SBIR PHASE I TOPIC 392: TARGETED RADIONUCLIDE THERAPY OF METASTATIC LIVER CANCER: PATIENT SPECIFIC OPTIMIZATION

对于被诊断为转移性结直肠癌(MCRC)的患者，在透视引导下使用Y-90微球进入肝动脉进行放射栓塞术可以减缓肝脏肿瘤的进展。治疗计划是基于对提供给治疗体积的平均吸收剂量(AD)的简单估计；因此，肿瘤剂量取决于肿瘤负担和肿瘤与背景的比率，导致一些患者剂量不足。基于更严格的、患者特定的AD给药到正常肝脏将允许安全地增加给药活度，可能改善肿瘤反应，而不会增加毒性。 这项工作的目标是通过使用严格的定量成像和剂量学方法实施基于云的治疗计划软件服务来改善mCRC患者的预后。我们将进行一项涉及3名患者的试验性研究，以展示招募、成像和执行治疗计划的可行性，验证导管放置的重复性，添加和验证定量的Tc-99m MAA SPECT/CT重建能力，验证从Tc-99m MAA估计的正常治疗肝脏的AD可以预测使用定量Y-90韧致辐射SPECT测量的正常肝脏AD，验证Tc-99m MAA SPECT/CT图像中的肝脏自动分割，开发和验证基于云计算的原则证明软件服务，以及获得二期项目剂量递增试验的批准。

Radioembolization using Y-90 microspheres delivered into the hepatic artery under fluoroscopy guidance has slowed tumor progression in the liver for patients diagnosed with metastatic colorectal cancer (mCRC). Treatment planning is based on a simple estimate of the average absorbed dose (AD) delivered to the treated volume; tumor dose thus depends on tumor burden and tumor-to-background ratio, resulting in under-dosing in some patients. Dosing based on more rigorous, patient-specific AD to normal liver would allow safely increasing administered activity, likely improving tumor response, without an increased toxicity. The goal of this work is to improve the outcome of patients with mCRC by implementing a cloud-based treatment planning software service using rigorous quantitative imaging and dosimetry methods. We will perform a pilot study involving 3 patients to demonstrate feasibility of recruiting, imaging, and performing the treatment planning, validate the reproducibility catheter placement, add and verify quantitative Tc-99m MAA SPECT/CT reconstruction capability, verify that AD to normal treated liver estimated from Tc-99m MAA predicts the normal liver AD measured using quantitative Y-90 bremsstrahlung SPECT, validate automated segmentation of liver in Tc-99m MAA SPECT/CT images, develop and validate a proof-of-principle cloud-based software service; and obtain approval for the Phase II project’s dose escalation trial.