Radiation Therapy For Vestibular Schwannomas Research Articles

Collagen Family Genes Associated with Risk of Recurrence after Radiation Therapy for Vestibular Schwannoma and Pan-Cancer Analysis.

Background The safety of radiotherapy techniques in the treatment of vestibular schwannoma (VS) shows a high rate of tumor control with few side effects. Neuropeptide Y (NPY) may have a potential relevance to the recurrence of VS. Further research is still needed on the key genes that determine the sensitivity of VS to radiation therapy. Materials and Methods Transcriptional microarray data and clinical information data from VS patients were downloaded from GSE141801, and vascular-related genes associated with recurrence after radiation therapy for VS were obtained by combining information from MSigDB. Logistics regression was applied to construct a column line graph prediction model for recurrence status after radiation therapy. Pan-cancer analysis was also performed to investigate the cooccurrence of these genes in tumorigenesis. Results We identified eight VS recurrence-related genes from the GSE141801 dataset. All of these genes were highly expressed in the VS recurrence samples. Four collagen family genes (COL5A1, COL3A1, COL4A1, and COL15A1) were further screened, and a model was constructed to predict the risk of recurrence of VS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these four collagen family genes play important roles in a variety of biological functions and cellular pathways. Pan-cancer analysis further revealed that the expression of these genes was significantly heterogeneous across immune phenotypes and significantly associated with immune infiltration. Finally, Neuropeptide Y (NPY) was found to be significantly and negatively correlated with the expression of COL5A1, COL3A1, and COL4A1. Conclusions Four collagen family genes have been identified as possible predictors of recurrence after radiation therapy for VS. Pan-cancer analysis reveals potential associations between the pathogenesis of VS and other tumorigenic factors. The relevance of NPY to VS was also revealed for the first time.

The biological underpinnings of radiation therapy for vestibular schwannomas: Review of the literature.

ObjectiveRadiation therapy is a mainstay in the treatment of numerous neoplasms. Numerous publications have reported good clinical outcomes for primary radiation therapy for Vestibular Schwannomas (VS). However, there are relatively few pathologic specimens of VSs available to evaluate post‐radiation, which has led to a relative dearth in research on the cellular mechanisms underlying the effects of radiation therapy on VSs.MethodsHere we review the latest literature on the complex biological effects of radiation therapy on these benign tumors—including resistance to oxidative stress, mechanisms of DNA damage repair, alterations in normal growth factor pathways, changes in surrounding vasculature, and alterations in immune responses following radiation.ResultsAlthough VSs are highly radioresistant, radiotherapy is often successful in arresting their growth.ConclusionBy better understanding the mechanisms underlying these effects, we could potentially harness such mechanisms in the future to potentiate the clinical effects of radiotherapy on VSs.Level of EvidenceN/A.

Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic Radiation Therapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities

To examine long-term local control of vestibular schwannoma and side effects in patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) in British Columbia. From August 1998 to May 2009, 207 patients were treated with radiation therapy (RT) at British Columbia Cancer Agency. 136 (66%) received SRS, and 71 (34%) received SRT. Dose prescriptions were 50Gy/25 fractions for SRT and 12Gy/1 fraction for SRS. Our multidisciplinary provincial neuro-stereotactic conference recommended SRT for tumors >3cm and for patients with serviceable hearing (Gardner-Robertson classes I and II). Median follow-up was 7.7years to the last MRI and 6.4years to the last clinical assessment. Local control for SRS versus SRT was 94% versus 87% at 5years and 90% versus 85% at 10years (P=.2). Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction were 25% and 25% after SRS, compared with 7% and 12% after SRT (P=.01). Five- and 10-year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15% after SRS, versus 13% and 15% after SRT (P=.93). In the 49 patients with serviceable hearing at baseline who were treated with SRT, hearing preservation was 55% at 3years, 37% at 5years, and 29% at 7years. In multivariable analysis, better pretreatment ipsilateral pure tone average was significantly associated with hearing preservation (hazard ratio 1.03; 95% confidence interval 1.00-1.07; P=.04). Both SRS and SRT provided excellent long-term local control of vestibular schwannoma. Stereotactic radiosurgery was associated with higher rates of trigeminal nerve dysfunction. Even with a fractionated course, hearing preservation declined steadily with long-term audiometric follow-up.

Surgery after Radiation Therapy for Vestibular Schwannoma

Surgery after Radiation Therapy for Vestibular Schwannoma

Surgery after Radiation Therapy for Vestibular Schwannoma

Surgery after Radiation Therapy for Vestibular Schwannoma

Fractionated stereotactic radiation therapy for vestibular schwannomas: Dosimetric factors predictive of hearing outcomes

PurposeTo determine dosimetric factors predictive of hearing loss in vestibular schwannoma (VS) patients treated with definitive fractionated stereotactic radiation therapy (FSRT), and to report tumor control, serviceable hearing preservation, and cranial nerve toxicities. Methods and materialsWe identified 45 patients (29 men and 16 women) with unilateral sporadic VS, who underwent definitive FSRT. All patients had serviceable hearing prior to treatment, defined as Gardner-Robertson Class 1 or 2. All patients underwent an audiogram before the start of treatment and serial audiometric assessments after treatment. The median audiometric follow-up time was 35.2 months (range, 5.0-89.7 months). Patients underwent a median of 4.5 (range, 1-9) posttreatment audiograms. The ipsilateral cochlea was contoured retrospectively, and dosimetric data were used to determine factors predictive of losing serviceable hearing. The median clinical follow-up time was 29.9 months (range, 1.5-83.6 months). ResultsAt the time of the last audiometric follow-up, 62% of patients retained serviceable hearing. The actuarial 1-, 2-, and 3-year serviceable hearing preservation rates were 83%, 75%, and 51%, respectively. The estimated median time to loss of serviceable hearing was 42.2 months. On multivariate analysis, cochlear volume <0.15 mL (hazard ratio, 2.849; 95% confidence interval, 1.116-7.270; P = .029) and mean cochlear dose <4000 cGy (hazard ratio, 3.178; 95% confidence interval, 1.116-9.049; P = .030) were statistically significant variables associated with serviceable hearing preservation. The actuarial tumor control was 100%. Three of 39 patients (8%) developed hemifacial spasm after FSRT (House-Brackmann Grade 3), 2 of which completely resolved. No patients experienced deterioration in trigeminal nerve function after FSRT. ConclusionsFractionated stereotactic radiation therapy can provide excellent tumor control with acceptable clinical outcomes. The mean dose to the cochlea is highly predictive of the probability of maintaining serviceable hearing after FSRT.

Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model

Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS.

Immediate Versus Delayed Treatment Does Not Influence Long-term Outcomes After Radiation Therapy for Vestibular Schwannoma

Purpose/Objective(s): Observation after detection is now frequently selected as a primary management option for vestibular schwannoma (VS). It is uncertain whether this approach affects patient outcomes. It is possible that patients treated at time of progression are at an increased risk of treatment failure compared to patients treated at the time of initial detection, even among patients who may not have progressed for many years without treatment. In this study, we explore whether the decision for early or delayed treatment impacts treatment success among patients treated with hypofractionated stereotactic radiation therapy (HSRT). Materials/Methods: A retrospective review of 432 VS patients treated with HSRT regimens of 25Gy in 5 fractions or 12-15Gy in 1 fraction was performed. Patients were stratified as: (1) Early (nZ291, 67.4%), patients treated at time of initial presentation and (2) Delayed (nZ141, 32.6%), patients with radiological and/or clinical progression during a period of observation. Continuous data are summarized using median (interquartile range) and categorical data via frequency (percentage). Outcomes were measured from the date of treatment. Results: The median follow-up was 73.3 (48.7-102.9) months in the early group and 61.5 (41.0-88.7) months in the Delayed group. Baseline demographics and median baseline tumor volume (BTV) between the two groups were similar, except for older age at treatment (P 0.05). No significant differences were observed between groups with regards to median tumor volume at last follow-up, treatment failure requiring salvage microsurgery, or rate of clinical/radiological progression after treatment. Of note, a greater reduction in baseline tumor volume was observed in the Delayed group (median: -41.1%, IQR: -66.7% 9.4%) compared to the Early group (median: -32.5%, IQR: -66.7% 11.0%); however, this finding was not significant (P>0.05). Salvage microsurgery was required in 11 (3.8%) patients in the early group and 3 (2.1%) patients in the Delayed group. Ultimately, radiation therapy was equally successful in most patients in both groups (Early: nZ280, 96.2% vs Delayed: nZ138, 97.9%, PZ0.6). Conclusion: We report no difference in treatment failure rates among VS patients treated at time of initial detection versus those treated at time of progression. These data suggest that delaying RT-related toxicity by postponing RT until progression may be a reasonable approach. Author Disclosure: E.W. Sankey: None. A.E. Marciscano: None. I. Jusue-Torres: Research Grant; Salisbury Family Foundation. A. Liu: None. H.W. Francis: None. M. Lim: None. K.J. Redmond: Research Grant; Elekta Ab oligometastases research consortium. D. Rigamonti: Research Grant; Nicholl Family Foundation, Salisbury Family Foundation. L.R. Kleinberg: None.

Single institution experience treating 104 vestibular schwannomas with fractionated stereotactic radiation therapy or stereotactic radiosurgery

The pupose of this study is to assess the long-term outcome and toxicity of fractionated stereotactic radiation therapy (FSRT) and stereotactic radiosurgery (SRS) for 100 vestibular schwannomas treated at a single institution. From 1993 to 2007, 104 patients underwent were treated with radiation therapy for vestibular schwannoma. Forty-eight patients received SRS, with a median prescription dose of 12.5 Gy for SRS (range 9.7-16 Gy). For FSRT, two different fraction schedules were employed: a conventional schedule (ConFSRT) of 1.8 Gy per fraction (Gy/F) for 25 or 28 fractions to a total dose of 45 or 50.4 Gy (n = 19); and a once weekly hypofractionated course (HypoFSRT) consisting of 4 Gy/F for 5 fractions to a total dose of 20 Gy (n = 37). Patients treated with FSRT had better baseline hearing, facial, and trigeminal nerve function, and were more likely to have a diagnosis of NF2. The 5-year progression free rate (PFR) was 97.0 after SRS, 90.5% after HypoFSRT, and 100.0% after ConFSRT (p = NS). Univariate analysis demonstrated that NF2 and larger tumor size (greater than the median) correlated with poorer local control, but prior surgical resection did not. Serviceable hearing was preserved in 60.0% of SRS patients, 63.2% of HypoFSRT patients, and 44.4% of ConFSRT patients (p = 0.6). Similarly, there were no significant differences in 5-year rates of trigeminal toxicity facial nerve toxicity, vestibular dysfunction, or tinnitus. Equivalent 5-year PFR and toxicity rates are shown for patients with vestibular schwanoma selected for SRS, HypoFSRT, and ConFSRT after multidisciplinary evaluation. Factors correlating with tumor progression included NF2 and larger tumor size.

Long-term Outcome of Stereotactic Radiation Therapy for Vestibular Schwannomas

Long-term Outcome of Stereotactic Radiation Therapy for Vestibular Schwannomas

Symptomatic Outcomes in Relation to Tumor Expansion After Fractionated Stereotactic Radiation Therapy for Vestibular Schwannomas: Single-Institutional Long-Term Experience

The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.

Current strategies in management of intracanalicular vestibular schwannoma

The current practitioner is more often managing intracanalicular vestibular schwannomas than in the past, as improved imaging and heightened awareness leads to earlier diagnosis of these tumors. The role of observation, microsurgery, and radiation treatment in the management of intracanalicular tumors continues to evolve. The goal of this article is to evaluate and summarize recent literature pertaining to the management of intracanalicular vestibular schwannomas. Watchful waiting is an important management option for patients with minimal symptoms. The literature on the natural history of small vestibular schwannomas continues to expand, with particular emphasis on the expected hearing outcomes. Microsurgical techniques also focus on hearing preservation. Presence of fundal fluid and good or normal hearing preoperatively are positive predictors of hearing preservation after surgery. Long-term follow-up after radiation therapy for vestibular schwannomas continues to demonstrate excellent tumor control rates, although hearing preservation rates are modest. Multiple factors, including status of hearing, presence of vestibular symptoms, patient age, medical comorbidities, institutional outcomes, and patient preferences, help determine the management strategy for patients with an intracanalicular vestibular schwannoma.

Radiation necrosis of the brain after radiosurgery for vestibular schwannoma

Objective The objective of this study was to obtain a better understanding of radiation-induced brain necrosis after stereotactic radiation therapy for vestibular schwannomas. Study design We conducted a retrospective case analysis. Setting The study took place at a tertiary referral center. Patients We report on the case of a patient treated with stereotactic radiation who developed radiation-induced necrosis of the ipsilateral temporal lobe. Intervention The various interventions in patients with radiation-induced necrosis include steroid treatment, decompression, and hyperbaric oxygen therapy; these are discussed briefly in this article. Owing to the limited symptoms in our patient, she was observed. Main outcome measure The outcome measure that we evaluated was radiation-induced necrosis of the brain after stereotactic radiation therapy for a vestibular schwannoma. Results Patients who undergo stereotactic radiation therapy for vestibular schwannomas are at risk for radiation-induced brain necrosis. Conclusion We support the development of a national database that would track the long-term complications of stereotactic radiation therapy to help patients make a more informed decision for the treatment of their vestibular schwannomas.

Radiosurgery and stereotactic radiation therapy for vestibular schwannoma in neurofibromatosis type 2 patients

Neurofibromatosis type 2 (NF2) patients typically suffer from bilateral vestibular schwannoma (VS) and are at risk for developing bilateral deafness, bilateral trigeminal and bilateral facial nerve function loss. Previous reports suggest that treatment outcomes in these patients are worse compared to patients with sporadic solitary VS. Especially in NF2 patients who acquired unilateral hearing loss already, avoidance of hearing loss on the opposite side poses a challenge for stereotactic radiosurgery. We studied our treatment results in NF2 patients treated for VS with linac based radiosurgery (RS) and stereotactic radiation therapy (SRT). In 204 VS patients treated with RS or SRT in Amsterdam starting from 1992, we identified 25 NF2 patients with bilateral tumors. Indications for treatment were either tumor progression on sequential MRI and/or progressive hearing loss. Stereotactic irradiation was administered to all patients using 5 non-coplanar arcs with a single isocenter to a dose of 10–12.5 Gy in a single fraction or 20–25 Gy in 5 fractions in 1 week prescribed to the 80% isodose encompassing the tumor. In the first patients a single round collimator was used for every treatment. In subsequent patients conformal arcs were used. Dynamic conformal arcs application, resulting in superior dose distributions, is used currently. Five patients were followed less than 1 year. Of the remaining 20 patients, 5 were ipsilateral deaf prior to treatment. Consequently 15 patients were at risk for treatment related hearing loss. They showed a mean Pure Tone Average (PTA) of 51 dB (8–112) prior to treatment. On the untreated side, all patients showed hearing loss and 8 (53%) were deaf. After treatment all patients were assessed at yearly intervals including MRI and pure tone audiometry. Median follow-up time was 51 months (12–109). Local tumor control was obtained in all 20 patients and no treatment related trigeminal or facial nerve toxicity was observed. Hearing status was assessed yearly after treatment. This revealed that the mean PTA in the 15 hearing patients dropped from 51 to 77 dB (40–120). In 6 of these patients (40%) the additional PTA loss ranged from 0–15 dB, in another 6 patients (40%) it ranged from 15–45 dB and in 3 of these patients (20%) it was more than 45 dB. No additional hearing loss was observed beyond 36 months after treatment. Excellent local control rates can be obtained with RS and SRT for VS in NF2 patients, with minimal facial and trigeminal nerve toxicity. Hearing preservation, however, remains disappointing with 60% of the patients losing 15 dB or more of PTA on the irradiated side. This seems worse than our previously reported outcomes of SRS and RS in patients with solitary sporadic tumors. Improvements may be expected by application of dynamic conformal beam shaping

Radiosurgery and stereotactic radiation therapy for vestibular schwannoma in neurofibromatosis type 2 patients

Radiosurgery and stereotactic radiation therapy for vestibular schwannoma in neurofibromatosis type 2 patients

Implementation of a clinical pathway in management of the postoperative vestibular schwannoma patient.

The purpose of the study was to evaluate the effectiveness of a new clinical pathway in management of patients with postoperative vestibular schwannoma. The impact on duration of hospitalization and quality of care was evaluated. The study was a retrospective review of 59 consecutive patients undergoing surgical intervention for vestibular schwannoma between January 1995 and July 1999. A new clinical pathway for management of postoperative vestibular schwannoma patients was implemented at The California Ear Institute at Stanford (Palo Alto, CA) in January 1995. All patients undergoing surgical intervention subsequent to initiation of the pathway were included in the study. Data including surgical approach, patient age, sex, and tumor size were included. Duration of hospitalization and postoperative complications were recorded. During the same time period, data for patients undergoing radiation therapy for vestibular schwannomas were evaluated for length of hospital stay and in-hospital complications. Data were compared with norms recorded in the literature for duration of hospitalization and complications following surgical intervention. Fifty-nine patients underwent 35 middle fossa approaches and 24 translabyrinthine approaches to their tumors. The average patient age was 53 years; there were 34 female and 25 male patients. The average length of hospital stay was 3.83 days (SD = 1.4 days) with a range from 2 to 10 days. Postoperative complications were observed in 19% of patients, including eight (13%) cerebrospinal fluid (CSF) leaks, two requiring lumbar drains (3.4%); one hematoma (1.6%), one postoperative fever (1.6%), and one dural tear with associated hyponatremia (1.6%). These results compared favorably with previously recorded average hospital stays of 5.95 to 9.5 days 1,5-7 and CSF leak complication rates of 7% to 15%.9,10 Implementation of a clinical pathway for management of the patient with postoperative vestibular schwannoma improves efficiency of patient care, allowing decreased duration of hospitalization. This goal is achieved without increasing complication rates and, in our experience, actually improving the quality of clinical care. The cost-effectiveness of clinical pathways may become increasingly important in a managed care-driven environment.