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光谱双探测器计算机断层扫描对Ⅰ期肺腺癌表达的预测价值:一种新型列线图的开发与验证

Predictive value of spectral dual-detector computed tomography for expression in stage I lung adenocarcinoma: development and validation of a novel nomogram.

作者信息

Wang Tong, Fan Zheng, Yue Yong, Lu Xiaomei, Deng Xiaoxu, Hou Yang

机构信息

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Quant Imaging Med Surg. 2024 Aug 1;14(8):5983-6001. doi: 10.21037/qims-24-15. Epub 2024 Jul 24.

Abstract

BACKGROUND

Programmed death ligand-1 () expression serves a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in the treatment of patients with early-stage lung adenocarcinoma (LA). However, only a limited number of studies have explored the relationship between expression and spectral dual-layer detector-based computed tomography (SDCT) quantification, qualitative parameters, and clinical biomarkers. Therefore, this study was conducted to clarify this relationship in stage I LA and to develop a nomogram to assist in preoperative individualized identification of -positive expression.

METHODS

We analyzed SDCT parameters and expression in patients diagnosed with invasive nonmucinous LA through postoperative pathology. Patients were categorized into -positive and -negative expression groups based on a threshold of 1%. A retrospective set (N=356) was used to develop and internally validate the radiological and biomarker features collected from predictive models. Univariate analysis was employed to reduce dimensionality, and logistic regression was used to establish a nomogram for predicting expression. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, and external validation was performed in an independent set (N=80).

RESULTS

The proportions of solid components and pleural indentations were higher in the -positive group, as indicated by the computed tomography (CT) value, CT at 40 keV (CT40keV; a/v), electron density (ED; a/v), and thymidine kinase 1 (TK1) exhibiting a positive correlation with expression. In contrast, the effective atomic number (Zeff; a/v) showed a negative correlation with expression [r=-0.4266 (Zeff.a), -0.1131 (Zeff.v); P<0.05]. After univariate analysis, 18 parameters were found to be associated with expression. Multiple regression analysis was performed on significant parameters with an area under the curve (AUC) >0.6, and CT value [AUC =0.627; odds ratio (OR) =0.993; P=0.033], CT40keV.a (AUC =0.642; OR =1.006; P=0.025), arterial Zeff (Zeff.a) (AUC =0.756; OR =0.102; P<0.001), arterial ED (ED.a) (AUC =0.641; OR =1.158, P<0.001), venous ED (ED.v) (AUC =0.607; OR =0.864; P<0.001), TK1 (AUC =0.601; OR =1.245; P=0.026), and diameter of solid components (Dsolid) (AUC =0.632; OR =1.058; P=0.04) were found to be independent risk factors for PD-L1 expression in stage I LA. These seven predictive factors were integrated into the development of an SDCT parameter-clinical nomogram, which demonstrated satisfactory discrimination ability in the training set [AUC =0.853; 95% confidence interval (CI): 0.76-0.947], internal validation set (AUC =0.824; 95% CI: 0.775-0.874), and external validation set (AUC =0.825; 95% CI: 0.733-0.918). Decision curve analyses also revealed the highest net benefit for the nomogram across a broad threshold probability range (20-80%), with a clinical impact curve (CIC) indicating its clinical validity. Comparisons with other models demonstrated the superior discriminatory accuracy of the nomogram over any individual variable (all P values <0.05).

CONCLUSIONS

Quantitative parameters derived from SDCT demonstrated the ability to predict for expression in early-stage LA, with Zeff.a being notably effective. The nomogram established in combination with TK1 showed excellent predictive performance and good calibration. This approach may facilitate the improved noninvasive prediction of expression.

摘要

背景

程序性死亡配体-1(PD-L1)表达可作为免疫检查点抑制剂(ICI)治疗早期肺腺癌(LA)患者疗效的预测生物标志物。然而,仅有少数研究探讨了PD-L1表达与基于光谱双层探测器的计算机断层扫描(SDCT)定量、定性参数及临床生物标志物之间的关系。因此,本研究旨在阐明I期LA中这种关系,并开发一种列线图以协助术前个体化识别PD-L1阳性表达。

方法

我们通过术后病理分析了诊断为浸润性非黏液性LA患者的SDCT参数和PD-L1表达。根据1%的阈值将患者分为PD-L1阳性和阴性表达组。使用回顾性数据集(N = 356)来开发并内部验证从预测模型收集的放射学和生物标志物特征。采用单因素分析进行降维,并使用逻辑回归建立预测PD-L1表达的列线图。使用受试者工作特征(ROC)曲线评估模型的预测性能,并在独立数据集(N = 80)中进行外部验证。

结果

PD-L1阳性组的实性成分比例和胸膜凹陷比例更高,计算机断层扫描(CT)值、40 keV时的CT(CT40keV;a/v)、电子密度(ED;a/v)和胸苷激酶1(TK1)与PD-L1表达呈正相关。相比之下,有效原子序数(Zeff;a/v)与PD-L1表达呈负相关[r = -0.4266(Zeff.a),-0.1131(Zeff.v);P < 0.05]。单因素分析后,发现18个参数与PD-L1表达相关。对曲线下面积(AUC)>0.6的显著参数进行多元回归分析,发现CT值[AUC = 0.627;比值比(OR)= 0.993;P = 0.033]、CT40keV.a(AUC = 0.642;OR = 1.006;P = 0.025)、动脉Zeff(Zeff.a)(AUC = 0.756;OR = 0.102;P < 0.001)、动脉ED(ED.a)(AUC = 0.641;OR = 1.158,P < 0.001)、静脉ED(ED.v)(AUC = 0.607;OR = 0.864;P < 0.001)、TK1(AUC = 0.601;OR = 1.245;P = 0.026)和实性成分直径(Dsolid)(AUC = 0.632;OR = 1.058;P = 0.04)是I期LA中PD-L1表达的独立危险因素。将这七个预测因素整合到SDCT参数 - 临床列线图的开发中,该列线图在训练集[AUC = 0.853;95%置信区间(CI):0.76 - 0.947]、内部验证集(AUC = 0.824;95% CI:0.775 - 0.874)和外部验证集(AUC = 0.825;95% CI:0.733 - 0.918)中表现出令人满意的鉴别能力。决策曲线分析还显示,在广泛的阈值概率范围(20 - 80%)内,列线图的净效益最高,临床影响曲线(CIC)表明其临床有效性。与其他模型的比较表明,列线图的鉴别准确性优于任何单个变量(所有P值<0.05)。

结论

从SDCT得出的定量参数显示出预测早期LA中PD-L1表达的能力,其中Zeff.a尤为有效。结合TK1建立的列线图显示出优异的预测性能和良好的校准。这种方法可能有助于改进PD-L1表达的无创预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dbf/11320513/b72c77af99dd/qims-14-08-5983-f1.jpg

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