Efficacy and comorbidities of hypofractionated and single-dose radiosurgery for vestibular schwannomas: a systematic review and meta-analysis.
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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 (SRS), which can be delivered in either single-fraction (SRS) or hypofractionated stereotactic radiotherapy (hSRT) (3-5 treatments) regimens. 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.
SUBMITTER: Tosi U
PROVIDER: S-EPMC8278347 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Gamma 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. OBJECTIVE:To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas. METHODS:We 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. RESULTS:The 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). CONCLUSION:Whereas 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.
| S-EPMC6855984 | biostudies-literature
Project description:INTRODUCTION:This study explores the possibility of a relationship between the sphericity degree of a target volume with the dose distribution. This relationship is evaluated based on the ratio isodose volume / target volume (IV/TV) and the metrics coverage, i.e., selectivity, gradient index, conformity index and mean dose when planning radiosurgery for vestibular schwannoma. METHODS:Sphericity degree (?) was calculated for each target volume (TV) of 64 patients who underwent stereotactic radiosurgery (SRS) for vestibular schwannoma. The calculation of this parameter was developed using the theoretical definition for operational sphericity ? = VP/VCS. The values found are evaluated considering the following metrics:-Coverage (C), selectivity (S), gradient index (GI), Paddick conformity index (CIPaddick) and dose distribution (IV/TV). The planning was also carried out considering a spherical target volume defined in a spherical phantom. The spherical volume is the same as the target used in the treatment plan. The planning of the spherical target was considered as a reference plan to evaluate the dose distribution inside and outside the volume. RESULTS:It was possible to observe that the majority of target volumes has (?) around 0,66-0,77, corresponding to 54,7% of the total. Considering the mean values for metrics, the results are: C = 0,98, S = 0,78, GI = 3,11 and CI = 0,81. The dose distribution was equivalent for treatment plans and reference plans. Quantitative analysis for IV/TV shows that these values are higher than 30% for treatment plans where shot density is large. CONCLUSION:This study demonstrates that de sphericity degree (?) can be related to the dose distribution (IV/TV). Therefore the sphericity degree is a good parameter to evaluate the dose distribution of a plan for vestibular schwannoma treatment, considering the reference plan as being a spherical target using a leksell gamma knife® perfexion (LGKP). This study shows that the sphericity degree offers important information of the dose distribution outside and inside the target volume. This is not evaluated by the other parameters already implemented as metric to analyzing the GKP plans.
| S-EPMC6953829 | biostudies-literature
Project description:BackgroundThe optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.MethodsBetween January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated.ResultsA total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81-121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40-90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG.ConclusionsSalvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.
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Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. In order to find target to fight against vestibular schwannoma, we performed an analysis of gene expression by microarrays.
2013-03-01 | E-GEOD-39645 | biostudies-arrayexpress
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them.
2013-03-01 | GSE39645 | GEO
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.
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Project description:Vestibular schwannomas (VSs) grow in the region where the energy from mobile phone use is absorbed. We examined the associations of VSs with mobile phone use. This study included 119 patients who had undergone surgical tumor removal. We used two approaches in this investigation. First, a case-control study for the association of mobile phone use and incidence of VSs was conducted. Both cases and controls were investigated with questions based on INTERPHONE guidelines. Amount of mobile phone use according to duration, daily amount, and cumulative hours were compared between two groups. We also conducted a case-case study. The location and volume of the tumors were investigated by MRI. Associations between the estimated amount of mobile phone use and tumor volume and between the laterality of phone use and tumor location were analyzed. In a case-control study, the odds ratio (OR) of tumor incidence according to mobile phone use was 0.956. In the case-case study, tumor volume and estimated cumulative hours showed a strong correlation (r(2)?=?0.144, p?=?0.002), and regular mobile phone users showed tumors of a markedly larger volume than those of non-regular users (p?<?0.001). When the analysis was limited to regular users who had serviceable hearing, laterality showed a strong correlation with tumor side (OR?=?4.5). We found that tumors may coincide with the more frequently used ear of mobile phones and tumor volume that showed strong correlation with amount of mobile phone use, thus there is a possibility that mobile phone use may affect tumor growth.
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Project description:Background and Purpose: The risk factors for progression in vestibular schwannomas (VSs) after incomplete resection (IR) remain to be elucidated. The purpose of this study was to investigate the risk factors for progression in remnant VSs after surgery. Methods: From January 2009 to January 2018, 140 consecutive patients who underwent IR of VSs via suboccipital retrosigmoid approach in our institution were retrospectively analyzed. During follow-up, if progression was detected, the patient was classified into Progressive Group (PG); if the residual tumor was stable or shrank, the patient was classified into Stable Group (SG). Univariate analysis and multivariate analysis were used to evaluate the risk factors for progression after IR of VSs. Results: After a mean follow-up of 80.4 months (range, 24-134 months), 35 (25.0%) patients (PG) had a progression, and no progression was detected in 105 (75.0%) patients (SG). The average tumor size was 36.5 ± 8.9 mm in PG and 31.0 ± 9.8 mm in SG, respectively. The residual tumor volume was 304.6 ± 443.3 mm3 in PG and 75.9 ± 60.0 mm3 in SG, respectively. Univariate analysis showed that preoperative tumor size, residual tumor volume, and irregular internal auditory canal (IAC) expansion were significantly different between the two groups, whereas gender, age, cystic component, or Ki-67 labeling index (LI) did not differ significantly between the two groups. Multivariate analysis showed residual tumor volume was the independent risk factor for progression. Conclusions: VSs that underwent IR with larger preoperative size, greater residual tumor volume, or irregular IAC expansion may have a higher progression rate. Strict follow-up with shorter interval in these patients to detect early progression is necessary.
| S-EPMC8660677 | biostudies-literature
Project description:Largely, watchful waiting is the initial policy for patients with small-sized or medium-sized vestibular schwannoma, because of slow growth and relatively minor complaints, that do not improve by an intervention. If intervention (microsurgery, radiosurgery or fractionated radiotherapy) becomes necessary, the choice of intervention appears to be driven by the patient's or clinician's preference rather than by evidence based. This study addresses the existing evidence based on controlled studies of these interventions.A systematic Boolean search was performed focused on controlled intervention studies. The quality of the retrieved studies was assessed based on the Sign-50 criteria on cohort studies.Pubmed/Medline, Embase, Cochrane Central Register of Controlled Trials and reference lists.Six eligibility criteria included a controlled intervention study on a newly diagnosed solitary, vestibular schwannoma reporting on clinical outcomes. Two prospective and four retrospective observational, controlled studies published before November 2011 were selected.Two reviewers independently assessed the methodological quality of the studies and extracted the outcome data using predefined formats.Neither randomised studies, nor controlled studies on fractionated radiotherapy were retrieved. Six studies compared radiosurgery and microsurgery in a controlled way. All but one were confined to solitary tumours less than 30 mm in diameter and had no earlier interventions. Four studies qualified for trustworthy conclusions. Among all four, radiosurgery showed the best outcomes: there were no direct mortality, no surgical or anaesthesiological complications, but better facial nerve outcome, better preservation of useful hearing and better quality of life.The available evidence indicates radiosurgery to be the best practice for solitary vestibular schwannomas up to 30 mm in cisternal diameter.
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Project description:Introduction: Many proposed algorithms for tumor detection rely on 2.5/3D convolutional neural networks (CNNs) and the input of segmentations for training. The purpose of this study is therefore to assess the performance of tumor detection on single MRI slices containing vestibular schwannomas (VS) as a computationally inexpensive alternative that does not require the creation of segmentations. Methods: A total of 2992 T1-weighted contrast-enhanced axial slices containing VS from the MRIs of 633 patients were labeled according to tumor location, of which 2538 slices from 539 patients were used for training a CNN (ResNet-34) to classify them according to the side of the tumor as a surrogate for detection and 454 slices from 94 patients were used for internal validation. The model was then externally validated on contrast-enhanced and non-contrast-enhanced slices from a different institution. Categorical accuracy was noted, and the results of the predictions for the validation set are provided with confusion matrices. Results: The model achieved an accuracy of 0.928 (95% CI: 0.869-0.987) on contrast-enhanced slices and 0.795 (95% CI: 0.702-0.888) on non-contrast-enhanced slices from the external validation cohorts. The implementation of Gradient-weighted Class Activation Mapping (Grad-CAM) revealed that the focus of the model was not limited to the contrast-enhancing tumor but to a larger area of the cerebellum and the cerebellopontine angle. Conclusions: Single-slice predictions might constitute a computationally inexpensive alternative to training 2.5/3D-CNNs for certain detection tasks in medical imaging even without the use of segmentations. Head-to-head comparisons between 2D and more sophisticated architectures could help to determine the difference in accuracy, especially for more difficult tasks.
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