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型技术，图像引导的骨髓比较强度调节疗法（IG-BMS-IMRT）是否可以降低患者的血液毒性（HT）接受并发化疗和骨盆放射疗法（CRT）。辐射诱导的HT是一个重大的临床问题，限制了骨盆恶性肿瘤患者可以进行化学疗法的强度。次要目标是确定骨髓（BM）子区域的功能特性，并验证一种新型的MRI技术来量化BM脂肪含量。具体目的是：（SA1）测试IG-BMS-IMRT是否会减少接受化学放疗的宫颈癌患者的HT； （SA2）确定“临界” 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相对降低50％。我们将在50名患者的前瞻性II期多机构临床试验中检验这一假设，其主要HT的主要终点。我们将获取基线18f-3'-fluoro-3'-脱氧-L-胸腺苷发射断层扫描（FLT-PET）和定量脂肪分数MRI扫描以识别活跃的BM子区域。我们将根据先前开发的协议进行细分BM，然后将其用作IMRT计划期间的主要回避结构。主动BM的剂量限制来自我们开发的以前的毒性模型。我们将获得治疗后和后脂肪分数MRI扫描，以量化BM子区域的变化。作为次要分析，我们将使用基于高维数据分析和可变形图像注册的先前开发的技术来测试“关键”中FLT示踪剂的吸收和FF的变化更大的“关键”。对于AIM 2，我们将测试MR脂肪分数估计在不同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法相关。该项目的最终结果将确定IG-BMS-IMRT是否对毒性具有强大的生理原理和临床上的显着影响，并将确定该方法是否应该继续前进到III期试验与常规RT。 公共卫生相关性：在这个项目中，我们将测试现代辐射技术（强度调节辐射疗法（IMRT））是否旨在备用功能性骨髓子区域，该区域通过18f-3'-fluoro-3'-deoxy-deoxy-deoxy-deoxy-deoxy- L-胸腺苷正电子发射断层扫描（FLT-PET）和定量磁共振脂肪分数成像（理想）可以降低接受化学疗法和放射线的宫颈癌患者的血液学毒性。我们还进行次要分析以测试特定骨髓子区域的功能特性，以验证骨髓成像的理想技术。这项研究很重要，因为辐射诱导的血液学毒性通常是骨盆恶性肿瘤患者的最佳化疗递送的障碍，因此，骨髓的IMRT技术将具有广泛的适用性。