Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Department of Radiation Oncology, Ajou University School of Medicine, Suwon, South Korea.
Med Phys. 2023 Oct;50(10):6409-6420. doi: 10.1002/mp.16398. Epub 2023 Apr 6.
Heart toxicity, such as major acute coronary events (ACE), following breast radiation therapy (RT) is of utmost concern. Thus, many studies have been investigating the effect of mean heart dose (MHD) and dose received in heart sub-structures on toxicity. Most studies focused on the dose thresholds in the heart and its sub-structures, while few studies adopted such computational methods as deep neural networks (DNN) and radiomics. This work aims to construct a feature-driven predictive model for ACE after breast RT.
A recently proposed two-step predictive model that extracts a number of features from a deep auto-segmentation network and processes the selected features for prediction was adopted. This work refined the auto-segmenting network and feature processing algorithms to enhance performance in cardiac toxicity prediction. In the predictive model, the deep convolutional neural network (CNN) extracted features from 3D computed tomography (CT) images and dose distributions in three automatically segmented heart sub-structures, including the left anterior descending artery (LAD), right coronary artery (RCA), and left ventricle (LV). The optimal feature processing workflow for the extracted features was explored to enhance the prediction accuracy. The regions associated with toxicity were visualized using a class activation map (CAM)-based technique. Our proposed model was validated against a conventional DNN (convolutional and fully connected layers) and radiomics with a patient cohort of 84 cases, including 29 and 55 patient cases with and without ACE. Of the entire 84 cases, 12 randomly chosen cases (5 toxicity and 7 non-toxicity cases) were set aside for independent test, and the remaining 72 cases were applied to 4-fold stratified cross-validation.
Our predictive model outperformed the conventional DNN by 38% and 10% and radiomics-based predictive models by 9% and 10% in AUC for 4-fold cross-validations and independent test, respectively. The degree of enhancement was greater when incorporating dose information and heart sub-structures into feature extraction. The model whose inputs were CT, dose, and three sub-structures (LV, LAD, and RCA) reached 96% prediction accuracy on average and 0.94 area under the curve (AUC) on average in the cross-validation, and also achieved prediction accuracy of 83% and AUC of 0.83 in the independent test. On 10 correctly predicted cases out of 12 for the independent test, the activation maps implied that for cases of ACE toxicity, the higher intensity was more likely to be observed inside the LV.
The proposed model characterized by modifications in model input with dose distributions and cardiac sub-structures, and serial processing of feature extraction and feature selection techniques can improve the predictive performance in ACE following breast RT.
乳腺癌放射治疗(RT)后心脏毒性,如主要急性冠状动脉事件(ACE),是最令人关注的问题。因此,许多研究都在研究平均心脏剂量(MHD)和心脏亚结构接受剂量对毒性的影响。大多数研究都集中在心脏及其亚结构的剂量阈值上,而少数研究采用了深度学习神经网络(DNN)和放射组学等计算方法。本研究旨在构建一个用于预测乳腺癌 RT 后 ACE 的基于特征的预测模型。
采用了一种最近提出的两步预测模型,该模型从深度自动分割网络中提取了一些特征,并对所选特征进行预测。本研究改进了自动分割网络和特征处理算法,以提高心脏毒性预测的性能。在预测模型中,深度卷积神经网络(CNN)从 3D 计算机断层扫描(CT)图像和三个自动分割的心脏亚结构中的剂量分布中提取特征,包括左前降支(LAD)、右冠状动脉(RCA)和左心室(LV)。还探索了最优的特征处理工作流程,以提高预测准确性。使用基于类激活图(CAM)的技术可视化与毒性相关的区域。我们的模型通过 84 例患者队列(包括 29 例和 55 例 ACE 患者)与传统 DNN(卷积和全连接层)和放射组学进行了验证。在整个 84 例患者中,随机选择了 12 例(5 例毒性和 7 例非毒性)进行独立测试,其余 72 例用于 4 倍分层交叉验证。
我们的预测模型在 AUC 方面分别比传统 DNN 提高了 38%和 10%,比基于放射组学的预测模型提高了 9%和 10%,在 4 倍交叉验证和独立测试中的表现均优于传统 DNN 和放射组学。当将剂量信息和心脏亚结构纳入特征提取时,增强程度更大。输入为 CT、剂量和三个亚结构(LV、LAD 和 RCA)的模型在交叉验证中的平均预测准确率为 96%,平均 AUC 为 0.94,在独立测试中的预测准确率为 83%,AUC 为 0.83。在独立测试中,12 例正确预测的病例中有 10 例,激活图表明对于 ACE 毒性病例,更有可能在 LV 内部观察到更高的强度。
该模型的特点是在模型输入中加入剂量分布和心脏亚结构,并对特征提取和特征选择技术进行串行处理,可提高乳腺癌 RT 后 ACE 的预测性能。