OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients

Schaner, Philip E.; Pettus, Jason R.; Flood, Ann Barry; Williams, Benjamin B.; Jarvis, Lesley A.; Chen, Eunice; Pastel, David A.; Zuurbier, Rebecca A.; diFlorio-Alexander, Roberta; Swartz, Harold M.; Kuppusamy, Periannan

doi:10.3389/fonc.2020.572060

Cited by 19 publications

(20 citation statements)

References 17 publications

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“…Other direct procedures used in the clinical setting include fiberoptic sensors and electron paramagnetic resonance (EPR) oximetry, the latter method also being minimally invasive, requires only application of the paramagnetic material. (EPR studies have been discussed in Swartz et al [8] and Schaner et al [36]).…”

Section: Direct Assessment Of the Oxygenation Status And Detection Of Tumor Hypoxia Using Po 2 Polarographymentioning

confidence: 99%

Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors

2021

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Immature and chaotic vascular networks with critically increased intervascular distances are characteristic features of malignant tumors. Spatial and temporal heterogeneities of blood flow and associated availabilities of O2, together with limited diffusive O2 transport, and -in some patients- anemia, obligatorily lead to tumor hypoxia (= critically reduced O2 levels) on macro- and microscopic scales. This detrimental condition, recently classified as a key hallmark of malignant growth, acts (a) as a barrier in most antitumor treatments, and (b) leads to malignant progression based on hypoxia-induced changes of the genome, transcriptome, and proteome, and finally to poor patient survival. This knowledge is, to a great extent, based on the systematic detection of tumor hypoxia in the clinical setting since the late 1980s. Precise assessment of the tumor oxygenation status was made possible using minimally invasive polarographic pO2 microsensors in a series of research projects. To assess tumor hypoxia in the clinical setting, it is highly desirable to use technologies with (a) high spatial and temporal resolutions, (b) the capability to judge the severity of tumor hypoxia, (c) to allow mapping of pO2 of the whole tumor mass, and (d) to enable serial investigations in order to verify treatment-related changes in tumor hypoxia. Selection and treatment of cancer patients according to their individual tumor oxygenation/hypoxia status for intensified and/or personalized hypoxia-targeted treatment strategies should be the ultimate goal.

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Section: Direct Assessment Of the Oxygenation Status And Detection Of Tumor Hypoxia Using Po 2 Polarographymentioning

confidence: 99%

Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors

2021

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“…The objectives of this first-in-human device study were to establish the safety of OxyChip implantation and subsequent EPR oximetry in human tumors, as well as to establish the feasibility of using the OxyChip for repeated measurements of tumor oxygen to obtain clinically useful data. We have recently reported on the safety of the OxyChip after implantation into human tumors (51). The results showed that OxyChip implantation followed by EPR oximetry was safe and feasible without any significant clinical adverse effects in all 24 patients studied.…”

Section: Discussionmentioning

confidence: 96%

“…The OxyChip is classified as a Class III medical device by the FDA's Center for Device and Radiological Health. Based on biological evaluation (ISO 10993-12:2012 guidelines) and preclinical testing data (36), the FDA granted investigational device exemption (IDE) status to the OxyChip for a clinical study to collect safety data associated with the OxyChip and to assess the feasibility of making pO 2 measurements in tumors, especially in cancer patients (49)(50)(51). The OxyChips were steam-sterilized in a clinical autoclave at gravity cycle (set at 121°C/15 PSIG for 30 minutes) with appropriate biological and chemical indicators and stored in a sterile environment prior to implantation.…”

Section: Oxychip Implantationmentioning

confidence: 99%

“…The OxyChips were removed as part of the en bloc tumor resection during SOC surgery. This information is reported in detail in a separate report (51). Both gross and microscopic evaluations of the tissue surrounding the OxyChip were performed.…”

Section: Characterization Of Explanted Oxychipsmentioning

confidence: 99%

“…In one patient (patient 18) who was implanted with image guidance and treated with neoadjuvant radiotherapy the OxyChip was assessed to be within the tumor on initial placement; however, it was found 6 mm outside viable tumor at pathologic analysis. Further evaluation of patient-reported outcomes, adverse events, and pathologic findings associated with OxyChip implantation have been published separately (51).…”

Section: Oxychip Retrieval and Assessment Of Implant Location In The Tumormentioning

confidence: 99%

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First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip

et al. 2021

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ObjectiveThe overall objective of this clinical study was to validate an implantable oxygen sensor, called the ‘OxyChip’, as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing.MethodsPatients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry.ResultsTwenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4–128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6–73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5–144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation.ConclusionsMeasurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.

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OxyChip embedded with radio‐opaque gold nanoparticles for anatomic registration and oximetry in tissues

Kmiec

Hebert

Tse

et al. 2021

Magnetic Resonance in Med

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Purpose: Electron paramagnetic resonance oximetry using the OxyChip as an implantable oxygen sensor can directly and repeatedly measure tissue oxygen levels. A phase I, first-in-human clinical study has established the safety and feasibility of using OxyChip for reliable and repeated measurements of oxygen levels in a variety of tumors and treatment regimens. A limitation in these studies is the inability to easily locate and identify the implanted probes in the tissue, particularly in the long term, thus limiting spatial/anatomical registration of the implant for proper interpretation of the oxygen data. In this study, we have developed and evaluated an enhanced oxygen-sensing probe embedded with gold nanoparticles (GNP), called the OxyChip-GNP, to enable visualization of the sensor using routine clinical imaging modalities. Methods:In vitro characterization, imaging, and histopathology studies were carried out using tissue phantoms, excised tissues, and in vivo animal models (mice and rats). Results:The results demonstrated a substantial enhancement of ultrasound and CT contrast using the OxyChip-GNP without compromising its electron paramagnetic resonance and oxygen-sensing properties or biocompatibility. Conclusions:The OxyChips embedded with gold nanoparticles (OxyChip-GNP) can be readily identified in soft tissues using standard clinical imaging modalities such as CT, cone beam-CT, or ultrasound imaging while maintaining its capability to make repeated in vivo measurements of tissue oxygen levels over the long term. This unique capability of the OxyChip-GNP facilitates precisely localized in vivo oxygen measurements in the clinical setting.

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OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients

Abstract: Conclusion: This report of the first-in-humans trial of OxyChip implantation and EPR oximetry demonstrated no significant clinical pathology or unanticipated serious adverse device events. Use of the OxyChip in the clinic was thus safe and feasible.

Cited by 19 publications

References 17 publications

Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors

Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip

OxyChip embedded with radio‐opaque gold nanoparticles for anatomic registration and oximetry in tissues

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