Development and Validation of Prognostic Radiomic Markers of Response and Recurrence for Patients with Colorectal Liver Metastases

总结 结直肠癌是美国癌症相关死亡率的第二大原因。超过50% 的结直肠癌患者在其一生中会发生肝转移，存活率<10%， 近三年这种疾病的一个主要治疗问题是没有肝细胞癌的预后标志物。 复发或预测治疗前的反应是已知的。这项研究的目的是填补这一空白， 提供用于个性化治疗的非侵入性和客观的预后定量成像标记物， 结直肠肝转移（CRLM）。我们的单机构数据支持定量成像特征 从常规CT扫描中提取的数据预测对全身和区域化疗的体积反应， 识别肝脏复发风险高和生存率低的患者。在开发这些新的 由于缺乏优化、标准化和验证，这些都是临床使用的关键障碍，因此限制了标记物的使用。 本应用程序的目标是通过标准化图像来开发和验证强大的成像功能 采集，以改善临床试验使用的自动化工具，并验证成像的预测能力 具有外部数据的特征。我们与德克萨斯大学医学博士安德森癌症中心合作， Rensselaer Polytechnic Institute和GE Research，促进拟议的 技术进入全球医疗中心。我们的中心假设是定量CT成像 这些特征为预测CRLM的缓解、肝脏复发和生存提供了新的可靠指标 患者具体而言，我们将（1）利用外部数据验证预测性和预后性成像特征，（2） 前瞻性评估对比增强CT成像特征的重复性和再现性，以及（3） 通过充分利用正弦图数据，开发一个综合的放射学管道。我们已经集结了一批 来自外科、肿瘤内科、病理学、放射学、生物统计学和图像分析领域的专家。结合 在西方世界CRLM最大的临床经验，这种应用是一个独特的和无与伦比的 有机会定义CRLM的放射组学。集成到现有的临床工作流程中意味着小型医疗 没有高度专业化的放射学小组的中心将受益于两个开发的预测算法， 通过低成本的软件更新，成功完成我们的目标将提供有效的 具有常规临床使用途径的预后成像标记物，这对于 提高这种致命疾病的患者存活率。

SUMMARY Colorectal cancer is the second leading cause of cancer-related mortality in the United States. More than 50% of patients with colorectal cancer will develop liver metastases in their lifetime with a dismal <10% surviving past three years. A major therapeutic problem in this disease is that no markers prognostic of hepatic recurrence or predictive of response prior to treatment are known. The goal of this research is to fill this gap by providing non-invasive and objective prognostic quantitative imaging markers for personalized treatment of colorectal liver metastases (CRLM). Our single-institution data support that quantitative imaging features extracted from routine CT scans predict volumetric response to systemic and regional chemotherapy and identify patients at high risk of hepatic recurrence and poor survival. Progress in developing these novel markers is limited by a lack of optimization, standardization, and validation, all critical barriers to clinical use. The objectives of this application are to develop and validate robust imaging features by standardizing image acquisition, to improve automated tools for clinical trial use, and to validate the predictive power of imaging features with external data. We have partnered with University of Texas MD Anderson Cancer Center, Rensselaer Polytechnic Institute, and GE Research, facilitating the widespread integration of the proposed technology into medical centers worldwide. Our central hypothesis is that quantitative CT-based imaging features provide novel and robust indices for predicting response, hepatic recurrence, and survival in CRLM patients. Specifically, we will (1) validate predictive and prognostic imaging features with external data, (2) prospectively assess repeatability and reproducibility of contrast-enhanced CT imaging features, and (3) develop an integrated rawdiomics pipeline by fully utilizing sinogram data. We have assembled a critical mass of experts in surgery, medical oncology, pathology, radiology, biostatistics, and image analysis. Combined with the largest clinical experience in CRLM in the western world, this application is a unique and unrivaled opportunity to define radiomics of CRLM. Integration into existing clinical workflows means that small medical centers without highly specialized radiology groups would benefit from predictive algorithms developed at two high-volume centers via a low-cost software update. Successful completion of our aims will provide validated prognostic imaging markers with a pathway to routine clinical use, which are of paramount importance to improving patient survival of this deadly disease.