FLT-PET/CT for Therapy Monitoring of DLBCL

FLT-PET/CT 用于 DLBCL 治疗监测

• 批准号: 8265619
• 负责人: Luis Fayad
• 金额: $ 63.18万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265619
• 关键词: Affect; Area; Biopsy; Cell Proliferation; Cells; Combined Modality Therapy; Data; Development; Disease; Disease Progression; Disease-Free Survival; Enrollment; Event; Image; Infiltration; Inflammatory; Institution; International Prognostic Index; Investigation; Lead; Lymphoma; Malignant Neoplasms; Methods; Monitor; Nature; Negative Finding; Outcome; Patients; Positron-Emission Tomography; Predictive Value; Radiation therapy; Reporting; Research Design; Research Methodology; Residual Tumors; Scanning; Staging; Testing; Time; Tracer; X-Ray Computed Tomography; chemotherapy; clinical practice; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; in vivo; indexing; large cell Diffuse non-Hodgkin' s lymphoma; macrophage; molecular imaging; monocyte; neoplastic cell; novel; prognostic; response; rituximab; tool; tumor; tumor specificity; uptake

DESCRIPTION (provided by applicant): Currently for lymphoma patients, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/ computed tomography (CT) is used for interim restaging or therapy monitoring after 1-4 cycles of chemo-/chemoimmunotherapy. An excellent negative predictive value (NPV) of > 80% with only a moderate positive predictive value (PPV) of between 25%- 70% has been reported. It has been shown that a substantial portion of the false-positive FDG-PET findings in this setting were caused by early post-therapy inflammatory changes. This hampers the accuracy and reliability of this test and, hence, its acceptance as an early prognostic tool in the clinical practice setting. An important recent advance in the area of molecular imaging of lymphoma is the development of the PET tracer18F-fluorothymidine (FLT) as an in vivo marker of cell proliferation. FLT uptake in lymphomas has been shown to be proportional to the Ki-67 index, a recognized histopathological marker of cell proliferation and since less affected by postherapy inflammatory changes caused by macrophages/monocyte infiltration, it is also a more tumor-specific tracer when compared to FDG. This higher tumor- specificity may be advantageous in early response assessment following chemo-/chemoimmunotherapy, radiation therapy (RT) or combined modality therapy. In this application, we propose to compare the predictive values of interim FLT- PET/CT and FGD-PET/CT in diffuse large B-cell lymphoma (DLBCL) patients after 2 cycles of R-CHOP chemotherapy. Our hypothesis is that FLT-PET/CT will have a substantially higher PPV when compared to FDG-PET/CT (i.e., e 91% vs. d 68%) while providing a similar or only slightly lower NPV and, therefore, prove superior to FDG-PET in this setting. We propose to prospectively study 137 DLBCL patients at 5 institutions. Study patients will be scanned by FLT-PET/CT and FDG-PET/CT 18-24 days after the second cycle of R-CHOP. After completion of six cycles of chemotherapy, conventional staging methods (CSM) will be performed in all patients to assess response and determine appropriate patient management. Patients will be followed for event-free survival (EFS) and overall survival (OS) for at least 24 months post- therapy or until definite determination of persistent disease (by biopsy) or disease progression (both considered an event). Specifically, we intend to: 1. Investigate whether the PPV of FLT-PET/CT is significantly higher (i.e., e 91% vs. d 68%) than that of FDG-PET/CT by following-up patients for at least 24 months posttherapy or until evidence of or disease progression. 2. Investigate whether the EFS of patients with FDG-PET/CT-positive and FLT-PET/CT negative scans is not significantly lower than that of patients with concordantly negative FDG-PET/CT and FLT-PET/CT scans (i.e., < 65% vs. 85%) and, therefore confirming that the NPV of FLT-PET/CT is similar to that of FDG-PET/CT. 3. Correlate interim FLT- PET/CT and FDG-PET/CT with the International Prognostic Index (IPI), a well-established predictor of outcome in DLBCL. The demonstration of superiority of FLT-PET/CT over FDG-PET/CT is expected to lead to greater confidence in using interim PET in patient management. This increased reliability could potentially even render repeat biopsy unnecessary for midtherapy treatment decisions. This would represent a significant advance in the use of PET imaging for personalized therapy with an expectedly positive impact on patient management and/or outcome of patients with DLBCL.

描述（由申请人提供）：目前针对淋巴瘤患者，18F氟脱氧葡萄糖（FDG） - positron发射断层扫描（PET）/计算机断层扫描（CT）用于1-4循环化学 - /化学疗法后进行中及时restaging或治疗监测。据报道，仅报道了一个出色的阴性预测值（NPV）> 80％，仅报告了中等正预测值（PPV）在25％-70％之间。已经表明，在这种情况下，大部分假阳性FDG-PET发现是由早期疗法后炎症性变化引起的。这缩减了该测试的准确性和可靠性，因此，它在临床实践环境中接受了早期预后工具。淋巴瘤分子成像区域的一个重要进展是PET痕迹18F-氟噻甲别发（FLT）作为细胞增殖的体内标记。淋巴瘤中的FLT摄取已被证明与Ki-67指数成正比，这是一种公认​​的细胞增殖组织病理学标志物，并且由于与FDG相比，巨噬细胞/单核细胞浸润引起的巨噬细胞/单核细胞浸润引起的炎症性炎症变化较小，因此它也是更大的肿瘤特异性示意剂。在化学/化学免疫疗法，放射治疗（RT）或组合局部疗法后，这种较高的肿瘤特异性在早期反应评估中可能是有利的。在此应用中，我们建议在2个循环的R-Chop化学疗法周期后比较弥漫性大B细胞淋巴瘤（DLBCL）患者中临时FLT-PET/CT和FGD-PET/CT的预测值。我们的假设是，与FDG-PET/CT相比，FLT-PET/CT的PPV将大大较高（即E 91％vs. D 68％），而在这种情况下提供了相似或仅略低的NPV，因此在这种情况下证明了比FDG-PET优越。我们建议在5个机构中前瞻性研究137名DLBCL患者。在第二个R-Chop周期后18-24天，将通过FLT-PET/CT和FDG-PET/CT/CT扫描研究患者。完成六个化疗周期后，将在所有患者中进行常规分期方法（CSM），以评估反应并确定适当的患者管理。在治疗后至少24个月，或直到确定持续性疾病（通过活检）或疾病进展（均认为是事件），将遵循患者至少24个月的无事件生存期（EFS）和总生存期（OS）。具体而言，我们打算：1。研究FLT-PET/CT的PPV是否明显更高（即E 91％vs. D 68％）比FDG-PET/CT的pPV通过跟踪24个月后的患者或直到疾病进展或疾病进展的证据。 2。研究FDG-PET/CT阳性和FLT-PET/CT阴性扫描患者的EFS是否显着低于与一致的FDG-PET/CT/CT和FLT-PET/CT扫描（即<65％vs. 85％）的患者的EFS，因此确认了FLT/CT的NPV。 3。将临时PET/CT和FDG-PET/CT与国际预后指数（IPI）相关联，这是DLBCL结果的公认预测指标。 FLT-PET/CT优于FDG-PET/CT的优越性预计将使使用临时PET在患者管理中提高信心。这种提高的可靠性甚至可能使重复活检对于中治疗的决策不必要。这将代表使用PET成像进行个性化疗法的重大进步，并对DLBCL患者的患者管理和/或结果产生积极影响。