Image guided surgery for the resection of brain tumours

Extent of resection is believed to be a key prognostic factor in neuro-oncology. Image guided surgery uses a variety of tools or technologies to help achieve this goal. It is not clear whether any of these, sometimes very expensive, tools (or their combination) should be recommended as part of standard care for patient with brain tumours. We set out to determine if image guided surgery offers any advantage in terms of extent of resection over surgery without any image guidance and if any one tool or technology was more effective.

To compare image guided surgery with surgery either not using any image guidance or to compare surgery using two different forms of image guidance. The primary outcome criteria was extent of resection and adverse events. Other outcome criteria were overall survival; progression free survival; and quality of life (QoL).

The following databases were searched, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2013), MEDLINE (1948 to March, week 10, 2013) and EMBASE (1970 to 2013, week 10). Reference lists of all identified studies were searched. Two journals, the Journal of Neuro-Oncology and Neuro-oncology, were handsearched from 1991 to 2013, including all conference abstracts. Neuro-oncologists, trial authors and manufacturers were contacted regarding ongoing and unpublished trials.

Study participants included patients of all ages with a presumed new or recurrent brain tumour (any location or histology) from clinical examination and imaging (computed tomography (CT), magnetic resonance imaging (MRI) or both). Image guidance interventions included intra-operative MRI (iMRI); fluorescence guided surgery; neuronavigation including diffusion tensor imaging (DTI); and ultrasonography. Included studies had to be randomised controlled trials (RCTs) with comparisons made either with patients having surgery without the image guidance tool in question or with another type of image guidance tool. Subgroups were to include high grade glioma; low grade glioma; brain metastasis; skull base meningiomas; and sellar or parasellar tumours.

Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a pre-specified pro forma.

Four RCTs were identified, each using a different image guided technique: 1. iMRI (58 patients), 2. 5-aminolevulinic acid (5-ALA) fluorescence guided surgery (322 patients), 3. neuronavigation (45 patients) and 4. DTI-neuronavigation (238 patients). Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies, especially for the study using DTI-neuronavigation. All studies included patients with high grade glioma, with one study also including patients with low grade glioma. The extent of resection was increased with iMRI (risk ratio (RR) (incomplete resection) 0.13, 95% CI 0.02 to 0.96, low quality evidence), 5-ALA (RR 0.55, 95% CI 0.42 to 0.71) and DTI-neuronavigation (RR 0.35, 95% CI 0.20 to 0.63, very low quality evidence). Insufficient data were available to evaluate the effects of neuronavigation on extent of resection. Reporting of adverse events was incomplete, with a suggestion of significant reporting bias. Overall, reported events were low in most studies, but there was concern that surgical resection using 5-ALA may lead to more frequent early neurological deficits. There was no clear evidence of improvement in overall survival (OS) with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07) or DTI-neuronavigation (HR 0.57, 95% CI 0.32 to 1.00) in patients with high grade glioma. Progression-free survival (PFS) data were not available in the appropriate format for analysis.Data for quality of life (QoL) were only available for one study and suffered from significant attrition bias.

There is low to very low quality evidence (according to GRADE criteria) that image guided surgery using iMRI, 5-ALA or DTI-neuronavigation increases the proportion of patients with high grade glioma that have a complete tumour resection on post-operative MRI. There is a theoretical concern that maximising the extent of resection may lead to more frequent adverse events but this was poorly reported in the included studies. Effects of image guided surgery on survival and QoL are unclear. Further research, including studies of ultrasound guided surgery, is needed.