Abstract
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.
Highlights
Most solid tumors contain regions of acute and chronic hypoxia that can negatively impact treatment outcomes in cancer patients [1,2,3,4,5,6,7]
The results indicated that in about 27% of the measurements (9 out of 33) the tumors were severely hypoxic and 67% (6 out of 9) of them could be sensitized to radiation with ≥20% oxygen enhancement ratio (OER) gain
The results of the present study establish, for the first time, that tumor oxygen levels can be measured in cancer patients repeatedly using EPR oximetry with the OxyChip to obtain both initial baseline values and values after interventions designed to increase tumor oxygenation
Summary
Most solid tumors contain regions of acute and chronic hypoxia that can negatively impact treatment outcomes in cancer patients [1,2,3,4,5,6,7]. In a subset of patients who participated in a translational side study, a histologic marker of hypoxia (pimonidazole) was used to analyze biopsy specimens This subset analysis revealed that ARCON improved both regional control and disease-free survival in the group of patients with hypoxic tumors, while the group of patients whose tumors did not have hypoxia (as defined by localization of pimonidazole) did not benefit from the ARCON protocol. These data emphasize the need for individualized oxygen-based stratification of patients to evaluate the efficacy of hyperoxygenation interventions to enhance therapeutic outcomes [17].
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