At home monitoring for 177Lu DOTATATE treatment personalization

在家监测 177Lu DOTATATE 治疗个性化

• 批准号: 10066324
• 负责人: Robert S Miyaoka
• 金额: $ 21.81万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-06 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066324
• 关键词: Age; Asia; Australia; Biological; Bone Marrow; Clinic; Clinic Visits; Control Groups; Country; Data; Diagnosis; Dose; Electronics; Electrons; Europe; Evaluation; Gender; Goals; Half-Life; Health Status; Home; Hour; Image; Individual; Instruction; Kidney; Lead; Liver; Location; Measurement; Measures; Methods; Midgut; Monitor; Monte Carlo Method; Neuroendocrine Tumors; Octreotide; Organ; PET/CT scan; Patients; Photons; Physicians; Pilot Projects; Positioning Attribute; Progression-Free Survivals; Protocols documentation; Publishing; Radiation; Radionuclide therapy; Resources; Risk; Running; Secure; Silicon; Spleen; Standardization; Structure; Techniques; Technology; Testing; Therapeutic; Time; Treatment Protocols; United States; Visit; Weight; Work; X-Ray Computed Tomography; attenuation; base; cohort; cost; design; detector; dose information; dosimetry; improved; improved outcome; individualized medicine; interest; light weight; personalized medicine; photomultiplier; precision medicine; prototype; serial imaging; sex; side effect; single photon emission computed tomography; somatostatin receptor 2; standard of care; targeted treatment; theranostics; therapeutic effectiveness; tool; tumor; web site; wireless fidelity

For patients with metastatic, somatostatin-receptor-2 (SSTR2) positive neuroendocrine tumors (NETs), targeted therapy using 177Lu-DOTATATE greatly increases progression-free survival (PFS), as shown in the NETTER-1 trial. PFS at month 20 was 65.2% (95% CI, 50.0 - 76.8) for midgut NETs treated with 177Lu- DOTATATE plus octreotide compared to 10.8% (95% CI, 3.5 - 23.0) in a control group receiving 60 mg octreotide long-acting release every 4 weeks. Now that 177Lu-DOTATATE has FDA approval it will likely become the standard of care for symptomatic NET patients and those with metastatic spread. However, FDA package instructions call for patients to receive four 7.4 GBq treatments, regardless of size, weight, gender or patient health status. Traditionally, targeted radionuclide therapies are personalized based upon dose to the main organs at risk. Standardized therapy is counter to the ideals of personalized medicine and will lead to non-optimum therapeutic dosing for many patients. The scientific premise of this proposal is that practical tools to accurately assess dose to organs at risk will enable treatment personalization and improve outcomes beyond the proposed standard of care (i.e., 4×7.4 GBq 177Lu-DOTATATE) protocol. In Aim 1 methods to measure individual organ dose information from a wearable, low cost, multi-detector personalized home dosimetry (MDPHD) vest will be developed using Monte Carlo simulation tools. In Aim 2, a prototype MDPHD vest for organ specific dose estimation will be fabricated. The vest will consist of 6-15 small, spectrographic counting detectors and weigh between 480-750 grams depending upon the number of detectors incorporated into the vest. It will be designed to be light weight, form fitting and will have alignment features to enable consistent day to day wearing/positioning of the vest with respect to the patient's internal organs. Time to put on, align and collect data will be less than 8 minutes each day. The vest will further be equipped with electronics that can acquire, store and send the data via Wi-Fi to a secure web-site for near real time data monitoring. In Aim 3, a small pilot study to compare individual organ dosimetry estimates using a streamlined protocol (i.e., one SPECT/CT combined with an in-clinic MDPHD vest measurement at 24-hr post- therapy and daily at-home MDPHD vest measurements for 7-21 days) versus 3-time point (i.e., 1, 4 and 7 day) in-clinic SPECT/CT imaging (i.e., standard protocol followed in many non-US countries) will be conducted. At the end of this project, methods to create and utilize a MDPHD vest will have been tested and validated and the MDPHD vests will be ready for evaluation on a larger patient cohort.

对于转移性，生长抑素受体-2（SSTR2）阳性神经内分泌肿瘤（NETS）的患者， 使用177LU-葡萄糖的靶向治疗大大增加了无进展的生存（PFS），如图所示 Netter-1试验。第20个月的PFS为65.2％（95％CI，50.0-76.8），用于177lu- 在接收60毫克的对照组中，dotatate Plus Octreotide为10.8％（95％CI，3.5-23.0） 每4周释放Ocroteotide长效。现在177lu-dotatate已获得FDA批准 成为有症状的净患者和转移性扩散患者的护理标准。但是，FDA 包装说明要求患者接受四种7.4 GBQ治疗，无论大小，体重，性别或性别如何 患者健康状况。传统上，有针对性的放射线疗法是根据剂量为个性化的 有风险的主要器官。标准化疗法与个性化医学的思想相反，将导致 许多患者的非临时治疗剂量。该提议的科学前提是实用工具 要准确评估对处于危险的器官的剂量，将使治疗个性化并改善结果 超出提议的护理标准（即4×7.4 GBQ 177LU-DOTATATE）协议​​。 在AIM 1中，从可穿戴，低成本，多探测器中测量单个器官剂量信息的方法 个性化的家用剂量法（MDPHD）背心将使用蒙特卡洛模拟工具开发。在AIM 2中 将制造用于器官特异性剂量估计的原型MDPHD背心。背心将由6-15个小， 光谱学计数检测器和重量在480-750克之间，具体取决于数量 探测器纳入背心。它将设计为重量轻，形成合身，并具有对齐方式 功能以使背心的日常佩戴/定位相对于患者的内部 器官。是时候穿上，对齐和收集数据每天不到8分钟。背心将进一步 配备了可以通过Wi-Fi获取，存储和将数据发送到安全的网站的电子产品 时间数据监视。在AIM 3中，一项小型试验研究，用于比较单个器官剂量测定法的估计值 简化的方案（即，一个SPECT/CT与临界MDPHD背心在24小时后 - 治疗和每天的家庭MDPHD背心测量值7-21天）与三个时间点（即1、4和7天） 将进行临界SPECT/CT成像（即在许多非美国国家遵循的标准协议）。 该项目的结束，创建和使用MDPHD背心的方法将经过测试和验证，并 MDPHD背心将准备在较大的患者队列上进行评估。