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

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

Abstract

Introduction: Tumor hypoxia confers both a poor prognosis and increased resistance to oncologic therapies, and therefore, hypoxia modification with reliable oxygen profiling during anticancer treatment is desirable. The OxyChip is an implantable oxygen sensor that can detect tumor oxygen levels using electron paramagnetic resonance (EPR) oximetry. We report initial safety and feasibility outcomes after OxyChip implantation in a first-in-humans clinical trial (NCT02706197, www.clinicaltrials.gov). Materials and Methods: Twenty-four patients were enrolled. Eligible patients had a tumor ≤ 3 cm from the skin surface with planned surgical resection as part of standard-of-care therapy. Most patients had a squamous cell carcinoma of the skin (33%) or a breast malignancy (33%). After an initial cohort of six patients who received surgery alone, eligibility was expanded to patients receiving either chemotherapy or radiotherapy prior to surgical resection. The OxyChip was implanted into the tumor using an 18-G needle; a subset of patients had ultrasound-guided implantation. Electron paramagnetic resonance oximetry was carried out using a custom-built clinical EPR scanner. Patients were evaluated for associated toxicity using the Common Terminology Criteria for Adverse Events (CTCAE); evaluations started immediately after OxyChip placement, occurred during every EPR oximetry measurement, and continued periodically after removal. The OxyChip was removed during standard-of-care surgery, and pathologic analysis of the tissue surrounding the OxyChip was performed. Results: Eighteen patients received surgery alone, while five underwent chemotherapy and one underwent radiotherapy prior to surgery. No unanticipated serious adverse device events occurred. The maximum severity of any adverse event as graded by the CTCAE was 1 (least severe), and all were related to events typically associated with implantation. After surgical resection, 45% of the patients had no histopathologic findings specifically associated with the OxyChip. All tissue pathology was "anticipated" excepting a patient with greater than expected inflammatory findings, which was assessed to be related to the tumor as opposed to the OxyChip. 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.

Keywords: OxyChip; clinical trial; electron paramagnetic resonance; feasibility; hypoxia; oximetry; safety.

Copyright © 2020 Schaner, Pettus, Flood, Williams, Jarvis, Chen, Pastel, Zuurbier, diFlorio-Alexander, Swartz and Kuppusamy.

Figures

Figure 1
Figure 1
OxyChip implantation. (A) OxyChip prior to implantation. (B) Implantation needle, with the OxyChip inside, being inserted into a squamous cell carcinoma of the skin. Due to the depth and size of the malignancy, no image guidance was used, and depth of insertion was determined using needle graduations. (C,D) Implantation under ultrasound guidance into a breast malignancy. (C) The implantation needle, with OxyChip inside, being inserted into the malignancy (hypoechoic area labeled with a star) prior to OxyChip deployment. (D) OxyChip after deployment within the malignancy (hypoechoic area labeled with a star). The needle is being retracted after deployment of the OxyChip.
Figure 2
Figure 2
Pathologic findings associated with OxyChip in invasive ductal carcinomas of the breast. (A) OxyChip in situ (white arrow) adjacent to the nipple within a gross specimen. (B) Low-power view of tissue surrounding the OxyChip defect (arrow); the patient received surgery alone 10 days after OxyChip placement. (C) High-power view of the same patient in (B). The OxyChip was present within the borders of invasive carcinoma (*). (D) Benign adipose tissue surrounding the OxyChip in a patient who received neoadjuvant chemotherapy followed by surgery. The OxyChip was in place for 131 days, and there is no definite evidence of tissue response or inflammation.
Figure 3
Figure 3
Pathologic findings associated with the OxyChip in non-breast malignancies. (A) Tissue surrounding the OxyChip in a patient with a squamous cell carcinoma (SCC) of the left nasal skin, including associated foreign body giant cells (arrow), likely due to tumor keratin reaction at the site of injection. (B) Tissue surrounding the OxyChip in a patient with a melanoma of the scalp, including peritumoral injection-related tumor necrosis (*). (C) Tissue surrounding the OxyChip in a patient with a follicular thyroid cancer, showing no identifiable tissue response. (D) Tissue surrounding the OxyChip in a patient with an SCC of the frontal scalp, showing no identifiable tissue response.

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