Clinical and Statistical Considerations when Assessing Oxygen Levels in Tumors: Illustrative Results from Clinical EPR Oximetry Studies

Flood, Ann Barry; Schaner, Philip E.; Vaupel, Peter; Williams, Benjamin B.; Gallez, Bernard; Chen, E. Y.; Ali, Arif; Liu, T.; Lawson, Victoria H.; Schreiber, Wilson; Swartz, Harold M.

doi:10.1007/978-3-030-34461-0_20

Cited by 10 publications

(5 citation statements)

References 38 publications

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“…Another example of heterogeneity is presented in Figure 2. These O 2 measurements were taken in a breast cancer patient using EPR oximetry with Carlo Erba ink as the O 2 sensor (Flood et al, 2020;Jeong et al, 2019). The data are presented as line widths, because the EPR oximetry technique using India Ink as a sensor undoubtably gathers data from volumes too large to have homogenous oxygen levels; however, because this sensor remains in the same place in the tissue, it still can provide very useful indications of changes over time and/or the impact of interventions such as breathing enriched oxygen.…”

Section: Distributions Of Levels Of Oxygen In Tissues: Examples and Causesmentioning

confidence: 99%

“…While measurements of O 2 in tissues have been recognized as an important factor in the clinical evaluation and treatment of many diseases, especially cancer (Busk, Overgaard, & Horsman, 2020), and pathologies involving ischemia (such as in peripheral vascular disease and wound healing), insufficient attention often has been paid to the meaning of the values that have been obtained. (Note: this review is derived, in part, from a series of recent papers on this topic; Flood et al, 2020; Instead, all too often, when a measurement technique has indicated that the level of O 2 in a given tissue is "X," that is, is some specific quantitative number for the O 2 in the tissue, researchers, and clinicians alike assume that "X" is a reliable, accurate representation of the "true" oxygenation status of the tissue. This approach ignores the complexity and dynamics of O 2 in living biological systems.…”

Section: Introductionmentioning

confidence: 99%

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How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen‐dependent pathologies

et al. 2020

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It is well understood that the level of molecular oxygen (O 2 ) in tissue is a very important factor impacting both physiology and pathological processes as well as responsiveness to some treatments. Data on O 2 in tissue could be effectively utilized to enhance precision medicine. However, the nature of the data that can be obtained using existing clinically applicable techniques is often misunderstood, and this can confound the effective use of the information. Attempts to make clinical measurements of O 2 in tissues will inevitably provide data that are aggregated over time and space and therefore will not fully represent the inherent heterogeneity of O 2 in tissues. Additionally, the nature of existing techniques to measure O 2 may result in uneven sampling of the volume of interest and therefore may not provide accurate information on the “average” O 2 in the measured volume. By recognizing the potential limitations of the O 2 measurements, one can focus on the important and useful information that can be obtained from these techniques. The most valuable clinical characterizations of oxygen are likely to be derived from a series of measurements that provide data about factors that can change levels of O 2 , which then can be exploited both diagnostically and therapeutically. The clinical utility of such data ultimately needs to be verified by careful studies of outcomes related to the measured changes in levels of O 2 .

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Section: Distributions Of Levels Of Oxygen In Tissues: Examples and Causesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen‐dependent pathologies

et al. 2020

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“…Such a tool though has not been applied in patients with pancreatic cancer, and the probes themselves have not attained regulatory approval for the application in human subjects [123]. Similarly, in another method for the quantitative assessment of tumor oxygenation, electron paramagnetic resonance (EPR) oximetry [125], which makes use of the paramagnetic nature of oxygen and applies oxygen reporters, has been limited in human application to superficial tumors. This again negates the potential of applying such a strategy in pancreatic cancer.…”

Section: Detection Of Hypoxia In the Tme Of Patients With Pdac 61 Dir...mentioning

confidence: 99%

Hypoxia, a Targetable Culprit to Counter Pancreatic Cancer Resistance to Therapy

Khouzam

Lehn

Mayr

et al. 2023

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment is associated with resistance to therapies and promotes angiogenesis, giving rise to a chaotic and leaky vasculature that is inefficient at shuttling oxygen and nutrients. Hypoxia and its downstream effectors have been implicated in immune resistance and could be contributing to the lack of response to immunotherapy experienced by patients with PDAC. Paradoxically, increasing evidence has shown hypoxia to augment genomic instability and mutagenesis in cancer, suggesting that hypoxic tumor cells could have increased production of neoantigens that can potentially enable their clearance by cytotoxic immune cells. Strategies aimed at relieving this condition have been on the rise, and one such approach opts for normalizing the tumor vasculature to reverse hypoxia and its downstream support of tumor pathogenesis. An important consideration for the successful implementation of such strategies in the clinic is that not all PDACs are equally hypoxic, therefore hypoxia-detection approaches should be integrated to enable optimal patient selection for achieving improved patient outcomes.

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“…EPR oximetry requires the respective implantation of an exogenous particulate or the injection of a soluble agent into the tumor to quantify pO 2 (132)(133)(134)140). Detection is therefore limited to superficial tumors; however investigations to assess and put forth safer and more informative oxygen sensors that can work at any tissue depth are ongoing (133,(141)(142)(143), and some are being applied in clinical studies (144). Regarding EPRI, the recent introduction of nontoxic, water-soluble, and biocompatible paramagnetic probes could lead to its clinical translation, enabling the non-invasive, real-time quantification of pO 2 in a three-dimensional format (134,140,145).…”

Section: Detection Of Hypoxia In the Context Of Vascular Normalizationmentioning

confidence: 99%

Tumor Hypoxia Regulates Immune Escape/Invasion: Influence on Angiogenesis and Potential Impact of Hypoxic Biomarkers on Cancer Therapies

et al. 2021

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The environmental and metabolic pressures in the tumor microenvironment (TME) play a key role in molding tumor development by impacting the stromal and immune cell fractions, TME composition and activation. Hypoxia triggers a cascade of events that promote tumor growth, enhance resistance to the anti-tumor immune response and instigate tumor angiogenesis. During growth, the developing angiogenesis is pathological and gives rise to a haphazardly shaped and leaky tumor vasculature with abnormal properties. Accordingly, aberrantly vascularized TME induces immunosuppression and maintains a continuous hypoxic state. Normalizing the tumor vasculature to restore its vascular integrity, should hence enhance tumor perfusion, relieving hypoxia, and reshaping anti-tumor immunity. Emerging vascular normalization strategies have a great potential in achieving a stable normalization, resulting in mature and functional blood vessels that alleviate tumor hypoxia. Biomarkers enabling the detection and monitoring of tumor hypoxia could be highly advantageous in aiding the translation of novel normalization strategies to clinical application, alone, or in combination with other treatment modalities, such as immunotherapy.

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Clinical and Statistical Considerations when Assessing Oxygen Levels in Tumors: Illustrative Results from Clinical EPR Oximetry Studies

Cited by 10 publications

References 38 publications

How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen‐dependent pathologies

How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen‐dependent pathologies

Hypoxia, a Targetable Culprit to Counter Pancreatic Cancer Resistance to Therapy

Tumor Hypoxia Regulates Immune Escape/Invasion: Influence on Angiogenesis and Potential Impact of Hypoxic Biomarkers on Cancer Therapies

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