Abstract
OBJECTIVE
High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence.


METHODS
PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models.


RESULTS
This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65–9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127–3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905–3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival.


CONCLUSIONS
IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.
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References
150
[1]
Advisory Board: WSJ: Intraoperative imaging gaining traction. Wall Street Journal Daily Briefing. February 19, 2015 (https://www.advisory.com/daily-briefing/2015/02/19/intraoperative%20imaging) [Accessed January 9, 2020]
[2]
Barbosa BJ, Mariano ED, Batista CM, Marie SK, Teixeira MJ, Pereira CU, : Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies. Neurosurg Rev 38:217–227, 2015
[3]
Borenstein M, Hedges LV, Higgins JP, Rothstein HR: A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1:97–111, 2010
[4]
Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, : Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498, 2015
[5]
Brown S, Hutton B, Clifford T, Coyle D, Grima D, Wells G, : A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL. Syst Rev 3:110, 2014
[6]
Bruch JD, Ho J, Watts C, Price SJ: A single centre case control study of the efficacy and safety of 5-aminolevulinic acid guided resections of grade IV (WHO) glioblastomas. Neuro Oncol 13 (Suppl 2):ii1–ii14, 2011 (Abstract)
[7]
Chakraborty S, Zavarella S, Salas S, Schulder M: Intraoperative MRI for resection of intracranial meningiomas. J Exp Ther Oncol 12:157–162, 2017
[8]
Chen LF, Yang Y, Ma XD, Yu XG, Gui QP, Xu BN, : Optimizing the extent of resection and minimizing the morbidity in insular high-grade glioma surgery by high-field intraoperative MRI guidance. Turk Neurosurg 27:696–706, 2017
[9]
Chung IW, Eljamel S: Risk factors for developing oral 5-aminolevulinic acid-induced side effects in patients undergoing fluorescence guided resection. Photodiagn Photodyn Ther 10:362–367, 2013
[10]
Coburger J, Engelke J, Scheuerle A, Thal DR, Hlavac M, Wirtz CR, : Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA-enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment. Neurosurg Focus 36(2):E3, 2014
[11]
Coburger J, Hagel V, Wirtz CR, König R: Surgery for glioblastoma: impact of the combined use of 5-aminolevulinic acid and intraoperative MRI on extent of resection and survival. PLoS One 10:e0131872, 2015
[12]
Coburger J, Scheuerle A, Pala A, Thal D, Wirtz CR, König R: Histopathological insights on imaging results of intraoperative magnetic resonance imaging, 5-aminolevulinic acid, and intraoperative ultrasound in glioblastoma surgery. Neurosurgery 81:165–174, 2017
[13]
Coburger J, Wirtz CR: Fluorescence guided surgery by 5-ALA and intraoperative MRI in high grade glioma: a systematic review. J Neurooncol 141:533–546, 2019
[14]
Cook Children’s: Promise: The Winter Issue 2016 [Press Release]. Fort Worth, TX: Cook Children’s Health Care System, 2016, p 29 (https://cookchildrens.org/SiteCollectionDocuments/giving/promise-magazine/Promise-Holiday2016.pdf) [Accessed January 9, 2020]
[15]
Cui Z, Pan L, Song H, Xu X, Xu B, Yu X, : Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease. J Neurosurg 124:62–69, 2016
[16]
Dias S, Sutton AJ, Ades AE, Welton NJ: Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making 33:607–617, 2013
[17]
Díez Valle R, Slof J, Galván J, Arza C, Romariz C, Vidal C: Observational, retrospective study of the effectiveness of 5-aminolevulinic acid in malignant glioma surgery in Spain (The VISIONA study). Neurologia 29:131–138, 2014
[18]
Eljamel MS, 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. Photodiagn Photodyn Ther 16:35–43, 2016
[19]
Esteves S, Alves M, Castel-Branco M, Stummer W: A pilot cost-effectiveness analysis of treatments in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic acid compared with white-light surgery. Neurosurgery 76:552–562, 2015
[20]
Eyüpoglu IY, Hore N, Merkel A, Buslei R, Buchfelder M, Savaskan N: Supra-complete surgery via dual intraoperative visualization approach (DiVA) prolongs patient survival in glioblastoma. Oncotarget 7:25755–25768, 2016
[21]
Eyüpoglu IY, Hore N, Savaskan NE, Grummich P, Roessler K, Buchfelder M, : Improving the extent of malignant glioma resection by dual intraoperative visualization approach. PLoS One 7:e44885, 2012
[22]
Filss CP, Galldiks N, Stoffels G, Sabel M, Wittsack HJ, Turowski B, : Comparison of 18F-FET PET and perfusion-weighted MR imaging: a PET/MR imaging hybrid study in patients with brain tumors. J Nucl Med 55:540–545, 2014
[23]
Gerard IJ, Kersten-Oertel M, Petrecca K, Sirhan D, Hall JA, Collins DL: Brain shift in neuronavigation of brain tumors: a review. Med Image Anal 35:403–420, 2017
[24]
Gessler F, Forster MT, Duetzmann S, Mittelbronn M, Hattingen E, Franz K, : Combination of intraoperative magnetic resonance imaging and intraoperative fluorescence to enhance the resection of contrast enhancing gliomas. Neurosurgery 77:16–22, 2015
[25]
Hadani M, Spiegelman R, Feldman Z, Berkenstadt H, Ram Z: Novel, compact, intraoperative magnetic resonance imaging-guided system for conventional neurosurgical operating rooms. Neurosurgery 48:799–809, 2001
[26]
Hauser SB, Kockro RA, Actor B, Sarnthein J, Bernays RL: Combining 5-aminolevulinic acid fluorescence and intraoperative magnetic resonance imaging in glioblastoma surgery: a histology-based evaluation. Neurosurgery 78:475–483, 2016
[27]
Henegar MM, Moran CJ, Silbergeld DL: Early postoperative magnetic resonance imaging following nonneoplastic cortical resection. J Neurosurg 84:174–179, 1996
[28]
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, : The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928, 2011
[29]
Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 327:557–560, 2003
[30]
Jaber M, Ewelt C, Wölfer J, Brokinkel B, Thomas C, Hasselblatt M, : Is visible aminolevulinic acid-induced fluorescence an independent biomarker for prognosis in histologically confirmed (World Health Organization 2016) low-grade gliomas? Neurosurgery 84:1214–1224, 2019
[31]
Jenkinson MD, Barone DG, Bryant A, Vale L, Bulbeck H, Lawrie TA, : Intraoperative imaging technology to maximise extent of resection for glioma. Cochrane Database Syst Rev 1:CD012788, 2018
[32]
Kim SK, Choi SH, Kim YH, Park CK: Impact of fluorescence-guided surgery on the improvement of clinical outcomes in glioblastoma patients. Neurooncol Pract 1:81–85, 2014
[33]
Knauth M, Aras N, Wirtz CR, Dörfler A, Engelhorn T, Sartor K: Surgically induced intracranial contrast enhancement: potential source of diagnostic error in intraoperative MR imaging. AJNR Am J Neuroradiol 20:1547–1553, 1999
[34]
Knauth M, Wirtz CR, Aras N, Sartor K: Low-field interventional MRI in neurosurgery: finding the right dose of contrast medium. Neuroradiology 43:254–258, 2001
[35]
Kubben PL, Scholtes F, Schijns OE, Ter Laak-Poort MP, Teernstra OP, Kessels AG, : Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: a randomized controlled trial. Surg Neurol Int 5:70, 2014
[36]
Kubben PL, ter Meulen KJ, Schijns OE, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H: Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol 12:1062–1070, 2011
[37]
McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K, Burger PC, : Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery 63:700–708, 2008
[38]
Moher D, Liberati A, Tetzlaff J, Altman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8:336–341, 2010
[39]
Napolitano M, Vaz G, Lawson TM, Docquier MA, van Maanen A, Duprez T, : Glioblastoma surgery with and without intraoperative MRI at 3.0T. Neurochirurgie 60:143–150, 2014
[40]
Nickel K, Renovanz M, König J, Stöckelmaier L, Hickmann AK, Nadji-Ohl M, : The patients’ view: impact of the extent of resection, intraoperative imaging, and awake surgery on health-related quality of life in high-grade glioma patients—results of a multicenter cross-sectional study. Neurosurg Rev 41:207–219, 2018
[41]
Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, : CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro Oncol 19 (suppl_5):v1–v88, 2017
[42]
Pamir MN, Ozduman K, Dinçer A, Yildiz E, Peker S, Ozek MM: First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection. J Neurosurg 112:57–69, 2010
[43]
Pruitt R, Gamble A, Black K, Schulder M, Mehta AD: Complication avoidance in laser interstitial thermal therapy: lessons learned. J Neurosurg 126:1238–1245, 2017
[44]
Quick-Weller J, Lescher S, Forster MT, Konczalla J, Seifert V, Senft C: Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma. Br J Neurosurg 30:313–317, 2016
[45]
Roder C, Bisdas S, Ebner FH, Honegger J, Naegele T, Ernemann U, : Maximizing the extent of resection and survival benefit of patients in glioblastoma surgery: high-field iMRI versus conventional and 5-ALA-assisted surgery. Eur J Surg Oncol 40:297–304, 2014
[46]
Roder C, Breitkopf M Ms, Bisdas S, Freitas RdaS, Dimostheni A, : Beneficial impact of high-field intraoperative magnetic resonance imaging on the efficacy of pediatric low-grade glioma surgery. Neurosurg Focus 40(3):E13, 2016
[47]
Roessler K, Becherer A, Donat M, Cejna M, Zachenhofer I: Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography (18F-FET PET) in glioblastoma surgery. Neurol Res 34:314–317, 2012
[48]
Sacino MF, Ho CY, Murnick J, Keating RF, Gaillard WD, Oluigbo CO: The role of intraoperative MRI in resective epilepsy surgery for peri-eloquent cortex cortical dysplasias and heterotopias in pediatric patients. Neurosurg Focus 40(3):E16, 2016
[49]
Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS: An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8, 2011
[50]
Schardt C, Adams MB, Owens T, Keitz S, Fontelo P: Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med Inform Decis Mak 7:16, 2007

Showing 50 of 150 references