Liu Qiu-Ping, Tang Jie, Chen Yi-Zhang, Guo Fen, Ma Ling, Pan Lan-Lan, Tian Yi-Tong, Wu Xiao-Feng, Zhang Yu-Dong, Chen Xiao-Feng
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Oncology, Liyang People's Hospital, Liyang, China.
JHEP Rep. 2023 Apr 22;5(7):100763. doi: 10.1016/j.jhepr.2023.100763. eCollection 2023 Jul.
BACKGROUND & AIMS: Immunotherapy is an option for the treatment of advanced biliary tract cancer (BTC), although it has a low response rate. In this post hoc analysis, we investigated the predictive value of an immuno-genomic-radiomics (IGR) analysis for patients with BTC treated with camrelizumab plus gemcitabine and oxaliplatin (GEMOX) therapy.
Thirty-two patients with BTC treated with camrelizumab plus GEMOX were prospectively enrolled. The relationship between high-throughput computed tomography (CT) radiomics features with immuno-genomic expression was tested and scaled with a full correlation matrix analysis. Odds ratio (OR) of IGR expression for objective response to camrelizumab plus GEMOX was tested with logistic regression analysis. Association of IGR expression with progression-free survival (PFS) and overall survival (OS) was analysed with a Cox proportional hazard regression.
CT radiomics correlated with CD8 T cells ( = -0.72-0.71, = 0.004-0.047), tumour mutation burden (TMB) ( = 0.59, = 0.039), and mutation ( = -0.58-0.57, = 0.020-0.034). There was no significant correlation between radiomics and programmed cell death protein ligand 1 expression ( >0.96). Among all IGR biomarkers, only four radiomics features were independent predictors of objective response (OR = 0.09-3.81; = 0.011-0.044). Combining independent radiomics features into an objective response prediction model achieved an area under the curve of 0.869. In a Cox analysis, radiomics signature [hazard ratio (HR) = 6.90, <0.001], (HR = 3.31, = 0.013), and blood TMB (HR = 1.13, = 0.023) were independent predictors of PFS. Radiomics signature (HR = 6.58, <0.001) and CD8 T cells (HR = 0.22, = 0.004) were independent predictors of OS. Prognostic models integrating these features achieved concordance indexes of 0.677 and 0.681 for PFS and OS, respectively.
Radiomics could act as a non-invasive immuno-genomic surrogate of BTC, which could further aid in response prediction for patients with BTC treated with immunotherapy. However, multicenter and larger sample studies are required to validate these results.
Immunotherapy is an alternative for the treatment of advanced BTC, whereas tumour response is heterogeneous. In a analysis of the single-arm phase II clinical trial (NCT03486678), we found that CT radiomics features were associated with the tumour microenvironment and that IGR expression was a promising marker for tumour response and long-term survival.
analysis of NCT03486678.
免疫疗法是晚期胆管癌（BTC）的一种治疗选择，尽管其缓解率较低。在这项事后分析中，我们研究了免疫基因组-放射组学（IGR）分析对接受卡瑞利珠单抗联合吉西他滨和奥沙利铂（GEMOX）治疗的BTC患者的预测价值。
前瞻性纳入32例接受卡瑞利珠单抗联合GEMOX治疗的BTC患者。通过全相关矩阵分析测试并缩放高通量计算机断层扫描（CT）放射组学特征与免疫基因组表达之间的关系。采用逻辑回归分析检验IGR表达对卡瑞利珠单抗联合GEMOX客观缓解的比值比（OR）。通过Cox比例风险回归分析IGR表达与无进展生存期（PFS）和总生存期（OS）的关联。
CT放射组学与CD8 T细胞（r = -0.72 - 0.71，P = 0.004 - 0.047）、肿瘤突变负荷（TMB）（r = 0.59，P = 0.039）和KRAS突变（r = -0.58 - 0.57，P = 0.020 - 0.034）相关。放射组学与程序性细胞死亡蛋白配体1表达之间无显著相关性（P > 0.96）。在所有IGR生物标志物中，只有四个放射组学特征是客观缓解的独立预测因子（OR = 0.09 - 3.81；P = 0.011 - 0.044）。将独立的放射组学特征组合成客观缓解预测模型，曲线下面积为0.869。在Cox分析中，放射组学特征[风险比（HR） = 6.90，P < 0.001]、KRAS（HR = 3.31，P = 0.013）和血液TMB（HR = 1.13，P = 0.023）是PFS的独立预测因子。放射组学特征（HR = 6.58，P < 0.001）和CD8 T细胞（HR = 0.22，P = 0.004）是OS的独立预测因子。整合这些特征的预后模型的PFS和OS一致性指数分别为0.677和0.681。
放射组学可作为BTC的一种非侵入性免疫基因组替代指标，可进一步辅助预测接受免疫治疗的BTC患者的缓解情况。然而，需要多中心、大样本研究来验证这些结果。
免疫疗法是晚期BTC的一种替代治疗方法，而肿瘤反应具有异质性。在一项单臂II期临床试验（NCT03486678）的事后分析中，我们发现CT放射组学特征与肿瘤微环境相关，且IGR表达是肿瘤反应和长期生存的一个有前景的标志物。
NCT03486678的事后分析
