Lin Zijian, Wang Weidong, Yan Yongcong, Ma Zifeng, Xiao Zhiyu, Mao Kai
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China.
Department of Interventional Radiography, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China.
Int J Surg. 2025 May 1;111(5):3342-3355. doi: 10.1097/JS9.0000000000002322.
The majority of patients with hepatocellular carcinoma (HCC) miss the opportunity of radical resection, making immune check-point inhibitors (ICIs)-based conversion therapy a primary option. However, challenges persist in predicting response and identifying the optimal patient subset. The objective is to develop a CT-based clinical-radiomics model to predict durable clinical benefit (DCB) of ICIs-based treatment in potentially convertible HCC patients.
The radiomics features were extracted by pyradiomics in training set, and machine learning models was generated based on the selected radiomics features. Deep learning models were created using two different protocols. Integrated models were constructed by incorporating radiomics scores, deep learning scores, and clinical variables selected through multivariate analysis. Furthermore, we analyzed the relationship between integrated model scores and clinical outcomes related to conversion therapy in the entire cohort. Finally, radiogenomic analysis was conducted on bulk RNA and DNA sequencing data.
The top-performing integrated model demonstrated excellent predictive accuracy with an area under the curve (AUC) of 0.96 (95% CI: 0.94-0.99) in the training set and 0.88 (95% CI: 0.77-0.99) in the test set, effectively stratifying survival risk across the entire cohort and revealing significant disparity in overall survival (OS), as evidenced by Kaplan-Meier survival curves ( P < 0.0001). Moreover, integrated model scores exhibited associations with sequential resection among patients who achieved DCB and pathological complete response (pCR) among those who underwent sequential resection procedures. Notably, higher radiomics model was correlated with MHC I expression, angiogenesis-related processes, CD8 T cell-related gene sets, as well as a higher frequency of TP53 mutations along with increased levels of mutation burden and neoantigen.
The deep learning-based clinical-radiomics model exhibited satisfactory predictive capability in forecasting the DCB derived from ICIs-based conversion therapy in potentially convertible HCC, and was associated with a diverse range of immune-related mechanisms.
大多数肝细胞癌(HCC)患者错失了根治性切除的机会,这使得基于免疫检查点抑制剂(ICI)的转化治疗成为主要选择。然而,在预测反应和确定最佳患者亚组方面仍存在挑战。目的是建立一种基于CT的临床放射组学模型,以预测潜在可转化HCC患者接受基于ICI治疗的持久临床获益(DCB)。
在训练集中通过pyradiomics提取放射组学特征,并基于所选放射组学特征生成机器学习模型。使用两种不同方案创建深度学习模型。通过纳入放射组学评分、深度学习评分以及通过多变量分析选择的临床变量来构建综合模型。此外,我们分析了综合模型评分与整个队列中与转化治疗相关的临床结局之间的关系。最后,对大量RNA和DNA测序数据进行放射基因组分析。
表现最佳的综合模型在训练集中曲线下面积(AUC)为0.96(95%CI:0.94 - 0.99),在测试集中为0.88(95%CI:0.77 - 0.99),显示出优异的预测准确性,有效分层了整个队列的生存风险,并揭示了总生存期(OS)的显著差异,Kaplan - Meier生存曲线证明了这一点(P < 0.0001)。此外,综合模型评分与实现DCB的患者中的序贯切除以及接受序贯切除手术的患者中的病理完全缓解(pCR)相关。值得注意的是,较高的放射组学模型与MHC I表达、血管生成相关过程、CD8 T细胞相关基因集以及TP53突变频率较高、突变负担水平增加和新抗原水平升高相关。
基于深度学习的临床放射组学模型在预测潜在可转化HCC患者接受基于ICI的转化治疗所产生的DCB方面表现出令人满意的预测能力,并且与多种免疫相关机制有关。