AUTHOR=Schaner Philip E. , Williams Benjamin B. , Chen Eunice Y. , Pettus Jason R. , Schreiber Wilson A. , Kmiec Maciej M. , Jarvis Lesley A. , Pastel David A. , Zuurbier Rebecca A. , DiFlorio-Alexander Roberta M. , Paydarfar Joseph A. , Gosselin Benoit J. , Barth Richard J. , Rosenkranz Kari M. , Petryakov Sergey V. , Hou Huagang , Tse Dan , Pletnev Alexandre , Flood Ann Barry , Wood Victoria A. , Hebert Kendra A. , Mosher Robyn E. , Demidenko Eugene , Swartz Harold M. , Kuppusamy Periannan TITLE=First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.743256 DOI=10.3389/fonc.2021.743256 ISSN=2234-943X ABSTRACT=Objective

The 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.

Methods

Patients 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.

Results

Twenty-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.

Conclusions

Measurement 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.