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。外束放疗（XRT）为 通常有效，但限制在宽度疾病或与放射敏感性组织相邻的肿瘤中。 放射性药物治疗（RPT），一种治疗方式，起源于甲状腺癌的放射碘治疗， 它的利用已成为化学和生物治疗的有效替代方法。 RPT已完成XRT。 与肿瘤细胞结合以传递靶向辐射的药物。它针对转移，同时提供 辐射促进肿瘤。将XRT与RPT结合（例如，与化学疗法相对）可以精确 确定对正常器官的潜在毒性，因为这两种方式都涉及辐射的影响 正常组织可以通过治疗计划来量化和预测。 我们治疗宽度转移的方法是将增强的剂量计工具商业化，这将使 联合XRT和RPT（CXRPT）常规癌症治疗。我们将评估CXRPT的安全性和可行性 在甲状腺癌患者中，他们不太可能单独使用放射性碘治疗并且是好的 CXRPT的候选人。放射性药物成像和剂量学有限责任公司（快速）将提供该方法论 和CXRPT的软件；约翰·霍普金斯大学（Johns Hopkins University），医学院将实施CXRPT。 具体目的： 1。在分化的甲状腺癌患者中对CXRPT进行I期临床试验。 建立CXRPT的安全性，为更大的多臂试验提供理由，该试验将表现出更高的效率 当前治疗。 2。在基于云的软件包3D-RD-X中实现CXRPT方法；验证结果 基于云的软件包针对本地化软件包。 3。获取3D-RD-X的事件FDA清除所需的数据。 目标2和3是生成商业上可行的软件包的重要步骤，该软件包将启用 CXRPT的宽度实现。 该建议将引入一种适用于RPT存在​​的癌症的新型治疗组合 或可能开发。调查团队已经是高度协作的。 Rapid的创始人以前有 为甲状腺癌患者实施了高级剂量测定法，并在该领域有很长的记录。这个建议 将实现从根本上进行新的治疗范式，该范式利用广泛可用的放疗治疗 新型RPT的持续发展。我们预计一旦我们 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