CC BY 4.0 · J Neurol Surg A Cent Eur Neurosurg 2024; 85(01): 074-087
DOI: 10.1055/s-0043-1769128
Review Article

Prognostic Factors and Resectability Predictors in Insular Gliomas: A Systematic Review

1   Division of Medicine, University College London Medical School, London, United Kingdom of Great Britain and Northern Ireland
Niraj S. Kumar
1   Division of Medicine, University College London Medical School, London, United Kingdom of Great Britain and Northern Ireland
› Author Affiliations


Background Insular gliomas (INGs) remain a surgically intimidating glioma subgroup encased by eloquent cortical parcels and white matter language tracts, and traversed by multiple middle cerebral artery branches. The predictive power of prognostic factors affecting overall survival (OS), progression-free survival (PFS), and resectability of INGs remain disputed. This comprehensive systematic review analyses prognostic factors and resectability predictors of INGs substantiating pragmatic management options.

Materials and Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and the Cochrane Handbook of Systematic Reviews of Interventions guidelines. The PubMed, MEDLINE, and Embase databases were searched in April 2022. All clinical studies with ≥10 patients harboring INGs with any intervention and reporting predictors of OS, PFS, and tumor resectability in INGs were included. Molecular ING prognosticators were also included. Studies combining insular and other gliomas analysis, case studies, experimental and animal studies, conference abstracts, letters to the editor, and articles in other languages were excluded.

Results Of the 2,384 articles returned, 27 fulfilled the inclusion criteria totaling 1,985 patients. The review yielded 18 OS and 17 PFS prognosticators. These were classified as preoperative (radiologic; clinical), intraoperative, and postoperative (molecular; histopathologic; clinical) prognosticators. In addition, 21 resectability predictors were categorized as preoperative (radiologic; clinical), intraoperative (surgical approach and assistive technology), and postoperative (histopathologic; clinical). The quality assessment revealed 24/27 studies had low risk of bias. One study with moderate and two studies with high risk of bias were included.

Conclusion Negative prognosticators reported in ≥2 studies included putaminal or paralimbic involvement and higher tumor grade, while seizures at presentation, isocitrate dehydrogenase (IDH) mutation, increased extent of resection, and higher Karnofsky Performance Status preoperatively and at 3 months postoperation were positive prognosticators. Resectability predictors reported in ≥2 studies included the positive predictors of zone I/zone IV tumor location and intraoperative imaging use and the negative predictor of encased lenticulostriate arteries. Paralimbic INGs are not a single entity with homogeneous prognosis. Integration of identified prognosticators in a prospective trial to devise a grading system for INGs can improve clinical decision-making.

Publication History

Received: 08 January 2023

Accepted: 03 April 2023

Article published online:
24 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Duffau H, Capelle L. Preferential brain locations of low-grade gliomas. Cancer 2004; 100 (12) 2622-2626
  • 2 Acer N, Turgut M. . Measurements of the insula volume using MRI. In: Turgut M, Yurttaş C, Tubbs R, eds. Island of Reil (Insula) in the Human Brain. Cham: Springer; 2018:101–111
  • 3 Sanai N, Polley M-Y, Berger MS. Insular glioma resection: assessment of patient morbidity, survival, and tumor progression. J Neurosurg 2010; 112 (01) 1-9
  • 4 Johannesen TB, Langmark F, Lote K. Progress in long-term survival in adult patients with supratentorial low-grade gliomas: a population-based study of 993 patients in whom tumors were diagnosed between 1970 and 1993. J Neurosurg 2003; 99 (05) 854-862
  • 5 Singh A, Das KK, Khatri D. et al. Insular glioblastoma: surgical challenges, survival outcomes and prognostic factors. Br J Neurosurg 2023; 37 (01) 26-34
  • 6 Jiang H, Cui Y, Wang J, Lin S. Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system. Oncotarget 2017; 8 (12) 20354-20361
  • 7 Vergani F, Martino J, Gozé C, Rigau V, Duffau H. World Health Organization grade II gliomas and subventricular zone: anatomic, genetic, and clinical considerations. Neurosurgery 2011; 68 (05) 1293-1298 , discussion 1298–1299
  • 8 Shofty B, Artzi M, Ben Bashat D. et al. MRI radiomics analysis of molecular alterations in low-grade gliomas. Int J CARS 2018; 13 (04) 563-571
  • 9 Metellus P, Coulibaly B, Colin C. et al. Triple-negative, low-grade gliomas: a highly aggressive tumor with dismal prognosis. J Clin Oncol 2011; 29 (15, suppl): 2023-2023
  • 10 Metellus P, Coulibaly B, Colin C. et al. Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis. Acta Neuropathol 2010; 120 (06) 719-729
  • 11 Gozé C, Rigau V, Gibert L, Maudelonde T, Duffau H. Lack of complete 1p19q deletion in a consecutive series of 12 WHO grade II gliomas involving the insula: a marker of worse prognosis?. J Neurooncol 2009; 91 (01) 1-5
  • 12 Roelz R, Strohmaier D, Jabbarli R. et al. Residual tumor volume as best outcome predictor in low grade glioma: a nine-years near-randomized survey of surgery vs. Biopsy. Sci Rep 2016; 6: 32286
  • 13 Smith JS, Chang EF, Lamborn KR. et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 2008; 26 (08) 1338-1345
  • 14 Leroy H-A, Delmaire C, Le Rhun E, Drumez E, Lejeune J-P, Reyns N. High-field intraoperative MRI and glioma surgery: results after the first 100 consecutive patients. Acta Neurochir (Wien) 2019; 161 (07) 1467-1474
  • 15 Zhang CH. Variations in management of low grade gliomas across UK neurosurgical units. Neuro-oncol 2014
  • 16 Kim Y-H, Kim C-Y. Current surgical management of insular gliomas. Neurosurg Clin N Am 2012; 23 (02) 199-206, vii
  • 17 Hervey-Jumper SL, Berger MS. Insular glioma surgery: an evolution of thought and practice. J Neurosurg 2019; 130 (01) 9-16
  • 18 Higgins JPT, Altman DG, Gøtzsche PC. et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928-d5928
  • 19 Moher D, Shamseer L, Clarke M. et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Rev Esp Nutr Humana Diet 2016; 20 (02) 148-160
  • 20 Shamseer L, Moher D, Clarke M. et al; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 350: g7647
  • 21 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 (06) 803-820
  • 22 Kawaguchi T, Kumabe T, Saito R. et al. Practical surgical indicators to identify candidates for radical resection of insulo-opercular gliomas. J Neurosurg 2014; 121 (05) 1124-1132
  • 23 Wang Y, Wang Y, Fan X. et al. Putamen involvement and survival outcomes in patients with insular low-grade gliomas. J Neurosurg 2017; 126 (06) 1788-1794
  • 24 Eseonu CI, ReFaey K, Garcia O, Raghuraman G, Quinones-Hinojosa A. Volumetric analysis of extent of resection, survival, and surgical outcomes for insular gliomas. World Neurosurg 2017; 103: 265-274
  • 25 Compes P, Tabouret E, Etcheverry A. et al. Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016. J Neurooncol 2019; 142 (03) 511-520
  • 26 Tang C, Zhang ZY, Chen LC. et al. Subgroup characteristics of insular low-grade glioma based on clinical and molecular analysis of 42 cases. J Neurooncol 2016; 126 (03) 499-507
  • 27 Hameed NUF, Qiu T, Zhuang D. et al. Transcortical insular glioma resection: clinical outcome and predictors. J Neurosurg 2018; 131 (03) 706-716
  • 28 Ghaffari-Rafi A, Samandouras G. Effect of treatment modalities on progression-free survival and overall survival in molecularly subtyped world health organization grade II diffuse gliomas: a systematic review. World Neurosurg 2020; 133: 366-380.e2
  • 29 Microsoft Excel [Computer Software] Version 1910. Microsoft Corporation; 2020. Accessed April 30, 2022. Available at:
  • 30 Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med 2013; 158 (04) 280-286
  • 31 Hayden JA, Côté P, Bombardier C. Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med 2006; 144 (06) 427-437
  • 32 Grooten WJA, Tseli E, Äng BO. et al. Elaborating on the assessment of the risk of bias in prognostic studies in pain rehabilitation using QUIPS-aspects of interrater agreement. Diagn Progn Res 2019; 3 (01) 5
  • 33 Simon M, Neuloh G, von Lehe M, Meyer B, Schramm J. Insular gliomas: the case for surgical management. J Neurosurg 2009; 110 (04) 685-695
  • 34 Skrap M, Mondani M, Tomasino B. et al. Surgery of insular nonenhancing gliomas: volumetric analysis of tumoral resection, clinical outcome, and survival in a consecutive series of 66 cases. Neurosurgery 2012; 70 (05) 1081-1093 , discussion 1093–1094
  • 35 Capizzano AA, Kirby P, Moritani T. Limbic tumors of the temporal lobe: radiologic-pathologic correlation. Clin Neuroradiol 2015; 25 (02) 127-135
  • 36 Schätz CR, Kreth FW, Faist M, Warnke PC, Volk B, Ostertag CB. Interstitial 125-iodine radiosurgery of low-grade gliomas of the insula of Reil. Acta Neurochir (Wien) 1994; 130 (1–4): 80-89
  • 37 Sughrue M, Bonney PA, Burks JD. et al. Multilobar insular-involving gliomas: results with hyperaggressive resection. Cureus 2017; 9 (08) e1623
  • 38 Gozé C, Mansour L, Rigau V, Duffau H. Distinct IDH1/IDH2 mutation profiles in purely insular versus paralimbic WHO grade II gliomas. J Neurosurg 2013; 118 (04) 866-872
  • 39 Martino J, Mato D, de Lucas EM. et al. Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas: implications for surgical approach to the insular region. J Neurosurg 2015; 123 (04) 1081-1092
  • 40 Morshed RA, Young JS, Han SJ, Hervey-Jumper SL, Berger MS. Perioperative outcomes following reoperation for recurrent insular gliomas. J Neurosurg 2018; 131 (02) 467-473
  • 41 Chen L-F, Yang Y, Ma X-D. et al. Optimizing the extent of resection and minimizing the morbidity in insular high-grade glioma surgery by high-field intraoperative MRI guidance. Turk Neurosurg 2017; 27 (05) 696-706
  • 42 Zhuang D-X, Wu J-S, Yao C-J. et al. Intraoperative multi-information-guided resection of dominant-sided insular gliomas in a 3-T intraoperative magnetic resonance imaging integrated neurosurgical suite. World Neurosurg 2016; 89: 84-92
  • 43 Barbosa BJAP, Dimostheni A, Teixeira MJ, Tatagiba M, Lepski G. Insular gliomas and the role of intraoperative assistive technologies: results from a volumetry-based retrospective cohort. Clin Neurol Neurosurg 2016; 149: 104-110
  • 44 Pitskhelauri D, Bykanov A, Konovalov A. et al. Transsylvian insular glioma surgery: new classification system, clinical outcome in a consecutive series of 79 cases. Oper Neurosurg (Hagerstown) 2021; 20 (06) 541-548
  • 45 Wu A, Aldape K, Lang FF. High rate of deletion of chromosomes 1p and 19q in insular oligodendroglial tumors. J Neurooncol 2010; 99 (01) 57-64
  • 46 Ozyurt E, Kaya AH, Tanriverdi T, Tuzgen S, Oguzoglu SA, Hanefioglu MH. New classification for insular tumors and surgical results of 40 patients. Neurosurg Q 2003; 13 (02) 138-148
  • 47 Moshel YA, Marcus JDS, Parker EC, Kelly PJ. Resection of insular gliomas: the importance of lenticulostriate artery position. J Neurosurg 2008; 109 (05) 825-834
  • 48 Przybylowski CJ, Baranoski JF, So VM, Wilson J, Sanai N. Surgical morbidity of transsylvian versus transcortical approaches to insular gliomas. J Neurosurg 2019; 132 (06) 1731-1738
  • 49 Li Z, Li G, Liu Z. et al. Transcortical approach for insular gliomas: a series of 253 patients. J Neurooncol 2020; 147 (01) 59-66
  • 50 Rossi M, Gay L, Conti Nibali M. et al. Challenging giant insular gliomas with brain mapping: evaluation of neurosurgical, neurological, neuropsychological, and quality of life results in a large mono-institutional series. Front Oncol 2021; 11: 629166
  • 51 Rao AS, Thakar S, Sai Kiran NA, Aryan S, Mohan D, Hegde AS. Analogous three-dimensional constructive interference in steady state sequences enhance the utility of three-dimensional time of flight magnetic resonance angiography in delineating lenticulostriate arteries in insular gliomas: evidence from a prospective clinicoradiologic analysis of 48 patients. World Neurosurg 2018; 109: e426-e433
  • 52 Benet A, Hervey-Jumper SL, Sánchez JJG, Lawton MT, Berger MS. Surgical assessment of the insula. Part 1: surgical anatomy and morphometric analysis of the transsylvian and transcortical approaches to the insula. J Neurosurg 2016; 124 (02) 469-481
  • 53 Saito R, Kumabe T, Inoue T. et al. Magnetic resonance imaging for preoperative identification of the lenticulostriate arteries in insular glioma surgery. Technical note. J Neurosurg 2009; 111 (02) 278-281
  • 54 Gilbertson RJ, Gutmann DH. Tumorigenesis in the brain: location, location, location. Cancer Res 2007; 67 (12) 5579-5582
  • 55 Lai A, Kharbanda S, Pope WB. et al. Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J Clin Oncol 2011; 29 (34) 4482-4490
  • 56 Wang Y, Zhang T, Li S. et al. Anatomical localization of isocitrate dehydrogenase 1 mutation: a voxel-based radiographic study of 146 low-grade gliomas. Eur J Neurol 2015; 22 (02) 348-354
  • 57 Martino J, Vergani F, Robles SG, Duffau H. New insights into the anatomic dissection of the temporal stem with special emphasis on the inferior fronto-occipital fasciculus: implications in surgical approach to left mesiotemporal and temporoinsular structures. Neurosurgery 2010; 66 (3, Suppl Operative): 4-12
  • 58 Wang DD, Hervey-Jumper SL, Chang EF. Seizure outcome after surgical resection of insular glioma. Clin Neurosurg 2017; 64 (Supplement 1): 290
  • 59 Pallud J, Audureau E, Blonski M. et al. Epileptic seizures in diffuse low-grade gliomas in adults. Brain 2014; 137 (Pt 2): 449-462
  • 60 Kerkhof M, Vecht CJ. Seizure characteristics and prognostic factors of gliomas. Epilepsia 2013; 54 (Suppl 9): 12-17
  • 61 Phan K, Ng W, Lu VM. et al. Association between IDH1 and IDH2 mutations and preoperative seizures in patients with low-grade versus high-grade glioma: a systematic review and meta-analysis. World Neurosurg 2018; 111: e539-e545
  • 62 Chen H, Judkins J, Thomas C. et al. Mutant IDH1 and seizures in patients with glioma. Neurology 2017; 88 (19) 1805-1813
  • 63 Still MEH, Roux A, Huberfeld G. et al. Extent of resection and residual tumor thresholds for postoperative total seizure freedom in epileptic adult patients harboring a supratentorial diffuse low-grade glioma. Neurosurgery 2019; 85 (02) E332-E340
  • 64 McGirt MJ, Mukherjee D, Chaichana KL, Than KD, Weingart JD, Quinones-Hinojosa A. Association of surgically acquired motor and language deficits on overall survival after resection of glioblastoma multiforme. Neurosurgery 2009; 65 (03) 463-469 , discussion 469–470
  • 65 Yaşargil MG, von Ammon K, Cavazos E, Doczi T, Reeves JD, Roth P. Tumours of the limbic and paralimbic systems. Acta Neurochir (Wien) 1992; 118 (1–2): 40-52