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. 2018 Jan 22;1(1):CD012788.
doi: 10.1002/14651858.CD012788.pub2.

Intraoperative imaging technology to maximise extent of resection for glioma

Affiliations

Intraoperative imaging technology to maximise extent of resection for glioma

Michael D Jenkinson et al. Cochrane Database Syst Rev. .

Abstract

Background: Extent of resection is considered to be a prognostic factor in neuro-oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another.

Objectives: To establish the overall effectiveness and safety of intraoperative imaging technology in resection of glioma. To supplement this review of effects, we also wished to identify cost analyses and economic evaluations as part of a Brief Economic Commentary (BEC).

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980 to 2017, week 27). We searched the reference lists of all identified studies. We handsearched two journals, the Journal of Neuro-Oncology and Neuro-oncology, from 1991 to 2017, including all conference abstracts. We contacted neuro-oncologists, trial authors, and manufacturers regarding ongoing and unpublished trials.

Selection criteria: Randomised controlled trials evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included intraoperative MRI (iMRI), fluorescence-guided surgery, ultrasound, and neuronavigation (with or without additional image processing, e.g. tractography).

Data collection and analysis: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma.

Main results: We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound.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. All studies included people with high-grade glioma only.Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low-quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection.Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low-quality evidence). Progression-free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low-quality evidence).

Authors' conclusions: Intra-operative imaging technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly. Further research, including studies of ultrasound-guided surgery, is needed.

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Conflict of interest statement

Michael Jenkinson: no conflict of interest related to this review. Damiano Barone: no conflict of interest related to this review. Andrew Bryant: no conflict of interest related to this review. Luke Vale: no conflict of interest related to this review. Helen Bulbeck: no conflict of interest related to this review. Theresa Lawrie: no conflict of interest related to this review. Michael Hart: no conflict of interest related to this review. Colin Watts: no conflict of interest related to this review.

Figures

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1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Update of

  • doi: 10.1002/14651858.CD012788

References

References to studies included in this review

Kubben 2014 {published data only (unpublished sought but not used)}
    1. Kubben PL, Scholtes F, Schijns OEMG, Ter Laak-Poort MP, Teernstra OPM, Kessels AGH, et al. Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: a randomized controlled trial. Surgical Neurology International 2014;5:70. - PMC - PubMed
Senft 2011 {published data only (unpublished sought but not used)}
    1. Senft C, Bink A, Franz K, Gasser T, Seifert V. Intra-operative MRI-guided vs. conventional microsurgical brain tumor resection - results of a prospective randomized trial. In: Journal of Neurosurgery: Abstract number 602.. Vol. 115. 2011.
    1. Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncology 2011;12(11):997-1003. - PubMed
    1. Senft C, Bink A, Heckelmann M, Gasser T, Seifert V. Glioma extent of resection and ultra-low-field iMRI: interim analysis of a prospective randomized controlled trial. Acta Neurochirurgica Supplementum 2011;109:49-53 [CRSREF: 3298840]. - PubMed
Stummer 2006 {published data only}
    1. Pichelmeier U, Bink A, Schackert G, Stummer W, ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro-oncology 2008;10(6):1025-34 [CRSREF: 3298842]. - PMC - PubMed
    1. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Roulen HJ, ALA Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncology 2006;7(5):392-401. - PubMed
    1. Stummer W, Reulen H-J, Meinel T, Pichelmeier U, Schumacher W, Tonn J-C, et al, ALA-Glioma Study Group. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 2008;62:564-76 [CRSREF: 32988]. - PubMed
    1. Stummer W, Tonn J-C, Mehdorn HM, Nestler U, Franz K, Goetz C, et al, ALA-Glioma Study group. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Journal of Neurosurgery 2011;114(3):613-23 [CRSREF: 3298845]. - PubMed
Willems 2006 {published data only}
    1. Willems PW, Taphoorn MJ, Burger H, Berkelbach van der Sprenkel JW, Tulleken CAF. Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial. Journal of Neurosurgery 2006;104(3):360-8. - PubMed

References to studies excluded from this review

Chen 2011 {published data only}
    1. Chen X, Meng X, Zhang J, Wang F, Zhao Y, Xu B-N. Low-grade insular glioma resection with 1.5T intra-operative MRI: preliminary results of a prospective randomized trial. Neuro-oncology 2011;13:iii57.
Chen 2012 {published data only (unpublished sought but not used)}
    1. Chen X, Meng X, Zhang J, Li F, Li J, Xu B-N. Low-grade insular glioma resection with 1.5t intra-operative MRI: preliminary results of a prospective randomized trial. Journal of Neurosurgery 2012;117(2):A406-A407.
Czyz 2011 {published data only}
    1. Czyz M, Tabakow P, Lechowicz-Glogowska B, Jarmundowicz W. Prospective study on the efficacy of low-field intraoperative magnetic resonance imaging in neurosurgical operations. Neurologia i Neurochirurgia Polska 2011;45(3):226-34. - PubMed
Eljamel 2008 {published data only}
    1. Eljamel MS, Goodman C, Moseley H. ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre phase III randomised controlled trial. Lasers in Medical Science 2008;23(4):361-7. - PubMed
Koc 2008 {published data only}
    1. Koc K. Fluorescein sodium-guided surgery in glioblastoma multiforme: a prospective evaluation. British Journal of Neurosurgery 2008;22(1):99-103. - PubMed
Rohde 2011 {published data only}
    1. Rohde V, Coenen VA. Intraoperative 3-dimensional ultrasound for resection control during brain tumour removal: preliminary results of a prospective randomized study. Acta Neuropathologica. Supplementum 2011;109:187-190. - PubMed
Seddighi 2016 {published data only (unpublished sought but not used)}
    1. Seddighi A, Seddighi AS, Nikouei A, Mohseni G. Image guided surgery using neuronavigation system in resection of cerebral gliomas involving eloquent cortical areas in pediatric population. Neuro-oncology 2016;18:iii128.
Stepp 2007 {published data only}
    1. Stepp H, Beck T, Pongratz T, Meinel T, Kreth FW, Tonn JCh, et al. ALA and malignant glioma: fluorescence-guided resection and photodynamic treatment. Journal of Environmental Pathology, Toxicology and Oncology 2007;26(2):157-64. - PubMed
Stummer 2017 {published data only}
    1. Stummer W, Stepp H, Wiestler OD, Pichlmeier U. Randomized, prospective double-blinded study comparing 3 different doses of 5-aminolevulinic acid for fluorescence-guided resections of malignant gliomas. Neurosurgery 2017;81(2):230-9. - PMC - PubMed
Wu 2003 {published data only (unpublished sought but not used)}
    1. Wu J-S, Zhou L-F, Hong X-N, Mao Y, Du G-H. Role of diffusion tensor imaging in neuronavigation surgery of brain tumors involving pyramidal tracts. Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery] 2003;41(9):662-6. - PubMed
Wu 2004 {published data only (unpublished sought but not used)}
    1. Wu J-S, Zhou L-F, Gao G-J, Mao Y, Du G-H. Integrating functional magnetic resonance imaging in neuronavigation surgery of brain tumors involving motor cortex. Chinese Medical Journal 2004;84(8):632-6. - PubMed
Wu 2007 {published data only}
    1. Wu J-S, Mao Y, Zhou L-F, Tang W-J, Hu J, Song Y-Y, et al. Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts. Neurosurgery 2007;61(5):935-9. - PubMed
Zhang 2015 {published data only}
    1. Zhang J, Chen X, Zhao Y, Wang F, Li F, Xu B. Impact of intraoperative magnetic resonance imaging and functional neuronavigation on surgical outcome in patients with gliomas involving language areas. Neurosurgical Review 2015;38(2):319-30. - PubMed

References to ongoing studies

NCT00752323 {published data only}
    1. Sloan A. Imaging procedure using ALA in finding residual tumor in grade IV malignant astrocytoma. ClinicalTrials.gov 2008.
NCT00977327 {published data only}
    1. Kanner A. Comparison of Neuro-navigational Systems for Resection-Control of Brain Tumors. ClinicalTrials.gov August 2009.
NCT01502280 (BALANCE) {published data only}
    1. Honea N. Fluorescence-guided Surgery for Low- and High-grade Gliomas. ClinicalTrials.gov December 2011.
NCT01798771 (IMAGER) {published data only}
    1. Senft C. Intraoperative MRI and 5-ALA Guidance to Improve the Extent of Resection in Brain Tumor Surgery (IMAGER). ClinicalTrials.gov February 2013.
Wu 2014 {published data only (unpublished sought but not used)}
    1. Wu J-S, Gong X, Song Y-Y, Zhuang D-X, Yao C-J, Qiu T-M, et al. 3.0T iMRI guided resection in cerebral glioma surgery: interim analysis of a prospective, randomized, triple-blind, parallel-controlled trial. Clinical Neurosurgery 2013;60:167. - PubMed
    1. Wu J-S, Gong X, Song Y-Y, Zhuang D-X, Yao C-J, Qiu T-M, et al. 3.0-T intraoperative magnetic resonance imaging-guided resection in cerebral glioma surgery: interim analysis of a prospective, randomized, triple-blind, parallel-controlled trial. Neurosurgery 2014;61(Suppl 1):145-54. - PubMed

Additional references

Barone 2014
    1. Barone BG, Lawrie TA, Hart MG. Image guided surgery for the resection of brain tumours. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No: CD009685. [DOI: 10.1002/14651858.CD009685.pub2] - DOI - PMC - PubMed
Black 1997
    1. Black PM, Moriarty T, Alexander E 3rd, Stieg P, Woodard EJ, Gleason PL, et al. Development and implementation of intraoperative magnetic resonance imaging and its neurosurgical applications. Neurosurgery 1997;41(4):831-42. - PubMed
CRD 2008
    1. Centre for Reviews and Dissemination. Systematic Reviews: CRD’s guidance for undertaking reviews in health care. York: York Publishing Services Limited, 2008. www.york.ac.uk/inst/crd.
Deeks 2001
    1. Deeks JJ, Altman DG, Bradburn MJ. Systematic review in healthcare: meta-analysis in context. In: Egger M, Davey Smith G, Altman DG, editors(s). Statistical Methods for Examining Heterogeneity and Combining Results From Several Studies in Meta-analysis. 2nd edition. London: BMJ Publication Group, 2001.
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials 1986;7:177–88. - PubMed
Eljamel 2016
    1. Eljamel S, Mahboob SO. The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI. Photodiagnostic and Photodynamic Therapy 2016;16:35-43. - PubMed
Esteves 2015
    1. Esteves S, Alves M, Castel-Branco M, Stummer W. A pilot cost-effectiveness analysis of treatment in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic acid compared to white-light surgery. Neurosurgery 2015;76(5):552-62. - PMC - PubMed
GNOSIS 2007
    1. Chang S, Vogelbaum M, Lang FF, Haines S, Kunwar S, Chiocca EA, et al. GNOSIS: guidelines for neuro-oncology: standards for investigational studies - reporting of surgically based therapeutic clinical trials. Journal of Neuro-Oncology 2007;82:211-20. - PubMed
Hall 2003
    1. Hall WA, Kowalik K, Liu H, Truwit CL, Kucharezyk J. Costs and benefits of intraoperative MR-guided brain tumor resection. Acta Neurochirurgica. Supplement 2003;85:137-42. - PubMed
Hart 2011
    1. Hart MG, Grant R, Metcalfe SE. Biopsy versus resection for high grade glioma. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No: CD002034. [DOI: 10.1002/14651858.CD002034] - DOI - PMC - PubMed
Hensen 2008
    1. Hensen JW, Ulmer S, Harris GJ. Brain tumor imaging in clinical trials. American Journal of Neuroradiology 2008;24(3):419-24. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S, (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available at handbook.cochrane.org.
Juni 2001
    1. Juni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. BMJ 2001;323:42–6. - PMC - PubMed
Karnofsky 1948
    1. Karnofsky DA. The use of nitrogen mustards in the palliative treatment of carcinoma. Cancer 1948;1:634–56.
Kowalik 2000
    1. Kowalik K, Truwit C, Hall W, Kucharczyk. Initial assessment of costs and benefits of MRI-guided brain tumor resection. European Radiology 2000;10 (Suppl 3):s366-7. - PubMed
Langendam 2013
    1. Langendam MW, Akl EA, Dahm P, Glasziou P, Guyatt G, Schunemann HJ. Assessing and presenting summaries of evidence in Cochrane Reviews. Systematic Reviews 2013;23(2):81. - PMC - PubMed
Louis 2016
    1. Louis DN, Perry A, Reifenberger G, Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 WHO Classification of Tumours of the Central Nervous System: a summary. Acta Neuropathologica 2016;131:803-20. - PubMed
Makary 2011
    1. Makary M, Chiocca EA, Erminy N, Antor M, Bergese S, Abdel-Rasoul M, et al. Clinical and economic outcomes of low-field intraoperative MRI-guided tumor resection neurosurgery. Journal of magnetic resonance imaging 2011;34:1022-1033. - PubMed
Mauer 2008
    1. Mauer ME, Bottomley A, Taphoorn MJB. Evaluating health-related quality of life and symptom burden in brain tumour patients: instruments for use in clinical trials and clinical practice. Current Opinion in Neurology 2008;21:741–53. - PubMed
Meader 2014
    1. Meader N, King K, Llewellyn A, Norman G, Brown J, Rodgers M, et al. A checklist designed to aid consistency and reproducibility of GRADE assessments: development and pilot validation. Systematic Reviews 2104;3:82. - PMC - PubMed
MedDRA 2008
    1. Medical Dictionary for Regulatory Authorities (MedDRA). www.meddramsso.com/MSSOWeb/index.htm (accessed prior to 14 December 2017) 2008.
Miwa 2004
    1. Miwa K, Shinoda J, Yano H, Okumura A, Iwama T, Nakashima T, et al. Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study. Journal of Neurology, Neurosurgery and Psychiatry 2004;75:1457-62. - PMC - PubMed
NICE 2006
    1. NICE: National Collaborating Centre for Cancer. Improving outcomes for people with brain and other CNS tumours - evidence review. www.nice.org.uk/nicemedia/live/10905/28965/28965.pdf (accessed prior to 14 December 2017).
Ohgaki 2009
    1. Ohgaki H. Epidemiology of brain tumors. Methods in Molecular Biology 2009;472:323-42. - PubMed
Oken 1982
    1. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology 1982;5(6):649–55. - PubMed
Parmar 1998
    1. Parmar MKB, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature of endpoints. Statistics in Medicine 1998;17:2815–34. - PubMed
Pichlmeier 2008
    1. Pichlmeier U, Bink A, Schackert G, Stummer W, ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro-oncology 2008;10:1025-34. - PMC - PubMed
Regula 1995
    1. Regula J, MacRobert AJ, Gorchein A, Buonaccorsi GA, Thorpe SM, Spencer GM, et al. Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX - a pilot study. Gut 1995;36:67–75. - PMC - PubMed
Review Manager 2014 [Computer program]
    1. Review Manager (RevMan). Version 5.3.5. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Schulder 2003
    1. Schulder M, Carmel P. Intraoperative magnetic resonance imaging: impact on brain tumor surgery. Cancer Control 2003;10(2):115-24. - PubMed
Seifert 2003
    1. Seifert V. Intraoperative MRI in neurosurgery: technical overkill or the future of brain surgery? Neurology India 2003;51:329-32. - PubMed
Slof 2015
    1. Slof J, Diez Valle R, Galvin J. Cost-effectiveness of 5-aminolevulinic acid-induced fluorescence in malignant glioma surgery. Neurologia 2015;30(3):163-8. - PubMed
Stummer 1998
    1. Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 1998;42:518–25. - PubMed
Stummer 2000
    1. Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. Journal of Neurosurgery 2000;93:1003–13. - PubMed
Stupp 2005
    1. Stupp R, Mason WP, den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine 2005;352:987-96. - PubMed
Unsgaard 2006
    1. Unsgaard G, Rygh OM, Selbekk T, Müller TB, Kolstad F, Lindseth F, et al. Intra-operative 3D ultrasound in neurosurgery. Acta Neurochirurgica 2006;148(3):235-53. - PubMed
Wallace 2017
    1. Wallace BC, Noel-Storr A, Marshall IJ, Cohen AM, Smalheiser NR, Thomas J. Identifying reports of randomized controlled trials (RCTs) via a hybrid machine learning and crowd sourcing approach. Journal of the American Medical Informatics Association 2017;24(06):1165-8. - PMC - PubMed
Watts 2016
    1. Watts C, Sanai N. Surgical approaches for the gliomas. Handbook of Clinical Neurology 2016;134:51-69. - PubMed
Wen 2010
    1. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria in high grade gliomas: response assessment in Neuro-Oncology Working Group. Journal of Clinical Oncology 2010;28(11):1963–72. - PubMed

References to other published versions of this review

Jenkinson 2017
    1. Jenkinson MD, Barone DG, Hart MG, Bryant A, Lawrie TA, Watts C. Intraoperative imaging technology to maximise extent of resection for glioma. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No: CD012788. [DOI: 10.1002/14651858.CD012788] - DOI - PMC - PubMed

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