Combination Radiopharmaceutical Therapy and External Beam Radiotherapy

放射药物治疗与外照射放射治疗的联合治疗

• 批准号: 10668390
• 负责人: Robert Francois Hobbs
• 金额: $ 54.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-03 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668390
• 关键词: 3-Dimensional; Address; Area; Binding; Biological Response Modifier Therapy; Cancer Patient; Characteristics; Clinical Trials; Combined Modality Therapy; Commercial grade; Computer software; Data; Development; Digital Imaging and Communications in Medicine; Disease; Disparate; Disseminated Malignant Neoplasm; Dose; Elements; Endocrinology; Engineering; Epithelium; FDA approved; Grant; Image; Industrialization; Intellectual Property; Licensing; Malignant Neoplasms; Malignant neoplasm of thyroid; Maps; Marketing; Medical Oncology; Methodology; Methods; Modality; Neoplasm Metastasis; Normal tissue morphology; Organ; Output; Patients; Pharmacologic Substance; Phase; Phase I Clinical Trials; Physics; Prediction of Response to Therapy; Qualifying; Radiation; Radiation Oncology; Radiation Tolerance; Radiation therapy; Radioactive; Radioactive Iodine; Radiopharmaceuticals; Recording of previous events; Safety; Software Tools; Solid; Solid Neoplasm; System; Therapeutic; Thinking; Tissues; Toxic effect; Treatment outcome; United States National Institutes of Health; Universities; Widespread Disease; Work; absorption; cancer cell; cancer therapy; cell killing; chemotherapy; clinical implementation; cloud based; commercialization; dosimetry; experience; improved; individual patient; industry partner; interest; medical schools; member; multi-arm trial; neoplastic cell; novel; radiation delivery; radioiodine therapy; reconstruction; safety and feasibility; safety assessment; single photon emission computed tomography; software development; success; targeted delivery; thyroid neoplasm; tool; treatment optimization; treatment planning; tumor; uptake

Problem: Treatment options for late stage metastatic cancer are limited. External beam radiotherapy (XRT) is generally effective, but limited against widespread disease or tumors adjacent to radiosensitive tissue. Radiopharmaceutical therapy (RPT), a therapeutic modality with origins in radioiodine therapy of thyroid cancer, has become an effective alternative to chemo- and biologic therapy. RPT is complementary to XRT. It exploits pharmaceuticals that bind to tumor cells to deliver targeted radiation. It targets metastases while providing a radiation boost to tumors. Combining XRT with RPT (e.g., as opposed to chemotherapy) allows a precise determination of potential toxicity to normal organs since both modalities involve radiation whose effects on normal tissues can be quantified and predicted by treatment planning. Our solution to treating widespread metastases is to commercialize enhanced dosimetric tools that will make combination XRT and RPT (CXRPT) a routine cancer treatment. We will assess safety and feasibility of CXRPT in thyroid cancer patients who are not likely to be effectively treated with radioiodine alone and who are good candidates for CXRPT. Radiopharmaceutical Imaging and Dosimetry, LLC (Rapid) will provide the methodology and software for CXRPT; Johns Hopkins University, School of Medicine will implement CXRPT. Specific aims: 1. Conduct a phase I clinical trial of CXRPT in differentiated thyroid cancer patients. Establish safety of CXRPT, provide a rationale for a larger multi-arm trial that will demonstrate greater efficacy over current treatment. 2. Implement the CXRPT methodology in a cloud-based software package, 3D-RD-X; validate results from the cloud-based package against the localized package. 3. Obtain data needed for eventual FDA clearance of 3D-RD-X. Aims 2 and 3 are essential steps towards generating a commercially viable software package that will enable widespread implementation of CXRPT. This proposal will introduce a novel treatment combination applicable to every cancer for which RPT exists or may be developed. The investigative team is already highly collaborative. Rapid’s founders have previously implemented advanced dosimetry for thyroid cancer patients and have a long record in this area. This proposal will enable a fundamentally new treatment paradigm that leverages widely available radiotherapy treatment with ongoing development of novel RPTs. We expect widespread implementation and commercial interest once we have demonstrated feasibility and provided the software tool to implement this treatment approach.

问题：晚期转移性癌症的治疗选择有限。外照射放射治疗 (XRT) 是 通常有效，但对邻近放射敏感组织的广泛疾病或肿瘤有限。 放射性药物治疗（RPT）是一种起源于甲状腺癌放射性碘治疗的治疗方式， 已成为化学疗法和生物疗法的有效替代方案。 RPT 是 XRT 的补充。它利用 与肿瘤细胞结合以提供靶向放射的药物。它针对转移，同时提供 辐射对肿瘤有促进作用。将 XRT 与 RPT 相结合（例如，与化疗相反）可以实现精确的治疗 确定对正常器官的潜在毒性，因为两种方式都涉及辐射，其对正常器官的影响 正常组织可以通过治疗计划进行量化和预测。 我们治疗广泛转移的解决方案是将增强的剂量测定工具商业化，这将使 XRT 和 RPT 组合 (CXRPT) 是一种常规癌症治疗方法。我们将评估CXRPT的安全性和可行性 对于单独使用放射性碘不太可能有效治疗且病情良好的甲状腺癌患者 CXRPT 的候选人。放射性药物成像和剂量测定有限责任公司（Rapid）将提供方法 以及 CXRPT 软件；约翰霍普金斯大学医学院将实施 CXRPT。 具体目标： 1. 在分化型甲状腺癌患者中进行CXRPT I期临床试验。 确定 CXRPT 的安全性，为更大规模的多臂试验提供理论依据，以证明其更有效 超过目前的治疗。 2. 在基于云的软件包 3D-RD-X 中实施 CXRPT 方法；验证结果 基于云的包与本地化包的对比。 3. 获取最终 FDA 批准 3D-RD-X 所需的数据。 目标 2 和 3 是生成商业上可行的软件包的重要步骤，该软件包将能够 CXRPT 的广泛实施。 该提案将引入一种新的治疗组合，适用于存在 RPT 的每种癌症 或可能被开发。调查团队已经高度协作。 Rapid 的创始人此前曾 对甲状腺癌患者实施了先进的剂量测定，并在该领域拥有悠久的记录。这个提议 将实现一种全新的治疗模式，利用广泛可用的放射治疗 新型 RPT 的持续开发。一旦我们完成，我们预计会得到广泛的实施和商业利益 已经证明了可行性并提供了实施这种治疗方法的软件工具。

项目成果

An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 2: Overall Variabilities in Absorbed Dose.

• DOI: 10.2967/jnumed.122.265094
• 发表时间: 2023-07
• 期刊: JOURNAL OF NUCLEAR MEDICINE
• 影响因子: 9.3
• 作者: Brosch-Lenz, Julia;Ke, Suqi;Wang, Hao;Frey, Eric;Dewaraja, Yuni K.;Sunderland, John;Uribe, Carlos
• 通讯作者: Uribe, Carlos