Noninvasive Characterization of Tumor Angiogenesis and Oxygenation in Bevacizumab-treated Recurrent Glioblastoma by Using Dynamic Susceptibility MRI: Secondary Analysis of the European Organization for Research and Treatment of Cancer 26101 Trial

Kickingereder, Philipp; Brugnara, Gianluca; Hansen, Mikkel Bo; Nowosielski, Martha; Pflüger, Irada; Schell, Marianne; Isensee, Fabian; Foltyn, Martha; Neuberger, Ulf; Keßler, Tobias; Sahm, Felix; Heiland, Sabine; Weller, Michael; Platten, Michael; Deimling, Andreas von; Maier‐Hein, Klaus H.; Østergaard, Leif; Bent, Martin J. van den; Wick, Wolfgang; Bendszus, Martin

doi:10.1148/radiol.2020200978

Cited by 25 publications

(12 citation statements)

References 32 publications

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“…Malignant gliomas are characterized by a high degree of angiogenesis, resulting in increased neovasculature and vasodilatation [ 39 ]. Histologically, the abnormal number of tumour vessels can be measured by determination of the microvascular density [ 40 ].…”

Section: Angiogenesismentioning

confidence: 99%

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

Tang

Romero

Jaspers

et al. 2022

Magn Reson Mater Phy

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As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1–2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.

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Section: Angiogenesismentioning

confidence: 99%

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

Tang

Romero

Jaspers

et al. 2022

Magn Reson Mater Phy

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“…In particular, ex vivo imaging techniques, including histology imaging [ 45 ] and micro-CT [ 46 , 47 , 48 ], can quantify tumor microvasculature and angiogenesis on excised tissue specimens and serve as the gold standard measurement. Less invasive observations of tumor-associated vasculature can now be achieved thanks to the development of in vivo imaging techniques [ 49 ], such as x-ray [ 50 ] and computed tomography (CT) [ 51 , 52 , 53 ], positron emission tomography (PET) [ 54 , 55 ], MRI [ 52 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ], and optical imaging [ 63 , 64 ]. There are two main classes of imaging techniques applied to studying tumor-associated vasculature: (1) angiography, which is a technique used to visualize the vasculature structure, and (2) functional techniques used to quantify the properties of the tissue and vasculature.…”

Section: Overview Of Experimental Techniques Across Scalesmentioning

confidence: 99%

Biologically-Based Mathematical Modeling of Tumor Vasculature and Angiogenesis via Time-Resolved Imaging Data

Hormuth

Phillips

et al. 2021

Cancers

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Tumor-associated vasculature is responsible for the delivery of nutrients, removal of waste, and allowing growth beyond 2–3 mm3. Additionally, the vascular network, which is changing in both space and time, fundamentally influences tumor response to both systemic and radiation therapy. Thus, a robust understanding of vascular dynamics is necessary to accurately predict tumor growth, as well as establish optimal treatment protocols to achieve optimal tumor control. Such a goal requires the intimate integration of both theory and experiment. Quantitative and time-resolved imaging methods have emerged as technologies able to visualize and characterize tumor vascular properties before and during therapy at the tissue and cell scale. Parallel to, but separate from those developments, mathematical modeling techniques have been developed to enable in silico investigations into theoretical tumor and vascular dynamics. In particular, recent efforts have sought to integrate both theory and experiment to enable data-driven mathematical modeling. Such mathematical models are calibrated by data obtained from individual tumor-vascular systems to predict future vascular growth, delivery of systemic agents, and response to radiotherapy. In this review, we discuss experimental techniques for visualizing and quantifying vascular dynamics including magnetic resonance imaging, microfluidic devices, and confocal microscopy. We then focus on the integration of these experimental measures with biologically based mathematical models to generate testable predictions.

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“…Although some advances have been realized in the treatment of GBM, such as the application of temozolomide and bevacizumab, patients with GBM still encounter poor treatment effect and drug resistance. (Tan et al, 2017;Jiapaer et al, 2018;Kickingereder et al, 2020;Reardon et al, 2020;Nayak et al, 2021;Tesileanu et al, 2022;Zeng et al, 2022). Tumor therapeutic field (TTF) therapy has also been approved by the FDA for recurrent (2011) and newly diagnosed (2015) GBM, but the lack of generalizability of data from previous studies has prevented TTF from being widely used.…”

Section: Introductionmentioning

confidence: 99%

Multiomics integration reveals the effect of Orexin A on glioblastoma

Yang

Huan²,

Yue³

et al. 2023

Front. Pharmacol.

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Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.

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Noninvasive Characterization of Tumor Angiogenesis and Oxygenation in Bevacizumab-treated Recurrent Glioblastoma by Using Dynamic Susceptibility MRI: Secondary Analysis of the European Organization for Research and Treatment of Cancer 26101 Trial

Abstract: Noninvasive characterization of tumor angiogenesis and oxygenation in bevacizumab-treated recurrent glioblastoma by using dynamic susceptibility MRI: secondary analysis of the European Organization for Research and Treatment of Cancer 26101 Trial.

Cited by 25 publications

References 32 publications

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

Biologically-Based Mathematical Modeling of Tumor Vasculature and Angiogenesis via Time-Resolved Imaging Data

Multiomics integration reveals the effect of Orexin A on glioblastoma

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