Project 02 - Non-invasive imaging metrics for determining non-response

项目 02 - 用于确定无反应的非侵入性成像指标

• 批准号: 10013138
• 负责人: Nola M. Hylton-Watson
• 金额: $ 33.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-08 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10013138
• 关键词: American College of Radiology Imaging Network; Biological; Biopsy; Breast; Cancer Burden; Characteristics; Classification; Clinical; Clinical Research; Clinical Trials; Custom; Data; Data Set; Databases; Diagnostic; Diffusion Magnetic Resonance Imaging; Early treatment; Enrollment; Goals; Guidelines; Heterogeneity; Histopathology; Image; Intervention; Link; Magnetic Resonance Imaging; Measurement; Measures; Modeling; Modification; Molecular; Monitor; Multicenter Trials; Neoadjuvant Therapy; Nodal; Operative Surgical Procedures; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Phase; Pilot Projects; Positron-Emission Tomography; Primary Neoplasm; Recurrence; Residual Cancers; Residual Tumors; Risk; Sensitivity and Specificity; Sequential Treatment; Site; Testing; Time; Toxic effect; Woman; base; biological heterogeneity; chemotherapy; determinants of treatment resistance; drug mechanism; fluorodeoxyglucose; high risk; imaging modality; improved; improved outcome; individual response; individualized medicine; insight; malignant breast neoplasm; non-invasive imaging; phase 3 testing; predicting response; predictive modeling; prognostic; prognostic value; programs; repository; response; risk minimization; serial imaging; targeted treatment; therapeutic candidate; treatment optimization; treatment response; treatment strategy; trial design; tumor

ABSTRACT/SUMMARY Increasing understanding of the heterogeneity of breast cancer is leading to tailored therapies that hold promise for improving outcomes. The I-SPY2 TRIAL is a phase II, multicenter trial designed to test new treatment strategies for breast cancer and to quickly identify promising candidate therapies for subsequent phase III testing. MRI is used in I-SPY2 to monitor primary tumor response to neoadjuvant chemotherapy (NAC) and to provide prognostic information. The overall objective of the Program Project is to develop and implement an adaptive strategy to redirect NAC based on early treatment response indicators. The goal is to improve outcomes for women with stage 2/3 breast cancer who remain at highest risk for recurrence, and minimize chemo-toxicities in women at lowest risk. As a component of the Program Project, Project 2 will systematically develop integrated imaging predictive models that can be used to decide mid-treatment modification of NAC based on individual response. These models will be initially developed using the extensive existing DCE-MRI database in I-SPY2, and augmented over time with imaging data emerging from more recent addition of DWI and PET. Information from Project 3 about molecular determinants of treatment resistance will be used to further refine the prognostic ability of imaging models. We will look more closely at the relationship between measures of residual disease by MRI and histopathology, in order to further improve MRI's ability to serve as a non-invasive surrogate of residual disease. Lastly, recognizing that PET imaging may provide additional insight into drug mechanism of action in combination with MRI, we will begin to expand the use of PET through a pilot study performed at a sub-set of sites using dedicated breast PET (dbPET) scanners. Project 2 leverages the substantial existing data set from the multi-agent I-SPY2 clinical trial, consisting of serial MRIs linked to outcomes for over 1000 subjects receiving experimental treatments. We expect the successful completion of aims to afford more powerful non-invasive imaging methods that will facilitate the personalization of NAC and improve overall outcomes for patients with breast cancer.

摘要/总结 对乳腺癌异质性的了解不断加深，有望带来有希望的定制疗法 以改善结果。 I-SPY2 试验是一项 II 期、多中心试验，旨在测试新疗法 乳腺癌的策略，并快速确定有希望的候选疗法用于后续的 III 期测试。 I-SPY2 中使用 MRI 来监测原发肿瘤对新辅助化疗 (NAC) 的反应并提供 预后信息。该计划项目的总体目标是开发和实施适应性 根据早期治疗反应指标重新定向 NAC 的策略。目标是改善结果 患有 2/3 期乳腺癌的女性仍然处于复发风险最高的状态，并最大限度地减少化疗毒性 风险最低的女性。作为该计划项目的组成部分，项目2将系统地开发集成的 影像预测模型可用于根据个体情况决定 NAC 的治疗中期修改 回复。这些模型最初将使用 I-SPY2 中广泛的现有 DCE-MRI 数据库进行开发， 并随着时间的推移，通过最近添加的 DWI 和 PET 产生的成像数据进行增强。信息 项目 3 中关于治疗耐药性的分子决定因素将用于进一步完善预后 成像模型的能力。我们将通过以下方式更仔细地研究残留疾病测量之间的关系： MRI 和组织病理学，以进一步提高 MRI 作为残留物非侵入性替代的能力 疾病。最后，认识到 PET 成像可以提供对药物作用机制的额外见解 与 MRI 相结合，我们将通过在一组子集进行的试点研究来开始扩大 PET 的使用 使用专用乳房 PET (dbPET) 扫描仪的站点。项目 2 利用了来自 多药物 I-SPY2 临床试验，包括与 1000 多名接受治疗的受试者的结果相关的系列 MRI 实验性治疗。我们期望成功完成目标，提供更强大的非侵入性 成像方法将促进 NAC 的个性化并改善患有以下疾病的患者的总体结果 乳腺癌。