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并与晚期上皮卵巢癌（AOC）中治疗耐药性的生物分子标志物相关的能力。绝大多数卵巢癌患者都患有该疾病的晚期阶段，并使用肿瘤还原性手术进行治疗，然后进行多药铂基化疗。在近四分之一的病例中，为了实现有效的疾病控制，在手术延伸之前，给予新辅助化疗。尽管采用了积极的治疗方法，但大多数患有AOC的女性可能会因抗化疗疾病而死亡，并确定这些患者是关键，因为这可能会允许早期治疗改性，从而避免使用徒劳的有毒化学疗法治疗长期治疗。该项目将重点介绍F-18氟氧化葡萄糖（FDG）PET的两个角色：（a）评估AOC对化学疗法的早期反应，以及（b）作为独立的预后指标。我们的建议是使用动力学分析的定量方法使用串行FDG PET扫描的第一项此类研究，以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（其中许多可能是新型治疗剂的靶标），以评估治疗耐药性和抗药性。具体目的是：（1）将串行FDG扫描的FDG吸收变化与早期治疗反应和临床终点相关联； （2）通过分类和回归树（CART）分析，确定FDG PET糖酵解和化学耐药性和肿瘤负担（血清CA125水平）的生物标志物之间的关联，以衡量整体积极的潜在潜力，并提供一个临床决策支持框架，并可以通过将合格的患者引导到新颖的靶向/组合组合治疗中，从而提供个性化治疗。使用在新辅助化疗过程中进行的连续FDG扫描（FDG 2和3），我们将确定表现出的FDG摄取量显着降低的患者是否会对治疗产生更好，更长的持久反应。最后一次FDG扫描（FDG PET＃3）将有助于评估非反应性疾病，并有助于在手术时进行组织采样。我们还将研究定量测量的作用，例如FDG（KI）的代谢率（Ki）vis-vis半定量特异性摄取量（SUV）量度在AOC患者的预后评估中。我们将与化学耐药性分子标记物在肿瘤中的肿瘤中的FDG摄取相关联，以表征这些患者的肿瘤侵袭性和治疗反应。这项试验研究的结果将导致一种分类算法，该算法结合了FDG和生物标志物数据（使用CART分析），以识别化学抗性患者，并提供衡量卵巢癌的侵略性。早期鉴定非反应者将有助于设计研究，以引入替代治疗方案。这将为未来的大规模研究和更多合理的治疗选择奠定基础，以改善AOC患者的生存。公共卫生相关性：这项试点研究将通过探索FDG PET成像的非侵入性作用以及生物标志物在评估卵巢癌患者评估侵略性和早期治疗反应方面的非侵入性作用，为大规模试验奠定了基础。鉴定耐药性和对化学疗法的缺乏反应将指导选择替代治疗方案，并有助于避免非反应者中不必要的毒性。