Evaluation of dynamic contrast-enhanced MRI biomarkers for stratified cancer medicine: How do permeability and perfusion vary between human tumours?

Little, Ross A.; Barjat, Hervé; Hare, Jennifer I.; Jenner, Mary; Watson, Yvonne; Cheung, Susan; Holliday, Katherine Frances; Zhang, Weijuan; O’Connor, James P.B.; Barry, Simon T.; Puri, Sanyogitta; Parker, Geoffrey; Waterton, John C.

doi:10.1016/j.mri.2017.11.008

Cited by 20 publications

(14 citation statements)

References 36 publications

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“…Modern MRI techniques, including dynamic contrast-enhanced MRI, are also available for high resolution imaging of tumor perfusion or cell-membrane permeability ( 177 ). This technique could be particularly useful for assessment of specific metastatic sites, e.g., hepatic metastasis ( 178 ).…”

Section: Imaging Biomarkersmentioning

confidence: 99%

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

2018

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BackgroundImmune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma. In some of these malignancies approval was based on the detection of biomarkers such as PD-L1 expression or high microsatellite instability.MethodsWe review the current status of prognostic and predictive biomarkers used in ICI for melanoma and other malignancies. We include clinical, tissue, blood, and stool biomarkers, as well as imaging biomarkers.ResultsSeveral biomarkers have been studied in ICI for metastatic melanoma. In clinical practice, pre-treatment tumor burden measured by means of imaging and serum lactate dehydrogenase level is already being used to estimate the likelihood of effective ICI treatment. In peripheral blood, the number of different immune cell types, such as lymphocytes, neutrophils, and eosinophils, as well as different soluble factors, have been correlated with clinical outcome. For intra-tumoral biomarkers, expression of the PD-1 ligand PD-L1 has been found to be of some predictive value for anti-PD-1-directed therapy for NSCLC and melanoma. A high mutational load, particularly when accompanied by neoantigens, seems to facilitate immune response and correlates with patient survival for all entities treated by use of ICI. Tumor microenvironment also seems to be of major importance. Interestingly, even the gut microbiome has been found to correlate with response to ICI, most likely through immuno-stimulatory effects of distinct bacteria. New imaging biomarkers, e.g., for PET, and magnetic resonance imaging are also being investigated, and results suggest they will make early prediction of patient response possible.ConclusionSeveral promising results are available regarding possible biomarkers for response to ICI, which need to be validated in large clinical trials. A better understanding of how ICI works will enable the development of biomarkers that can predict the response of individual patients.

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Section: Imaging Biomarkersmentioning

confidence: 99%

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

2018

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“…DCE MRI has been broadly applied to interrogate tumor perfusion by tracking the dynamics of an injected gadolinium-based small-molecule contrast agent (10). Unfortunately, an increasing number of reports suggesting longterm toxicity of gadolinium chelates (11) may limit future use and typical voxel sizes of approximately 2 Â 2 Â 4 mm 3 (12) limit interrogation of spatial heterogeneity (5). To avoid the use of contrast agents, label-free MRI techniques that are sensitive to perfusion such as arterial spin labeling (ASL) may be used; however, ASL can suffer from low signal-to-noise ratio, typically requiring voxel sizes of over approximately 3 Â 3 Â 4 mm 3 in patients (13).…”

Section: Introductionmentioning

confidence: 99%

Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis

et al. 2018

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Measuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths, OT can interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these techniques and tumor hypoxia quantified Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods. Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic. http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg .

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“…Functional MRI which concluded DSC-MRI and DCE-MRI could effectively evaluate vascular permeability and angiogenesis [12]. Some studies have shown that value of relative cerebral blood volume (rCBV) could be seen as one of the most valuable parameters for evaluating tumor classi cation [13]. Wang et al [14] found that glioma had no recurrence according to rCBV < 1 by means of perfusion weighted imaging (PWI), while rCBV > 2 suggested greater possibility of recurrence, DSE based on PWI could assess tumor status and predict tumor behavior.…”

Section: Discussionmentioning

confidence: 99%

Evaluate the Feasibility of Gd-based Contrast Clearance Differenceto Delineate Subvolume Target in Primary and Metastatic Brain Tumors Radiotherapy- A Prospective Study

Wang

Gong

et al. 2020

Preprint

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Background: To evaluate the feasibility ofdelineating subvolume target in brain tumor radiotherapy using gd-based contrast clearance difference.Methods：Twenty-six patients with malignant brain tumor were scanned with MRI. The first and second acquisitions of standard T2-weighted images (T2WI) andT1-weighted images (T1WI) were respectively performed?> at 5 minutes and 60 minutesafter injection of contrast agent. Delayed contrast extravasation MRI(DCEM) computed by Brainlab concludesregions of contrast agent clearance which represent active tumor，andregions of contrast accumulation which represent non-tumor tissues. Based on T2WI images,14 patients were divided into group A and group B, with andwithout liquefaction necrosis, respectively. Then,gross target volume (GTV) was delineated on T1WI images. Based on the GTV, active tumor (GTV tumor) and non-tumorregions(GTV non-tumor) were delineated on T1WI-DCEM fusion images, whileliquefaction necrosis (GTVliquefaction)and non-liquefaction(GTVnon-liquefaction)were delineated on T1-T2WI fusion images. Finally, the differences between different subvolumes were compared by paired t-test.Results：In group A,the mean value of GTVA was 21.38±25.70 cm3, and the GTVnon-liquefaction and GTVliquefaction were 13.65±18.15cm3 and6.30±7.57cm3, respectively. The GTV tumor was 10.40±13.52 cm3 whilethe GTV non-tumor was 9.55±14.57 cm3, The GTVnon-liquefaction increased by an average of 28.2%（P＜0.05）,compared to GTV tumor . While the GTV non-tumor increased by an average of 46.3% (P＜0.05), compared tothe GTVliquefaction.In group B, the mean value of GTVB on enhanced T1WI was4.39±3.75 cm3. The GTV non-tumorreduced by an average of 50.3% (P＜0.05) , compared totheGTV tumor.Conclusion：Comparedto T2WI, the DCEM has advantages in identifyingthe liquefaction areaand could clearly differentiatesubvolume of active tumor from non-liquefaction necrosis.DCEMis meaningful in guiding the delineation of subvolume in primary and metastatic brain tumors.

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Evaluation of dynamic contrast-enhanced MRI biomarkers for stratified cancer medicine: How do permeability and perfusion vary between human tumours?

Cited by 20 publications

References 36 publications

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis

Evaluate the Feasibility of Gd-based Contrast Clearance Differenceto Delineate Subvolume Target in Primary and Metastatic Brain Tumors Radiotherapy- A Prospective Study

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