Quantitative oxygen sensing to enable personalized oncology treatment planning

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Project Summary and Abstract Tumor oxygen levels are predictive of outcomes for patients receiving radiation therapy for cervical cancer. The effectiveness of radiation therapy is controlled by tumor oxygen with reduced effectiveness occurring in low oxygen regions. The survival rate for cervical cancer patients with a low oxygen tumor is 40% less than for patients with an oxygenated tumor. Resistance to therapy can be overcome by delivering an elevated dose of radiation. Existing oxygen sensing techniques cannot enable this treatment personalization because they are either impractically invasive or are indirect and qualitative. An appropriate dose escalation technique should enable localized delivery of elevated doses to only the low oxygen regions of a tumor. Interstitial high dose rate (HDR-brachy) is part of the current standard of care for many cervical cancer patients and involves the short- term placement (1 to 3 days) of plastic catheters (up to 30+, 2 mm diameter hollow tubes) throughout the tumor to serve as conduits for the temporary placement of radioactive seeds. Dose distribution is controlled by seed position and dwell time within the catheters which allows for hyper-localized and well-controlled dose escalation. The proposed oxygen sensor will address the unmet medical need for direct and quantitative measurements of tumor oxygen. This sensor leverages a proprietary oxygen sensing polymer, is made completely of silicone and is passive, wireless, and measured non-invasively using magnetic resonance imaging (MRI). This leverages the growing trend of using MRI during treatment planning and the catheter placement of HDR-brachy catheters. In the United States, MRI use has increased from 2% in 2007 to 34% in 2014, and it is the recommended imaging modality throughout Europe. The proposed device format is a new HDR-brachy catheter that includes the oxygen sensing polymer on the outside surface to achieve multiple discrete oxygen measurements along the length of the device, fast equilibration with tissue oxygen, and has a fully functional inner channel for radioactive seed placement. This will combine the ability to measure tissue oxygen levels and hyper-localize dose escalation. It will leverage the current standard of care to provide clinicians with actionable and easy to interpret oxygen measurements to personalize and improve clinical decisions. This sensor format is also readily translatable to other cancers treated with HDR-brachy and where patients suffer from treatment resistance and poor outcomes tied to low oxygen levels including prostate and head and neck cancers.