Comb External Beam Radiotherapy with 153Sm-EDTMP to Treat High Risk

使用 153Sm-EDTMP 梳状外照射放射治疗治疗高风险

• 批准号: 9549230
• 负责人: David M. Loeb
• 金额: $ 2.97万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9549230
• 关键词: Aftercare; Avidity; Biological; Biological Markers; Characteristics; Clinical; Clinical Trials; Comb animal structure; Computer software; Data; Development; Diagnostic radiologic examination; Dose; Excision; External Beam Radiation Therapy; Foundations; Generations; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Hypoxia; Individual; Infusion procedures; Intensity-Modulated Radiotherapy; Lesion; Measures; Miso; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Operative Surgical Procedures; Organ; Patients; Phase II Clinical Trials; Positron-Emission Tomography; Publishing; Radiation; Radiation therapy; Radiopharmaceuticals; Resistance; Samarium SM 153 lexidronam; Stable Disease; Techniques; Testing; Therapeutic; Toxic effect; Tracer; Treatment Efficacy; Treatment Protocols; Unresectable; Variant; Work; base; chemotherapy; combinatorial; cytotoxic radiation; cytotoxicity; dosage; dosimetry; experience; free radical oxygen; high risk; indexing; novel; osteosarcoma; phase 2 study; predicting response; prospective; public health relevance; radioresistant; response; treatment planning; treatment response; treatment strategy; tumor

DESCRIPTION (provided by applicant): Radiation therapy is rarely used in the treatment of osteosarcoma. The dose required to provide effective local control (80-100 Gy) causes too much damage to surrounding normal tissue to be delivered routinely and safely. Despite the introduction of effective systemic chemotherapy, osteosarcoma patients who cannot achieve a complete surgical resection are never cured. Thus, there is an urgent need for the development of effective local control measures for patients whose tumors are unresectable. Our group has been studying a radiopharmaceutical, 153Sm-EDTMP, for this purpose. This agent can deliver cytotoxic radiation to tumors with exquisite precision, sparing surrounding normal tissue more than 2 mm away. So far, efficacy has been limited because of difficulties delivering sufficient radiation by this means. In the proposed clinical trial, we are testing the hypothesis that tandem treatments with 153Sm-EDTMP can deliver sufficient radiation to allow more tolerable doses of external beam radiotherapy to be administered, and that if the biological equivalent dose of the combination treatment reaches 80-100 Gy, effective local control can be accomplished. Our project will also test the hypothesis that calculating the tumor absorbed dose after administration of a small activity of 153Sm-EDTMP will allow us to calculate a larger activity to administer that will allow us to precisely reach our target dose of 80-100 Gy. Our published work has demonstrated a linear relationship between administered activity and absorbed dose in each patient (though not between patients) after administration of fixed amounts of activity. Our current treatment plan will allow variation in the second administration, with the administered activity to be based on dosimetry calculations after the first treatment. Finally, in previous clincal trials we found little correlation between tumor absorbed dose and clinical response. It is not clear what characteristics account for this variable response to treatment. Hypoxic tumors are less responsive to standard radiation than normoxic tumors, probably because part of the cytotoxicity of radiation therapy involves the generation of oxygen free radicals. We will use a novel technique, [18F]-MISO PET to test the hypothesis that hypoxia makes tumors resistant to radiopharmaceuticals, just as it contributes to resistance to external beam radiotherapy. In summary, this work will build on our prior experience treating osteosarcoma patients with 153Sm-EDTMP, using individualized dosing, combining the radiopharmaceutical with standard external beam radiotherapy, and evaluating the ability of [18F]-MISO PET to predict response to therapy. These results will allow us to continue to develop this promising agent for a group of patients not normally treated with radiation. In addition, this treatment approach can provide the basis for combining radiopharmaceuticals with external beam radiotherapy for other tumor types as well.

描述（由申请人提供）：放射治疗很少用于骨肉瘤的治疗。提供有效局部控制所需的剂量（80-100戈瑞）会对周围正常组织造成太大的损伤，无法常规和安全地提供。尽管引入了有效的全身化疗，但不能完全手术切除的骨肉瘤患者永远无法治愈。因此，对于肿瘤不能切除的患者，迫切需要制定有效的局部控制措施。为此，我们小组一直在研究一种放射性药物，153Sm-EDTMP。这种药物可以精确地向肿瘤传递细胞毒性辐射，使周围正常组织远离2毫米。到目前为止，由于难以通过这种方式提供足够的辐射，效果有限。在拟议的临床试验中，我们正在测试假设，153Sm-EDTMP串联治疗可以提供足够的辐射，允许更耐受的外束放疗剂量，如果联合治疗的生物等效剂量达到80-100 Gy，可以实现有效的局部控制。我们的项目还将验证计算给药后肿瘤吸收剂量的假设