Neuro-Oncology Reviews

Volume 28 Number 25 - Special issue*
30 September 2026

Home > Publications > Neuro-Oncology Reviews > Volume 28, Year 2026 > Number 25, 30 September

The effects of surgery on glioblastoma progression and recurrence

1. The clinical effects of cytoreduction: extent of resection, residual tumour volume, overall survival, and progression-free survival.

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.
A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival.
J Neurosurg. 2001 Aug;95(2):190-8. doi: 10.3171/jns.2001.95.2.0190. PMID: 11780887. ˍ

Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS.
An extent of resection threshold for newly diagnosed glioblastomas.
J Neurosurg. 2011 Mar 18;115(1):3-8. doi: 10.3171/2011.2.jns10998. PMID: 21417701. ˍ

Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH, Vogelbaum MA.
Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma.
J Neurosurg. 2014 Sep 5;121(5):1115-23. doi: 10.3171/2014.7.JNS132449. PMID: 25192475. ˍ

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.
Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma.
Neuro Oncol. 2013 Nov 26;16(1):113-22. doi: 10.1093/neuonc/not137. PMID: 24285550. ˍ

Molinaro AM, Hervey-Jumper S, Morshed RA, Young J, Han SJ, Chunduru P, Zhang Y, Phillips JJ, Shai A, Lafontaine M, Crane J, Chandra A, Flanigan P, Jahangiri A, Cioffi G, Ostrom Q, Anderson JE, Badve C, Barnholtz-Sloan J, Sloan AE, Erickson BJ, Decker PA, Kosel ML, LaChance D, Eckel-Passow J, Jenkins R, Villanueva-Meyer J, Rice T, Wrensch M, Wiencke JK, Oberheim Bush NA, Taylor J, Butowski N, Prados M, Clarke J, Chang S, Chang E, Aghi M, Theodosopoulos P, McDermott M, Berger MS.
Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma.
JAMA Oncol. 2020 Apr 1;6(4):495-503. doi: 10.1001/jamaoncol.2019.6143. PMID: 32027343. ˍ

Gerritsen JKW, Zwarthoed RH, Kilgallon JL, Nawabi NL, Versyck G, Jessurun CAC, Pruijn KP, Fisher FL, Larivière E, Solie L, Mekary RA, Satoer DD, Schouten JW, Bos EM, Kloet A, Tewarie RN, Smith TR, Dirven CMF, De Vleeschouwer S, Vincent AJPE, Broekman MLD.
Impact of maximal extent of resection on postoperative deficits, patient functioning, and survival within clinically important glioblastoma subgroups.
Neuro Oncol. 2022 Nov 24;25(5):958-972. doi: 10.1093/neuonc/noac255. PMID: 36420703. ˍ

Goldbrunner R, Foroglou N, Signorelli F, Schucht P, Jakola AS, Minniti G, Rola R, Renovanz M, Preusser M, Furtner J, Grossman R, Mawrin C, Demetriades A, Weller M, Simon M.
EANS-EANO guidelines on the extent of resection in gliomas.
Neuro Oncol. 2025 Sep 17;28(1):38-54. doi: 10.1093/neuonc/noaf217. PMID: 40973061. ˍ

2. Surgery-induced changes in the tumour microenvironment: tissue injury, inflammatory signalling, angiogenesis, wound healing, and immune responses

Okolie O, Bago JR, Schmid RS, Irvin DM, Bash RE, Miller CR, Hingtgen SD.
Reactive astrocytes potentiate tumor aggressiveness in a murine glioma resection and recurrence model.
Neuro Oncol. 2016 Jun 13;18(12):1622-1633. doi: 10.1093/neuonc/now117. PMID: 27298311. ˍ

Knudsen AM, Halle B, Cédile O, Burton M, Baun C, Thisgaard H, Anand A, Hubert C, Thomassen M, Michaelsen SR, Olsen BB, Dahlrot RH, Bjerkvig R, Lathia JD, Kristensen BW.
Surgical resection of glioblastomas induces pleiotrophin-mediated self-renewal of glioblastoma stem cells in recurrent tumors.
Neuro Oncol. 2021 Dec 29;24(7):1074-1087. doi: 10.1093/neuonc/noab302. PMID: 34964899. ˍ

Bastiancich C, Snacel-Fazy E, Fernandez S, Robert S, Stacchini R, Plantureux L, Boissonneau S, Testud B, Guillet B, Debarbieux F, Luche H, Figarella-Branger D, Estève MA, Tabouret E, Tchoghandjian A.
Tailoring glioblastoma treatment based on longitudinal analysis of post-surgical tumor microenvironment.
J Exp Clin Cancer Res. 2024 Nov 28;43(1):311. doi: 10.1186/s13046-024-03231-4. PMID: 39605004. ˍ

Huang W, Li J, Geng X, Li S, Zou Y, Li Y, Jing C, Yu H.
The Reactive Astrocytes After Surgical Brain Injury Potentiates the Migration, Invasion, and Angiogenesis of C6 Glioma.
World Neurosurg. 2022 Oct 21;168:e595-e606. doi: 10.1016/j.wneu.2022.10.064. PMID: 36280046˰ ˍ

3. Cellular mechanisms of postoperative regrowth: glioma stem-like cells, invasion, cellular plasticity, and treatment resistance

Weil S, Osswald M, Solecki G, Grosch J, Jung E, Lemke D, Ratliff M, Hänggi D, Wick W, Winkler F.
Tumor microtubes convey resistance to surgical lesions and chemotherapy in gliomas.
Neuro Oncol. 2017 Apr 17;19(10):1316-1326. doi: 10.1093/neuonc/nox070. PMID: 28419303. ˍ

Dirkse A, Golebiewska A, Buder T, Nazarov PV, Muller A, Poovathingal S, Brons NHC, Leite S, Sauvageot N, Sarkisjan D, Seyfrid M, Fritah S, Stieber D, Michelucci A, Hertel F, Herold-Mende C, Azuaje F, Skupin A, Bjerkvig R, Deutsch A, Voss-Böhme A, Niclou SP.
Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment.
Nat Commun. 2019 Apr 16;10(1):1787. doi: 10.1038/s41467-019-09853-z. PMID: 30992437. ˍ

Minata M, Audia A, Shi J, Lu S, Bernstock J, Pavlyukov MS, Das A, Kim SH, Shin YJ, Lee Y, Koo H, Snigdha K, Waghmare I, Guo X, Mohyeldin A, Gallego-Perez D, Wang J, Chen D, Cheng P, Mukheef F, Contreras M, Reyes JF, Vaillant B, Sulman EP, Cheng SY, Markert JM, Tannous BA, Lu X, Kango-Singh M, Lee LJ, Nam DH, Nakano I, Bhat KP.
Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation.
Cell Rep. 2019 Feb 12;26(7):1893-1905.e7. doi: 10.1016/j.celrep.2019.01.076. PMID: 30759398. ˍ

Knudsen AM, Halle B, Cédile O, Burton M, Baun C, Thisgaard H, Anand A, Hubert C, Thomassen M, Michaelsen SR, Olsen BB, Dahlrot RH, Bjerkvig R, Lathia JD, Kristensen BW.
Surgical resection of glioblastomas induces pleiotrophin-mediated self-renewal of glioblastoma stem cells in recurrent tumors.
Neuro Oncol. 2021 Dec 29;24(7):1074-1087. doi: 10.1093/neuonc/noab302. PMID: 34964899. ˍ

Castellan M, Guarnieri A, Fujimura A, Zanconato F, Battilana G, Panciera T, Sladitschek HL, Contessotto P, Citron A, Grilli A, Romano O, Bicciato S, Fassan M, Porcù E, Rosato A, Cordenonsi M, Piccolo S.
Single-cell analyses reveal YAP/TAZ as regulators of stemness and cell plasticity in Glioblastoma.
Nat Cancer. 2020 Dec 7;2(2):174-188. doi: 10.1038/s43018-020-00150-z. PMID: 33644767. ˍ

4. Patterns and timing of recurrence: local versus distant recurrence, the resection margin, molecular heterogeneity, and the influence of radiochemotherapy

van Solinge TS, Nieland L, Chiocca EA, Broekman MLD.
Advances in local therapy for glioblastoma - taking the fight to the tumour.
Nat Rev Neurol. 2022 Mar 11;18(4):221-236. doi: 10.1038/s41582-022-00621-0. PMID: 35277681. ˍ

Kim H, Zheng S, Amini SS, Virk SM, Mikkelsen T, Brat DJ, Grimsby J, Sougnez C, Muller F, Hu J, Sloan AE, Cohen ML, Van Meir EG, Scarpace L, Laird PW, Weinstein JN, Lander ES, Gabriel S, Getz G, Meyerson M, Chin L, Barnholtz-Sloan JS, Verhaak RG.
Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.
Genome Res. 2015 Feb 3;25(3):316-27. doi: 10.1101/gr.180612.114. PMID: 25650244. ˍ

Vollmuth P, Karschnia P, Sahm F, Park YW, Ahn SS, Jain R.
A Radiologist's Guide to IDH-Wildtype Glioblastoma for Efficient Communication With Clinicians: Part II-Essential Information on Post-Treatment Imaging.
Korean J Radiol. 2025 Jan 10;26(4):368-389. doi: 10.3348/kjr.2024.0983. PMID: 40015559. ˍ

Zhang T, Chen N, Wang J, Yu SC.
Research advances in the recurrence patterns of glioblastoma.
Biochim Biophys Acta Rev Cancer. 2026 Aug 15;1881(5):189681. doi: 10.1016/j.bbcan.2026.189681. PMID: 42603639˰ ˍ

Chojak R, Drewes NB, Slychan K, Lukas RV.
Spatial patterns of progression in reported glioblastoma cohorts after upfront chemoradiation and salvage therapy: a systematic review and meta-analysis.
J Neurooncol. 2026 Jul 30;179(1):20. doi: 10.1007/s11060-026-05734-w. PMID: 42530690. ˍ

Feldheim JA, Grieger J, Schmidt T, Oster C, Feldheim JJ, Wepner P, Hattingen E, Hagemann C, Sure U, Herrlinger U, Stuschke M, Scheffler B, Deuschl C, Kleinschnitz C, Lazaridis L, Kebir S, Schäfer N, Glas M.
Regrowth Patterns in Glioblastoma--Survival and Predictors.
Cancer Med. 2026 Apr 2;15(4):e71764. doi: 10.1002/cam4.71764. PMID: 41927498. ˍ

5. Translational implications: maximal safe resection, supramarginal surgery, intraoperative technologies, local drug delivery, and strategies to target the postoperative microenvironment

Geens W, Rizani G, Del Gaudio N, Buyck F, Van Gestel F, Bruneau M, Neyns B, Duerinck J.
Extent of resection and its association with overall survival in newly diagnosed IDH wildtype glioblastoma treated with concomitant radiochemotherapy: a systematic review and meta-analysis.
Brain Spine. 2025 Nov 21;5:105867. doi: 10.1016/j.bas.2025.105867. PMID: 41450869. ˍ

John S, Khaliq T, Khan J.
Survival Impact of Supramarginal Resection According to MGMT Promoter Methylation Status in Glioblastoma: A Systematic Review and Meta-analysis.
J Pak Med Assoc. 2026 Sep 30;76(Suppl 1)(9):S30. doi: 10.47391/JPMA-7ANOS-ABS-29. PMID: 42817692. ˍ

Chaulagain D, Smolanka V, Smolanka A, Qureshi K, Yangi K, Devnyak O, Chaurasia B.
Efficacy Assessment of Supramarginal Resection Versus Gross Total Resection in Glioblastoma: A Systematic Literature Review and Meta-Analysis.
Brain Behav. 2026 Apr 16;16(4):e71424. doi: 10.1002/brb3.71424. PMID: 41992815. ˍ

Jenkinson MD, Barone DG, Bryant A, Vale L, Bulbeck H, Lawrie TA, Hart MG, Watts C.
Intraoperative imaging technology to maximise extent of resection for glioma.
Cochrane Database Syst Rev. 2018 Jan 22;1(1):CD012788. doi: 10.1002/14651858.CD012788.pub2. PMID: 29355914. ˍ

Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group.
Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.
Lancet Oncol. 2006 Apr 12;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9. PMID: 16648043. Trial registration ID: NCT00241670. ˍ

Kartal A, Kim MJ, Chanbour H, Tsehay Y, Alomari S.
Limitations of Gliadel Wafers and Strategies for Next-Generation Local Delivery Systems for Glioblastoma.
Cancers (Basel). 2026 Mar 11;18(6):907. doi: 10.3390/cancers18060907. PMID: 41899511. ˍ

Naik A, Smith EJ, Barreau A, Nyaeme M, Cramer SW, Najafali D, Krist DT, Arnold PM, Hassaneen W.
Comparison of fluorescein sodium, 5-ALA, and intraoperative MRI for resection of high-grade gliomas: A systematic review and network meta-analysis.
J Clin Neurosci. 2022 Feb 23;98:240-247. doi: 10.1016/j.jocn.2022.02.028. PMID: 35219089. ˍ

6. Critical assessment of the evidence, causal inference, and priorities for future research

Knudsen AM, Halle B, Cédile O, Burton M, Baun C, Thisgaard H, Anand A, Hubert C, Thomassen M, Michaelsen SR, Olsen BB, Dahlrot RH, Bjerkvig R, Lathia JD, Kristensen BW.
Surgical resection of glioblastomas induces pleiotrophin-mediated self-renewal of glioblastoma stem cells in recurrent tumors.
Neuro Oncol. 2021 Dec 29;24(7):1074-1087. doi: 10.1093/neuonc/noab302. PMID: 34964899. ˍ

Bastiancich C, Snacel-Fazy E, Fernandez S, Robert S, Stacchini R, Plantureux L, Boissonneau S, Testud B, Guillet B, Debarbieux F, Luche H, Figarella-Branger D, Estève MA, Tabouret E, Tchoghandjian A.
Tailoring glioblastoma treatment based on longitudinal analysis of post-surgical tumor microenvironment.
J Exp Clin Cancer Res. 2024 Nov 28;43(1):311. doi: 10.1186/s13046-024-03231-4. PMID: 39605004. ˍ

Van Nieuwenhuyze J, Ziani Zeryouh A, De Vleeschauwer S, Riva M, Coosemans A.
Tumor resection in glioblastoma mouse models: Surgical techniques and translational potential.
Neurooncol Adv. 2026 Feb 16;8(1):vdag044. doi: 10.1093/noajnl/vdag044. PMID: 41890360. ˍ

Wang M, Bergès R, Malfanti A, Préat V, Bastiancich C.
Local delivery of doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma.
Drug Deliv Transl Res. 2023 Oct 27;14(12):3322-3338. doi: 10.1007/s13346-023-01456-y. PMID: 37889402. ˍ

Abdelnabi D, Lastakchi S, Watts C, Atkins H, Hingtgen S, Valdivia A, McConville C.
Local administration of irinotecan using an implantable drug delivery device stops high-grade glioma tumor recurrence in a glioblastoma tumor model.
Drug Deliv Transl Res. 2024 Feb 6;14(11):3070-3088. doi: 10.1007/s13346-024-01524-x. PMID: 38319555. ˍ

Pesce C, Rodella G, Fragassi A, Garofalo M, Salmaso S, Caliceti P, Gallez B, Malfanti A.
Localized treatment of glioblastoma: a review of clinical strategies and advances in drug delivery systems.
Nanomedicine (Lond). 2025 Aug 28;20(20):2571-2599. doi: 10.1080/17435889.2025.2550239. PMID: 40874730. ˍ

*AI assistance: This issue was prepared with the assistance of ChatGPT (OpenAI). The editor is solely responsible for the final content.