Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
J Immunother Cancer. 2023 May;11(5). doi: 10.1136/jitc-2022-006514.
Immune checkpoint inhibitors (ICIs)-based therapy, is regarded as one of the major breakthroughs in cancer treatment. However, it is challenging to accurately identify patients who may benefit from ICIs. Current biomarkers for predicting the efficacy of ICIs require pathological slides, and their accuracy is limited. Here we aim to develop a radiomics model that could accurately predict response of ICIs for patients with advanced breast cancer (ABC).
Pretreatment contrast-enhanced CT (CECT) image and clinicopathological features of 240 patients with ABC who underwent ICIs-based treatment in three academic hospitals from February 2018 to January 2022 were assigned into a training cohort and an independent validation cohort. For radiomic features extraction, CECT images of patients 1 month prior to ICIs-based therapies were first delineated with regions of interest. Data dimension reduction, feature selection and radiomics model construction were carried out with multilayer perceptron. Combined the radiomics signatures with independent clinicopathological characteristics, the model was integrated by multivariable logistic regression analysis.
Among the 240 patients, 171 from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center were evaluated as a training cohort, while other 69 from Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Sun Yat-sen University were the validation cohort. The area under the curve (AUC) of radiomics model was 0.994 (95% CI: 0.988 to 1.000) in the training and 0.920 (95% CI: 0.824 to 1.000) in the validation set, respectively, which were significantly better than the performance of clinical model (0.672 for training and 0.634 for validation set). The integrated clinical-radiomics model showed increased but not statistical different predictive ability in both the training (AUC=0.997, 95% CI: 0.993 to 1.000) and validation set (AUC=0.961, 95% CI: 0.885 to 1.000) compared with the radiomics model. Furthermore, the radiomics model could divide patients under ICIs-therapies into high-risk and low-risk group with significantly different progression-free survival both in training (HR=2.705, 95% CI: 1.888 to 3.876, p<0.001) and validation set (HR=2.625, 95% CI: 1.506 to 4.574, p=0.001), respectively. Subgroup analyses showed that the radiomics model was not influenced by programmed death-ligand 1 status, tumor metastatic burden or molecular subtype.
This radiomics model provided an innovative and accurate way that could stratify patients with ABC who may benefit more from ICIs-based therapies.
免疫检查点抑制剂(ICIs)治疗被认为是癌症治疗的重大突破之一。然而,准确识别可能从 ICI 中获益的患者具有挑战性。目前预测 ICI 疗效的生物标志物需要病理切片,其准确性有限。在这里,我们旨在开发一种放射组学模型,能够准确预测晚期乳腺癌(ABC)患者对 ICI 的反应。
将 240 名在三家学术医院接受 ICI 治疗的 ABC 患者的预处理对比增强 CT(CECT)图像和临床病理特征分为训练队列和独立验证队列。对于放射组学特征提取,首先用感兴趣区域对 ICI 治疗前 1 个月的患者的 CECT 图像进行描绘。采用多层感知机进行数据降维、特征选择和放射组学模型构建。将放射组学特征与独立的临床病理特征相结合,通过多变量逻辑回归分析进行模型整合。
在 240 名患者中,中山大学孙逸仙纪念医院和中山大学肿瘤防治中心的 171 名患者被评估为训练队列,而中山大学肿瘤防治中心和中山大学第一附属医院的另外 69 名患者为验证队列。放射组学模型在训练中的 AUC 为 0.994(95%CI:0.988 至 1.000),在验证中的 AUC 为 0.920(95%CI:0.824 至 1.000),均明显优于临床模型的性能(训练中的 AUC 为 0.672,验证中的 AUC 为 0.634)。临床-放射组学综合模型在训练(AUC=0.997,95%CI:0.993 至 1.000)和验证(AUC=0.961,95%CI:0.885 至 1.000)中均表现出增加但无统计学差异的预测能力。此外,放射组学模型可以将接受 ICI 治疗的患者分为高危和低危组,在训练(HR=2.705,95%CI:1.888 至 3.876,p<0.001)和验证(HR=2.625,95%CI:1.506 至 4.574,p=0.001)中均有显著不同的无进展生存期。亚组分析表明,放射组学模型不受程序性死亡配体 1 状态、肿瘤转移负担或分子亚型的影响。
该放射组学模型为预测可能从 ICI 治疗中获益更多的 ABC 患者提供了一种创新且准确的方法。