Project description:BackgroundThe choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).MethodsUsing PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2021 referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies or case series reporting a cohort of ICVS managed with CS, MR, or SRS. Primary outcome measures included tumor control, the need for additional treatment, hearing outcomes, and posttreatment neurological deficits. These were pooled using meta-analytical techniques and compared using meta-regression with random effect.ResultsForty studies were included (2371 patients). The weighted pooled estimates for tumor control were 96% and 65% in SRS and CS series, respectively (P < .001). Need for further treatment was reported in 1%, 2%, and 25% for SRS, MR, and CS, respectively (P = .001). Hearing preservation was reported in 67%, 68%, and 55% for SRS, MR, and CS, respectively (P = .21). Persistent facial nerve deficit was reported in 0.1% and 10% for SRS and MR series, respectively (P = .01).ConclusionsSRS is a noninvasive treatment with at least equivalent rates of tumor control and hearing preservation as compared to MR, with the caveat of better facial nerve preservation. As compared to CS, upfront SRS is an effective treatment in achieving tumor control with similar rates of hearing preservation.
Project description:PurposeDespite excellent tumor control after stereotactic radiosurgery (SRS) for vestibular schwannoma (VS), the hearing preservation rate remains unsatisfactorily low. Although many factors have been associated with hearing loss, the dose to cochlea has gained more interest in recent years. However, studies investigating the relation between cochlear dose and hearing outcomes have produced inconsistent results. The purpose of this work is to systematically review the literature and critically analyze the studies that investigated the correlation between cochlear dose and hearing loss.Methods and materialsA literature search of Ovid MEDLINE, Embase, and Scopus was performed. Studies were included if the SRS dose used was 11 to 14 Gy and included adult patients with sporadic VS, initially serviceable hearing, and at least 24 months of mean or median follow-up.ResultsTwenty-one cohort studies and 1 case-control study were eligible for inclusion, and none were considered to be truly prospective. There was substantial heterogeneity between studies in terms of baseline hearing status, cochlear dosimetry, definition and reporting of hearing outcome, and duration of follow-up, limiting comparison between studies and precluding formal meta-analysis. Eleven studies showed a statistically significant correlation between cochlear dose and hearing outcome, but there was considerable variation in the reported cochlear dose parameter that predicted hearing outcome and whether it was an independent predictor. The definition of hearing outcome and whether the outcome variable is continuous or dichotomous have a bearing on the reported correlation between cochlear dose and hearing outcome.ConclusionsWhether cochlear dose is a predictor of hearing preservation after SRS for VS could not be unequivocally determined. Future studies should use consistent cochlear dosimetry and hearing outcomes for reliable assessment. In the meantime, based on currently available data, a practical approach will be to aim for a mean cochlear dose <4 to 6 Gy without compromising tumor dose.
Project description:BackgroundVolumetric natural history studies specifically on large vestibular schwannomas (VSs), commonly classified as Koos grade 4, are lacking. The aim of the current study is to present the volumetric tumor evolution in sporadic Koos grade 4 VSs and possible predictors for tumor growth.MethodsVolumetric tumor measurements and tumor evolution patterns from serial MRI studies were analyzed from selected consecutive patients with Koos grade 4 VS undergoing initial wait-and-scan management between January 2001 and July 2020. The significant volumetric threshold was defined as a change in volume of ≥10%.ResultsAmong 215 tumors with a median size (IQR) of 2.7 cm3 (1.8-4.2), 147 tumors (68%) demonstrated growth and 75 tumors (35%) demonstrated shrinkage during follow-up. Growth-free survival rates (95% CI) at 1, 2, 5, and 10 years were 55% (48-61), 36% (29-42), 29% (23-36), and 28% (21-34), respectively and did not significantly differ in tumors> 20 mm (Chi-square = .40; P-value = .53). Four tumor evolution patterns (% of total) were observed: continued growth (60); initial growth then shrinkage (7); continued shrinkage (27); and stability (5). Good hearing (adjusted HR 2.21, 95% CI 1.48-3.30; P < .001) and peritumoral edema (adjusted HR 2.22, 95% CI 1.18-4.13; P = .01) at diagnosis were significantly associated with an increased likelihood of growth.ConclusionsKoos grade 4 VSs show a wide variety in size and growth. Due to variable growth patterns, an initial wait-and-scan strategy with short scan intervals may be an acceptable option in selected tumors, if no significant clinical symptoms of mass effect that warrant treatment are present.
Project description:PurposeWe sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS).Methods and materialsStudies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions.ResultsData were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented.ConclusionsWith current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.
Project description:BackgroundLarge 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.MethodsPubMed 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.ResultsTwenty-two studies were identified that met selection criteria for analysis from an initial pool of 1272 reports. They were evaluated according to treatment protocol: 1) single-dose SRS (13 studies, 483 patients), 2) combination of MS and SRS (7 studies, 182 patients), and 3) fractionated SRS (3 studies, 82 patients). Tumor control was achieved in 89%, 94%, and 91% of patients, respectively. Odds ratios (ORs) of post- over pretreatment serviceable hearing were 0.42 (P < .01), 0.47 (P = .05), and 0.60 (P = .22); for facial nerve impairment, these ORs were 1.08 (P = .69), 3.45 (P = .28), and 0.87 (P = .71), respectively.ConclusionsThe management of large VS remains challenging. All treatment modalities resulted in high tumor control rates and worsening of pretreatment hearing. None, however, caused significant facial nerve impairment, suggesting that management strategies incorporating focal irradiation can be successful.
Project description:BackgroundGamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored.ObjectiveTo evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas.MethodsWe retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression.ResultsThe study cohort included 227 patients with available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rates were 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044).ConclusionWhereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effects may impact post-treatment functional outcomes. Further research remains warranted.
Project description:ObjectiveHearing loss is the most common initial symptom in patients with sporadic vestibular schwannomas (SVS). Hearing preservation is an important goal of both conservative and surgical therapy. However, the mechanism of SVS-associated hearing loss remains unclear. Thus, we performed this systematic review to summarize the current understanding of hearing loss in the SVS and distill a testable hypothesis to further illuminate its underlying mechanism.MethodsA systematic review querying four databases (PubMed, Medline, Embase, and Web of Science) was performed to identify studies evaluating hearing loss in patients with SVS and exploring the potential mechanisms of hearing impairment.ResultsA total of 50 articles were eligible and included in this review. After analysis, the retrieved studies could be categorized into four types: (1) 29 studies explore the relationship between hearing loss and the growth pattern of the tumor (e.g., tumor size/volume, growth rate, tumor location, etc.); (2) ten studies investigate the potential role of cochlear dysfunction in hearing deterioration, including structural abnormality, protein elevation in perilymph, and cochlear malfunctioning; (3) two studies looked into SVS-induced impairment of auditory pathway and cortex; (4) in the rest nine studies, researchers explored the molecular mechanism underlying hearing loss in SVS, which involves molecular and genetic alterations, inflammatory response, growth factors, and other tumor-associated secretions.ConclusionsMultiple factors may contribute to the hearing impairment in SVS, including the growth pattern of tumor, cochlear dysfunction, impairment of auditory pathway and cortex, genetic and molecular changes. However, our current understanding is still limited, and future studies are needed to explore this multifactorial hypothesis and dig deeper into its underlying mechanism.
Project description:BackgroundAn understanding of the hearing outcomes is needed for treatment counseling for patients with vestibular schwannomas (VS).ObjectiveTo determine long-term hearing results following stereotactic radiosurgery (SRS) for VS and identify any influential variables.MethodsTertiary hospital retrospective cohort.ResultsThere were 579 tumors (576 patients) treated with SRS. Eighty-two percent (473) of tumors had ≥1 yr and 59% (344 ≥3 yr follow-up. In the 244 tumor ears, with measurable hearing before SRS who were followed ≥1 yr, 14% (31) had improved hearing, 13% (29) unchanged hearing, and 74% (158) had worsened hearing. In 175 patients with ≥3 yr follow-up and who had measurable hearing pretreatment, 6% (11 ears) improved hearing, 31% (54 ears) unchanged hearing, and 63% (110 ears) had worsened hearing. Patients with tumors with larger target volumes (P = .040) and with neurofibromatosis type 2 (NF2; P = .017) were associated with poorer hearing (P = .040). Patients with word recognition scores (WRS) of 50% or poorer had tumors with a larger volume (P = .0002), larger linear size (P = .032), and NF2 (P = .045). Traditionally reported hearing outcomes using the Gardner Robertson maintenance of PTA ≤50 db or WRS ≥50% were 48% at 3 yr, which overestimates hearing outcomes compared to the above reporting standards.ConclusionHearing declines over time in VS treated with SRS in a high proportion of cases. The frequency and magnitude of long-term hearing decline following SRS argues against prophylactic radiation for small tumors in hearing ears with undetermined growth behavior.
Project description:Background/Objectives: Vestibular schwannomas (VSs), also called acoustic neuromas, are benign tumors affecting the vestibulocochlear nerve, often leading to hearing loss and balance issues. This condition is particularly challenging in patients with neurofibromatosis type 2 (NF2), where VSs tend to develop bilaterally. Conventional treatments, such as surgery and radiotherapy, although effective, carry risks like hearing loss and nerve damage. Bevacizumab, a VEGF-targeting monoclonal antibody, has emerged as a less invasive treatment option, showing potential for tumor volume reduction and hearing preservation. This systematic review aims to assess the efficacy of bevacizumab in controlling tumor volume, preserving hearing, and identifying associated adverse events. Methods: A comprehensive systematic review was performed using PRISMA guidelines. PubMed and Cochrane Library databases were searched for studies evaluating the effects of bevacizumab on VS, focusing on key outcomes like tumor volume reduction, hearing preservation, and adverse events. Data extraction and quality assessment were independently conducted by two reviewers using the Newcastle-Ottawa Scale. Results: Nine studies involving 176 patients were included. Bevacizumab showed a partial tumor volume reduction (≥20%) in 40% of cases and disease stabilization in 50%, while 10% experienced tumor progression. Hearing outcomes revealed improvement in 36% of patients, stabilization in 46%, and deterioration in 18%. Severe adverse effects, including hypertension and thromboembolic events, occurred in 13% of patients, while 18% reported no side effects. Tumor regrowth was observed in some patients after treatment discontinuation, emphasizing the need for long-term monitoring. Conclusions: Bevacizumab demonstrates effectiveness in managing VS, particularly in NF2 patients, by reducing tumor size and preserving hearing in a substantial proportion of cases. However, the variability in patient response and the risk of adverse events underscore the need for individualized treatment approaches and further research, including randomized controlled trials, to optimize its clinical application.
Project description:The efficacy of radiosurgery for neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) remains debatable. We retrospectively analyzed radiosurgical outcomes for NF2-associated VS compared to sporadic VS using our database of 422 consecutive VS patients. Twenty-five patients with 30 NF2-associated VSs with a mean follow-up of 121 months were identified. NF2-associated VSs exhibited excellent tumor control (10-year cumulative rate, 92% vs. 92% in sporadic VSs; p = 0.945) and worse overall survival (73% vs. 97%; p = 0.005), mainly due to tumor progression other than the treated VSs. The presence of NF2 was not associated with failed tumor control via multivariate Cox proportional hazard analyses. No difference in radiation-induced adverse events (RAEs) was confirmed between cohorts, and prescription dose (hazard ratio 8.30, 95% confidence interval 3.19-21.62, p < 0.001) was confirmed as a risk for cranial nerve injuries via multivariate analysis. Further analysis after propensity score matching using age, volume, and sex as covariates showed that NF2-associated VSs exhibited excellent local control (100% vs. 93%; p = 0.240) and worse overall survival (67% vs. 100%; p = 0.002) with no significant difference in RAEs. Excellent long-term tumor control and minimal invasiveness may make radiosurgery a favorable therapeutic option for NF2 patients with small to medium VS, preferably with non-functional hearing or deafness in combination with postoperative tumor growth or progressive non-operated tumors, or with functional hearing by patients' wish.