A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma



Due to the infiltrative nature of glioblastoma (GBM) outside of the contrast-enhancing region on MRI, there is interest in exploring supratotal resections (SpTR) that extend beyond the contrast-enhancing portion of the tumor. However, there is currently no consensus on the potential survival benefit of SpTR in GBM compared to gross total resection (GTR). In this study, we compare the impact of SpTR versus GTR on overall survival (OS) of GBM patients.


We performed a systematic review and meta-analysis of literature published on PubMed, Embase, The Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov, from inception to August 16, 2018, to identify articles comparing OS after SpTR versus GTR.


We identified 8902 unique citations, of which 11 articles met study inclusion criteria. 810 patients underwent SpTR out of a total of 2056 patients. 9 of 11 studies demonstrated improved outcomes with SpTR compared to GTR (median improvement in OS of 10.5 months), with no significant difference in postoperative complication rate. Overall study quality was variable, with ten studies presenting level IV evidence and one study presenting level IIIb evidence. Subgroup meta-analysis based on SpTR definition demonstrated a statistically significant 35% lower risk of mortality in patients who underwent anatomical SpTR compared to patients who underwent GTR (Hazard ratio = 0.65, 95% CI 0.47- 0.91, p = 0.003).


Our systematic review indicates SpTR may be associated with improved OS compared to GTR for GBM, especially with anatomical SpTR. However, this is limited by variable study design and significant clinical and methodological heterogeneity among studies. There is need for prospective clinical data to further guide parameters regarding the use of SpTR in GBM.

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  1. 1.

    Omuro A, DeAngelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA—J Am Med Assoc 310:1842–1850

    CAS  Article  Google Scholar 

  2. 2.

    Brada M, Hoang-Xuan K, Rampling R et al (2014) Glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 61:e9–e16. https://doi.org/10.1007/s10517-015-2864-2

    CAS  Article  Google Scholar 

  3. 3.

    Sanai N, Berger MS (2008) Glioma extent of resection and methods. Neurosurgery 62:753–766. https://doi.org/10.1227/01.NEU.0000310769.20996.BD

    Article  PubMed  Google Scholar 

  4. 4.

    Lacroix M, Abi-Said D, Fourney DR et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: Prognosis, extent of resection, and survival. J Neurosurg 95:190–198. https://doi.org/10.3171/jns.2001.95.2.0190

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Brown TJ, Brennan MC, Li M et al (2016) Association of the extent of resection with survival in glioblastoma a systematic review and meta-Analysis. JAMA Oncol 2:1460–1469. https://doi.org/10.1001/jamaoncol.2016.1373

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Sanai N, Polley M-Y, McDermott MW et al (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8. https://doi.org/10.3171/2011.2.JNS10998

    Article  PubMed  Google Scholar 

  7. 7.

    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. https://doi.org/10.3171/2015.5.JNS142087

    Article  PubMed  Google Scholar 

  8. 8.

    Dandy WE (1928) Removal of right cerebral hemisphere for certain tumors with hemiplegia: preliminary report. J Am Med Assoc 90:823–825. https://doi.org/10.1001/jama.1928.02690380007003

    Article  Google Scholar 

  9. 9.

    Baldock AL, Ahn S, Rockne R et al (2014) Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas. PLoS ONE 9:e99057. https://doi.org/10.1371/journal.pone.0099057

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Darmanis S, Sloan SA, Croote D et al (2017) Single-cell RNA-Seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Rep 21:1399–1410. https://doi.org/10.1016/j.celrep.2017.10.030

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Eyüpoglu IY, Buchfelder M, Savaskan NE (2013) Surgical resection of malignant gliomas-role in optimizing patient outcome. Nat Rev Neurol 9:141–151

    Article  Google Scholar 

  12. 12.

    Eidel O, Burth S, Neumann JO et al (2017) Tumor infiltration in enhancing and non-enhancing parts of glioblastoma: a correlation with histopathology. PLoS ONE. https://doi.org/10.1371/journal.pone.0169292

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Giese A, Bjerkvig R, Berens ME, Westphal M (2003) Cost of migration: invasion of malignant gliomas treatment. J Clin Oncol 21:1624–1636. https://doi.org/10.1200/JC0.2003.05.063

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Rahman M, Abbatematteo J, De Leo EK et al (2017) The effects of new or worsened postoperative neurological deficits on survival of patients with glioblastoma. J Neurosurg 127:123–131. https://doi.org/10.3171/2016.7.JNS16396

    Article  PubMed  Google Scholar 

  15. 15.

    McGirt MJ, Mukherjee D, Chaichana KL et al (2009) Association of surgically acquired motor and language deficits on overall survival after resection of glioblastoma multiforme. Neurosurgery 65:463–469. https://doi.org/10.1227/01.NEU.0000349763.42238.E9

    Article  PubMed  Google Scholar 

  16. 16.

    De Leeuw CN, Vogelbaum MA (2019) Supratotal resection in glioma: a systematic review. Neuro Oncol 21:179–188. https://doi.org/10.1093/neuonc/noy166

    Article  PubMed  Google Scholar 

  17. 17.

    Incekara F, Koene S, Vincent AJPE et al (2019) Association between supratotal glioblastoma resection and patient survival: a systematic review and meta-analysis. World Neurosurg 127:617–624.e2

    Article  Google Scholar 

  18. 18.

    Liberati A, Altman DG, Tetzlaff J, et al. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med, 6

  19. 19.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Covidence—Better systematic review management

  21. 21.

    OCEBM Levels of Evidence—CEBM. https://www.cebm.net/index.aspx?o=5653

  22. 22.

    Guyot P, Ades AE, Ouwens MJNM, Welton NJ (2012) Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. https://doi.org/10.1186/1471-2288-12-9

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Liu Z, Rich B, Hanley JA (2015) Recovering the raw data behind a non-parametric survival curve. Syst Rev. https://doi.org/10.1186/2046-4053-3-151

    Article  Google Scholar 

  24. 24.

    Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. https://doi.org/10.1002/sim.1186

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Glenn CA, Baker CM, Conner AK et al (2018) An examination of the role of supramaximal resection of temporal lobe glioblastoma multiforme. World Neurosurg 114:e747–e755. https://doi.org/10.1016/j.wneu.2018.03.072

    Article  PubMed  Google Scholar 

  26. 26.

    Esquenazi Y, Friedman E, Liu Z et al (2017) The Survival advantage of “supratotal” resection of glioblastoma using selective cortical mapping and the subpial technique. Neurosurgery 81:275–288. https://doi.org/10.1093/neuros/nyw174

    Article  PubMed  Google Scholar 

  27. 27.

    Grabowski MM, Recinos PF, Nowacki AS et al (2014) Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. J Neurosurg 121:1115–1123. https://doi.org/10.3171/2014.7.JNS132449

    Article  PubMed  Google Scholar 

  28. 28.

    Mampre D, Ehresman J, Pinilla-Monsalve G et al (2018) Extending the resection beyond the contrast-enhancement for glioblastoma: feasibility, efficacy, and outcomes. Br J Neurosurg 32:528–535. https://doi.org/10.1080/02688697.2018.1498450

    Article  PubMed  Google Scholar 

  29. 29.

    De Bonis P, Anile C, Pompucci A et al (2013) The influence of surgery on recurrence pattern of glioblastoma. Clin Neurol Neurosurg 115:37–43. https://doi.org/10.1016/j.clineuro.2012.04.005

    Article  PubMed  Google Scholar 

  30. 30.

    Pessina F, Navarria P, Cozzi L et al (2017) Maximize surgical resection beyond contrast-enhancing boundaries in newly diagnosed glioblastoma multiforme: is it useful and safe? A single institution retrospective experience. J Neurooncol 135:129–139. https://doi.org/10.1007/s11060-017-2559-9

    Article  PubMed  Google Scholar 

  31. 31.

    Hamada S, Abou-Zeid A (2016) Anatomical resection in glioblastoma: extent of resection and its impact on duration of survival. Egypt J Neurol Psychiatry Neurosurg. https://doi.org/10.4103/1110-1083.192655

    Article  Google Scholar 

  32. 32.

    Eypoglu IY, Hore N, Merkel A et al (2016) Supra-complete surgery via dual intraoperative visualization approach (DiVA) prolongs patient survival in glioblastoma. Oncotarget 7:25755–25768

    Article  Google Scholar 

  33. 33.

    Aldave G, Tejada S, Pay E et al (2013) Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic acid-guided surgery. Neurosurgery 72:915–920. https://doi.org/10.1227/NEU.0b013e31828c3974

    Article  PubMed  Google Scholar 

  34. 34.

    Grossman R, Shimony N, Shir D et al (2017) Dynamics of FLAIR volume changes in glioblastoma and prediction of survival. Ann Surg Oncol 24:794–800. https://doi.org/10.1245/s10434-016-5635-z

    Article  PubMed  Google Scholar 

  35. 35.

    Binabaj MM, Bahrami A, ShahidSales S et al (2018) The prognostic value of MGMT promoter methylation in glioblastoma: a meta-analysis of clinical trials. J Cell Physiol 233:378–386. https://doi.org/10.1002/jcp.25896

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Chen JR, Yao Y, Xu HZ, Qin ZY (2016) Isocitrate dehydrogenase (IDH)1/2 mutations as prognostic markers in patients with glioblastomas. Med (United States) 95:e2583. https://doi.org/10.1097/MD.0000000000002583

    CAS  Article  Google Scholar 

  37. 37.

    Yang P, Zhang W, Wang Y et al (2015) IDH mutation and MGMT promoter methylation in glioblastoma: results of a prospective registry. Oncotarget 6:40896–40906

    Article  Google Scholar 

  38. 38.

    Zou P, Xu H, Chen P et al (2013) IDH1/IDH2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis. PLoS ONE 8:e68782. https://doi.org/10.1371/journal.pone.0068782

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Beiko J, Suki D, Hess KR et al (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. https://doi.org/10.1093/neuonc/not159

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Chaichana K, Zadnik P, Weingart J et al (2013) Multiple resections for patients with glioblastoma: prolonging survival. J Neurosurg 118(4):812–920. https://doi.org/10.3171/2012.0.JNS1277

    Article  PubMed  Google Scholar 

  41. 41.

    Perrini P, Gambacciani C, Weiss A et al (2017) Survival outcomes following repeat surgery for recurrent glioblastoma: a single-center retrospective analysis. J Neurooncol 131(3):585–591. https://doi.org/10.1007/s11060-016-2330-7

    CAS  Article  PubMed  Google Scholar 

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M.L. obtains research support from Aegenus, Accuray, Bristol-Myer Squibb and DNAtrix.

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Correspondence to Debraj Mukherjee.

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C.B. is a consultant for Depuy-Synthes and M.L. is a consult for Tocagen, SQ Technologies, Stryker, and Baxter.

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Jackson, C., Choi, J., Khalafallah, A.M. et al. A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma. J Neurooncol 148, 419–431 (2020). https://doi.org/10.1007/s11060-020-03556-y

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  • Extent of resection
  • EOR
  • Glioblastoma
  • GBM
  • Supratotal resection
  • T2 FLAIR