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

Annals of Surgical Oncology volume 25, pages 558–564 (2018)Cite this article

A Correction to this article was published on 19 March 2018

This article has been updated

Abstract

Background

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

Objective

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.

Methods

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.

Results

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).

Conclusions

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.

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Change history

  • 19 March 2018

    Due to a metadata tagging error the names of Stephanie E. Combs and Jan S. Kirschke were indexed incorrectly. Stephanie E. is the author’s given name, and Jan S. is the author’s given name.

  • 19 March 2018

    Due to a metadata tagging error the names of Stephanie E. Combs and Jan S. Kirschke were indexed incorrectly. Stephanie E. is the author?s given name, and Jan S. is the author?s given name.

  • 19 March 2018

    Due to a metadata tagging error the names of Stephanie E. Combs and Jan S. Kirschke were indexed incorrectly. Stephanie E. is the author?s given name, and Jan S. is the author?s given name.

References

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  10. Sanai N, Polley MY, McDermott MW, et al. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011;115:3–8.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  18. Meyding-Lamade U, Forsting M, Albert F, et al. Accelerated methaemoglobin formation: potential pitfall in early postoperative MRI. Neuroradiology. 1993;35:178–80.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Disclosure

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.

Author information

Author notes

  1. Stefanie Bette and Melanie Barz are contributed equally to this work.

Affiliations

  1. Department of Neuroradiology, Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

    Stefanie Bette MD, Benedikt Wiestler MD, Claus Zimmer MD & Jan S. Kirschke MD

  2. Department of Neurosurgery, Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

    Melanie Barz MD, Julia Gerhardt MD, Niels Buchmann MD, Bernhard Meyer MD, Yu-Mi Ryang MD, Florian Ringel MD & Jens Gempt MD

  3. Department of Radiology, Ludwig-Maximilians-University, Munich, Germany

    Thomas Huber MD

  4. Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

    Stephanie E. Combs MD

  5. Department of Neurology, Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

    Friederike Schmidt-Graf MD

  6. Department of Neuropathology, Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

    Claire Delbridge MD

  7. Institute for Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, 85764, Oberschleißheim, Germany

    Stephanie E. Combs MD

  8. Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany

    Stephanie E. Combs MD

Authors
  1. Stefanie Bette MD
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  2. Melanie Barz MD
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  10. Claus Zimmer MD
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  11. Jan S. Kirschke MD
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  15. Jens Gempt MD
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Corresponding author

Correspondence to Jens Gempt MD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2017_6253_MOESM1_ESM.jpg

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)

Electronic supplementary Fig. 2 Univariate survival analysis (Kaplan–Meier). Supplementary material 2 (JPEG 169 kb)

Supplementary material 3 (DOCX 16 kb)

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Bette, S., Barz, M., Wiestler, B. et al. Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection. Ann Surg Oncol 25, 558–564 (2018). https://doi.org/10.1245/s10434-017-6253-0

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  • DOI: https://doi.org/10.1245/s10434-017-6253-0

Keywords

  • Methylation Of The O6-methylguanine-DNA Methyltransferase (MGMT)
  • Postoperative Tumor Volume
  • Combined Radiochemotherapy
  • Postoperative KPS
  • Adjuvant Treatment Regimens