Lung Cancer Prognosis: FLT PET and DNA Hypermethylation

肺癌预后：FLT PET 和 DNA 高甲基化

• 批准号: 6956139
• 负责人: HUBERT J VESSELLE
• 金额: $ 54.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6956139
• 关键词: DNA methylation; bioimaging /biomedical imaging; biomarker; cell proliferation; clinical research; human subject; lung imaging /visualization /scanning; neoplasm /cancer classification /staging; nonsmall cell lung cancer; positron emission tomography; prognosis; radiotracer

DESCRIPTION (provided by applicant): Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Thirty percent of patients with NSCLC are classified as stage I or II at time of presentation and undergo primary surgical resection with curative intent. However, as a result of initially undiagnosed microscopic metastases, over 50% will develop recurrent disease within two years of surgery. Recent studies have demonstrated that post-resection chemotherapy increases survival of stage I/II patients. But chemotherapy is associated with considerable morbidity and cost. Thus, an accurate method is needed for identifying patients at high risk of recurrence who would benefit most from such additional therapy, while sparing the patients at low risk of recurrence. Currently there is no way of preoperatively and non-invasively identifying the subset of stage I/II NSCLC patients who will recur post resection. Current preoperative staging of NSCLC by 2-[F-18]fluoro-2-deoxy- D-glucose (FDG) Positron Emission Tomography (PET) imaging and Computed Tomography does not permit identification of microscopic metastases. Further, although several studies have suggested that FDG uptake in the primary tumor could predict survival, these studies did not adjust uptake values for size of primary tumor, which is a well-established predictor of survival. When such adjustments are made, FDG uptake is no longer prognostic. Thus new approaches for non-invasive and preoperative prognostic assessment of NSCLC patients are needed. In the proposed study we hypothesize that the uptake of the new radiotracer, 3'-deoxy-3'- [F18]fluorothymidine (FLT), at PET, used in combination with detection of a panel of hypermethylated genes can provide a sensitive and specific approach to identification of stage I/II NSCLC patients at high risk of recurrence after surgical resection. Support for our hypothesis concerning the prognostic utility of FLT used in combination with tissue and/or blood-based biomarkers comes from 1) our pilot studies demonstrating that primary tumor FLT uptake strongly correlates with cellular proliferation, a known predictor of prognosis; 2) studies demonstrating the relationship between detection of 20 hypermethylated genes (in tissue or plasma) and the presence and behavior of cancers including NSCLC. This prognostic information will permit individualization and optimization of therapy for the 41,000 early stage NSCLC patients undergoing surgical resection each year in the United States.

描述（由申请人提供）：非小细胞肺癌（NSCLC）是美国癌症死亡的主要原因。30%的非小细胞肺癌患者在发病时被分类为I期或II期，并接受初步手术切除以达到治愈目的。然而，由于最初未确诊的显微转移，超过50%的患者会在手术后两年内复发。最近的研究表明，术后化疗可提高I/II期患者的生存率。但是化疗的发病率和费用都很高。因此，需要一种准确的方法来确定哪些复发风险高的患者将从这种额外的治疗中获益最多，同时保留低复发风险的患者。