Re-irradiation for recurrent glioblastoma multiforme

Barney, C.; Shukla, Gaurav; Bhamidipati, Deepak; Palmer, Joshua D.

doi:10.21037/cco.2017.06.18

Cited by 16 publications

(9 citation statements)

References 36 publications

(37 reference statements)

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“…However, surgery is not sufficient for a clean and complete resection of the tumor mass due to the infiltration of tumor cells into the normal brain parenchyma. The remaining tumor cells are often refractory to chemo drugs and radiation, thereby contributing to the high incidence of tumor recurrence that is robustly associated with a poor prognosis of GBM (6–9). Therefore, more effective treatments are needed.…”

Section: Introductionmentioning

confidence: 99%

Functional Blockade of Small GTPase RAN Inhibits Glioblastoma Cell Viability

et al. 2019

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Glioblastoma, the most common malignant tumor in the brain, lacks effective treatments and is currently incurable. To identify novel drug targets for this deadly cancer, the publicly available results of RNA interference screens from the Project Achilles database were analyzed. Ten candidate genes were identified as survival genes in 15 glioblastoma cell lines. RAN, member RAS oncogene family (RAN) was expressed in glioblastoma at the highest level among all candidates based upon cDNA microarray data. However, Kaplan-Meier survival analysis did not show any correlation between RAN mRNA levels and patient survival. Because RAN is a small GTPase that regulates nuclear transport controlled by karyopherin subunit beta 1 (KPNB1), RAN was further analyzed together with KPNB1. Indeed, GBM patients with high levels of RAN also had more KPNB1 and levels of KPNB1 alone did not relate to patient prognosis. Through a Cox multivariate analysis, GBM patients with high levels of RAN and KPNB1 showed significantly shorter life expectancy when temozolomide and promoter methylation of O6-methylguanine DNA methyltransferase were used as covariates. These results indicate that RAN and KPNB1 together are associated with drug resistance and GBM poor prognosis. Furthermore, the functional blockade of RAN and KPNB1 by importazole remarkably suppressed cell viability and activated apoptosis in GBM cells expressing high levels of RAN, while having a limited effect on astrocytes and GBM cells with undetectable RAN. Together, our results demonstrate that RAN activity is important for GBM survival and the functional blockade of RAN/KPNB1 is an appealing therapeutic approach.

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Section: Introductionmentioning

confidence: 99%

Functional Blockade of Small GTPase RAN Inhibits Glioblastoma Cell Viability

et al. 2019

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“…However, there are insufficient data for fractionated radiotherapy to be used routinely in the setting of recurrent GBM. Like fractionated radiotherapy, brachytherapy also enables a sharp dose gradient by placing a radiation source within the tumor volume to be treated [161]. This is usually carried out postoperatively, and it is offered to patients with a good performance status and more resectable small tumor in volume.…”

Section: Challenges In Hgg Standard Therapymentioning

confidence: 99%

“…This is usually carried out postoperatively, and it is offered to patients with a good performance status and more resectable small tumor in volume. One of the approaches in which brachytherapy can be utilized is by placing permanent iodine 125 (I-125) seeds in the resection cavity [161]. In a retrospective study by Darakchiev et al in 2008, utilizing brachytherapy in patients with GBM reported a favorable result with the median survival of 15.9 months [162].…”

Section: Challenges In Hgg Standard Therapymentioning

confidence: 99%

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Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

et al. 2021

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Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient’s response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.

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“…Surgery, radiation therapy (RT) and chemotherapy is the standard treatment in glioblastoma (GBM) [1]. In recurrent glioblastoma (rGBM), re-irradiation (re-RT) is an important therapeutic alternative, which may delay further disease progression and improve survival [2,3]. However, the re-RT can be associated with a high risk of brain edema, radiation necrosis, increased dose of corticosteroids and impaired quality of life.…”

Section: Introductionmentioning

confidence: 99%

FET-PET radiomics in recurrent glioblastoma: prognostic value for outcome after re-irradiation?

et al. 2021

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Purpose The value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET)-radiomics in the outcome assessment of patients with recurrent glioblastoma (rGBM) has not been evaluated until now. The aim of this study was to evaluate whether a prognostic model based on FET-PET radiomics features (RF) is feasible and can identify rGBM patients that would most benefit from re-irradiation. Methods We prospectively recruited rGBM patients who underwent FET-PET before re-irradiation (GLIAA-Pilot trial, DRKS00000633). Tumor volume was delineated using a semi-automatic method with a threshold of 1.8 times the standardized-uptake-value of the background. 135 FET-RF (histogram parameters, shape and texture features) were extracted. The analysis involved the characterization of tumor and non-tumor tissue with FET-RF and the evaluation of the prognostic value of FET-RF for time-to-progression (TTP), overall survival (OS) and recurrence location (RL). Results Thirty-two rGBM patients constituted our cohort. FET-RF discriminated significantly between tumor and non-tumor. The texture feature Small-Zone-Low-Gray-Level-Emphasis (SZLGE) showed the best performance for the prediction of TTP (p = 0.001, satisfying Bonferroni-multiple-test significance level). Additionally, two radiomics signatures could predict TTP (TTP-radiomics-signature, p = 0.001) and OS (OS-radiomics-signature, p = 0.038). SZLGE and the TTP-radiomics-signature additionally predicted RL. Specifically, high values for TTP-radiomics-signature and for SZLGE indicated not only earlier progression, but also a RL within the initial FET-PET active volume. Conclusion Our findings suggest that FET-PET radiomics could contribute to the prognostic assessment and selection of rGBM-patients benefiting from re-irradiation. Trial registration DRKS00000633. Registered on 8th of December in 2010. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000633.

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Re-irradiation for recurrent glioblastoma multiforme

Cited by 16 publications

References 36 publications

Functional Blockade of Small GTPase RAN Inhibits Glioblastoma Cell Viability

Functional Blockade of Small GTPase RAN Inhibits Glioblastoma Cell Viability

Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

FET-PET radiomics in recurrent glioblastoma: prognostic value for outcome after re-irradiation?

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