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: 7059330
• 负责人: HUBERT J VESSELLE
• 金额: $ 41.3万
• 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 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7059330
• 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，每年约有45000名新患者被诊断为局部晚期非小细胞肺癌(III期非小细胞肺癌)。这样的疾病范围在大多数情况下排除了一次切除的可能性，目前，通过同时进行化疗和放射治疗，然后对一些患者进行手术切除，或者对另一些患者进行额外的化疗，可以获得最佳的存活率。然而，为任何一种治疗方法选择患者的明确标准尚未建立。此外，III期NSCLC的最佳治疗方法尚不清楚，寻找它的方法仍然是经验性的。这些局限性的部分原因是无法用标准的基于解剖的成像来评估这些肿瘤对放化疗的反应，因为计算机断层扫描(CT)经常高估或低估治疗后的残留肿瘤。由于缺乏能够预测或跟踪肿瘤反应的肿瘤标志物，这些困难变得更加复杂。这项拟议的研究计划开发一种新的、更准确的肿瘤反应测量方法，通过在化疗前和化疗结束时使用FDGPET和Flt(3‘-脱氧-3’-[F-18]氟胸苷)PET来评估III期NSCLC患者。PET成像结果将与临床和病理肿瘤反应以及患者预后进行比较。虽然FDGPET已证明其作为未经治疗的患者的分期工具的有效性和准确性，但其在评估原发肿瘤和淋巴结反应方面的有效性是有限的。然而，FDGPET将提供有关放射治疗端口外远处转移疾病发展的有价值的信息，这是总体疗效评估的一个重要方面。新的示踪剂Flt已显示出其作为肺癌细胞增殖示踪剂的潜力，使其非常适合于评估非小细胞肺癌对放化疗的反应。我们还建议将这些双重示踪研究与肿瘤标本衍生的增殖和肿瘤耐药标记物进行比较，以验证Flt摄取在肿瘤反应中的意义。最后，我们建议开发一个模型来预测接受放化疗的III期非小细胞肺癌患者的结果，使用PET衍生的反应测量和标本衍生的耐药性测量。这项研究将初步验证Flt作为一种PET显像剂来评估肿瘤对治疗的反应。在这项研究的结论中，从III期NSCLC的反应中获得的洞察力将使临床医生能够为这些患者计划最佳的治疗方案。