Skip to main content

Impact of removed tumor volume and location on patient outcome in glioblastoma

Journal of Neuro-Oncology volume 135, pages 161–171 (2017)Cite this article

Abstract

Glioblastoma is an aggressive primary brain tumor with devastatingly poor prognosis. Multiple studies have shown the benefit of wider extent of resection (EOR) on patient overall survival (OS) and worsened survival with larger preoperative tumor volumes. However, the concomitant impact of postoperative tumor volume and eloquent location on OS has yet to be fully evaluated. We performed a retrospective chart review of adult patients treated for glioblastoma from January 2006 through December 2011. Adherence to standardized postoperative chemoradiation protocols was used as an inclusion criterion. Detailed volumetric and location analysis was performed on immediate preoperative and immediate postoperative magnetic resonance imaging. Cox proportional hazard modeling approach was employed to explore the modifying effects of EOR and eloquent location after adjusting for various confounders and associated characteristics, such as preoperative tumor volume and demographics. Of the 471 screened patients, 141 were excluded because they did not meet all inclusion criteria. The mean (±SD) age of the remaining 330 patients (60.6% male) was 58.9 ± 12.9 years; the mean preoperative and postoperative Karnofsky performance scores (KPSs) were 76.2 ± 10.3 and 80.0 ± 16.6, respectively. Preoperative tumor volume averaged 33.2 ± 29.0 ml, postoperative residual was 4.0 ± 8.1 ml, and average EOR was 88.6 ± 17.6%. The observed average follow-up was 17.6 ± 15.7 months, and mean OS was 16.7 ± 14.4 months. Survival analysis showed significantly shorter survival for patients with lesions in periventricular (16.8 ± 1.7 vs. 21.5 ± 1.4 mo, p = 0.03), deep nuclei/basal ganglia (11.6 ± 1.7 vs. 20.6 ± 1.2, p = 0.002), and multifocal (12.0 ± 1.4 vs. 21.3 ± 1.3 months, p = 0.0001) locations, but no significant influence on survival was seen for eloquent cortex sites (p = 0.14, range 0.07–0.9 for all individual locations). OS significantly improved with EOR in univariate analysis, averaging 22.3, 19.7, and 13.2 months for >90, 80–90, and 70–80% resection, respectively. Survival was 22.8, 19.0, and 12.7 months for 0, 0–5, and 5–10 ml postoperative residual, respectively. A hazard model showed that larger preoperative tumor volume [hazard ratio (HR) 1.05, 95% CI 1.02–1.07], greater age (HR 1.02, 95% CI 1.01–1.03), multifocality (HR 1.44, 95% CI 1.01–2.04), and deep nuclei/basal ganglia (HR 2.05, CI 1.27–3.3) were the most predictive of poor survival after adjusting for KPS and tumor location. There was a negligible but significant interaction between EOR and preoperative tumor volume (HR 0.9995, 95% CI 0.9993–0.9998), but EOR alone did not correlate with OS after adjusting for other factors. The interaction between EOR and preoperative tumor volume represented tumor volume removed during surgery. In conclusion, EOR alone was not an important predictor of outcome during GBM treatment once preoperative tumor volume, age, and deep nuclei/basal ganglia location were factored. Instead, the interaction between EOR and preoperative volume, representing reduced disease burden, was an important predictor of reducing OS. Removal of tumor from eloquent cortex did not impact postoperative KPS. These results suggest aggressive surgical treatment to reduce postoperative residual while maintaining postoperative KPS may aid patient survival outcomes for a given tumor size and location.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Karsy M, Neil JA, Guan J, Mahan MA, Colman H, Jensen RL (2015) A practical review of prognostic correlations of molecular biomarkers in glioblastoma. Neurosurg Focus 38(3):E4

    Article  PubMed  Google Scholar 

  2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiation Oncology G, National Cancer Institute of Canada Clinical Trials G (2009) 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 10:459–466

    CAS  Article  PubMed  Google Scholar 

  3. Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–764

    Article  PubMed  Google Scholar 

  4. Sanai N, Berger MS (2012) Recent surgical management of gliomas. Adv Exp Med Biol 746:12–25

    CAS  Article  PubMed  Google Scholar 

  5. Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH, Vogelbaum MA (2014) Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. J Neurosurg 121:1115–1123

    Article  PubMed  Google Scholar 

  6. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198

    CAS  Article  PubMed  Google Scholar 

  7. Bloch O, Han SJ, Cha S, Sun MZ, Aghi MK, McDermott MW, Berger MS, Parsa AT (2012) Impact of extent of resection for recurrent glioblastoma on overall survival: clinical article. J Neurosurg 117:1032–1038

    Article  PubMed  Google Scholar 

  8. Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8

    Article  PubMed  Google Scholar 

  9. Bauchet L, Mathieu-Daude H, Fabbro-Peray P, Rigau V, Fabbro M, Chinot O, Pallusseau L, Carnin C, Laine K, Schlama A, Thiebaut A, Patru MC, Bauchet F, Lionnet M, Wager M, Faillot T, Taillandier L, Figarella-Branger D, Capelle L, Loiseau H, Frappaz D, Campello C, Kerr C, Duffau H, Reme-Saumon M, Tretarre B, Daures JP, Henin D, Labrousse F, Menei P, Honnorat J, Societe Francaise de N, Club de Neuro-Oncologie of the Societe Francaise de N, Societe Francaise de N, Association des Neuro-Oncologues d’Expression F (2010) Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004. Neuro Oncol 12:725–735

    Article  PubMed  PubMed Central  Google Scholar 

  10. Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, Rohde V, Oppel F, Turowski B, Woiciechowsky C, Franz K, Pietsch T, Group AL-GS (2008) Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 62:564–576

    Article  PubMed  Google Scholar 

  11. 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 124:977–988

    Article  PubMed  Google Scholar 

  12. Wood JR, Green SB, Shapiro WR (1988) The prognostic importance of tumor size in malignant gliomas: a computed tomographic scan study by the Brain Tumor Cooperative Group. J Clin Oncol 6:338–343

    CAS  Article  PubMed  Google Scholar 

  13. Lobato RD, Alday R, Gomez PA, Rivas JJ, Dominguez J, Cabrera A, Madero S, Ayerbe J (1996) Brain oedema in patients with intracranial meningioma. Correlation between clinical, radiological, and histological factors and the presence and intensity of oedema. Acta Neurochir (Wien) 138:485–493

    CAS  Article  Google Scholar 

  14. Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, Raza SM, Pascual-Gallego M, Ibrahim A, Hernandez-Hermann M, Gomez L, Ye X, Weingart JD, Olivi A, Blakeley J, Gallia GL, Lim M, Brem H, Quinones-Hinojosa A (2014) Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol 16:113–122

    Article  PubMed  Google Scholar 

  15. Chaichana KL, Cabrera-Aldana EE, Jusue-Torres I, Wijesekera O, Olivi A, Rahman M, Quinones-Hinojosa A (2014) When gross total resection of a glioblastoma is possible, how much resection should be achieved? World Neurosurg 82:e257–265

    Article  PubMed  Google Scholar 

  16. Lamborn KR, Chang SM, Prados MD (2004) Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro Oncol 6:227–235

    Article  PubMed  PubMed Central  Google Scholar 

  17. McGirt MJ, Mukherjee D, Chaichana KL, Than KD, Weingart JD, Quinones-Hinojosa A (2009) Association of surgically acquired motor and language deficits on overall survival after resection of glioblastoma multiforme. Neurosurgery 65:463–469

    Article  PubMed  Google Scholar 

  18. Rahman M, Abbatematteo J, De Leo EK, Kubilis PS, Vaziri S, Bova F, Sayour E, Mitchell D, Quinones-Hinojosa A (2017) The effects of new or worsened postoperative neurological deficits on survival of patients with glioblastoma. J Neurosurg 127:1–9

    Article  Google Scholar 

  19. Karremann M, Rausche U, Roth D, Kuhn A, Pietsch T, Gielen GH, Warmuth-Metz M, Kortmann RD, Straeter R, Gnekow A, Wolff JE, Kramm CM (2013) Cerebellar location may predict an unfavourable prognosis in paediatric high-grade glioma. Br J Cancer 109:844–851

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Parsa AT, Wachhorst S, Lamborn KR, Prados MD, McDermott MW, Berger MS, Chang SM (2005) Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults. J Neurosurg 102:622–628

    Article  PubMed  Google Scholar 

  21. Ramakrishna R, Barber J, Kennedy G, Rizvi A, Goodkin R, Winn RH, Ojemann GA, Berger MS, Spence AM, Rostomily RC (2010) Imaging features of invasion and preoperative and postoperative tumor burden in previously untreated glioblastoma: correlation with survival. Surg Neurol Int. doi:10.4103/2152-7806.68337

    PubMed  PubMed Central  Google Scholar 

  22. Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 16:81–91

    CAS  Article  PubMed  Google Scholar 

  23. Gorlia T, Stupp R, Brandes AA, Rampling RR, Fumoleau P, Dittrich C, Campone MM, Twelves CC, Raymond E, Hegi ME, Lacombe D, van den Bent MJ (2012) New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer 48:1176–1184

    Article  PubMed  Google Scholar 

  24. Chaichana KL, McGirt MJ, Frazier J, Attenello F, Guerrero-Cazares H, Quinones-Hinojosa A (2008) Relationship of glioblastoma multiforme to the lateral ventricles predicts survival following tumor resection. J Neurooncol 89:219–224

    Article  PubMed  Google Scholar 

  25. Chaichana KL, Jusue-Torres I, Lemos AM, Gokaslan A, Cabrera-Aldana EE, Ashary A, Olivi A, Quinones-Hinojosa A (2014) The butterfly effect on glioblastoma: is volumetric extent of resection more effective than biopsy for these tumors? J Neurooncol 120:625–634

    Article  PubMed  PubMed Central  Google Scholar 

  26. Babu R, Komisarow JM, Agarwal VJ, Rahimpour S, Iyer A, Britt D, Karikari IO, Grossi PM, Thomas S, Friedman AH, Adamson C (2016) Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival. J Neurosurg 124:998–1007

    Article  PubMed  Google Scholar 

  27. Duffau H (2014) The huge plastic potential of adult brain and the role of connectomics: new insights provided by serial mappings in glioma surgery. Cortex 58:325–337

    Article  PubMed  Google Scholar 

  28. Zhang T, Wang Y, Fan X, Ma J, Li S, Jiang T, Wang L (2014) Anatomical localization of p53 mutated tumors: a radiographic study of human glioblastomas. J Neurol Sci 346:94–98

    CAS  Article  PubMed  Google Scholar 

  29. Wang Y, Fan X, Zhang C, Zhang T, Peng X, Li S, Wang L, Ma J, Jiang T (2014) Anatomical specificity of O-6-methylguanine DNA methyltransferase protein expression in glioblastomas. J Neurooncol 120:331–337

    CAS  Article  PubMed  Google Scholar 

  30. Chen R, Ravindra VM, Cohen AL, Jensen RL, Salzman KL, Prescot AP, Colman H (2015) Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas. Neurosurg Focus 38:E2

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Kristin Kraus, MSc, for her editorial assistance.

Funding

This study was not funded by any specific grant.

Author information

Affiliations

  1. Department of Neurosurgery, Clinical Neuroscience Center, University of Utah, Fifth Floor, 175 North Medical Drive, Salt Lake City, UT, 84132, USA

    Al-Wala Awad, Michael Karsy, Yizhe Xu & Mark A. Mahan

  2. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA

    Nader Sanai & Robert Spetzler

  3. Study Design & Biostatistics Center, University of Utah, Salt Lake City, UT, USA

    Yue Zhang

Authors
  1. Al-Wala Awad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Karsy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nader Sanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Spetzler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yizhe Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mark A. Mahan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark A. Mahan.

Ethics declarations

Conflict of interest

Wala Al-Awad, MD, declares that he has no conflict of interest. Michael Karsy, MD, PhD, declares that he has no conflict of interest. Nader Sanai, MD, declares that he has no conflict of interest. Robert Spetzler, MD, declares that he has no conflict of interest. Yue Zhang, PhD, declares that he has no conflict of interest. Yizhe Xu, MS, declares that she has no conflict of interest. Mark A. Mahan, MD, declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was handled under an exemption.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 85 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Awad, AW., Karsy, M., Sanai, N. et al. Impact of removed tumor volume and location on patient outcome in glioblastoma. J Neurooncol 135, 161–171 (2017). https://doi.org/10.1007/s11060-017-2562-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-017-2562-1

Keywords

  • Glioblastoma
  • Extent of resection
  • Postoperative residual
  • EOR
  • Overall survival
  • Removed tumor volume