FDG PET and Biomarkers in Treatment Response in Advanced Ovarian Cancer

FDG PET 和生物标志物在晚期卵巢癌治疗反应中的作用

• 批准号: 7673239
• 负责人: Joseph G Rajendran
• 金额: $ 35.61万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673239
• 关键词: Abdomen; Algorithms; Biological Assay; Biological Markers; Biological Markers; CA-125 Antigen; Cancer Patient; Cause of Death; Characteristics; Chemotherapy-Oncologic Procedure; Classification; Classification Scheme; Clinical; Combined Modality Therapy; Coupled; Data; Decision Making; Disease; Disease Resistance; Disease-Free Survival; Drug resistance; Early identification; Early treatment; Epidermal Growth Factor Receptor; Epithelial ovarian cancer; Evaluation; Extreme drug resistant tuberculosis; Foundations; Future; Glycolysis; Goals; Grant; Gynecologic; Her2/erbb2/neu Staining Method; Image; Immunohistochemistry; Individual; Institutes; Kinetics; Lead; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Metabolic; Metabolism; Methods; Modification; Monitor; Neoadjuvant Therapy; Operative Surgical Procedures; Outcome; PTGS2 gene; Patients; Peritonitis; Pharmaceutical Preparations; Phase; Pilot Projects; Platelet-Derived Growth Factor; Platinum; Platinum Compounds; Positron-Emission Tomography; Reaction Time; Recurrence; Reporting; Research Design; Resistance; Role; Scanning; Selection for Treatments; Serum; Staging; Therapeutic Agents; Time; Tissue Sample; Tissues; Toxic effect; Treatment Protocols; Treatment outcome; Trees; Tumor Burden; Tumor Debulking; Tumor Markers; Universities; Vascular Endothelial Growth Factors; Washington; Woman; advanced disease; alternative treatment; base; chemotherapy; clinical practice; disorder control; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; improved; innovation; molecular marker; novel; novel strategies; novel therapeutics; outcome forecast; prognostic; prognostic indicator; public health relevance; response; trait; treatment response; treatment strategy; tumor; uptake

DESCRIPTION (provided by applicant): The primary goal of this project is to evaluate the role of FDG PET and its ability to predict early treatment response and to correlate with bio-molecular markers of treatment resistance in advanced epithelial ovarian cancer (AOC). A vast majority of ovarian cancer patients present with advanced stages of the disease and are managed using tumor reductive surgery, followed by multi-agent platinum-based chemotherapy. In nearly one quarter of the cases, in order to achieve effective disease control, neoadjuvant chemotherapy is given prior to surgical debulking. In spite of aggressive treatment approaches, most women with AOC are likely to die with chemotherapy resistant disease and identifying these patients is key, since this may allow early treatment modifications, avoiding prolonged treatment with futile toxic chemotherapy regimens. This project will focus on two roles of F-18 Fluorodeoxyglucose (FDG) PET: (a) to evaluate early response of AOC to chemotherapy and (b) as an independent prognostic indicator. Our proposal is the first such study using serial FDG PET scans with quantitative approaches using kinetic analysis to accurately evaluate treatment response in patients with AOC undergoing neoadjuvant chemotherapy and correlating it with biomarkers of tumor aggressiveness and drug resistance (many of which may be targets for novel therapeutic agents) in evaluating treatment resistance and response. The specific aims are: (1) Correlate the changes in FDG uptake from serial FDG scans with early treatment response and clinical endpoints; (2) Determine the association between FDG PET measure of glycolysis and biomarkers of chemoresistance and tumor burden (serum CA125 levels) using classification and regression tree (CART) analysis to measure the overall aggressive potential and provide a clinical decision support framework that could personalize therapy by directing eligible patients to novel targeted/combination therapies. Using serial FDG scans (FDG 2 & 3) taken during the course of neoadjuvant chemotherapy, we will determine if patients who show a significant decrease in FDG uptake will have a better and longer lasting response to treatment. The last FDG scan (FDG PET #3) will help in evaluating non-responsive disease and help direct tissue sampling at the time of surgery. We will also investigate the role of quantitative measures such as the metabolic rate of FDG (Ki) vis-`-vis semi-quantitative specific uptake value (SUV) measure in the prognostic evaluation of AOC patients. We will correlate FDG uptake in tumors with molecular markers of chemoresistance in characterizing tumor aggressiveness and treatment response in these patients. The results from this pilot study will lead to a classification algorithm that combines FDG and biomarker data (using CART analysis) for identifying chemoresistant patients and would provide a measure of aggressiveness of ovarian cancer. Early identification of non-responders will help design studies that allow introduction of alternative treatment regimens. This will lay the foundation for future large-scale studies and more rational treatment selection to improve survival in patients with AOC. PUBLIC HEALTH RELEVANCE: This pilot study will set the stage for large scale trials by exploring the non-invasive role for FDG PET imaging along with biomarkers in evaluating aggressiveness and early treatment response in patients with advanced ovarian cancer. Identification of drug resistance and lack of response to chemotherapy will guide in selecting alternative treatment regimens and help avoid unnecessary toxicities in non-responders.

描述（由申请人提供）：该项目的主要目标是评估 FDG PET 的作用及其预测早期治疗反应的能力，以及与晚期上皮性卵巢癌 (AOC) 治疗耐药的生物分子标志物的相关性。绝大多数卵巢癌患者已处于疾病晚期，并通过肿瘤缩小手术进行治疗，然后进行多药铂类化疗。在近四分之一的病例中，为了实现有效的疾病控制，在手术减瘤之前进行新辅助化疗。尽管采取了积极的治疗方法，大多数患有 AOC 的女性仍可能死于化疗耐药性疾病，识别这些患者是关键，因为这可能允许及早调整治疗方案，避免长时间使用无效的有毒化疗方案进行治疗。该项目将重点关注 F-18 氟脱氧葡萄糖 (FDG) PET 的两个作用：(a) 评估 AOC 对化疗的早期反应；(b) 作为独立的预后指标。我们的提案是第一个此类研究，使用连续 FDG PET 扫描和定量方法，使用动力学分析来准确评估接受新辅助化疗的 AOC 患者的治疗反应，并将其与肿瘤侵袭性和耐药性的生物标志物相关联（其中许多可能是新的靶点）治疗剂）来评估治疗耐药性和反应。具体目标是：（1）将连续 FDG 扫描中 FDG 摄取的变化与早期治疗反应和临床终点相关联； (2) 使用分类和回归树 (CART) 分析确定糖酵解的 FDG PET 测量与化疗耐药和肿瘤负荷（血清 CA125 水平）的生物标志物之间的关联，以测量整体侵袭潜力并提供可以个性化治疗的临床决策支持框架通过指导符合条件的患者接受新型靶向/联合疗法。使用新辅助化疗过程中进行的连续 FDG 扫描（FDG 2 和 3），我们将确定 FDG 摄取显着下降的患者是否会对治疗产生更好、更持久的反应。最后一次 FDG 扫描（FDG PET #3）将有助于评估无反应性疾病，并有助于在手术时直接进行组织取样。我们还将研究定量测量的作用，例如 FDG 代谢率 (Ki) 与半定量比摄取值 (SUV) 测量在 AOC 患者预后评估中的作用。我们将把肿瘤中的 FDG 摄取与化疗耐药的分子标志物联系起来，以表征这些患者的肿瘤侵袭性和治疗反应。这项试点研究的结果将产生一种分类算法，该算法结合 FDG 和生物标志物数据（使用 CART 分析）来识别化疗耐药患者，并提供卵巢癌侵袭性的衡量标准。及早识别无反应者将有助于设计研究，从而引入替代治疗方案。这将为未来的大规模研究和更合理的治疗选择以提高 AOC 患者的生存奠定基础。公共健康相关性：这项试点研究将通过探索 FDG PET 成像以及生物标志物在评估晚期卵巢癌患者的侵袭性和早期治疗反应方面的非侵入性作用，为大规模试验奠定基础。耐药性和化疗缺乏反应的鉴定将指导选择替代治疗方案，并有助于避免无反应者出现不必要的毒性。