权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

MRI-Guided Radiotherapy and Biomarkers for Prostate Cancer

前列腺癌的 MRI 引导放射治疗和生物标志物

基本信息

批准号：
8125083
负责人：
Alan Pollack
金额：
$ 30.8万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-10 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8125083
关键词：
Aftercare Age Area Biochemical Biological Markers Biopsy Bystander Effect Caliber California Cancer Patient Cell Death Clinic Clinical Clinical Management Clinical Trials Collection Contrast Media Data Development Disease Dose Endothelial Cells Ensure External Beam Radiation Therapy Foundations Future Gadolinium Heterogeneity Image Immunohistochemistry Injection of therapeutic agent Intercellular Fluid Lead Left Lesion Life Magnetic Resonance Imaging Malignant neoplasm of prostate Maps Measures Methods Modeling Molecular Abnormality Natural History Normal tissue morphology Outcome Patients Pattern Pattern Recognition Permeability Phase I Clinical Trials Poaceae Prostate Prostatic Neoplasms Radiation Radiation therapy Radical Prostatectomy Relapse Risk Series Shapes Source Staging System Techniques Time Tissues Toxic effect Translating Transrectal Ultrasound Tumor Burden Tumor Tissue Tumor Volume Ultrasonography Variant arm base cell killing clinical practice follow-up gadolinium oxide high risk improved in vivo indexing men molecular marker neoplastic cell novel novel strategies pressure public health relevance randomized trial tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): Long-term follow up of prostate cancer patients treated with radiation therapy (RT) reveals that almost half suffer a relapse. Moreover, there is some evidence to support that the regions in the prostate with the greatest tumor burden are the regions that are at highest risk of harboring persistent disease after RT. We propose to use a novel method of high-dose ablative RT delivery to the tumor volume identified by imaging studies. Multiparameter MRI, and in particular Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) is very promising for the in vivo 3D localization of the tumor area. We have developed a novel approach for analysis of DCE-MRI based on an unsupervised pattern recognition technique. Our preliminary data suggest that the technique is sensitive in detecting the presence/absence of tumor and its results can be directly translated to the RT planning system for tailored radiation dose delivery. The RT technique, deemed Lattice Extreme Ablative Dose (LEAD) RT, involves the creation of high doses shaped in cylinders through the DCE- MRI defined region(s) and adjacent apparently normal prostate in a lattice framework. We propose a single- arm phase I clinical trial for LEAD RT delivery in a single fraction of 12-14 Gy prior to standard fractions (2.0 Gy per day) for an additional 76 Gy. The hypothesized benefits of the approach are induction of tumor endothelial cell death and possibly bystander effects including reduced tumor interstitial fluid pressure in densely populated tumors due to rapid cell kill. We also hypothesize that the resulting improved oxygenation of the tumor tissue will enhance the effect of the standard external beam RT component. By using dose cylinders with small diameters (6-7 mm) and not attempting to cover the full extent of the tumor, normal tissues will be more easily spared. As more men are presenting with prostate cancer at younger ages and are living longer, the need to ensure complete tumor cell eradication after RT, while keeping normal tissue toxicity and complications low is of paramount importance for the clinical management of the disease. In this proposal we also aim to develop an approach for obtaining biomarkers from directed biopsies using DCE-MRI tumor maps fused to real-time transrectal ultrasound images via the ArtemisTM system (Eigen Inc., Grass Valley, California). Biomarkers from biopsies from the index lesion(s) will be compared to those from tumor in other areas of the prostate. We will establish a novel approach to assessing biomarkers in these aggressive areas versus other tumor regions, which will better set the stage for identifying how molecular abnormalities dictate patient outcome during radiotherapy. PUBLIC HEALTH RELEVANCE: We propose to use a novel method for delivery of an ablative radiation dose to define by imaging. tumor area in the prostate. By using concentrated dose cylinders with small diameter normal tissues will be more easily spared while potentially eradicating the tumor cells successfully. We will determine the feasibility and toxicity of the approach in a Phase I clinical trial.

描述(申请人提供)：对接受放射治疗(RT)的前列腺癌患者进行的长期随访显示，几乎一半的患者复发。此外，有一些证据支持前列腺中肿瘤负担最重的区域是放疗后持续疾病风险最高的区域。我们建议使用一种新的方法，高剂量的消融性RT传输到通过成像研究确定的肿瘤体积。多参数磁共振成像，特别是动态增强磁共振成像(DCE-MRI)在活体肿瘤区域三维定位方面具有很好的应用前景。我们开发了一种新的基于无监督模式识别技术的DCE-MRI分析方法。我们的初步数据表明，该技术在检测肿瘤的存在/不存在方面是敏感的，其结果可以直接转换到RT计划系统，以进行量身定制的放射剂量传递。放射治疗技术被认为是格子极限消融剂量(LEAD)放射治疗，涉及通过DCE-MRI定义区(S)和晶格框架中相邻的明显正常的前列腺创建高剂量圆柱形。我们建议进行一项单臂I期临床试验，先于标准剂量(2.0Gy日)进行单次12-14Gy铅放射治疗，再进行76Gy.该方法的假设好处是诱导肿瘤内皮细胞死亡和可能的旁观者效应，包括由于快速细胞杀伤而降低了人口稠密肿瘤的肿瘤间质液体压力。我们还假设，由此产生的肿瘤组织氧合的改善将增强标准外束RT组件的效果。通过使用小直径(6-7毫米)的剂量圆柱体，并且不试图覆盖肿瘤的全部范围，正常组织将更容易幸免。随着越来越多的男性在更年轻的年龄和更长的寿命中出现前列腺癌，需要确保放疗后肿瘤细胞完全根除，同时保持正常组织毒性和并发症较低，这对该疾病的临床治疗至关重要。在这项提案中，我们还致力于开发一种方法，通过ArtemisTM系统(Eigen Inc.，Grass Valley，California)使用DCE-MRI肿瘤地图与实时经直肠超声图像融合，从定向活检中获得生物标记物。来自指标性病变(S)活检的生物标记物将与来自前列腺其他区域肿瘤的生物标记物进行比较。我们将建立一种新的方法来评估这些侵袭性区域与其他肿瘤区域的生物标记物，这将更好地为确定放射治疗期间分子异常如何决定患者结果奠定基础。公共卫生相关性：我们建议使用一种新的方法来提供消融性辐射剂量，以通过成像来定义。前列腺中的肿瘤区。通过使用小直径的浓缩剂量柱，正常组织将更容易幸免，同时有可能成功根除肿瘤细胞。我们将在I期临床试验中确定该方法的可行性和毒性。