Quantitative oxygen sensing to enable personalized oncology treatment planning

项目摘要和摘要 肿瘤含氧量可以预测接受宫颈癌放射治疗的患者的预后。这个 放射治疗的有效性是由肿瘤氧气控制的，在低氧条件下会降低疗效 氧气区。低氧肿瘤宫颈癌患者的存活率比低氧肿瘤患者低40%。 有氧合肿瘤的病人。对治疗的耐药性可以通过提供更高剂量的 辐射。现有的氧气传感技术无法实现这种治疗的个性化，因为它们 要么是不切实际的侵入性的，要么是间接的和定性的。适当的剂量递增技术应该是 使增加的剂量仅能局部输送到肿瘤的低氧区域。间隙高剂量率 (HDR-brachy)是许多宫颈癌患者当前护理标准的一部分，涉及短期- 在整个肿瘤内定期放置(1-3天)塑料导管(直径达30+2毫米的中空管) 作为临时放置放射性种子的管道。剂量分布由种子控制 导管内的位置和停留时间，允许超局部化和良好控制的剂量递增。 拟议的氧传感器将解决未得到满足的医疗需求，即直接和定量测量 肿瘤氧气。该传感器利用专有的氧气传感聚合物，完全由硅胶和 是被动的、无线的，并且使用磁共振成像(MRI)进行非侵入性测量。这充分利用了 在治疗计划和HDR-短程导管的导管放置中使用MRI的趋势越来越大。在……里面 在美国，核磁共振的使用率从2007年的2%上升到2014年的34%，这是推荐的成像方法 整个欧洲的情态。建议的装置形式是一种新的HDR-Brachy导管，其中包括氧气 在外表面传感聚合物以实现沿长度方向的多次离散氧测量 该装置与组织氧快速平衡，并具有用于放射性种子的全功能内通道 放置。这将结合测量组织氧水平和超局部化剂量升级的能力。它 将利用当前的护理标准为临床医生提供可操作且易于解释的氧气 用于个性化和改进临床决策的测量。该传感器格式也可容易地翻译为 用HDR-brachy治疗的其他癌症，患者存在治疗耐药性和不良结局 与低氧水平有关，包括前列腺癌和头颈癌。

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.