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）。这种疾病程度使得大多数患者无法进行一期切除术，目前，通过同时进行化疗和放疗，然后对某些患者进行手术切除，或对另一些患者进行额外的化疗，可以实现最佳生存率。然而，尚未建立选择患者接受任一治疗方法的明确标准。此外，III 期 NSCLC 的最佳治疗方案尚不清楚，且仍需凭经验进行寻找。这些限制部分是由于无法使用标准的基于解剖学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。拟议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，开发一种新颖且更准确的肿瘤反应测量方法。 PET 成像结果将与临床和病理肿瘤反应以及患者结果进行比较。尽管 FDG PET 已证明其作为未经治疗患者的分期工具的有用性和准确性，但其在评估原发肿瘤和淋巴结反应方面的功效有限。然而，FDG PET 将提供有关放射治疗端口外远处转移性疾病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示踪剂研究与肿瘤标本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重要性。最后，我们建议开发一个模型，通过使用 PET 衍生的反应测量和标本衍生的耐药测量来预测接受放化疗的 III 期 NSCLC 患者的结果。这项研究将初步验证 FLT 作为 PET 显像剂来评估肿瘤对治疗的反应。在这项研究结束时，从 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规划最佳治疗方案。

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.