FLT PET to Plan the Best Therapy for Lung Cancer

FLT PET 规划肺癌最佳治疗方案

• 批准号: 6874458
• 负责人: HUBERT J VESSELLE
• 金额: $ 41.06万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874458
• 关键词: biomarker; cell proliferation; clinical chemistry; clinical research; combination cancer therapy; diagnosis design /evaluation; diagnosis quality /standard; human subject; human therapy evaluation; immunocytochemistry; lung imaging /visualization /scanning; metastasis; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer radiation therapy; neoplasm /cancer surgery; neoplastic process; nonsmall cell lung cancer; outcomes research; patient care planning; positron emission tomography; protein biosynthesis; reagent /indicator; therapy design /development; western blottings

DESCRIPTION (provided by applicant): Approximately 45,000 new patients are diagnosed with locally advanced non-small cell lung cancer (stage III NSCLC) each year in the United States. Such disease extent precludes a primary resection for most and at the present time, the best survival rates are achieved by administering concurrent chemotherapy and radiotherapy followed by surgical resection for some or by additional chemotherapy for others. However, definite criteria to select patients for either therapeutic approach are not established. Furthermore, the optimal therapy for stage III NSCLC is not yet known and the search for it remains empirical. These limitations result in part from an inability to assess the response of these tumors to chemoradiotherapy with standard anatomically based imaging as Computed Tomography (CT) often overestimates or underestimates residual tumor after therapy. These difficulties are compounded by the lack of tumor markers able to predict or track tumor response. The proposed study plans to develop a novel and more accurate measure of tumor response by evaluating stage III NSCLC patients with FDG PET and FLT (3'-deoxy-3'-[F-18]fluorothymidine) PET prior to and at the conclusion of chemoradiotherapy. PET imaging findings will be compared to clinical and pathological tumor response and to patient outcome. Although FDG PET has demonstrated its usefulness and accuracy as a staging tool in untreated patients, its efficacy in the evaluation of the primary tumor and lymph node response is limited. However, FDG PET will provide valuable information regarding the development of distant metastatic disease outside of radiotherapy ports, an important aspect of the overall response assessment. The new tracer FLT has shown its potential as a tracer of cellular proliferation in lung cancer making it ideally suited to evaluating NSCLC response to chemoradiotherapy. We also propose to make comparisons of these dual tracer studies with tumor specimen-derived markers of proliferation and tumor resistance to validate the significance of FLT uptake in tumor response. Finally, we propose to develop a model to predict the outcome of stage III NSCLC patients treated with chemoradiotherapy by using PET-derived measures of response and specimen-derived measures of resistance. This study will constitute the initial validation of FLT as a PET imaging agent to assess tumor response to therapy. At the conclusion of this study, the insight gained in the response of stage III NSCLCs will allow clinicians to plan the best therapy for these patients.

描述（由申请人提供）： 在美国，大约有45,000名新患者被诊断出患有局部晚期非小细胞肺癌（III期NSCLC）。这种疾病程度排除了大多数和目前的主要切除术，通过进行同时进行化学疗法和放射疗法，然后进行手术切除，或者通过对其他人进行其他化学疗法来实现最佳生存率。但是，尚未确定选择任何一种治疗方法的患者的明确标准。此外，尚不清楚第三阶段NSCLC的最佳疗法，并且对其进行搜索仍然是经验性的。这些局限性的部分原因是无法评估这些肿瘤对化学放射疗法的反应，而标准的基于解剖学的成像通常是计算机断层扫描（CT），通常会高估或低估治疗后残留的肿瘤。由于缺乏能够预测或跟踪肿瘤反应的肿瘤标记，这些困难使这些困难更加复杂。拟议的研究计划通过评估FDG PET和FLT的III期NSCLC患者（3'-Deoxy-3' - [F-18]氟噻氨酰胺）PET，以开发一种新颖，更准确的肿瘤反应测量。化学放疗。 PET成像发现将与临床和病理肿瘤反应以及患者结局进行比较。尽管FDG PET在未经治疗的患者中证明了其作为分期工具的有用性和准确性，但其在评估原发性肿瘤和淋巴结反应中的功效受到限制。但是，FDG PET将提供有关放射疗法端口以外远处转移性疾病发展的有价值的信息，这是整体反应评估的重要方面。新的示踪剂FLT显示出其作为肺癌细胞增殖的示踪剂的潜力，因此非常适合评估NSCLC对化学放疗的反应。我们还建议将这些双重示踪剂研究与肿瘤标本衍生的增殖和抗肿瘤耐药性标记进行比较，以验证FLT摄取在肿瘤反应中的重要性。最后，我们建议开发一个模型，以预测通过使用PET衍生的反应和标本衍生的耐药度测量的测量方法，以预测接受化学放射治疗的III期NSCLC患者的结果。这项研究将构成FLT作为宠物成像剂的初步验证，以评估肿瘤对治疗的反应。在这项研究的结论中，在III期NSCLC的反应中获得的洞察力将使临床医生可以为这些患者计划最佳疗法。