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

摘要/摘要 对乳腺癌异质性的日益了解导致了有希望的量身定制的治疗方法 以改善结果。I-SPY2试验是一项旨在测试新疗法的II期多中心试验 乳腺癌的治疗策略，并为随后的第三阶段测试快速确定有前景的候选治疗方法。 在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自适应 根据早期治疗反应指标调整NAC方向的战略。目标是改善以下方面的结果 患有2/3期乳腺癌的女性，复发风险仍然最高，并将化疗毒性降至最低 风险最低的女性。作为计划项目的组成部分，项目2将系统地开发综合 可用于基于个体的NAC治疗中期调整的影像预测模型 回应。这些模型最初将使用i-SPY2中现有的广泛的DCE-MRI数据库来开发， 随着时间的推移，随着时间的推移，来自最近增加的DWI和PET的成像数据增加了。信息 项目3中关于治疗耐药的分子决定因素将被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密切地研究残留病衡量标准之间的关系 MRI和组织病理学，以进一步提高MRI作为残留物的无创性替代品的能力 疾病。最后，认识到PET成像可能提供对药物作用机制的额外洞察 结合核磁共振成像，我们将开始通过在一个子集进行的试点研究来扩大PET的使用 使用专用乳房PET(DBPET)扫描仪的网站。项目2利用了大量现有的数据集 多代理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磁共振成像 实验性治疗。我们期待AIMS的成功完成，以提供更强大的非侵入性 影像方法将促进NAC的个性化并改善患者的整体预后 乳腺癌。

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.