Image-guided bone marrow-sparing IMRT for cervical cancer

图像引导保留骨髓的 IMRT 治疗宫颈癌

• 批准号: 8204379
• 负责人: Loren K. Mell
• 金额: $ 32.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-12 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204379
• 关键词: Accounting; Acute; Aftercare; Antibiotics; Anus; Biochemical; Biological Assay; Bone Marrow; Bone Marrow Aspiration; Bone Marrow Stem Cell; Cancer Patient; Cervical; Clinical; Data; Data Analyses; Doctor of Medicine; Dose; Fatty acid glycerol esters; Functional Imaging; Growth Factor; Hospitalization; Image; Imaging Techniques; Infection; Intensity-Modulated Radiotherapy; Lead; Location; MRI Scans; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Maps; Marrow; Measures; Methods; Modeling; Multi-Institutional Clinical Trial; Myelosuppression; Normal tissue morphology; Outcome; Pathologic; Patients; Pelvic Cancer; Pelvis; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Physiological; Positron-Emission Tomography; Property; Protocols documentation; Radiation; Radiation Dose Unit; Radiation therapy; Relative (related person); Research; Sampling; Specimen; Statistical Models; Structure; Techniques; Testing; Thymidine; Toxic effect; Tracer; Variant; Vulva; X-Ray Computed Tomography; base; cell injury; chemotherapy; clinically relevant; clinically significant; design; hip bone; image registration; improved; innovation; irradiation; novel; prospective; response; spine bone structure; therapy design; uptake

DESCRIPTION (provided by applicant): The primary objective of the proposed research is to test whether a novel technique, image-guided bone marrow-sparing intensity modulated radiation therapy (IG-BMS-IMRT), can reduce hematologic toxicity (HT) in patients receiving concurrent chemotherapy and pelvic radiation therapy (CRT). Radiation-induced HT is a significant clinical problem limiting the intensity of chemotherapy that can be delivered in patients with pelvic malignancies. Secondary objectives are to determine the functional properties of bone marrow (BM) subregions and to validate a novel MRI technique to quantify BM fat content. The specific aims are: (SA1) to test whether IG-BMS-IMRT will reduce HT for cervical cancer patients undergoing chemoradiotherapy; (SA2) to determine the functional properties of "critical" BM subregions in which models have found that increased radiation dose leads to increased HT; and (SA3) to validate the technical and biochemical properties of MR fat quantification techniques in bone marrow specimens. Our main hypothesis is that IG-BMS-IMRT will lead to a relative reduction of acute HT of 50% compared to historical controls. We will test this hypothesis in a prospective phase II multi-institutional clinical trial of 50 patients, with the primary endpoint of acute HT. We will acquire baseline 18F-3'-fluoro-3'-deoxy-L-thymidine positron emission tomography (FLT-PET) and quantitative fat fraction MRI scans to identify active BM subregions. We will segment the BM based on a previously developed protocol, then use this as a primary avoidance structure during IMRT planning. Dosimetric limits on active BM are derived from previous toxicity models we developed. We will obtain mid- and post-treatment fat fraction MRI scans to quantify changes in BM subregions. As a secondary analysis, we will test the hypothesis that FLT tracer uptake and changes in FF are greater in "critical" compared to non-"critical" BM subregions, using previously developed techniques based on high-dimensional data analysis and deformable image registration. For aim 2, we will test whether MR fat fraction estimates are stable under varying protocol conditions, and whether they correlate with biochemical and histological assays of fat content. The end result of this project will determine whether IG-BMS-IMRT has a strong physiologic rationale and clinically significant impact on toxicity, and will determine whether this approach should move forward to a phase III trial versus conventional RT. PUBLIC HEALTH RELEVANCE: In this project, we will test whether a modern radiation technique (intensity modulated radiation therapy (IMRT)) designed to spare functional bone marrow subregions, identified by a combination of 18F-3'-fluoro-3'- deoxy-L-thymidine positron emission tomography (FLT-PET) and quantitative magnetic resonance fat fraction imaging (IDEAL), can reduce hematologic toxicity in cervical cancer patients undergoing chemotherapy and radiation. We also perform secondary analysis to test functional properties of specific bone marrow subregions to validate the IDEAL technique for bone marrow imaging. The study is important because radiation-induced hematologic toxicity is a barrier to optimal chemotherapy delivery in general for patients with pelvic malignancies, so bone marrow-sparing IMRT techniques would have wide applicability.

描述（由申请人提供）：拟议研究的主要目的是测试一种新技术，即图像引导骨髓保留强度调制放射治疗（IG-BMS-IMRT）是否可以减少接受同步化疗和盆腔放射治疗（CRT）的患者的血液毒性（HT）。放射诱发的 HT 是一个重要的临床问题，限制了盆腔恶性肿瘤患者化疗的强度。次要目标是确定骨髓 (BM) 分区的功能特性，并验证量化 BM 脂肪含量的新型 MRI 技术。具体目的是：（SA1）测试IG-BMS-IMRT是否会降低接受放化疗的宫颈癌患者的HT； (SA2) 确定“关键”BM 子区域的功能特性，其中模型发现辐射剂量增加会导致 HT 增加； (SA3) 验证骨髓标本中 MR 脂肪定量技术的技术和生化特性。我们的主要假设是，与历史对照相比，IG-BMS-IMRT 将导致急性 HT 相对减少 50%。我们将在一项有 50 名患者参加的前瞻性 II 期多机构临床试验中检验这一假设，主要终点是急性 HT。我们将获取基线 18F-3'-氟-3'-脱氧-L-胸苷正电子发射断层扫描 (FLT-PET) 和定量脂肪分数 MRI 扫描，以识别活跃的 BM 分区。我们将根据先前开发的协议对 BM 进行分段，然后在 IMRT 计划期间将其用作主要回避结构。活性 BM 的剂量限值源自我们之前开发的毒性模型。我们将获得治疗中期和治疗后的脂肪分数 MRI 扫描，以量化 BM 分区的变化。作为二次分析，我们将使用先前开发的基于高维数据分析和可变形图像配准的技术来测试以下假设：与非“关键”BM 子区域相比，“关键”区域中 FLT 示踪剂的吸收和 FF 的变化更大。对于目标 2，我们将测试 MR 脂肪分数估计值在不同的方案条件下是否稳定，以及它们是否与脂肪含量的生化和组织学测定相关。该项目的最终结果将确定 IG-BMS-IMRT 是否具有强大的生理学原理和对毒性的临床显着影响，并将确定该方法与传统 RT 相比是否应进入 III 期试验。 公共健康相关性：在本项目中，我们将测试旨在保护功能性骨髓分区的现代放射技术（调强放射治疗 (IMRT)）是否可以减少以下疾病的血液毒性：该技术通过 18F-3'-氟-3'-脱氧-L-胸苷正电子发射断层扫描 (FLT-PET) 和定量磁共振脂肪分数成像 (IDEAL) 相结合进行鉴定。 接受化疗和放疗的宫颈癌患者。我们还进行二次分析来测试特定骨髓分区的功能特性，以验证用于骨髓成像的 IDEAL 技术。这项研究很重要，因为放射引起的血液毒性通常是盆腔恶性肿瘤患者最佳化疗的障碍，因此保留骨髓的 IMRT 技术将具有广泛的适用性。