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The impact of 5-aminolevulinic acid on extent of resection in newly diagnosed high grade gliomas: a systematic review and single institutional experience

  • Sameah A. Haider
  • Seokchun Lim
  • Steven N. Kalkanis
  • Ian Y. Lee
Topic Review

Abstract

Background

Glioma surgery at its nascency relied predominantly on visual and tactile feedback for the removal of grossly abnormal tissue. This technique has inherent limitations in delineating infiltrative tumor from normal brain, thus limiting the ability to achieve a gross total resection consistently. Since extent of resection (EOR) is consistently correlated with measures of survival, fluorescence-guided surgery shows promise in improving our ability to treat high-grade gliomas (HGG). 5-Aminolevulinic acid (5-ALA) is a prodrug preferentially metabolized by glioma cells that allows direct, real-time visualization of pathologic tissue through fluorescence under blue light.

Objective

To report the relationship between 5-ALA and EOR in newly diagnosed HGG. To report our institutional experience including nuances of workflow.

Methods

The authors performed a systematic review of the available literature between 1998 and 2018 to isolate studies addressing the impact of fluorescence-guided surgery with 5-ALA on the EOR in newly diagnosed HGG. Search strategy was in adherence to the preferred reporting items for systematic reviews and meta-analyses methodology.

Results

Out of 741 unique articles, eight fulfilled our strict inclusion criteria. Fluorescence-guided resection led to greater EOR in all studies, with six demonstrating statistical significance (p < 0.05). Two studies additionally demonstrated statistically significant increase in progression-free survival in the 5-ALA groups.

Conclusions

5-ALA has an unambiguously positive impact on improving EOR for newly diagnosed HGG. Since the nature of modern glioma surgery includes a complex arsenal of surgical adjuncts, 5-ALA is seldom examined in isolation and can be complemented by intraoperative MRI.

Keywords

Aminolevulinic acid 5-Aminolevulinic acid Fluorescence-guided surgery High-grade glioma Extent of resection 

Abbreviations

5-ALA

5-Aminolevulinic acid

CE

Contrast enhancing

EOR

Extent of resection

EMA

European Medicines Agency

FDA

Food and Drug Administration

FGS

Fluorescence-guided surgery

FLAIR

Fluid attenuated inversion recovery

GTR

Gross total resection

HGG

High-grade glioma

iMRI

Intraoperative magnetic resonance imaging

KPS

Karnofsky Performance Scale

MRI

Magnetic resonance sequence

OS

Overall survival

PFS

Progression-free survival

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

Notes

Compliance with ethical standards

Conflict of interest

Dr. Lee has consulting agreements with Medtronic and Monteris. Dr. Kalkanis has consulting agreements with Arbor Pharmaceuticals and Synaptive Medical. Dr. Haider and Dr. Lim declare that they have no conflict of interest.

References

  1. 1.
    Marko NF, Weil RJ, Schroeder JL, Lang FF, Suki D, Sawaya RE (2014) Extent of resection of glioblastoma revisited: personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery. J Clin Oncol 32(8):774–782.  https://doi.org/10.1200/jco.2013.51.8886 CrossRefGoogle Scholar
  2. 2.
    Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C, Chaudhary N, Sagher O (2012) Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg 117(5):851–859.  https://doi.org/10.3171/2012.8.Jns12234 CrossRefGoogle Scholar
  3. 3.
    Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115(1):3–8.  https://doi.org/10.3171/2011.2.Jns10998 CrossRefGoogle Scholar
  4. 4.
    Eljamel S (2015) 5-ALA fluorescence image guided resection of glioblastoma multiforme: a meta-analysis of the literature. Int J Mol Sci 16(5):10443–10456.  https://doi.org/10.3390/ijms160510443 CrossRefGoogle Scholar
  5. 5.
    Gessler F, Forster MT, Duetzmann S, Mittelbronn M, Hattingen E, Franz K, Seifert V, Senft C (2015) Combination of intraoperative magnetic resonance imaging and intraoperative fluorescence to enhance the resection of contrast enhancing gliomas. Neurosurgery 77(1):16–22.  https://doi.org/10.1227/neu.0000000000000729 (Discussion 22)CrossRefGoogle Scholar
  6. 6.
    Jenkinson MD, Barone DG, Bryant A, Vale L, Bulbeck H, Lawrie TA, Hart MG, Watts C (2018) Intraoperative imaging technology to maximise extent of resection for glioma. The Cochrane database of systematic reviews. 1:Cd012788.  https://doi.org/10.1002/14651858.CD012788.pub2
  7. 7.
    Kittle D, Mamelak A, Parrish-Novak J, Hansen S, Patil R, Wadhone-Gangalum P, Ljubimova J, Black KL, Butte P (2014) Fluorescence-guided tumor visualization using the tumor paint BLZ-100. Cureus.  https://doi.org/10.7759/cureus.210 Google Scholar
  8. 8.
    Prada F, Bene MD, Fornaro R, Vetrano IG, Martegani A, Aiani L, Sconfienza LM, Mauri G, Solbiati L, Pollo B, DiMeco F (2016) Identification of residual tumor with intraoperative contrast-enhanced ultrasound during glioblastoma resection. Neurosurg Focus 40(3):E7.  https://doi.org/10.3171/2015.11.Focus15573 CrossRefGoogle Scholar
  9. 9.
    Stummer W, Suero Molina E (2017) Fluorescence imaging/agents in tumor resection. Neurosurg Clin N Am 28(4):569–583.  https://doi.org/10.1016/j.nec.2017.05.009 CrossRefGoogle Scholar
  10. 10.
    Yamada S, Muragaki Y, Maruyama T, Komori T, Okada Y (2015) Role of neurochemical navigation with 5-aminolevulinic acid during intraoperative MRI-guided resection of intracranial malignant gliomas. Clin Neurol Neurosurg 130:134–139.  https://doi.org/10.1016/j.clineuro.2015.01.005 CrossRefGoogle Scholar
  11. 11.
    Marbacher S, Klinger E, Schwyzer L, Fischer I, Nevzati E, Diepers M, Roelcke U, Fathi AR, Coluccia D, Fandino J (2014) Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases. Neurosurg Focus 36(2):E10.  https://doi.org/10.3171/2013.12.Focus13464 CrossRefGoogle Scholar
  12. 12.
    Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, Goetz AE, Kiefmann R, Reulen HJ (1998) Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42(3):518–525 (Discussion 525–516)CrossRefGoogle Scholar
  13. 13.
    CHMP (2007) Gliolan; INN 5-aminolevulinic hydrochloric acid scientific discussion. London, UK. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000744/WC500021788.pdf
  14. 14.
    Hadley MN, Walters BC, Grabb PA, Oyesiku NM, Przybylski GJ, Resnick DK, Ryken TC (2002) Methodology of guideline development. Neurosurgery 50(3 Suppl):S2–S6.  https://doi.org/10.1097/00006123-200203001-00004 Google Scholar
  15. 15.
    Eyupoglu IY, Hore N, Savaskan NE, Grummich P, Roessler K, Buchfelder M, Ganslandt O (2012) Improving the extent of malignant glioma resection by dual intraoperative visualization approach. PloS ONE 7(9):e44885.  https://doi.org/10.1371/journal.pone.0044885 CrossRefGoogle Scholar
  16. 16.
    Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7(5):392–401.  https://doi.org/10.1016/s1470-2045(06)70665-9 CrossRefGoogle Scholar
  17. 17.
    Coburger J, Hagel V, Wirtz CR, Konig R (2015) Surgery for glioblastoma: impact of the combined use of 5-aminolevulinic acid and intraoperative MRI on extent of resection and survival. PloS ONE 10(6):e0131872.  https://doi.org/10.1371/journal.pone.0131872 CrossRefGoogle Scholar
  18. 18.
    Schatlo B, Fandino J, Smoll NR, Wetzel O, Remonda L, Marbacher S, Perrig W, Landolt H, Fathi AR (2015) Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery. Neuro-oncology 17(12):1560–1567.  https://doi.org/10.1093/neuonc/nov049 CrossRefGoogle Scholar
  19. 19.
    Roder C, Bisdas S, Ebner FH, Honegger J, Naegele T, Ernemann U, Tatagiba M (2014) 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(3):297–304.  https://doi.org/10.1016/j.ejso.2013.11.022 CrossRefGoogle Scholar
  20. 20.
    Kim SK, Choi SH, Kim YH, Park C-K (2014) Impact of fluorescence-guided surgery on the improvement of clinical outcomes in glioblastoma patients. Neurooncol Pract 1(3):81–85.  https://doi.org/10.1093/nop/npu011 Google Scholar
  21. 21.
    Kaufman MB (2017) Pharmaceutical approval update. Pharm Ther 42(11):673–683Google Scholar
  22. 22.
    Della Puppa A, Ciccarino P, Lombardi G, Rolma G, Cecchin D, Rossetto M (2014) 5-Aminolevulinic acid fluorescence in high grade glioma surgery: surgical outcome, intraoperative findings, and fluorescence patterns. BioMed Res Int 2014:232561.  https://doi.org/10.1155/2014/232561 Google Scholar
  23. 23.
    Tsugu A, Ishizaka H, Mizokami Y, Osada T, Baba T, Yoshiyama M, Nishiyama J, Matsumae M (2011) Impact of the combination of 5-aminolevulinic acid-induced fluorescence with intraoperative magnetic resonance imaging-guided surgery for glioma. World Neurosur 76(1–2):120–127.  https://doi.org/10.1016/j.wneu.2011.02.005 CrossRefGoogle Scholar
  24. 24.
    Teixidor P, Arraez MA, Villalba G, Garcia R, Tardaguila M, Gonzalez JJ, Rimbau J, Vidal X, Montane E (2016) Safety and efficacy of 5-aminolevulinic acid for high grade glioma in usual clinical practice: a prospective cohort study. PloS ONE 11(2):e0149244.  https://doi.org/10.1371/journal.pone.0149244 CrossRefGoogle Scholar
  25. 25.
    Cozzens JW, Lokaitis BC, Moore BE, Amin DV, Espinosa JA, MacGregor M, Michael AP, Jones BA (2017) A phase 1 dose-escalation study of oral 5-aminolevulinic acid in adult patients undergoing resection of a newly diagnosed or recurrent high-grade glioma. Neurosurgery 81(1):46–55.  https://doi.org/10.1093/neuros/nyw182 CrossRefGoogle Scholar
  26. 26.
    Stummer W, Stepp H, Wiestler OD, Pichlmeier U (2017) Randomized, prospective double-blinded study comparing 3 different doses of 5-aminolevulinic acid for fluorescence-guided resections of malignant gliomas. Neurosurgery 81(2):230–239.  https://doi.org/10.1093/neuros/nyx074 CrossRefGoogle Scholar
  27. 27.
    Diez Valle R, Tejada Solis S, Idoate Gastearena MA, Garcia de Eulate R, Dominguez Echavarri P, Aristu Mendiroz J (2011) Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience. J Neurooncol 102(1):105–113.  https://doi.org/10.1007/s11060-010-0296-4 CrossRefGoogle Scholar
  28. 28.
    Idoate MA, Diez Valle R, Echeveste J, Tejada S (2011) Pathological characterization of the glioblastoma border as shown during surgery using 5-aminolevulinic acid-induced fluorescence. Neuropathology 31(6):575–582.  https://doi.org/10.1111/j.1440-1789.2011.01202.x CrossRefGoogle Scholar
  29. 29.
    Roberts DW, Valdes PA, Harris BT, Fontaine KM, Hartov A, Fan X, Ji S, Lollis SS, Pogue BW, Leblond F, Tosteson TD, Wilson BC, Paulsen KD (2011) Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between delta-aminolevulinic acid-induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters. Clinical article. J Neurosurg 114(3):595–603.  https://doi.org/10.3171/2010.2.Jns091322 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sameah A. Haider
    • 1
  • Seokchun Lim
    • 1
  • Steven N. Kalkanis
    • 1
  • Ian Y. Lee
    • 1
    • 2
  1. 1.Hermelin Brain Tumor Center, Department of NeurosurgeryHenry Ford Health SystemDetroitUSA
  2. 2.Department of Neurosurgery, K-11Henry Ford HospitalDetroitUSA

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