Glioblastoma recurrence

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

Less than 10% of recurrent gliomas recur away from the original tumor site 3).

A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections 4).

The natural history of recurrent Glioblastoma, 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 Glioblastoma.

The criteria used to define recurrent glioblastoma Glioblastoma remain ambiguous due to the varied presentation of new lesions. First, the infiltrative nature of Glioblastoma cells makes it difficult to eliminate microscopic disease despite macroscopic gross-total resection. Studies have shown that Glioblastoma recurrence most often occurs in the form of a local continuous growth within 2 to 3 cm from the border of the original lesion 5) 6) 7).

One of the factors that cause recurrence is the strong migratory capacity of Glioblastoma cells. Wanibuchi et al., reported that actin, alpha, cardiac muscle 1 (ACTC1) could serve as a marker to detect Glioblastoma migration in clinical cases 8).

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) 9).

Intratumoral heterogeneity and the presence of these CSCs may contribute to the treatment-resistant nature of Glioblastoma and its propensity to recur in patients 10) 11).

A 52-year-old woman was admitted for management of Glioblastoma recurrence. After tumor removal surgery, the patient experienced sustained Cerebrospinal fluid fistula 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 Cerebrospinal fluid fistula and the postoperative status of the patient was evaluated. No sign of Cerebrospinal fluid fistula was found in the immediate postoperative period. After 3 years, there were no complications including Cerebrospinal fluid fistula, wound dehiscence, and infection. Lee et al. hereby propose this method as a feasible therapeutic alternative for preventing Cerebrospinal fluid fistula in patients experiencing wound problem after neurosurgical procedures 12).

Corns et al. describe the case of a patient with Glioblastoma recurrence encroaching on Broca's area. Gross 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 T1-contrast 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 13).

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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.
Cancer Genome Atlas Research Network: Comprehensive ge- nomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068, 2008
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Lee H, Eom YS, Pyon JK. A method to prevent Cerebrospinal fluid fistula: 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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