Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas, USA.
Department of Head and Neck Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Med Phys. 2023 Apr;50(4):2212-2223. doi: 10.1002/mp.16132. Epub 2022 Dec 17.
A reliable locoregional recurrence (LRR) prediction model is important for the personalized management of head and neck cancers (HNC) patients who received radiotherapy. This work aims to develop a delta-radiomics feature-based multi-classifier, multi-objective, and multi-modality (Delta-mCOM) model for post-treatment HNC LRR prediction. Furthermore, we aim to adopt a learning with rejection option (LRO) strategy to boost the reliability of Delta-mCOM model by rejecting prediction for samples with high prediction uncertainties.
In this retrospective study, we collected PET/CT image and clinical data from 224 HNC patients who received radiotherapy (RT) at our institution. We calculated the differences between radiomics features extracted from PET/CT images acquired before and after radiotherapy and used them in conjunction with pre-treatment radiomics features as the input features. Using clinical parameters, PET radiomics features, and CT radiomics features, we built and optimized three separate single-modality models. We used multiple classifiers for model construction and employed sensitivity and specificity simultaneously as the training objectives for each of them. Then, for testing samples, we fused the output probabilities from all these single-modality models to obtain the final output probabilities of the Delta-mCOM model. In the LRO strategy, we estimated the epistemic and aleatoric uncertainties when predicting with a trained Delta-mCOM model and identified patients associated with prediction of higher reliability (low uncertainty estimates). The epistemic and aleatoric uncertainties were estimated using an AutoEncoder-style anomaly detection model and test-time augmentation (TTA) with predictions made from the Delta-mCOM model, respectively. Predictions with higher epistemic uncertainty or higher aleatoric uncertainty than given thresholds were deemed unreliable, and they were rejected before providing a final prediction. In this study, different thresholds corresponding to different low-reliability prediction rejection ratios were applied. Their values are based on the estimated epistemic and aleatoric uncertainties distribution of the validation data.
The Delta-mCOM model performed significantly better than the single-modality models, whether trained with pre-, post-treatment radiomics features or concatenated BaseLine and Delta-Radiomics Features (BL-DRFs). It was numerically superior to the PET and CT fused BL-DRF model (nonstatistically significant). Using the LRO strategy for the Delta-mCOM model, most of the evaluation metrics improved as the rejection ratio increased from 0% to around 25%. Utilizing both epistemic and aleatoric uncertainty for rejection yielded nonstatistically significant improved metrics compared to each alone at approximately a 25% rejection ratio. Metrics were significantly better than the no-rejection method when the reject ratio was higher than 50%.
The inclusion of the delta-radiomics feature improved the accuracy of HNC LRR prediction, and the proposed Delta-mCOM model can give more reliable predictions by rejecting predictions for samples of high uncertainty using the LRO strategy.
对于接受放疗的头颈部癌症(HNC)患者,可靠的局部区域复发(LRR)预测模型对于患者的个性化管理非常重要。本研究旨在开发一种基于 delta 放射组学特征的多分类器、多目标和多模态(Delta-mCOM)模型,用于预测治疗后 HNC 的 LRR。此外,我们旨在采用带拒绝选项的学习(LRO)策略,通过拒绝对具有高预测不确定性的样本进行预测,从而提高 Delta-mCOM 模型的可靠性。
在这项回顾性研究中,我们收集了在我们机构接受放疗(RT)的 224 名 HNC 患者的 PET/CT 图像和临床数据。我们计算了从放疗前后采集的放射组学特征之间的差异,并将其与治疗前的放射组学特征一起作为输入特征。使用临床参数、PET 放射组学特征和 CT 放射组学特征,我们分别构建和优化了三个单模态模型。我们使用多个分类器来构建模型,并同时将敏感性和特异性作为每个模型的训练目标。然后,对于测试样本,我们融合了所有这些单模态模型的输出概率,以获得 Delta-mCOM 模型的最终输出概率。在 LRO 策略中,我们在使用训练好的 Delta-mCOM 模型进行预测时估计了认知和偶然不确定性,并确定了与预测可靠性更高(低不确定性估计)相关的患者。认知不确定性和偶然不确定性分别使用自编码器式异常检测模型和测试时扩充(TTA)进行估计,预测结果来自 Delta-mCOM 模型。预测的认知不确定性或偶然不确定性高于给定阈值的被认为是不可靠的,并在提供最终预测之前被拒绝。在这项研究中,应用了不同的阈值,对应于不同的低可靠性预测拒绝率。它们的值基于验证数据的认知和偶然不确定性分布估计。
Delta-mCOM 模型的表现明显优于单模态模型,无论是使用治疗前、后放射组学特征还是串联基线和 Delta 放射组学特征(BL-DRFs)进行训练。它在数值上优于 PET 和 CT 融合的 BL-DRF 模型(无统计学意义)。使用 LRO 策略对 Delta-mCOM 模型进行处理时,随着拒绝率从 0%增加到 25%左右,大多数评估指标都有所提高。与单独使用认知或偶然不确定性相比,在大约 25%的拒绝率下,使用两者结合的方法可以得到非统计学意义上的改进指标。当拒绝率高于 50%时,指标明显优于不拒绝方法。
Delta 放射组学特征的纳入提高了 HNC LRR 预测的准确性,并且通过使用 LRO 策略为具有高不确定性的样本拒绝预测,可以使所提出的 Delta-mCOM 模型提供更可靠的预测。