Combination Radiopharmaceutical Therapy and External Beam Radiotherapy

问题：晚期转移性癌症的治疗选择有限。外照射(XRT)是 一般有效，但仅限于对辐射敏感组织附近的广泛疾病或肿瘤有效。 放射性药物治疗(RPT)，一种起源于甲状腺癌的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是对XRT的补充。它利用了 与肿瘤细胞结合以提供靶向辐射的药物。它针对转移瘤，同时提供 对肿瘤的辐射促进作用。将XRT与RPT(例如，与化疗相反)相结合可以实现精确的 确定对正常器官的潜在毒性，因为这两种方式都涉及辐射，其影响 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学工具商业化，这种工具将使 XRT联合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 对于仅用放射性碘治疗不太可能有效的甲状腺癌患者，以及良好的患者 CXRPT的候选人。放射性药物成像和剂量测定公司(LLC(Rapid))将提供这种方法 约翰霍普金斯大学医学院将实施CXRPT。 具体目标： 1.进行CXRPT治疗分化型甲状腺癌的I期临床试验。 建立CXRPT的安全性，为将展示更大疗效的更大规模的多臂试验提供理论基础 过度的治疗。 2.在基于云的软件包3D-RD-X中实施CXRPT方法；验证来自 基于云的包与本地化包的对比。 3.获得FDA最终批准3D-RD-X所需的数据。 目标2和目标3是生成商业上可行的软件包的关键步骤，该软件包将支持 CXRPT的广泛实施。 这项提议将引入一种新的治疗组合，适用于每一种存在RPT的癌症 或者可能被开发出来。调查团队已经高度合作。Rapid的创始人此前曾 为甲状腺癌患者实施了先进的剂量测量，并在这方面有很长的记录。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RPTS。我们期待着广泛的实施和商业利益一旦我们 论证了该处理方法的可行性，并提供了实现该处理方法的软件工具。

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.