Abstract: 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.

Plain-language summary: Our search strategy was up to date as of March 2013. We found four trials looking at four different types of tools to help improve the amount of tumour that is removed. The tumour that they looked at was usually high grade glioma but one study also included patients with low grade glioma. Imaging interventions used during surgery included magnetic resonance imaging (iMRI) during surgery to assess the amount of remaining tumour, or a fluorescent dye (5-aminolevulinic acid (5-ALA)) to mark out the tumour. Two trials used pre-operative imaging to map out the location of a tumour, which was then used at the time of surgery to guide the resection (neuronavigation). All the studies were at significant risk of bias and some were small and stopped early. Others were funded by the manufacturers of the image guidance tool involved. We found low quality evidence that using image guided surgery can lead to more of the tumour being removed surgically in some people. It has not been proven that any of the techniques that were evaluated improve overall survival. Data about how each technique can affect a patient's quality of life was poorly reported. The side effects of each technique were also poorly reported, but they did not appear to be more common with image guided surgery. There is a concern that taking out more of the tumour using 5-ALA can lead to patients having a type of stroke early after surgery but long-term the risk seems to be no different between techniques. There was very low quality evidence for neuronavigation and no trials were identified for ultrasound guidance. Evidence for image guided surgery in removing brain tumours is sparse and of low quality. Further research is needed to assess two main questions. 1. Is removing more of the tumour better for the patient in the long-term? 2. What are the risks of making a patient symptomatically worse by taking out more of the tumour, and how may this affect a patient's quality of life?