影像学定量参数联合血清肿瘤标志物对胰腺导管腺癌术后预后的评估价值
DOI: 10.12449/JCH260620
Value of quantitative imaging parameters combined with serum tumor markers in prognostic evaluation after pancreatic ductal adenocarcinoma surgery
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摘要:
目的 探讨影像学定量参数联合血清肿瘤标志物构建的预测模型在胰腺导管腺癌(PDAC)患者术后预后评估中的应用价值。 方法 回顾性选取2020年4月—2023年3月于河北医科大学第四医院接受根治性切除术治疗的146例PDAC患者为研究对象,采用完全随机法将患者按照7∶3的比例分为训练集(n=102)和验证集(n=44)。所有患者进行增强计算机体层成像(CT)以及多参数磁共振成像扫描,记录动脉期、静脉期和延迟期CT值以及b值为800 s/mm2的表观扩散系数(ADC)、T2加权成像的信号强度(SI);检测患者血清糖类抗原19-9(CA19-9)及癌胚抗原(CEA)水平。计量资料两组间比较采用成组t检验;计数资料两组间比较采用χ2检验。Kaplan-Meier法绘制生存曲线,生存情况的比较采用Log-rank检验;采用单因素及多因素Logistic分析评估各临床及影像学指标与预后的关系,并采用最小绝对值收敛和选择算子(LASSO)-Cox回归模型筛选影响患者预后的重要因素,构建预后预测模型。采用受试者操作特征曲线分析该模型在训练集和验证集中的预后预测价值。 结果 Kaplan-Meier生存曲线分析显示,训练集患者的中位生存时间为33.00个月,验证集患者的中位生存时间为32.00个月,差异无统计学意义(P>0.05)。单因素分析结果显示,患者年龄、分化程度、淋巴结转移、肿瘤分期、血管侵犯、CA19-9、CEA、ADC及SI与患者生存预后有关(χ2值分别为5.906、13.116、12.807、17.277、14.611、7.275、14.339、9.506、13.137,P值均<0.05)。LASSO-Cox多因素回归分析显示,6个因素进入回归模型:肿瘤分期[风险比(HR)=8.934,95%CI:3.215~21.562,P<0.001]、淋巴结转移(HR=2.971,95%CI:1.298~5.647,P=0.002)、CA19-9(HR=3.948,95%CI:1.758~8.994,P<0.001)、CEA(HR=1.965,95%CI:1.083~3.664,P=0.039)、ADC(HR=2.873,95%CI:1.307~6.037,P=0.003)及SI(HR=3.107,95%CI:1.264~7.339,P=0.001)。基于上述指标构建的列线图模型在训练集中的预测曲线下面积为0.845[95%置信区间(CI):0.774~0.915],在验证集中的曲线下面积为0.919(95%CI:0.870~0.967)。 结论 基于LASSO-Cox回归构建的影像学定量参数-血清标志物联合模型可有效预测PDAC患者术后预后,有助于识别高风险患者,从而指导辅助治疗决策。 -
关键词:
- 胰腺肿瘤 /
- 体层摄影术, X线计算机 /
- 多参数磁共振成像 /
- 生物标记, 肿瘤 /
- 预后
Abstract:Objective To investigate the application value of a predictive model constructed based on quantitative imaging parameters and serum tumor markers in predicting the postoperative prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Methods A retrospective study was conducted among 146 patients with PDAC who underwent radical resection in Hebei Medical University Fourth Hospital from April 2020 to March 2023, and the patients were divided into a training set with 102 patients and a validation set of 44 patients at a ratio of 7∶3 using the completely randomized method. All patients underwent enhanced computed tomography (CT) and multi-parametric magnetic resonance imaging scans, and CT values in the arterial phase, the venous phase, and the delayed phase were recorded, as well as apparent diffusion coefficient (ADC) at b = 800 s/mm2 and signal intensity (SI) of T2 weighted imaging. The serum levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were also measured. The independent-samples t test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Kaplan-Meier survival curves were plotted for survival analysis; the univariate and multivariate Logistic regression analysis was used to investigate the association of clinical and imaging indicators with prognosis; the least absolute shrinkage and selection operator (LASSO)-Cox regression model was used to identify the important influencing factors for prognosis, and a prognostic prediction model was constructed. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the model in predicting prognosis in both the training set and the validation set. Results The Kaplan-Meier survival curve analysis showed a median survival time of 33.00 months in the training set and 32.00 months in the validation set, with no significant difference between the training set and the validation set (P>0.05). The univariate analysis showed that patient age, degree of tumor differentiation, lymph node metastasis, tumor stage, vascular invasion, CA19-9, CEA, ADC value, and SI value were significantly associated with the survival prognosis of patients (χ²=5.906, 13.116, 12.807, 17.277, 14.611, 7.275, 14.339, 9.506, and 13.137, all P<0.05). The LASSO-Cox multivariate regression analysis showed that six factors were incorporated into the regression model, i.e., tumor stage (HR=8.934, 95%CI: 3.215 — 21.562, P<0.001), lymph node metastasis (HR=2.971, 95%CI: 1.298 — 5.647, P=0.002), CA19-9 (HR=3.948, 95%CI: 1.758 — 8.994, P<0.001), CEA (HR=1.965, 95%CI: 1.083 — 3.664, P=0.039), ADC value (HR=2.873, 95%CI: 1.307 — 6.037, P=0.003), and SI value (HR=3.107, 95%CI: 1.264 — 7.339, P=0.001). The nomogram model constructed based on these factors had an area under the ROC curve of 0.845 (95%CI: 0.774 — 0.915) in the training set and 0.919 (95%CI: 0.870 — 0.967) in the validation set. Conclusion The combined model of quantitative imaging parameters and serum tumor markers constructed based on LASSO-Cox regression can effectively predict the postoperative prognosis of PDAC patients, thereby helping to identify high-risk patients and guide decision-making for adjuvant therapy. -
表 1 训练集及验证集患者临床资料比较
Table 1. Comparison of clinical data of patients in the training set and the validation set
临床资料 训练集(n=102) 验证集(n=44) 统计值 P值 性别[例(%)] χ2=0.186 0.666 男 48(47.06) 19(43.18) 女 54(52.94) 25(56.82) 年龄(岁) 55.23±8.64 54.58±6.59 t=0.446 0.656 高血压[例(%)] 25(24.51) 13(29.55) χ2=0.405 0.525 糖尿病[例(%)] 17(16.67) 6(13.64) χ2=0.213 0.645 分化程度[例(%)] χ2=0.251 0.617 中高分化 67(65.69) 27(61.36) 低分化 35(34.31) 17(38.64) 肿瘤最大径(cm) 3.57±1.21 3.74±1.30 t=0.762 0.448 肿瘤位置[例(%)] χ2=0.059 0.812 胰头颈部 67(65.69) 28(63.64) 胰体尾部 35(34.31) 16(36.36) 淋巴结转移[例(%)] 39(38.24) 15(34.09) χ2=0.227 0.634 肿瘤分期[例(%)] χ2=0.133 0.715 Ⅰ期 38(37.25) 15(34.09) Ⅱ~Ⅲ期 64(62.75) 29(65.91) 血管侵犯[例(%)] 41(40.20) 17(38.64) χ2=0.031 0.860 CA19-9(U/mL) 185.43±53.02 189.28±31.64 t=0.448 0.655 CEA(U/mL) 12.56±4.21 13.04±3.15 t=0.678 0.499 CT值(HU) 平扫期 34.83±3.19 36.04±3.95 t=1.953 0.053 动脉期 43.87±5.52 41.96±6.03 t=1.865 0.064 门静脉期 54.58±7.93 54.02±8.49 t=0.383 0.702 延迟期 60.21±5.68 59.38±6.10 t=0.792 0.430 ADC(×10-3 mm2/s) 1.21±0.31 1.27±0.28 t=1.104 0.272 SI(×10-3) 0.45±0.09 0.46±0.12 t=0.555 0.580 注:CA19-9,糖类抗原19-9;CEA,癌胚抗原;CT,计算机断层扫描;ADC,表观扩散系数;SI,信号强度。
表 2 训练集患者生存预后单因素分析
Table 2. Univariate analysis of survival prognosis of patients in the training set
因素 例数 中位生存期(月) 95%CI χ2值 P值 性别 0.159 0.690 男 48 34.00 27.512~40.488 女 54 32.00 22.398~41.602 年龄 5.906 0.015 ≥55岁 53 28.00 22.650~33.350 <55岁 49 38.00 34.193~41.807 高血压 25 32.00 23.840~40.160 0.438 0.508 糖尿病 17 31.00 18.899~43.101 0.823 0.364 分化程度 13.116 <0.001 中高分化 67 38.00 35.669~40.331 低分化 35 23.00 14.443~31.557 肿瘤最大径 0.233 0.629 ≥3.5 cm 55 34.00 28.627~39.373 <3.5 cm 47 28.00 14.806~41.194 肿瘤位置 0.273 0.602 胰头颈部 67 34.00 28.092~39.908 胰体尾部 35 33.00 22.706~43.294 淋巴结转移 39 24.00 16.658~31.342 12.807 <0.001 肿瘤分期 17.277 <0.001 Ⅰ期 38 43.00 34.006~51.994 Ⅱ~Ⅲ期 64 28.00 23.569~32.431 血管侵犯 41 25.00 19.772~30.228 14.611 <0.001 CA19-9 7.275 0.007 ≥185 U/mL 56 26.00 19.714~32.286 <185 U/mL 46 39.00 33.412~44.588 CEA 14.339 0.001 ≥12 U/mL 54 24.00 17.827~30.173 <12 U/mL 48 40.00 37.408~42.592 平扫期CT值 1.170 0.279 ≥34 HU 59 32.00 23.577~40.423 <34 HU 43 35.00 29.493~40.507 动脉期CT值 0.830 0.362 ≥43 HU 61 36.00 30.265~41.735 <43 HU 41 29.00 20.934~37.066 门静脉期CT值 0.072 0.788 ≥54 HU 63 34.00 28.920~39.080 <54 HU 39 32.00 21.115~42.885 延迟期CT值 0.802 0.370 ≥60 HU 57 37.00 26.994~47.006 <60 HU 45 32.00 26.840~37.160 ADC 9.506 0.002 ≥1.2×10-3 mm2/s 60 38.00 35.501~40.499 <1.2×10-3 mm2/s 42 27.00 20.649~33.351 SI 13.137 0.001 ≥0.45×10-3 58 26.00 19.506~32.494 <0.45×10-3 44 39.00 35.856~42.144 注:CA19-9,糖类抗原19-9;CEA,癌胚抗原;CT,计算机体层成像;ADC,表观扩散系数;SI,信号强度;CI,置信区间。
表 3 胰腺导管腺癌术后预后Cox多因素回归分析
Table 3. Cox multivariate regression analysis of prognosis after pancreatic ductal adenocarcinoma surgery
因素 HR 95%CI P值 肿瘤分期 8.934 3.215~21.562 <0.001 淋巴结转移 2.971 1.298~5.647 0.002 CA19-9 3.948 1.758~8.994 <0.001 CEA 1.965 1.083~3.664 0.039 ADC 2.873 1.307~6.037 0.003 SI 3.107 1.264~7.339 0.001 注:CA19-9,糖类抗原19-9;CEA,癌胚抗原;ADC,表观扩散系数;SI,信号强度;HR,风险比;CI,置信区间。
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