Recurrent glioblastoma

Recurrent glioblastoma (GBM)

Glioblastoma has an unfavorable prognosis mainly due to its high propensity for tumor recurrence. It has been suggested that GBM recurrence is inevitable after a median survival time of 32 to 36 weeks 1) 2).

Natural history

The natural history of recurrent GBM, is largely undefined for the following reasons:

1) Lack of uniform definition and criteria for tumor recurrence

2) Institutional variability in treatment philosophy

3) The heterogeneous nature of the disease, including location of recurrence and distinct mechanisms believed to contribute to known subtypes of GBM.

The criteria used to define recurrent glioblastoma GBM remain ambiguous due to the varied presentation of new lesions. First, the infiltrative nature of GBM cells makes it difficult to eliminate microscopic disease despite macroscopic gross-total resection. Studies have shown that GBM recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion 3) 4) 5).


One of the factors that cause recurrence is the strong migratory capacity of GBM cells. Wanibuchi et al., reported that actin, alpha, cardiac muscle 1 (ACTC1) could serve as a marker to detect GBM migration in clinical cases 6).

Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells (CSC) that contributes to tumor propagation, maintenance, and treatment resistance.

These cells are associated with vascular niches which regulate glioma stem cells (GSC) self-renewal and survival.

Studies suggest that while blood vessels support glioma stem cells, these tumor cells in turn may regulate and contribute to the tumor vasculature by transdifferentiating into endothelial cells directly or through the secretion of regulatory growth factors such as vascular endothelial growth factor (VEGF) and hepatoma derived growth factor (HDGF) 7).

Intratumoral heterogeneity and the presence of these CSCs may contribute to the treatment-resistant nature of GBM and its propensity to recur in patients 8) 9).


Recurrent Glioblastoma Diagnosis.

Differential Diagnosis

Recurrent Glioblastoma Differential Diagnosis.


see Recurrent glioblastoma treatment.


see Recurrent glioblastoma outcome.

Case series

see Recurrent glioblastoma case series.

Case reports

A 52-year-old woman was admitted for management of recurrent glioblastoma. After tumor removal surgery, the patient experienced sustained CSF leakage from the wound despite reparative attempts. The plastic surgery team performed wound repair procedure after remnant tumor removal by the neurosurgery team. Acellular dermal matrix was applied over the mesh plate to prevent CSF leakage and the postoperative status of the patient was evaluated. No sign of CSF leakage was found in the immediate postoperative period. After 3 years, there were no complications including CSF leakage, wound dehiscence, and infection. Lee et al. hereby propose this method as a feasible therapeutic alternative for preventing CSF leakage in patients experiencing wound problem after neurosurgical procedures 10).

Corns et al. describe the case of a patient with recurrent glioblastoma encroaching on Broca’s areaGross total resection of the tumour was achieved by combining two techniques, awake craniotomy to prevent damage to eloquent brain and 5 aminolevulinic acid fluorescence guided resection to maximise the extent of tumour resection. This technique led to gross total resection of all T1contrast enhancement tumour with the avoidance of neurological deficit. They recommend this technique in patients when awake surgery can be tolerated and gross total resection is the aim of surgery 11).



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Jhaveri N, Chen TC, Hofman FM. Tumor vasculature and glioma stem cells: contributions to glioma progression. Cancer Lett. 2014 Dec 16. pii: S0304-3835(14)00783-6. doi: 10.1016/j.canlet.2014.12.028. [Epub ahead of print] PubMed PMID: 25527451.

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Nickel GC, Barnholtz-Sloan J, Gould MP, McMahon S, Cohen A, Adams MD, et al: Characterizing mutational heterogeneity in a glioblastoma patient with double recurrence. PLoS ONE 7:e35262, 2012

Lee H, Eom YS, Pyon JK. A method to prevent cerebrospinal fluid leakage: Reinforcing acellular dermal matrix. Arch Craniofac Surg. 2020 Feb;21(1):45-48. doi: 10.7181/acfs.2019.00535. Epub 2020 Feb 20. PubMed PMID: 32126620.

Corns R, Mukherjee S, Johansen A, Sivakumar G. 5-aminolevulinic acid guidance during awake craniotomy to maximise extent of safe resection of glioblastoma multiforme. BMJ Case Rep. 2015 Jul 15;2015. pii: bcr2014208575. doi: 10.1136/bcr-2014-208575. PubMed PMID: 26177997.

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