论文标题

基于深度学习的预测对HER2靶向的新辅助化疗的反应预测,预处理动态乳房MRI:一项多机构验证研究

Deep learning-based prediction of response to HER2-targeted neoadjuvant chemotherapy from pre-treatment dynamic breast MRI: A multi-institutional validation study

论文作者

Braman, Nathaniel, Adoui, Mohammed El, Vulchi, Manasa, Turk, Paulette, Etesami, Maryam, Fu, Pingfu, Bera, Kaustav, Drisis, Stylianos, Varadan, Vinay, Plecha, Donna, Benjelloun, Mohammed, Abraham, Jame, Madabhushi, Anant

论文摘要

预测对新辅助治疗的反应是乳腺癌的烦恼挑战。在这项研究中,我们评估了深度学习能够预测从治疗前获得的预处理动态对比度增强(DCE)MRI对靶向HER2靶向的Neo-Adjuvant化学疗法(NAC)的反应的能力。在一项回顾性研究中,包括来自5个机构的157名HER2+乳腺癌患者的DCE-MRI数据,我们开发并验证了一种预测病理完全反应(PCR)对HER2靶向NAC的深度学习方法。接受单个机构接受Her2靶向新辅助化疗的100名患者用于训练(n = 85)和Tune(n = 15)卷积神经网络(CNN)以预测PCR。确定了利用前对比和对比后DCE-MRI采集后的多输入CNN,以实现验证集中的最佳响应预测(AUC = 0.93)。然后,使用预处理DCE-MRI数据对两个独立的测试队列进行了测试。它在第二个机构(AUC = 0.85,95%CI 0.67-1.0,p = .0008)和29例患者多中心试验的28例患者测试中取得了强劲的表现,其中包括来自3个其他机构的数据(AUC = 0.77,95%CI 0.58-0.97,P = 0.006)。发现基于深度学习的响应预测模型超过了一个多变量模型,该模型纳入了预测性临床变量(测试队列中的AUC <.65)和半定量DCE-MRI药代动力学测量值(测试队列中的AUC <.60)。这项工作中跨多个地点介绍的结果表明,经过进一步的验证,深度学习可以提供有效而可靠的工具来指导针对性的乳腺癌治疗,从而减少HER2+患者的过度治疗。

Predicting response to neoadjuvant therapy is a vexing challenge in breast cancer. In this study, we evaluate the ability of deep learning to predict response to HER2-targeted neo-adjuvant chemotherapy (NAC) from pre-treatment dynamic contrast-enhanced (DCE) MRI acquired prior to treatment. In a retrospective study encompassing DCE-MRI data from a total of 157 HER2+ breast cancer patients from 5 institutions, we developed and validated a deep learning approach for predicting pathological complete response (pCR) to HER2-targeted NAC prior to treatment. 100 patients who received HER2-targeted neoadjuvant chemotherapy at a single institution were used to train (n=85) and tune (n=15) a convolutional neural network (CNN) to predict pCR. A multi-input CNN leveraging both pre-contrast and late post-contrast DCE-MRI acquisitions was identified to achieve optimal response prediction within the validation set (AUC=0.93). This model was then tested on two independent testing cohorts with pre-treatment DCE-MRI data. It achieved strong performance in a 28 patient testing set from a second institution (AUC=0.85, 95% CI 0.67-1.0, p=.0008) and a 29 patient multicenter trial including data from 3 additional institutions (AUC=0.77, 95% CI 0.58-0.97, p=0.006). Deep learning-based response prediction model was found to exceed a multivariable model incorporating predictive clinical variables (AUC < .65 in testing cohorts) and a model of semi-quantitative DCE-MRI pharmacokinetic measurements (AUC < .60 in testing cohorts). The results presented in this work across multiple sites suggest that with further validation deep learning could provide an effective and reliable tool to guide targeted therapy in breast cancer, thus reducing overtreatment among HER2+ patients.

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