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: 10249155
• 负责人: Nola M. Hylton-Watson
• 金额: $ 33.8万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249155
• 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增加，这导致了有希望的定制治疗 来改善结果。I-SPY 2试验是一项II期多中心试验，旨在测试新的治疗方法 该研究旨在为乳腺癌提供有效的治疗策略，并为随后的III期试验快速确定有希望的候选疗法。 在I-SPY 2中使用MRI监测原发肿瘤对新辅助化疗（NAC）的反应，并提供 预测信息该计划项目的总体目标是制定和实施一个适应性的 根据早期治疗反应指标重新定向NAC的战略。目标是改善结果， 患有2/3期乳腺癌的女性复发风险仍然最高，并最大限度地减少化疗毒性 女性风险最低。作为该计划项目的一个组成部分，项目2将系统地开发综合 成像预测模型，可用于根据个体情况决定NAC的治疗中期调整 反应这些模型最初将使用I-SPY 2中广泛的现有DCE-MRI数据库开发， 并且随着时间的推移，利用从最近增加的DWI和PET中出现的成像数据来增强。信息 来自项目3的关于治疗耐药的分子决定因素的研究将用于进一步完善预后 成像模型的能力。我们将通过以下方法更仔细地研究残留疾病指标之间的关系： MRI和组织病理学，以进一步提高MRI作为残留的非侵入性替代物的能力 疾病最后，认识到PET成像可以为药物作用机制提供额外的见解， 结合MRI，我们将开始扩大PET的使用，通过在一个子集进行的试点研究， 使用专用乳腺PET（dbPET）扫描仪的研究中心。项目2利用了大量现有数据集， 多药物I-SPY 2临床试验，包括与1000多名接受 实验性治疗我们期待着目标的顺利完成，以提供更强大的非侵入性 成像方法，将促进NAC的个性化，并改善患者的整体结果， 乳腺癌