Maximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.
A total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.
One hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).
Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.
ABBREVIATIONS5-ALA = 5-aminolevulinic acid; ASA = American Society of Anesthesiologists; CRET = complete resection of contrast enhancing tumor; ECOG = Eastern Cooperative Oncology Group; EOR = extent of resection; GTR = gross-total resection; IDH-1 = isocitrate dehydrogenase 1; IQR = interquartile range; KPS = Karnofsky Performance Score; MGMT = O6-methylguanine-methyltransferase; OS = overall survival; PFS = progression-free survival; PR = partial resection; RANO = Response Assessment in Neuro-Oncology.
Correspondence Rasmus W. Hansen: Odense University Hospital, Odense, Denmark. firstname.lastname@example.org.INCLUDE WHEN CITING Published online October 4, 2019; DOI: 10.3171/2019.6.JNS191531.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
AcerbiF, BroggiM, SchebeschKM, HöhneJ, CavalloC, De LaurentisC, : Fluorescein-guided surgery for resection of high-grade gliomas: a multicentric prospective phase II study (FLUOGLIO). 24:52–61, 201810.1158/1078-0432.CCR-17-118429018053)| false
BrownTJ, BrennanMC, LiM, ChurchEW, BrandmeirNJ, RakszawskiKL, : Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. 2:1460–1469, 20162731065110.1001/jamaoncol.2016.1373)| false
DiazRJDiosRRHattabEMBurrellKRakopoulosPSabhaN: Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance. J Neurosurg122:1360–13692015
DiazRJ, DiosRR, HattabEM, BurrellK, RakopoulosP, SabhaN, : Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance. 122:1360–1369, 20152583991910.3171/2015.2.JNS132507)| false
GlennCA, BakerCM, ConnerAK, BurksJD, BonneyPA, BriggsRG, : An examination of the role of supramaximal resection of temporal lobe glioblastoma multiforme. 114:e747–e755, 201810.1016/j.wneu.2018.03.072)| false
KatsevmanGATurnerRCUrhieOVoelkerJLBhatiaS: Utility of sodium fluorescein for achieving resection targets in glioblastoma: increased gross- or near-total resections and prolonged survival. J Neurosurg[epub ahead of print February 8 2019. DOI: 10.3171/2018.10.JNS181174]
KatsevmanGA, TurnerRC, UrhieO, VoelkerJL, BhatiaS: Utility of sodium fluorescein for achieving resection targets in glioblastoma: increased gross- or near-total resections and prolonged survival. [epub ahead of print February 8, 2019. DOI: 10.3171/2018.10.JNS181174]30738388)| false
LacroixM, Abi-SaidD, FourneyDR, GokaslanZL, ShiW, DeMonteF, : A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. 95:190–198, 20011178088710.3171/jns.2001.95.2.0190)| false
LouisDNPerryAReifenbergerGvon DeimlingAFigarella-BrangerDCaveneeWK: The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol131:803–8202016
LouisDN, PerryA, ReifenbergerG, von DeimlingA, Figarella-BrangerD, CaveneeWK, : The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. 131:803–820, 201610.1007/s00401-016-1545-127157931)| false
MampreDEhresmanJPinilla-MonsalveGOsorioMAGOliviAQuinones-HinojosaA: Extending the resection beyond the contrast-enhancement for glioblastoma: feasibility, efficacy, and outcomes. Br J Neurosurg32:528–5352018
MaugeriR, VillaA, PinoM, ImperatoA, GiammalvaGR, CostantinoG, : With a little help from my friends: the role of intraoperative fluorescent dyes in the surgical management of high-grade gliomas. 8:E31, 201810.3390/brainsci802003129414911)| false
PreußM, RennerC, KruppW, ChristiansenH, FischerL, MerkenschlagerA, : The use of 5-aminolevulinic acid fluorescence guidance in resection of pediatric brain tumors. 29:1263–1267, 20132370886710.1007/s00381-013-2159-8)| false
SchebeschKMHoehneJHohenbergerCProescholdtMRiemenschneiderMJWendlC: Fluorescein sodium-guided resection of cerebral metastases—experience with the first 30 patients. Acta Neurochir (Wien)157:899–9042015
StummerWPichlmeierUMeinelTWiestlerODZanellaFReulenHJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol7:392–4012006
StummerW, PichlmeierU, MeinelT, WiestlerOD, ZanellaF, ReulenHJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. 7:392–401, 200610.1016/S1470-2045(06)70665-916648043)| false
YanoHNakayamaNOheNMiwaKShinodaJIwamaT: Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium. J Neurooncol133:389–3972017
YanoH, NakayamaN, OheN, MiwaK, ShinodaJ, IwamaT: Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium. 133:389–397, 20172843259010.1007/s11060-017-2445-5)| false