Role of ctDNA change as a response measure in the EA1183 patient population and how ctDNA changes correlate with metabolic response by serial FDG PET/CT

ctDNA 变化作为 EA1183 患者群体反应指标的作用以及 ctDNA 变化如何与连续 FDG PET/CT 的代谢反应相关

• 批准号: 10671013
• 负责人: Jennifer Marie Specht
• 金额: $ 25.49万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671013
• 关键词: American College of Radiology Imaging Network; Biological Assay; Biological Markers; Blood; Categories; Classification; Clinical; Clinical Trials; Collection; Data Set; Disease; Disease Progression; Eastern Cooperative Oncology Group; Enrollment; Exclusion; Future; Generations; Genomics; Goals; Guidelines; Image; Lesion; Liquid substance; Malignant Bone Neoplasm; Measurable Disease; Measurement; Measures; Metabolic; Metastatic Neoplasm to the Bone; Metastatic breast cancer; Methods; Modality; Monitor; Multi-Institutional Clinical Trial; Outcome; Outcome Study; PET/CT scan; Patients; Prediction of Response to Therapy; Progression-Free Survivals; Residual Neoplasm; Resistance; Role; Scanning; Site; Systemic Therapy; Testing; Time; Tracer; Tumor Biology; Tumor Markers; X-Ray Computed Tomography; blood-based biomarker; bone; burden of illness; cancer therapy; circulating biomarkers; clinical practice; clinical predictors; design; experience; fluorodeoxyglucose positron emission tomography; genome sequencing; glucose metabolism; imaging biomarker; improved; liquid biopsy; malignant breast neoplasm; patient population; patient response; predicting response; prospective; response; skeletal-related events; tool; treatment response; tumor; tumor DNA; tumor metabolism; uptake; whole genome

Project Summary: Patients with bone dominant (BD) and bone only (BO) metastatic breast cancer (MBC) represent a large patient population1,2 who are often excluded from clinical trials using RECIST 1.1 as the primary response assessment because bone lesions are classified as non-measurable, non-target lesions3. Current blood-based biomarkers such as tumor markers (CA15.3, CA27.29 and CEA) have similarly shown limited utility in assessing response to therapy in patients with MBC. There is therefore an important need for better measures of therapeutic response for patients with BD MBC. EA1183 FEATURE is a prospective, multicenter clinical trial approved by the NCI and sponsored by ECOG-ACRIN designed to evaluate the value of serial FDG-PET/CT to assess response in BD MBC. The trial will test the ability of tumor metabolic changes to predict the clinically meaningful outcomes of progression free survival (PFS) and time to skeletal-related event (tSRE). Measurement and characterization of ctDNA provides an option of non-invasively evaluating both disease burden and emergence of genomic changes in tumor biology. We propose to integrate fluid-based tumor monitoring (by serial collection of circulating tumor DNA, ctDNA) and FDG-PET/CT imaging to determine if these biomarkers, separately or combined, can predict a response to therapy for in patients with BO or BD MBC participating in the EA1183 FEATURE trial. We will also assess the extent to which FDG-PET/CT, ctDNA, or both can predict PFS as early as 4 weeks into therapy. We hypothesize that integration of imaging (FDG-PET/CT) and fluid-based, liquid biopsy (ctDNA) assays may permit characterization of therapy response for patients with BO and BD MBC in advance of currently used methods, possibly as early as 4 weeks. This R01 proposal will provide support for additional objectives in EA1183, which are the aims of our proposal: 1.) to assess ability of qualitative and quantitative changes in serial ctDNA measures to predict PFS and time to SRE in patients with BO or BD MBC beginning new systemic therapy in EA1183; 2) to determine if early metabolic changes in bone metastases assessed by FDG-PET/CT at 4 weeks after start of systemic therapy predict PFS and tSRE in patients with BO or BD MBC; 3) to evaluate the relationship between changes in ctDNA and metabolic response as assessed by FDG-PET/CT and to test the combined ability of FDG-PET/CT and ctDNA at 4 and 12 weeks after the start of new systemic therapy to predict PFS and SRE. The outcome of this study will be the generation of robust response endpoints for BD MBC to provide access to clinical trials and guide clinic al practice for the large group of patients with this type of MBC.

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