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

• 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
• 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

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 乳腺癌是第二个最常见的诊断恶性肿瘤，远距离扩散到其他器官是一个危险因素。 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， 连续放射学监测，以确保患者在正确的时间接受正确的治疗。这个过程 通常需要重复的CT或PET成像扫描，这是昂贵的并且使患者遭受潜在的不利影响。 反应，包括造影剂相关过敏和器官损伤。放射性监测的费用 急剧增加，至少和药物成本一样快。此外，由于放射性测试相对 罕见的是，许多人停留在无效的治疗太长时间。在此期间，疾病可能会进展， 患者治疗不足，长时间暴露于不必要的毒性，并承受巨大的成本负担， 尤其是新型靶向治疗药物。在另一端，患有持久性 在其管理过程中，可将反应归因于延长的放射成像。 癌症的基因组特征已经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测序的进步使得能够检测 肿瘤中的突变，现在在血液中循环的肿瘤DNA（ctDNA）中。无细胞循环肿瘤 DNA已被提议作为替代生物样品来定义原发性肿瘤的遗传变化 和/或转移性疾病的生物标记物，并用作诊断、鉴别和治疗癌症的生物标记物。 监测对治疗的反应。然而，下一代测序（NGS）ctDNA板是昂贵的 并且当用于疾病的连续监测时通常不报销。在本申请中，我们提出了一种 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 从基线NGS ctDNA测试构建的液滴PCR（ddPCR）测定。我们假设这个混血儿 该方法将为疾病进展的放射学检测提供大量的提前期， 适应性治疗的变化，将减少病人暴露于无效治疗的时间 以及暴露在不必要的毒性中这一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，降低与无效治疗相关毒性，改善临床试验 登记，并作为一个可行的方法，以解决癌症的健康不公平的服务不足 由于这些程序的成本，限制了对成像的访问的人群。