Dose-Response in Radionuclide Therapy

放射性核素治疗的剂量反应

• 批准号: 8184649
• 负责人: George Sgouros
• 金额: $ 37.15万
• 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/8184649
• 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. PUBLIC HEALTH RELEVANCE: Targeted radionuclide therapy is an emerging modality for cancer therapy that involves the delivery of radioactive atoms using carriers that preferentially bind to tumor cells. Such treatment is best implemented with patient-specific dosimetry calculations. Support of this proposal will develop the methodology and tools needed to improve radiopharmaceutical therapy by implementing a patient-specific, absorbed-dose-based approach to treatment.

描述（由申请人提供）：放射性药物治疗（RPT）是转移性癌症患者化学疗法的少数可行替代方法之一。在非霍奇金的淋巴瘤（NHL）中，RPT在治疗难治性患者中持续了持久的缓解。 RPT是神经内分泌和转移性甲状腺癌的唯一治疗方法，是一种新兴的转移性卵巢，前列腺和其他癌症的治疗方法。 Clintrials.gov列出了136次放射性核素治疗试验。通过假设在剂量升级试验中定义的最大耐受性活性（AA），将RPT像化学疗法一样给药。这种通用剂量导致了保守治疗，以控制肿瘤控制的代价低毒性。在先前的NIH支持下，我们已经开发了一种患者特异性剂量法（PSD）方法，并通过使甲状腺癌中的弥漫性肺转移和XRT/RPT的弥漫性肺转移疗法（例如，更具侵略性但安全的肺转移疗法）表现出优于通用治疗方法。成骨肉瘤的治疗计划，增加肿瘤剂量，同时将相邻的脊髓剂量保持在MTD以下。这种竞争性更新应用的目标是进一步提高准确性并评估对RPT的整体影响。具体：1。我们建议开发一种从宏尺度（成像）数据启用微尺度剂量测定的方法。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。我们将开发一种计算剂量测定结果的不确定性和置信度的方法。 3。需要以标准化的方式进行大量剂量反应研究来评估目标1和2的影响，而PSD通常对通过RPT改善肿瘤控制的影响。该软件包，3D放射性剂量测定法（3D-RD），并在AIMS 1和2中进行了修订，将用于对大量现有和潜在的，内部和协作进行PSD计算机构研究。单机构研究产生有限的数据；合作者研究的3D-RD分析利用来自其他站点的数据，并增加了患者人群库，以产生剂量反应研究的强大数据集。 4。3D-RD包括用于剂量速率和剂量非均匀性的放射生物学建模。这些模型的参数值当前无法在个人中进行测量。相反，使用文献价值。如果没有标准化，不同的研究人员/机构将使用不同的值，从而使整个研究的响应比较困难。为了支持目标3的剂量反应研究所需的标准化，我们将建立一个在线数据库的参考放射生物学参数值。这样的数据库将类似于ICRP的器官质量和组成的参考人物汇编。 RPT是转移性癌症的有前途的治疗方法。 RPT目前是根据化学疗法范例进行的。对该建议的支持将有助于带来理性的，基于广告的方法，以交付RPT。 公共卫生相关性：靶向放射性核素治疗是一种癌症治疗的新兴方式，涉及使用优先结合肿瘤细胞的载体递送放射性原子。最好通过患者特异性剂量计算来实施这种治疗方法。该建议的支持将开发通过实施一种基于患者的，吸收剂量的治疗方法来改善放射性药物治疗所需的方法和工具。