Impact of removed tumor volume and location on patient outcome in glioblastoma
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.
KeywordsGlioblastoma Extent of resection Postoperative residual EOR Overall survival Removed tumor volume
We thank Kristin Kraus, MSc, for her editorial assistance.
This study was not funded by any specific grant.
Compliance with ethical standards
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.
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 was handled under an exemption.
- 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 10:459–466CrossRefPubMedGoogle 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 95:190–198CrossRefPubMedGoogle 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 12:725–735CrossRefPubMedPubMedCentralGoogle 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 62:564–576CrossRefPubMedGoogle 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) 138:485–493CrossRefGoogle 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 16:113–122CrossRefPubMedGoogle 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 PubMedPubMedCentralGoogle 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 16:81–91CrossRefPubMedGoogle 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 48:1176–1184CrossRefPubMedGoogle Scholar