FLT PET to Plan the Best Therapy for Lung Cancer

描述（由申请人提供）： 在美国，每年约有45，000名新患者被诊断患有局部晚期非小细胞肺癌（III期NSCLC）。这样的疾病程度排除了大多数原发性切除术，目前，最好的生存率是通过同时给予化疗和放疗，然后对一些患者进行手术切除，或对另一些患者进行额外的化疗。然而，选择患者进行任何一种治疗方法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，对其的研究仍处于经验性阶段。这些局限性部分是由于无法用标准的基于解剖学的成像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。这些困难由于缺乏能够预测或跟踪肿瘤反应的肿瘤标志物而变得更加复杂。拟定的研究计划通过在放化疗之前和结束时使用FDG PET和FLT（3 '-脱氧-3'-[F-18]氟胸苷）PET评估III期NSCLC患者，开发一种新的更准确的肿瘤缓解测量方法。将PET成像结果与临床和病理肿瘤缓解以及患者结局进行比较。虽然FDG PET已被证明是一种有效和准确的分期工具，在未经治疗的患者，其疗效的评价原发性肿瘤和淋巴结的反应是有限的。然而，FDG PET将提供有关放射治疗端口以外的远处转移性疾病的发展的有价值的信息，这是总体反应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，使其非常适合评估NSCLC对放化疗的反应。我们还建议将这些双重示踪剂研究与肿瘤细胞衍生的增殖和肿瘤抗性标记物进行比较，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，通过使用PET衍生的反应措施和Escheren衍生的耐药措施来预测III期NSCLC患者接受放化疗治疗的结果。本研究将构成FLT作为PET显像剂评估肿瘤对治疗反应的初步验证。在本研究结束时，在III期NSCLC的反应中获得的见解将使临床医生能够为这些患者计划最佳治疗。

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.