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.

项目概要乳腺癌是第二大最常见的恶性肿瘤，并且远处扩散到其他器官是一种常见的癌症。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，需要一系列放射学监测，以确保患者在正确的时间接受正确的治疗。这个过程通常需要重复进行 CT 或 PET 成像扫描，费用昂贵且使患者面临潜在的不良反应反应，包括对比剂相关的过敏和器官损伤。放射监测费用急剧增加，至少与药品成本一样快。此外，由于放射性检测相对很少见，许多人接受无效治疗的时间太长。在此期间，疾病可能会进展，导致患者因长期接触不必要的毒性而得不到充分治疗，并承受巨大的费用负担，尤其是新的靶向治疗药物类别。另一方面，患有持久疾病的患者在治疗过程中，反应可能会被分配给长时间的放射成像。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准的癌症治疗。 DNA 测序技术的进步使得检测肿瘤中的突变以及现在在血液中循环的肿瘤 DNA (ctDNA) 中的突变。无细胞循环肿瘤 DNA 已被提议作为替代生物样本来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、预测和治疗的生物标志物监测治疗反应。然而，下一代测序 (NGS) ctDNA panel 价格昂贵当用于疾病的连续监测时通常不会得到报销。在此应用中，我们提出了一个使用定制数字技术对转移性乳腺癌患者进行动态分子监测的低成本策略根据基线 NGS ctDNA 测试构建的液滴 PCR (ddPCR) 检测。我们假设这种混合体该方法将比疾病进展的放射学检测提供更长的前置时间，从而允许进行适应性治疗改变，以减少患者接受无效治疗的时间以及接触不必要的毒性。这种节省成本的努力将大大改善疾病监测在转移性乳腺癌患者中，减少与无效治疗相关的毒性，改善临床试验入学率，并作为解决服务不足的癌症健康不平等问题的可行方法由于这些程序的成本，获得成像的机会有限的人群。