Dose-Response in Radionuclide Therapy

放射性核素治疗的剂量反应

• 批准号: 8484359
• 负责人: George Sgouros
• 金额: $ 37.09万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8484359
• 关键词: 3-Dimensional; 90Y; Accounting; Address; Adoption; Anatomy; Area; Binding; Clinical; Collaborations; Computer software; Data; Data Set; Databases; Development; Diagnostic; Diffuse; Disease remission; Disseminated Malignant Neoplasm; Dose; Dose-Limiting; Dose-Rate; Drug Kinetics; Exhibits; Generic Drugs; Grant; Housing; Human; Image; Individual; Institution; Kinetics; Label; Lead; Letters; Link; Literature; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of thyroid; Measures; Methodology; Methods; Modality; Modeling; Neoplasm Metastasis; Neurosecretory Systems; Non-Hodgkin' s Lymphoma; Organ; Ovarian; Patients; Positron-Emission Tomography; Property; Prostate; Published Comment; Radiation therapy; Radioactive; Radionuclide therapy; Radiopharmaceuticals; Refractory; Research Personnel; Resolution; Site; Spinal Cord; Standardization; Text; Therapeutic; Time; Toxic effect; Tracer; Translational Research; Treatment Efficacy; Uncertainty; United States National Institutes of Health; base; cancer therapy; chemotherapy; dosimetry; experience; improved; interest; man; neoplastic cell; osteosarcoma; patient population; prevent; prospective; response; single photon emission computed tomography; tool; treatment planning; tumor; wiki

DESCRIPTION (provided by applicant): Radiopharmaceutical therapy (RPT) is one of the few viable alternatives to chemotherapy for patients with metastatic cancer. In non-Hodgkin's lymphoma (NHL), RPT has yielded durable remissions in treatment- refractory patients. RPT is the only treatment for neuroendocrine and metastatic thyroid cancer and is an emerging treatment for metastatic ovarian, prostate and other cancers. ClinTrials.gov lists 136 radionuclide therapy trials. RPT is administered like chemotherapy, by assuming that a maximum tolerated administered activity (AA) defined in a dose escalation trial applies to all patients. Such generic dosing has led to conservative treatment, yielding low toxicity at the expense of tumor control. With prior NIH support we have developed a patient-specific dosimetry (PSD) methodology and have shown it to be superior to generic treatment by enabling, for example, more aggressive yet safe therapy of diffuse lung metastases in thyroid cancer and a combined XRT/RPT treatment plan for osteogenic sarcoma, boosting tumor dose while keeping adjacent spinal cord dose below the MTD. The objectives of this competing renewal application are to further improve accuracy and to evaluate overall impact on RPT. Specifically: 1. We propose to develop a method to enable micro-scale dosimetry from macro-scale (imaging) data. Imaging-based PSD accuracy is limited by imaging resolution. In some cases, micro-scale absorbed dose (AD) distributions are key to understanding and thereby avoiding normal organ toxicity. 2. In evaluating impact, statistical uncertainty is important to interpreting results and guiding treatment. We will develop a method to calculate the uncertainty and confidence level of dosimetry results. 3. Accrual of a large number of dose-response studies, in a standardized manner, is needed to evaluate the impact of Aims 1 and 2, and PSD, generally, on improving tumor control with RPT. The software package, 3-D Radiobiological Dosimetry (3D-RD) developed with prior NIH support, and revised in Aims 1 and 2, will be used to perform PSD calculations for a large number of existing and prospective, in- house, and collaborating institution studies. Single-institution studies yield limited data; 3D-RD analysis for collaborator studies leverages data from other sites and increases the patient population pool to yield a robust data set for dose-response studies. 4. 3D-RD includes radiobiological modeling for dose rate and dose non- uniformity. Parameters values for these models cannot currently be measured in individuals. Instead, literature values are used. Without standardization, different investigators/institutions will use different values making response comparisons across studies difficult. To support the standardization needed for the dose-response studies of aim 3 we will establish an on-line database of reference radiobiological parameter values. Such a database would be analogous to the ICRP reference man compilation of organ masses and compositions. RPT is a promising treatment for metastatic cancer. RPT is currently delivered according to a chemotherapy paradigm. Support for this proposal will help bring a rational, AD-based approach, to RPT delivery.

描述（由申请人提供）：对于转移性癌症患者，放射性药物治疗（RPT）是化疗的少数可行替代方案之一。在非霍奇金淋巴瘤 (NHL) 中，RPT 已使难治性患者获得持久缓解。 RPT是神经内分泌癌和转移性甲状腺癌的唯一治疗方法，也是转移性卵巢癌、前列腺癌和其他癌症的新兴治疗方法。 ClinTrials.gov 列出了 136 项放射性核素治疗试验。 RPT 的给药方式与化疗类似，假设剂量递增试验中定义的最大耐受给药活性 (AA) 适用于所有患者。这种通用剂量导致保守治疗，以牺牲肿瘤控制为代价产生低毒性。在 NIH 先前的支持下，我们开发了一种患者特异性剂量测定 (PSD) 方法，并通过对甲状腺癌弥漫性肺转移进行更积极且安全的治疗以及 XRT/RPT 联合治疗等方式证明其优于一般治疗成骨肉瘤的治疗计划，增加肿瘤剂量，同时保持邻近脊髓剂量低于 MTD。这一竞争性续订应用程序的目标是进一步提高准确性并评估对 RPT 的总体影响。具体来说： 1. 我们建议开发一种方法，能够根据宏观尺度（成像）数据进行微观尺度剂量测定。基于成像的 PSD 精度受到成像分辨率的限制。在某些情况下，微尺度吸收剂量（AD）分布是理解并避免正常器官毒性的关键。 2. 在评估影响时，统计不确定性对于解释结果和指导治疗很重要。我们将开发一种方法来计算剂量测定结果的不确定性和置信度。 3. 需要以标准化方式进行大量剂量反应研究，以评估目标 1 和 2 以及 PSD 对 RPT 改善肿瘤控制的总体影响。软件包 3-D 放射生物剂量测定 (3D-RD) 在 NIH 的先前支持下开发，并在目标 1 和 2 中进行了修订，将用于对大量现有和未来的、内部的和合作的项目执行 PSD 计算。机构研究。单一机构的研究得出的数据有限；合作者研究的 3D-RD 分析利用其他站点的数据并增加患者群体库，为剂量反应研究提供可靠的数据集。 4. 3D-RD 包括剂量率和剂量不均匀性的放射生物学模型。目前无法在个体中测量这些模型的参数值。相反，使用文献值。如果没有标准化，不同的研究人员/机构将使用不同的值，从而使研究之间的反应比较变得困难。为了支持目标 3 剂量反应研究所需的标准化，我们将建立一个参考放射生物学参数值的在线数据库。这样的数据库类似于 ICRP 参考人对器官质量和成分的汇编。 RPT 是一种有前景的转移性癌症治疗方法。 RPT 目前是根据化疗模式进行的。对该提案的支持将有助于为 RPT 交付带来合理的、基于 AD 的方法。