Annals of Surgical Oncology

, Volume 25, Issue 2, pp 558–564 | Cite as

Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection

  • Stefanie Bette
  • Melanie Barz
  • Benedikt Wiestler
  • Thomas Huber
  • Julia Gerhardt
  • Niels Buchmann
  • Stephanie E. Combs
  • Friederike Schmidt-Graf
  • Claire Delbridge
  • Claus Zimmer
  • Jan S. Kirschke
  • Bernhard Meyer
  • Yu-Mi Ryang
  • Florian Ringel
  • Jens GemptEmail author



Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy.


The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy.


Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm3). Survival analyses were performed, including prognostic factors such as age, Karnofsky performance score (KPS), O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, and adjuvant treatment regimen.


Pre- and postoperative tumor volume is significantly associated with pre- and postoperative KPS, as well as age (p < 0.001). Postoperative tumor volume remained a significant prognostic factor in a multivariate analysis, independent of other prognostic factors (hazard ratio 1.0365, 95% confidence interval 1.0235–1.0497, p < 0.001).


In the era of molecularly-driven radiochemotherapy, glioblastoma surgery remains a major prognostic factor. Even in situations in which a gross total resection cannot be achieved, maximum safe reduction of tumor burden should be attempted.



Benedikt Wiestler received funding from KKF TU Munich. Stefanie Bette, Thomas Huber, Bernhard Meyer, and Jens Gempt are consultants for Brainlab AG, Munich. Claus Zimmer has served on scientific advisory boards for Philips and Bayer Schering; serves as co-editor on the Advisory Board of Clinical Neuroradiology; has received speaker honoraria from Bayer-Schering and Philips; and has received research support and investigator fees for clinical studies from Biogen Idec, Quintiles, MSD Sharp & Dome, Boehringer Ingelheim, Inventive Health Clinical UK Ltd., Advance Cor, Brainsgate, Pfizer, Bayer-Schering, Novartis, Roche, Servier, Penumbra, WCT GmbH, Syngis, SSS International Clinical Research, PPD Germany GmbH, Worldwide Clinical Trials Ltd., Phenox, Covidien, Actelion, Medivation, Medtronic, Harrison Clinical Research, Concentric, Penumbra, Pharmtrace, Reverse Medical Corp., Premier Research Germany Ltd., Surpass Medical Ltd., and GlaxoSmithKline. Jan S. Kirschke received an ERC grant and has received speaker honoraria from Philips. Melanie Barz, Julia Gerhardt, Niels Buchmann, Stephanie E. Combs, Friederike Schmidt-Graf, Claire Delbridge, Yu-Mi Ryang, and Florian Ringel have nothing to disclose.

Supplementary material

10434_2017_6253_MOESM1_ESM.jpg (119 kb)
Electronic supplementary Fig. 1 Box plots for pre- and postoperative tumor volume and association with age and pre- and postoperative KPS. KPS Karnofsky performance score. Supplementary material 1 (JPEG 118 kb)
10434_2017_6253_MOESM2_ESM.jpg (170 kb)
Electronic supplementary Fig. 2 Univariate survival analysis (Kaplan–Meier). Supplementary material 2 (JPEG 169 kb)
10434_2017_6253_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 16 kb)


  1. 1.
    Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392–401.CrossRefPubMedGoogle Scholar
  2. 2.
    Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMedGoogle Scholar
  3. 3.
    Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66.CrossRefPubMedGoogle Scholar
  4. 4.
    Gorlia T, van den Bent MJ, Hegi ME, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol. 2008;9:29–38.CrossRefPubMedGoogle Scholar
  5. 5.
    Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.CrossRefPubMedGoogle Scholar
  6. 6.
    Senft C, Bink A, Franz K, et al. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol. 2011;12:997–1003.CrossRefPubMedGoogle Scholar
  7. 7.
    Stark AM, Stepper W, Mehdorn HM. Outcome evaluation in glioblastoma patients using different ranking scores: KPS, GOS, mRS and MRC. Eur J Cancer Care. 2010;19:39–44.CrossRefGoogle Scholar
  8. 8.
    Kreth FW, Thon N, Simon M, et al. Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol. 2013;24:3117–23.CrossRefPubMedGoogle Scholar
  9. 9.
    Li XZ, Li YB, Cao Y, et al. Prognostic implications of resection extent for patients with glioblastoma multiforme: a meta-analysis. J Neurosurg Sci. 2017;61:631–9.PubMedGoogle Scholar
  10. 10.
    Sanai N, Polley MY, McDermott MW, et al. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011;115:3–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Grabowski MM, Recinos PF, Nowacki AS, et al. Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. J Neurosurg. 2014;121:1115–23.CrossRefPubMedGoogle Scholar
  12. 12.
    Chaichana KL, Cabrera-Aldana EE, Jusue-Torres I, et al. When gross total resection of a glioblastoma is possible, how much resection should be achieved? World Neurosurg. 2014;82:e257–65.CrossRefPubMedGoogle Scholar
  13. 13.
    Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol. 2014;16:113–22.CrossRefPubMedGoogle Scholar
  14. 14.
    Brown TJ, Brennan MC, Li M, et al. Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol. 2016;2:1460–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Marko NF, Weil RJ, Schroeder JL et al. 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. 2014;32:774–82.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent. 2014;81:14–18.Google Scholar
  17. 17.
    Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20.CrossRefPubMedGoogle Scholar
  18. 18.
    Meyding-Lamade U, Forsting M, Albert F, et al. Accelerated methaemoglobin formation: potential pitfall in early postoperative MRI. Neuroradiology. 1993;35:178–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Felsberg J, Rapp M, Loeser S, et al. Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res. 2009;15:6683–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Stupp R, Hegi ME, Gorlia T, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1100–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Stupp R, Hegi ME, Neyns B, et al. Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010;28:2712–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95:190–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Orringer D, Lau D, Khatri S, et al. Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg. 2012;117:851–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Kubben PL, Postma AA, Kessels AG, et al. Intraobserver and interobserver agreement in volumetric assessment of glioblastoma multiforme resection. Neurosurgery. 2010;67:1329–34.CrossRefPubMedGoogle Scholar
  25. 25.
    Wiestler B, Claus R, Hartlieb SA, et al. Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective. Neuro Oncol. 2013;15:1017–26.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Stefanie Bette
    • 1
  • Melanie Barz
    • 2
  • Benedikt Wiestler
    • 1
  • Thomas Huber
    • 3
  • Julia Gerhardt
    • 2
  • Niels Buchmann
    • 2
  • Stephanie E. Combs
    • 4
    • 7
    • 8
  • Friederike Schmidt-Graf
    • 5
  • Claire Delbridge
    • 6
  • Claus Zimmer
    • 1
  • Jan S. Kirschke
    • 1
  • Bernhard Meyer
    • 2
  • Yu-Mi Ryang
    • 2
  • Florian Ringel
    • 2
  • Jens Gempt
    • 2
    Email author
  1. 1.Department of NeuroradiologyKlinikum rechts der Isar der Technischen UniversitatMunichGermany
  2. 2.Department of NeurosurgeryKlinikum rechts der Isar der Technischen UniversitatMunichGermany
  3. 3.Department of RadiologyLudwig-Maximilians-UniversityMunichGermany
  4. 4.Department of Radiation OncologyKlinikum rechts der Isar der Technischen UniversitatMunichGermany
  5. 5.Department of NeurologyKlinikum rechts der Isar der Technischen UniversitatMunichGermany
  6. 6.Department of NeuropathologyKlinikum rechts der Isar der Technischen UniversitatMunichGermany
  7. 7.Institute for Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS)Helmholtz Zentrum MünchenOberschleißheimGermany
  8. 8.Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site MunichMunichGermany

Personalised recommendations