Optimal extent of resection for glioblastoma according to site, extension, and size: a population-based study in the temozolomide era

  • Yi-Jun Kim
  • David J. Lee
  • Chul-Kee ParkEmail author
  • In Ah KimEmail author
Original Article


The effect of the extent of resection (EOR) on prognosis in glioblastoma may differ depending on various conditions. We evaluated the prognostic impact of the EOR for glioblastoma according to the tumor site, extension, and size. Data from glioblastoma patients who underwent gross total resection (GTR), subtotal resection (STR), or open biopsy between 2005 and 2014 were retrieved from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses for overall survival (OS) were performed. Between 2005–2009 and 2010–2014, the proportion of GTR and STR performed increased from 41.4 to 42.3% and 33.0 to 37.1%, respectively. EOR only affected OS in the 3 years after diagnosis. Median survival in the GTR (n = 4155), STR (n = 3498), and open biopsy (n = 2258) groups was 17, 13, and 13 months, respectively (p < .001). STR showed no significant difference in OS from open biopsy (p = .33). GTR increased OS for midline-crossing tumors. Although STR was more frequently performed than GTR for tumors ≥ 6 cm in size, GTR significantly increased the OS rate relative to STR for tumors 6–8 cm in size (p = .001). For tumors ≥ 8 cm, STR was comparable to GTR (p = .61) and superior to open biopsy (p = .05). GTR needs to be performed more frequently for glioblastoma measuring ≥ 6 cm or that have crossed the midline to increase OS. STR was marginally superior to open biopsy when the tumor was ≥ 8 cm.


Open biopsy Extent of resection Glioblastoma Gross total resection SEER database Subtotal resection 



This study was supported by funding provided to In An Kim by Seoul National University Bundang Hospital Research Fund (#182018-001 and #14-2018-003).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, informed consent was not required.

Supplementary material

10143_2018_1071_Fig6_ESM.png (305 kb)
Fig. S1

Two-year overall survival (OS) rate according to the surgery type, tumor size, and site. GTR, gross total resection; STR, subtotal resection; OB, open biopsy. *Pairwise comparison using a log-rank test adjusted using the Benjamini-Hochberg (BH) method with p < .05. (PNG 305 kb)

10143_2018_1071_MOESM1_ESM.tif (945 kb)
High Resolution Image (TIF 944 kb)
10143_2018_1071_Fig7_ESM.png (305 kb)
Fig. S2

Three-year OS rate according to the surgery type, tumor size, and site. GTR, gross total resection; STR, subtotal resection; OB, open biopsy. *Pairwise comparison using a log-rank test adjusted using the Benjamini-Hochberg (BH) method with p < .05. (PNG 305 kb)

10143_2018_1071_MOESM2_ESM.tif (895 kb)
High Resolution Image (TIF 894 kb)
10143_2018_1071_Fig8_ESM.png (2 mb)
Fig. S3

Two-year overall survival (OS) rate according to the surgery type, tumor size, and extension. GTR, gross total resection; STR, subtotal resection; OB, open biopsy. *Pairwise comparison using a log-rank test adjusted using the Benjamini-Hochberg (BH) method with p < .05. (PNG 2043 kb)

10143_2018_1071_MOESM3_ESM.tif (3.2 mb)
High Resolution Image (TIF 3327 kb)
10143_2018_1071_Fig9_ESM.png (1.7 mb)
Fig. S4

Three-year OS rate according to the surgery type, tumor size, and extension. GTR, gross total resection; STR, subtotal resection; OB, open biopsy. *Pairwise comparison using a log-rank test adjusted using the Benjamini-Hochberg (BH) method with p < .05. (PNG 1715 kb)

10143_2018_1071_MOESM4_ESM.tif (2.8 mb)
High Resolution Image (TIF 2894 kb)
10143_2018_1071_MOESM5_ESM.docx (23 kb)
ESM 1 (DOCX 23 kb)


  1. 1.
    Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefGoogle Scholar
  2. 2.
    Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–766CrossRefGoogle Scholar
  3. 3.
    Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen H-J, Group A-GS (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401CrossRefGoogle Scholar
  4. 4.
    Simpson J, Horton J, Scott C, Curran W, Rubin P, Fischbach J, Isaacson S, Rotman M, Asbell S, Nelson J (1993) Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 26:239–244CrossRefGoogle Scholar
  5. 5.
    Kreth FW, Warnke PC, Scheremet R, Ostertag CB (1993) Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme. J Neurosurg 78:762–766CrossRefGoogle Scholar
  6. 6.
    Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198CrossRefGoogle Scholar
  7. 7.
    Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, Patel AS, Rizk EB, Suki D, Sawaya R (2016) Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol 2:1460–1469CrossRefGoogle Scholar
  8. 8.
    Chaichana KL, Halthore AN, Parker SL, Olivi A, Weingart JD, Brem H, Quinones-Hinojosa A (2011) Factors involved in maintaining prolonged functional independence following supratentorial glioblastoma resection. J Neurosurg 114:604–612CrossRefGoogle Scholar
  9. 9.
    Li YM, Suki D, Hess K, Sawaya R (2016) The influence of maximum safe resection of glioblastoma on survival in 1229 patients: can we do better than gross-total resection? J Neurosurg 124:977–988CrossRefGoogle Scholar
  10. 10.
    Reyes-Botero G, Mokhtari K, Martin-Duverneuil N, Delattre J-Y, Laigle-Donadey F (2012) Adult brainstem gliomas. Oncologist 17:388–397CrossRefGoogle Scholar
  11. 11.
    Eljamel S (2015) 5-ALA fluorescence image guided resection of glioblastoma multiforme: a meta-analysis of the literature. Int J Mol Sci 16:10443–10456CrossRefGoogle Scholar
  12. 12.
    Almeida JP, Chaichana KL, Rincon-Torroella J, Quinones-Hinojosa A (2015) The value of extent of resection of glioblastomas: clinical evidence and current approach. Curr Neurol Neurosci Rep 15:517CrossRefGoogle Scholar
  13. 13.
    Coburger J, Renovanz M, Ganslandt O, Ringel F, Wirtz CR, von Riehm JS (2017) Evaluation of surgical decision making and resulting outcome in patients with highly eloquent glioblastoma: results of a multicenter assessment. Clin Neurol Neurosurg 162:29–35CrossRefGoogle Scholar
  14. 14.
    Noorbakhsh A, Tang JA, Marcus LP, McCutcheon B, Gonda DD, Schallhorn CS, Talamini MA, Chang DC, Carter BS, Chen CC (2014) Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis. J Neurosurg 120:31–39CrossRefGoogle Scholar
  15. 15.
    VanderWeele TJ, Ding P (2017) Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med 167:268–274CrossRefGoogle Scholar
  16. 16.
    Mathur MB, Ding P, Riddell CA, VanderWeele TJ (2018) Web site and R package for computing E-values. Epidemiology 29:e45–e47CrossRefGoogle Scholar
  17. 17.
    Kreth F-W, Thon N, Simon M, Westphal M, Schackert G, Nikkhah G, Hentschel B, Reifenberger G, Pietsch T, Weller M (2013) Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol 24:3117–3123CrossRefGoogle Scholar
  18. 18.
    Sanai N, Polley M-Y, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8CrossRefGoogle Scholar
  19. 19.
    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 32:774CrossRefGoogle Scholar
  20. 20.
    Han SJ, Sughrue ME (2012) The rise and fall of “biopsy and radiate”: a history of surgical nihilism in glioma treatment. Neurosurg Clin N Am 23:207–214Google Scholar
  21. 21.
    Rahman M, Abbatematteo J, De Leo EK, Kubilis PS, Vaziri S, Bova F, Sayour E, Mitchell D, Quinones-Hinojosa A (2016) The effects of new or worsened postoperative neurological deficits on survival of patients with glioblastoma. J Neurosurg 127:123–131Google Scholar
  22. 22.
    Aukland SM, Odberg MD, Gunny R, Eide GE, Rosendahl K (2008) Assessing ventricular size: is subjective evaluation accurate enough? New MRI-based normative standards for 19-year-olds. Neuroradiology 50:1005CrossRefGoogle Scholar
  23. 23.
    Weber DC, Miller RC, Villà S, Hanssens P, Baumert BG, Castadot P, Varlet P, Abacioglu U, Igdem S, Szutowicz E (2006) Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: a retrospective study from the Rare Cancer Network. Int J Radiat Oncol Biol Phys 66:179–186CrossRefGoogle Scholar
  24. 24.
    Nabors LB, Portnow J, Ammirati M, Baehring J, Brem H, Butowski N, Fenstermaker RA, Forsyth P, Hattangadi-Gluth J, Holdhoff M (2017) NCCN guidelines insights: central nervous system cancers, version 1.2017. J Natl Compr Cancer Netw 15:1331–1345CrossRefGoogle Scholar
  25. 25.
    Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926CrossRefGoogle Scholar
  26. 26.
    Perry JR, Laperriere N, O’callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W (2017) Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 376:1027–1037CrossRefGoogle Scholar
  27. 27.
    Louis DN, Perry A, Reifenberger G, Von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRefGoogle Scholar
  28. 28.
    Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, De Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefGoogle Scholar
  29. 29.
    Parsons DW, Jones S, Zhang X, Lin JC-H, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu I-M, Gallia GL (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–12Google Scholar
  30. 30.
    Nonoguchi N, Ohta T, Oh J-E, Kim Y-H, Kleihues P, Ohgaki H (2013) TERT promoter mutations in primary and secondary glioblastomas. Acta Neuropathol 126:931–937CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologySeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Center for Precision MedicineSeoul National University HospitalSeoulRepublic of Korea
  3. 3.The Warren Alpert Medical SchoolBrown UniversityProvidenceUSA
  4. 4.Department of NeurosurgerySeoul National University College of MedicineSeoulRepublic of Korea
  5. 5.Department of Radiation OncologySeoul National University Bundang HospitalSeongnam-siRepublic of Korea

Personalised recommendations