Rapid Response Monitoring with Circulating Tumor DNA in Metastatic Breast Cancer

转移性乳腺癌中循环肿瘤 DNA 的快速反应监测

基本信息

批准号：
10650926
负责人：
George Miles
金额：
$ 22.44万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650926
关键词：
Address Adverse reactions Allergic Reaction Automobile Driving Benchmarking Biological Biological Assay Biological Markers Blood Breast Cancer Patient CLIA certified Cancer Etiology Cancer Patient Cells Cessation of life Clinical Clinical Management Clinical Trials Collection Cost Savings Coupled DNA sequencing Data Detection Diagnosis Disease Disease Progression Distant Dose Drug Costs Evaluation Exposure to Flare Funding Genomics Half-Life Hybrids Hypersensitivity Image Immunotherapy Institution Intervention Investigation Kidney Diseases Laboratories Lead Malignant Neoplasms Metastatic breast cancer Methods Molecular Monitor Multicenter Trials Mutation Mutation Detection Neuropathy Oncology Organ Patients Peritoneum Pharmaceutical Preparations Plasma Positron-Emission Tomography Precision therapeutics Primary Neoplasm Process Prospective Studies Proteins Quality Control Quality of life Radiology Specialty Randomized Reporting Risk Sampling Scanning Site Staging Systemic Therapy Testing Time Toxic effect Tumor Biology Tumor Markers Tumor Promotion Tumor-Infiltrating Lymphocytes Underserved Population Variant X-Ray Computed Tomography advanced breast cancer advanced disease blood-based biomarker bone bone imaging burden of illness cancer therapy circulating DNA clinical care clinical trial enrollment computer framework cost cost effectiveness design digital digital measure effective therapy efficacy evaluation experience health inequalities high risk imaging modality improved ineffective therapies liquid biopsy malignant breast neoplasm minimally invasive molecular dynamics new therapeutic target next generation sequencing performance tests predictive marker procedure cost prognostication prospective radiological imaging response side effect standard of care targeted treatment treatment response trend tumor tumor DNA

项目摘要

Project Summary Breast cancer is the second most commonly diagnosed malignancy and distant spread to other organs is a leading cause of cancer death. The treatment of metastatic breast cancer remains very challenging and requires serial radiological monitoring to ensure that the patient is on the right treatment at the right time. This process typically requires repeat CT or PET imaging scans which are expensive and subject patients to potential adverse reactions, including contrast-related allergies and organ damage. The cost of radiological monitoring has increased dramatically, at least as rapid as drug costs. Furthermore, because the radiological testing is relatively infrequent, many stay on ineffective treatments too long. During this period the disease may progress, leaving the patient under-treated with prolonged exposure to unnecessary toxicities and at significant cost burden, especially with newer targeted-therapy drug classes. At the other end of the spectrum, patients with durable response may be assigned to prolonged radiological imaging over the course of their management. Genomic characterization of cancer has revolutionized our ability to decipher the complexities of tumor biology and promote more precise cancer treatments. Advances in DNA sequencing have enabled the detection of mutations in the tumor and now in tumor DNA that circulate in the blood (ctDNA). Cell-free circulating tumor DNA has been proposed as a surrogate biological sample to define the genetic change(s) of a primary tumor and/or metastatic disease in a cancer patient, and to serve as a biomarker for diagnosis, prognostication, and monitoring of response to therapy. However, next generation sequencing (NGS) ctDNA panels are expensive and are typically not reimbursed when used for serial monitoring of disease. In this application we propose a low-cost strategy for dynamic molecular monitoring of metastatic breast cancer patients using bespoke digital droplet PCR (ddPCR) assays constructed from a baseline NGS ctDNA test. We hypothesize that this hybrid approach will offer a substantial lead-time over radiological detection of disease progression, allowing for adaptive treatment changes that will reduce the time patients are exposed to ineffective treatment and exposure to unnecessary toxicities. This cost-saving effort will substantially improve disease monitoring in metastatic breast cancer patients, reduce toxicity associated with ineffective treatment, improve clinical trial enrollment and serve as a viable approach to addressing cancer health inequities among underserved populations with limited access to imaging due to the cost of these procedures.

项目摘要乳腺癌是第二个常见诊断的恶性肿瘤，并且远处传播到其他器官是癌症死亡的主要原因。转移性乳腺癌的治疗仍然非常具有挑战性，需要串行放射学监测，以确保患者在正确的时间进行正确的治疗。这个过程通常需要重复的CT或PET成像扫描，这些扫描价格昂贵，并受到潜在不利的对象反应，包括与对比相关的过敏和器官损伤。放射学监测的成本具有急剧增加，至少与药物成本一样快。此外，因为放射学测试相对很少有很多人在无效治疗上停留太久。在此期间，疾病可能会进展患者治疗的患者长期暴露于不必要的毒性，并承受着巨大的成本负担，特别是在较新的靶向治疗药物类别中。在光谱的另一端，耐用的患者在其管理过程中，可以将响应分配给长期放射学成像。癌症的基因组表征彻底改变了我们破译肿瘤生物学复杂性的能力并促进更精确的癌症治疗。 DNA测序的进步已使检测肿瘤中的突变，现在在血液中循环的肿瘤DNA中（ctDNA）。无细胞循环肿瘤 DNA已被认为是替代生物样品，以定义原发性肿瘤的遗传变化和/或癌症患者的转移性疾病，并作为诊断，预后和监测对治疗的反应。但是，下一代测序（NGS）CTDNA面板很昂贵通常，当用于疾病的串行监测时，通常不会偿还。在此应用程序中，我们提出了使用定制数字的转移性乳腺癌患者动态分子监测的低成本策略基线NGS CTDNA测试构建的液滴PCR（DDPCR）测定法。我们假设这种混合动力方法将在疾病进展的放射学检测方面提供大量的交付时间，从而使对于自适应治疗的变化，将减少患者暴露于无效治疗的时间并暴露于不必要的毒性。这项节省成本的工作将大大改善疾病监测在转移性乳腺癌患者中，降低与无效治疗相关的毒性，改善临床试验入学和作为解决贫乏的癌症健康不平等的可行方法由于这些程序的成本，访问成像的人群有限。