repeat SRS after previously failed SRS for VS is associated with high tumor control rates. Cranial nerve outcomes remain favorable, particularly for facial nerve. The rate of hearing loss appears similar to the one related to first SRS.

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RADT-16. HYPOFRACTIONATED RADIOTHERAPY AND STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.769 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii184-ii185

Author(s):

Umberto Tosi ◽

Sergio Guadix ◽

Anjile An ◽

Drew Wright ◽

Andrew Brandmaier ◽

...

Keyword(s):

Facial Nerve ◽

Stereotactic Radiosurgery ◽

Cranial Nerve ◽

Meta Analysis ◽

Post Treatment ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Significant Heterogeneity ◽

Ovid Medline ◽

Cochrane Reviews

Abstract BACKGROUND Vestibular schwannomas (VS) are tumors of the cerebellopontine angle with significant morbidity, causing hearing loss, tinnitus, and trigeminal and facial nerve compromise. Surgical resection is complex and often results in comorbidities, with radiation therapy being used to achieve tumor control. Both single dose stereotactic radiosurgery (SRS) and, in recent years, hypofractionated stereotactic radiotherapy (hSRT), where a total 18-25 Gy dose is given in approximately 3-5 fractions, have been utilized. It remains unclear, however, how each of these approaches fares compared to the other. METHODS Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Reviews were searched for studies either comparing hSRT with SRS or focusing on hSRT alone for the treatment of VS. Primary endpoints included tumor control, serviceable hearing, presence of tinnitus, and facial and trigeminal nerve symptoms. A random effects analysis was employed to compare pre- and post-treatment effects (hSRT alone) or SRS and hSRT outcomes (two-arm studies). RESULTS This analysis included 21 studies focusing on hSRT alone and 13 studies comparing SRS and hSRT. Significant heterogeneity was observed. Overall, when hSRT was analyzed alone, crude tumor control was achieved in 93% of 1571 patients at average follow-up of 49.9 months. There was no difference intra-group between pre- and post-treatment odds ratios (OR) of tinnitus, facial, or trigeminal impairment. However, serviceable hearing was diminished following hSRT (OR = 0.60, 95% CI: 0.44, 0.83, p = 0.002). Comparison with SRS showed no difference with respect to tumor control (p = 0.84), serviceable hearing (p = 0.65), trigeminal impairment (p = 0.96), or facial nerve impairment (p = 0.32). CONCLUSIONS hSRT achieved excellent tumor control and, with the exception of serviceable hearing, did not result in worse cranial nerve symptomatology. Analyzing two-arm studies showed that hSRT is a treatment modality comparable to SRS with respect to tumor control and cranial nerve comorbidities.

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Outcomes of Stereotactic Radiosurgery for Large Vestibular Schwannomas: a Systematic Review and Meta-Analysis

Neuro-Oncology Practice ◽

10.1093/nop/npab011 ◽

2021 ◽

Author(s):

Umberto Tosi ◽

Miguel E Tusa Lavieri ◽

Anjile An ◽

Omri Maayan ◽

Sergio W Guadix ◽

...

Keyword(s):

Facial Nerve ◽

Stereotactic Radiosurgery ◽

Cranial Nerve ◽

Meta Analysis ◽

Management Strategies ◽

Treatment Protocol ◽

Vestibular Schwannomas ◽

Treatment Modalities ◽

Tumor Control ◽

Pre Treatment

Abstract Background Large vestibular schwannomas (VS) pose a treatment challenge for both microsurgery (MS) and stereotactic radiosurgery (SRS). Technical developments have allowed for safer irradiation of large tumors. It remains unclear if SRS can achieve appropriate tumor control and acceptable cranial nerve toxicities. In this study, we assess outcomes of irradiation for large VS. Methods PubMed MEDLINE, EMBASE, Web of Science, and Cochrane were searched for all the studies assessing SRS outcome in large VS. Primary endpoints included clinical and radiographic tumor control, need for salvage surgery, serviceable hearing, cranial nerve V and VII impairment, presence of hydrocephalus requiring shunting, and presence of vertigo / dizziness. Results 22 studies were identified that met selection criteria for analysis from an initial pool of 1272 reports. They were evaluated according to treatment protocol: (i) single dose SRS (13 studies, 483 patients), (ii) combination of MS and SRS (7 studies, 182 patients), and (iii) fractionated SRS (3 studies, 82 patients). Tumor control was achieved in 89%, 94%, and 91% of patients, respectively. Odds ratio of post- over pre-treatment serviceable hearing were 0.42 (p < 0.01), 0.47 (p = 0.05), and 0.60 (p = 0.22); for facial nerve impairment, these OR were 1.08 (p = 0.69), 3.45 (p = 0.28), and 0.87 (p = 0.71) respectively. Conclusions The management of large VS remains challenging. All treatment modalities resulted in high tumor control rates and worsening of pre-treatment hearing. None, however, caused significant facial nerve impairment, suggesting that management strategies incorporating focal irradiation can be successful.

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Primary Treatment of Small-To-Medium (<3cm) Sporadic Vestibular Schwannomas: A Systematic Review And Meta-Analysis on Long-Term Hearing Preservation And Tumor Control Rates For Microsurgery Versus Radiosurgery.

10.21203/rs.3.rs-827189/v1 ◽

2021 ◽

Author(s):

Amey Rajan Savardekar ◽

Danielle L Terrell ◽

Saudamini Jayant Lele ◽

Ryan Robert Diaz ◽

Praneeth Reddy Keesari ◽

...

Keyword(s):

Systematic Review ◽

Stereotactic Radiosurgery ◽

Meta Analysis ◽

Treatment Options ◽

Hearing Preservation ◽

Primary Treatment ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Group 10

Abstract BackgroundOver the past two decades, the treatment of small-to-medium (<3cm) sporadic vestibular schwannomas (VS) has experienced a definite shift to stereotactic radiosurgery vis-a-vis microsurgery. We performed a systematic review and meta-analysis of VS patients primarily treated with stereotactic radiosurgery (SRS) or microsurgery (MS), with particular attention to hearing preservation outcomes (HPO), tumor control (TC), and facial nerve dysfunction (FND).MethodsA systematic review was conducted (Medline and Scopus database) for the period, January 2010 to June 2020 with appropriate MeSH. English language articles for small-to-medium sporadic VS (<3cm) utilizing SRS or MS as treatment modality, with minimum follow-up of 3 years, were included. Studies had to report an acceptable standardized hearing metric. HPO, TC, and FND rates were analyzed. ResultsThirty-two studies met inclusion criteria: 10 for microsurgery; 23 for radiosurgery (one comparative study included in both). HPO, at ~65 months follow-up, were comparable between MS group (10 studies; 809 patients) and SRS group (23 studies; 1234 patients) (56% versus 59%, p=0.1527). TC, at ~70 months follow-up, was significantly better in MS group (9 studies; 1635 patients) versus SRS group (19 studies; 2260 patients) (98% versus 92%, p < 0.0001). FND, at ~ 12 months follow-up, was significantly higher in MS group (8 studies; 1101 patients) versus SRS group (17 studies; 2285 patients) (10% versus 2%, p < 0.0001).ConclusionMS and SRS are comparable primary treatment options for small (<3cm) sporadic VS with respect to HPO at 5-year follow-up in patients with serviceable hearing at presentation. Approximately 50% patients for both modalities will likely lose serviceable hearing by that time-point. High TC rates (>90%) were seen with both modalities, with MS (98%) significantly better than SRS (92%). The post-treatment FND was significantly less with SRS group (2%) versus MS group (10%).

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Efficacy and Comorbidities of Hypofractionated and Single Dose Radiosurgery for Vestibular Schwannomas: a Systematic Review and Meta-Analysis

Neuro-Oncology Practice ◽

10.1093/nop/npab009 ◽

2021 ◽

Author(s):

Umberto Tosi ◽

Sergio Guadix ◽

Anjile An ◽

Drew Wright ◽

Paul J Christos ◽

...

Keyword(s):

Facial Nerve ◽

Cranial Nerve ◽

Meta Analysis ◽

Post Treatment ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Significant Heterogeneity ◽

Ovid Medline ◽

Cochrane Reviews ◽

Significant Difference

Abstract Background Vestibular schwannomas (VS) are tumors of the cerebellopontine angle with significant morbidity, causing hearing loss, tinnitus, and trigeminal and facial nerve compromise. An effective alternative to microsurgical resection is stereotactic radiosurgery, which can be delivered in either single fraction (SRS) or hypofractionated (3-5 treatments) regimens (hSRT). It remains unclear which fractionation regimen provides superior outcomes. Methods Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Reviews were searched for studies either comparing hSRT with SRS or focusing on hSRT alone in treating VS. Primary endpoints included tumor control, serviceable hearing, tinnitus, and cranial nerve V and VII symptoms. A random effects analysis was employed to compare pre- and post-treatment effects (hSRT alone) or SRS and hSRT outcomes (two-arm studies). Results This analysis included 21 studies focusing on hSRT alone and 13 studies comparing SRS and hSRT. Significant heterogeneity was observed. Overall, when hSRT was analyzed alone, crude tumor control was achieved in 94% (95% CI: 88%, 99%) of 1571 patients. There was no difference between pre- and post-treatment odds ratios (OR) of tinnitus, facial, or trigeminal impairment. Serviceable hearing was diminished following hSRT (OR = 0·60, 95% CI: 0·44, 0·83). Comparison with SRS showed no difference with respect to tumor control, serviceable hearing, trigeminal or facial nerve impairment. Conclusions hSRT achieved excellent tumor control and, with the exception of serviceable hearing, did not result in worse post-treatment cranial nerve symptomatology. Analysis of comparative studies between hSRT and SRS did not reveal any significant difference in either tumor control or treatment morbidities.

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Tumor Control Rates in Patients Undergoing Stereotactic Radiosurgery for Cystic Vestibular Schwannomas: A Systematic Review and Meta-Analysis

Neurosurgery ◽

10.1093/neuros/nyz310_648 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Kevin Ding ◽

Edwin Ng ◽

Prasanth Romiyo ◽

Dillon Dejam ◽

Courtney Duong ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Meta Analysis ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Limiting Factor ◽

Tumor Control Rate ◽

Pertinent Data ◽

Funnel Plots ◽

Initial Impressions

Abstract INTRODUCTION Cystic vestibular schwannomas (VS) represent a subtype that grows more rapidly due to expansion of cystic contents and are important candidates for stereotactic radiosurgery (SRS) intervention due to their tendency to adhere to the neurovasculature. However, the paucity of comprehensive outcomes data is currently a limiting factor to understanding the potential of using SRS to treat cystic VS. METHODS This study was conducted in accordance with the PRISMA guidelines. A search was conducted in October 2018 through the PubMed, Scopus, Embase, Web of Science, and Cochrane databases. Data on tumor control rates were extracted and analyzed using meta-analysis and tests for heterogeneity between articles, with the t2, Cochran's Q, and I2 statistics reported. Publication bias was assessed using funnel plots and Egger's testing. RESULTS A total of 246 patients underwent SRS for cystic VS, with reported mean or median follow-up of 49.7 to 150 mo. Following SRS treatment for cystic VS across all studies, 92% of patients had tumor control at follow up, (95%-CI: 88%-95%). In studies that specifically reported tumor control rate at 5 yr, control rate was also 92% (95%-CI: 87%-95%). Tumor control rate specifically for patients who underwent GammaKnife was 93% (95%-CI: 88%-95%). CONCLUSION Results of our meta-analysis suggest that SRS is a viable treatment option for cystic VS, exhibiting effective tumor control rates. Despite the paucity of pertinent data, our conclusions provide evidence in contrast to the initial impressions of SRS treatment for cystic VS within the neurosurgical community.

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Meta-analysis of tumor control rates in patients undergoing stereotactic radiosurgery for cystic vestibular schwannomas

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2019.105571 ◽

2020 ◽

Vol 188 ◽

pp. 105571 ◽

Cited By ~ 1

Author(s):

Kevin Ding ◽

Edwin Ng ◽

Prasanth Romiyo ◽

Dillon Dejam ◽

Methma Udawatta ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Meta Analysis ◽

Vestibular Schwannomas ◽

Tumor Control

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Proton Beam Radiosurgery for Vestibular Schwannoma: Tumor Control and Cranial Nerve Toxicity

Neurosurgery ◽

10.1227/01.neu.0000079369.59219.c0 ◽

2003 ◽

Vol 53 (3) ◽

pp. 577-588 ◽

Cited By ~ 81

Author(s):

Damien C. Weber ◽

Annie W. Chan ◽

Marc R. Bussiere ◽

Griffith R. Harsh ◽

Marek Ancukiewicz ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Proton Beam ◽

Trigeminal Nerve ◽

Cranial Nerve ◽

Univariate Analysis ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Transverse Diameter ◽

Nerve Function ◽

Function Preservation

Abstract OBJECTIVE We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery. METHODS Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5–35 mm), and the median tumor volume was 1.4 cm3 (range, 0.1–15.9 cm3). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were normal in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10–18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period was 38.7 months (range, 12–102.6 mo). RESULTS The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9–99.9%) and 93.6% (95% CI, 88.3–99.3%). Salvage radiosurgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95% CI, 81.2–98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation rates were 91.1% (95% CI, 85–97.6%) and 89.4% (95% CI, 82–96.7%). Univariate analysis revealed that prescribed dose (P = 0.005), maximum dose (P = 0.006), and the inhomogeneity coefficient (P = 0.03) were associated with a significant risk of long-term facial neuropathy. No other cranial nerve deficits or cancer relapses were observed. CONCLUSION Proton beam stereotactic radiosurgery has been shown to be an effective means of tumor control. A high radiological response rate was observed. Excellent facial and trigeminal nerve function preservation rates were achieved. A reduced prescribed dose is associated with a significant decrease in facial neuropathy.

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Stereotactic Radiosurgery of Cranial Nonvestibular Schwannomas: Results of Single- and Multisession Radiosurgery

Neurosurgery ◽

10.1227/neu.0b013e31820c0474 ◽

2011 ◽

Vol 68 (5) ◽

pp. 1200-1208 ◽

Cited By ~ 15

Author(s):

Clara Y. H. Choi ◽

Scott G. Soltys ◽

Iris C. Gibbs ◽

Griffith R. Harsh ◽

Gordon T. Sakamoto ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Cranial Nerve ◽

Medical Center ◽

Cranial Nerves ◽

Jugular Foramen ◽

Tumor Control ◽

Minimal Risk ◽

Invasive Treatment ◽

Non Invasive

Abstract BACKGROUND: Surgical resection of nonvestibular cranial schwannomas carries a considerable risk of postoperative complications. Stereotactic radiosurgery (SRS) offers a non-invasive treatment alternative. The efficacy and safety of multi-session SRS of nonvestibular cranial schwannomas has not been well studied. OBJECTIVE: To analyze the results of single- and multi-session SRS of nonvestibular cranial schwannomas. METHODS: From 2001 to 2007, 42 lesions in 40 patients were treated with SRS at Stanford University Medical Center, targeting schwannomas of cranial nerves IV (n = 1), V (n = 18), VII (n = 6), X (n = 5), XII (n = 2), jugular foramen (n = 8), and cavernous sinus (n = 2). SRS was delivered to a median marginal dose of 18 Gy (range, 15-33 Gy) in 1 to 3 sessions, targeting a median tumor volume of 3.2 cm3 (range, 0.1-23.7 cm3). The median doses for treatments in 1 (n = 18), 2 (n = 9), and 3 (n = 15) sessions were 17.5, 20, and 18 Gy, respectively. RESULTS: With a median follow-up of 29 months (range, 6-84 months), tumor control was achieved in 41 of the 42 lesions. Eighteen of 42 lesions (43%) decreased in size; 23 tumors (55%) remained stable. There were 2 cases of new or worsening cranial nerve deficits in patients treated in single session; no patient treated with multi-session SRS experienced any cranial nerve toxicity (P = 0.18). CONCLUSION: SRS of nonvestibular cranial schwannomas provides excellent tumor control with minimal risk of complications. There was a trend towards decreased complications with multi-session SRS.

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NCOG-11. POST-RADIOSURGICAL OUTCOMES OF CYSTIC VESTIBULAR SCHWANNOMAS, A SYSTEMATIC REVIEW AND META-ANALYSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.550 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii131-ii131

Author(s):

Nima Hamidi ◽

Elie Massaad ◽

Jacalynn Goetz ◽

Alireza Mansouri

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Random Effect ◽

Growth Patterns ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Shunt Operation ◽

Inverse Variance ◽

Meta Analyses

Abstract INTRODUCTION Vestibular schwannomas (VS) are benign neoplasms that present as cystic or solid variants. Cystic VS are associated with fast and unpredictable growth patterns, and their adherence to nearby structures can lead to poor surgical outcomes. While radiosurgery (RS) has gained popularity for VS, the heterogeneity of literature necessitates a systematic review. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), PubMed, EMBASE, Web of Science, and Cochrane were searched for observational studies reporting cystic and solid VS radiosurgical outcomes. Pooled estimates were calculated using random-effect models with generic inverse variance to compare tumor control rates between cystic and solid VS. Quality assessment was done using the Newcastle Ottawa Criteria (NOS). RESULTS The search yielded 2,989 studies from which 680 were selected for full-text screening and 6 were included in this review and meta-analysis. The quality of studies ranged between good (3 studies, NOS 7/9), fair (2 studies, NOS 6/9), and poor (1 study, NOS 4/9). The patient pool included 1,070 solid and 347 cystic VS, all treated by gamma knife RS. No difference in tumor control was observed (RR: 1.02, 95%CI 0.91-1.16, p=0.7). 3 studies reported post-RS complications. Haseguawa reported hydrocephalus in 7 of 74 cystic cases. Ryu reported 1 case of hydrocephalus and 1 case of trigeminal pain in their 14 cystic cases. Shirato reported 5 transient trigeminal Neuralgia, 1 transient vertigo and 1 shunt operation in their 20 cystic cases. CONCLUSION Evidence presented in this meta-analysis supports the safety and efficacy of radiosurgery in treating cystic VS.

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