Combination Radiopharmaceutical Therapy and External Beam Radiotherapy

问题：晚期转移性癌症的治疗选择有限。体外放射治疗（XRT） 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， 已经成为化疗和生物治疗的有效替代方案。RPT是XRT的补充。中国可以利用 与肿瘤细胞结合以提供靶向辐射的药物。它靶向转移，同时提供 对肿瘤的辐射增强。将XRT与RPT组合（例如，与化疗相反）允许精确的 确定对正常器官的潜在毒性，因为这两种方式都涉及辐射， 可以通过治疗计划来量化和预测正常组织。 我们治疗广泛转移的解决方案是商业化增强剂量测定工具， 联合XRT和RPT（CXRPT）是一种常规的癌症治疗方法。我们将评估CXRPT的安全性和可行性 在甲状腺癌患者中，仅用放射性碘不太可能有效治疗， 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 和软件;约翰霍普金斯大学医学院将实施CXRPT。 具体目标： 1.开展CXRPT在分化型甲状腺癌患者中的I期临床试验。 确定CXRPT的安全性，为证明更大疗效的更大规模多组试验提供依据 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 基于云的软件包与本地化软件包进行比较。 3.获得FDA最终批准3D-RD-X所需的数据。 目标2和目标3是产生商业上可行的软件包的基本步骤， CXRPT的广泛实施。 该提案将引入一种适用于RPT存在的每种癌症的新型治疗组合 或者可以被开发。调查小组已经高度合作。Rapid的创始人此前曾 为甲状腺癌患者实施了先进的剂量测定法，并在这一领域有着长期的记录。这项建议 将实现一种全新的治疗模式，利用广泛可用的放射治疗， 正在开发新的RPT。我们期待广泛的实施和商业利益，一旦我们 已经证明了可行性，并提供了软件工具来实现这种治疗方法。

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.