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Review
. 2015;4(2):91-104.
doi: 10.2217/cns.14.55.

Treating recurrent glioblastoma: an update

Carlos Kamiya-Matsuoka  1 , Mark R Gilbert
Affiliations
Review

Treating recurrent glioblastoma: an update

Carlos Kamiya-Matsuoka et al. CNS Oncol. 2015.

Abstract

Glioblastoma, the most aggressive of the gliomas, has a high recurrence and mortality rate. The nature of this poor prognosis resides in the molecular heterogeneity and phenotypic features of this tumor. Despite research advances in understanding the molecular biology, it has been difficult to translate this knowledge into effective treatment. Nearly all will have tumor recurrence, yet to date very few therapies have established efficacy as salvage regimens. This challenge is further complicated by imaging confounders and to an even greater degree by the ever increasing molecular heterogeneity that is thought to be both sporadic and treatment-induced. The development of novel clinical trial designs to support the development and testing of novel treatment regimens and drug delivery strategies underscore the need for more precise techniques in imaging and better surrogate markers to help determine treatment response. This review summarizes recent approaches to treat patients with recurrent glioblastoma and considers future perspectives.

Keywords: bevacizumab; glioblastoma; immunotherapy; lomustine; oncolytic viruses; pseudoprogression; re-irradiation; recurrent glioma; targeted therapy; temozolomide.

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Conflict of interest statement

Financial & competing interests disclosure

MR Gilbert reports personal fees and nonfinancial support from Genentech, personal fees from Merck, EMD Serono, Abbott, Bristol-Meyers Squibb, Novartis and Hoffman-La Roche, and nonfinancial support from GlaxoSmithKline, outside the submitted work. This study did not involve use of any grant funds. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. MRI from a patient with pseudoprogression and resection confirmed radiation necrosis.
(A) T1-weighted Gd-enhanced MRI and (B) T2-weighted and FLAIR postoperatively and 4 weeks postradiation showing large areas of contrast enhancement anterior to the surgical cavity (within the radiation field) (C) associated with vasogenic edema (D). Surgery was performed and revealed extensive necrosis with no evidence of tumor. FLAIR: Fluid-attenuated inversion recovery; Gd: Gadolinium.
<b>Figure 2.</b>
Figure 2.. MRI from a patient with pseudoresponse during treatment with bevacizumab.
A 33-year-old man with recurrent glioblastoma receiving bevacizumab. Axial T2 weighted and FLAIR sequence in the upper row (A, arrows) shows T2/FLAIR hyperintensity involving the region immediately adjacent to the resection cavity within the right frontal and parietal lobes, with no involvement of the corpus callosum (C). Six months after treatment with bevacizumab (lower row), there is extension of the abnormal signal to the right posterior parietal lobe as well as to the posterior body and splenium of the corpus callosum (E & G, arrows) with no contrast enhancement (F & H), suggesting nonenhancing tumor progression. Corresponding postcontrast images obtained at the same time points (B, D, F & H) indicate stable/unchanged enhancing component with a subtle foci posterior to the resection cavity (B & F). FLAIR: Fluid-attenuated inversion recovery; Gd: Gadolinium.
<b>Figure 3.</b>
Figure 3.. Frequent genetic alterations in three critical signaling pathways.
Significant copy number and mutation changes in (A) RAS/PI3K, (B) p53 and (C) RB signaling pathways. Red, activating genetic alterations; blue, inactivating mutations. Percentage of tumors affected are indicated next to each gene with boxes identifying the final percentage of patients with alterations within that specific pathway. Reproduced with kind permission from Nature Publishing Group [113].
See this image and copyright information in PMC

References

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    2. •• This study shown a significant benefit in terms of overall survival and 2-year survival, becoming the standard of care in newly diagnosed glioblastoma.

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