Radiosurgery for acoustic neuroma
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the role of radiosurgery versus conventional surgery, observation, another treatment modality or two or more of the above approaches for acoustic neuroma.
Background
Description of the condition
Acoustic neuromas, also known as vestibular schwannomas, are benign tumours of Schwann cell origin that occur on the eighth cranial nerve. Most commonly they arise from the covering cells of the inferior vestibular nerve. They represent 5% to 10% of all intracranial tumours (House 1974) and 80% to 90% of tumours of the cerebellopontine angle (Hart 1981).
The incidence of acoustic neuroma is about 0.7 to 1.0 per 100,000 and the prevalence is estimated at 2 in 10,000 people (Lin 2005). Several centres have reported an increasing incidence of diagnosed acoustic neuromas over recent years (Stangerup 2010). These tumours occur with about equal frequency in adult males and females, most frequently in patients between the ages of 30 and 60 years (Hart 1981). A number of patients may have central neurofibromatosis and they commonly have bilateral tumours.
Common presenting symptoms include hearing loss, tinnitus, and balance and gait disturbance. Tumour progression can lead to brainstem compression, cranial neuropathies and hydrocephalus (Hansasuta 2011). The diagnosis is established with magnetic resonance imaging (MRI), which can demonstrate tumours as small as a few millimetres. As imaging technology has improved, more small tumours have been diagnosed.
Treatment options include observation, microsurgical resection and stereotactic radiosurgery (Hansasuta 2011; Varughese 2012).
Surgical treatment of acoustic neuroma has been a central feature of neurosurgical practice for more than 100 years (Ramsden 1995), from the pioneering attempts to achieve simple decompression, to the contemporary era of preservation of function of the eighth and adjacent cranial nerves (Sampath 1998). However, while total tumour removal is possible in about 95% of patients, seventh cranial nerve preservation is only possible in about 80% (Samii 1997).
The non‐invasive technique of stereotactic radiosurgery, which delivers high‐dose irradiation to small, targeted tissue volumes, began with Leksell in 1969 (Leksell 1971) and represents an alternative to open surgical treatment, particularly for small tumours (up to 3 cm in diameter) and in elderly patients. Some use it as the primary treatment modality for all patients.
Observation with neuroradiologic follow‐up is the third treatment option, since many of these tumours grow slowly over years, or may not grow at all.
Description of the intervention
Radiosurgery is a procedure in which narrow beams of radiation are converged and targeted to a small volume of tissue within the brain. Stereotaxis refers to an accurate targeting technique for intracranial structures using an external reference frame fixed to the head. Stereotactic radiosurgery therefore refers to the non‐invasive destruction by irradiation of a particular intracranial target localised stereotactically.
In 1968, the first Leksell gamma unit, or gamma knife, was designed at the Karolinska Institute in Stockholm, Sweden. The unit evolved into the commercially available Leksell gamma unit, containing cobalt‐60 sources located in a hemispherical array around a common focal point. Stereotactic radiosurgery has become an important treatment option for many patients with intracranial and spinal disorders (Sheehan 2009), ranging from arterial venous malformations to benign and malignant neoplasms (Yu 1997).
A typical radiosurgical procedure begins with the application of the stereotactic head frame under local anaesthesia. An MRI is then performed and a radiosurgical protocol designed to deliver the radiation dose to the defined target volume. The procedure is usually performed as an outpatient procedure and is well tolerated by the patient, with few immediate side effects.
How the intervention might work
Radiation necrosis is induced in the targeted tissue volume. The desired response is long‐term growth control of the tumour (Niranjan 2004).
An observational study by Kondziolka and colleagues presented 162 patients followed for five years after radiosurgery and concluded that 61.7% of tumours were smaller, 32.7% unchanged and 5.6% larger, which suggests that about 94% of tumours can be effectively controlled by radiosurgery (Kondziolka 1998). Cranial nerve complications following radiosurgery have been significantly reduced by modifications in dose schedules (Noren 1993).
Why it is important to do this review
We are unaware of any published systematic review or guidelines on the subject of the effectiveness and safety of radiosurgery in comparison to other treatment methods. Equipoise exists, since the best candidates for radiosurgery are usually also ideal candidates for open surgery (patients with easily resectable small tumours of up to 3 cm in diameter). This dilemma is evident in everyday clinical practice, in centres which can offer radiosurgery as an alternative treatment. Furthermore, it is still unclear whether some of these patients can be managed by observation only. The decision on treatment modality is therefore currently based on clinician expert opinion and experience, which conflicts with the principles of evidence‐based medicine. The limited availability of radiosurgical equipment makes decision‐making even more complex.
This review could facilitate decision‐making in the clinical management of such patients. It could also affect public health policy in communities where investments in radiosurgical equipment of significant cost are being considered.
Objectives
To assess the role of radiosurgery versus conventional surgery, observation, another treatment modality or two or more of the above approaches for acoustic neuroma.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs, level 1 evidence) exploring the efficacy of radiosurgical treatment in acoustic neuroma. We will include studies irrespective of publication status and language.
Types of participants
Patients, irrespective of gender, age or race with a cerebellopontine angle tumour suitable for radiosurgical treatment, presumed to be acoustic neuroma. We will exclude patients previously surgically treated for acoustic neuromas.
Types of interventions
We will include studies where at least one of the arms in the trial was treated with radiosurgery by any protocol, dose or hardware.
We will be looking for the following comparisons:
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radiosurgery versus conventional surgery;
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radiosurgery versus observation;
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radiosurgery versus any other possible treatment or combination of treatments.
Types of outcome measures
Primary outcomes
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Proportion of patients in whom the tumour has not grown and whose symptoms (hearing loss, facial function, tinnitus, balance disturbance) have not deteriorated a) at 12 months, b) at two years, c) in the long term.
Secondary outcomes
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Tumour growth
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Changes in hearing loss
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Changes in facial function (assessed using a validated assessment instrument)
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Changes in tinnitus
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Changes in balance disturbance
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Quality of life
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Reported side effects of the radiosurgery (early, intermediate and late) including: the induction of secondary malignancies, peritumoral oedema, hydrocephalus and other cranial nerve neuropathies
Search methods for identification of studies
We will conduct systematic searches for randomised controlled trials. There will be no language, publication year or publication status restrictions. We may contact original authors for clarification and further data if trial reports are unclear, and we will arrange translations of papers where necessary.
Electronic searches
We will identify published, unpublished and ongoing studies by searching the following databases from their inception: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; ISRCTN; ClinicalTrials.gov; ICTRP and Google.
We will model subject strategies for databases on the search strategy designed for CENTRAL (Appendix 1). Where appropriate, we will combine subject strategies with adaptations of the highly sensitive search strategy designed by the Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Handbook 2011)).
Searching other resources
We will scan the reference lists of identified publications for additional trials and contact trial authors if necessary. We will search PubMed, TRIPdatabase, The Cochrane Library and Google to retrieve existing systematic reviews relevant to this systematic review, so that we can scan their reference lists for additional trials. We will search for conference abstracts using the Cochrane Ear, Nose and Throat Disorders Group Trials Register.
Data collection and analysis
Selection of studies
At least two members of the review team will independently select papers and make decisions about eligibility, based on the analysis of the title, abstract or MeSH terms. We will resolve all disagreements by discussion and consensus, or by including the third author's opinion. We will consult a statistician in cases of doubt about the study inclusion or data extraction. If necessary, we will contact the authors of the original papers to get additional data or clarify dubious issues in order to perform the systematic review. We will also translate studies published in other languages to English.
Data extraction and management
We will extract the relevant data from the selected studies and record it in customised forms. Two members of the review team will perform the extraction, after determining the study eligibility. We will discuss possible disagreements and if no consensus is reached, they will be resolved by the inclusion of the third author in the extraction process. We will contact authors of the original articles, if necessary.
We will extract the following data.
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Study design, setting and duration
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Participants
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Sample size
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Inclusion and exclusion criteria
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Details of the experimental intervention (protocol)
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Details of the control intervention
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Outcome (the effect of treatment, defined as tumour growth control at the six‐month to two‐year follow‐up)
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Presence of ethical approval
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Funding sources
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Conclusions as reported by the authors
Assessment of risk of bias in included studies
Dario Muzevic and Bruno Splavski will undertake assessment of the risk of bias of the included trials independently by with the following taken into consideration, as guided by the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011):
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sequence generation;
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allocation concealment;
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blinding;
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incomplete outcome data;
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selective outcome reporting; and
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other sources of bias.
We will use the Cochrane ‘Risk of bias’ tool in Review Manager (RevMan 5) (RevMan 2011), which involves describing each of these domains as reported in the trial and then assigning a judgement about the adequacy of each entry: 'low', 'high' or 'unclear' risk of bias.
Measures of treatment effect
We will analyse data using RevMan 5. We will analyse binary data using odds ratio (with 95% confidence interval) and continuous outcomes by calculating means and standard deviations. We will pool scores as continuous variables either using weighted means or standardised means.
Unit of analysis issues
The unit of analysis will be the individual patient.
Dealing with missing data
Missing summary data will not be a reason to exclude study from the review. If necessary, we will contact the authors of the original papers for more information on missing data.
Assessment of heterogeneity
We will test all included studies for clinical homogeneity. For studies considered to be clinically homogeneous, we will test the statistical heterogeneity using the Chi² test and the I² statistic. We will assume statistical significance of the Chi² test if P < 0.10. We will consider an I² statistic value greater than 50% to be substantial.
Assessment of reporting biases
Aside from within‐study biases tested as described in Assessment of risk of bias in included studies, we will assess between‐study biases by comparing outcomes stated in protocols to those reported or, where protocols are not available, by comparing outcomes listed in the methods section to those reported in the results section.
Data synthesis
We will use RevMan 5 to perform meta‐analysis, if we identify a sufficient number of studies (RevMan 2011). We will use a fixed‐effect model for dichotomous data.
Subgroup analysis and investigation of heterogeneity
No subgroup analysis is planned.
Sensitivity analysis
If necessary, we will perform sensitivity analysis by comparing the primary analysis with analysis of the subgroup of studies that excludes those with unclear or high risk of bias.
