预测肝细胞癌术后脊柱转移患者预后的模型构建及临床意义

Construction and clinical significance of a prognostic prediction model for patients with spinal metastasis after hepatocellular carcinoma resection

中文关键词:  脊柱转移瘤  肝细胞肝癌  预测模型

英文关键词:Spinal metastasis  Hepatocellular carcinoma  Prediction model

中文摘要:

  【摘要】 目的：分析影响肝细胞癌术后脊柱转移患者预后的因素，构建列线图预测模型。方法：回顾性分析2011年4月~2020年10月复旦大学附属中山医院收治的50例肝细胞癌术后脊柱转移患者的临床资料。男39例，女11例。获取患者基线资料，包括患者年龄、一般情况[卡氏评分（karnofsky performance scale，KPS）]、实验室检查指标（白蛋白、血红蛋白、白细胞、肝功能指标、高敏感C反应蛋白等）、脊髓神经功能损害情况（Frankel分级）、肿瘤标志物水平（甲胎蛋白、癌胚抗原、糖类抗原199等）、骨转移灶分布、骨转移灶数量、内脏转移情况、脊柱稳定性[脊柱肿瘤不稳定评分（spinal instability neoplastic score，SINS）]、硬膜及脊髓压迫程度[硬膜外脊髓压迫（epidural spinal cord compression，ESCC）评分]、改良Tokuhashi评分、Tomita评分、新英格兰脊柱转移瘤评分、脊柱转移瘤治疗情况等。基于临床特征与患者的生存期进行分析，采用单因素和多因素Cox回归分析筛选肝细胞癌术后脊柱转移患者的预后影响因素，基于影响因素分析结果构建列线图预测模型，采用Bootstrap法进行内部验证。对列线图预测模型与脊柱转移相关评分系统预测模型进行比较分析，验证该模型对肝细胞癌术后脊柱转移患者预后的预测价值。结果：50例患者的年龄为32~85岁（54.3±10.9岁），中位生存期为33个月（95%CI：27～39个月）。经单因素和多因素Cox回归分析显示脊柱转移瘤手术、高敏感C反应蛋白、血红蛋白是肝细胞癌术后脊柱转移患者预后的独立预测因素（P<0.05）。基于影响因素分析结果构建列线图预测模型，经Bootstrap内部验证显示，该模型的预测校准曲线贴近标准曲线，一致性指数为0.697。绘制受试者工作特征（receiver operating characteristic，ROC）曲线，结果显示，列线图预测模型预测肝细胞癌术后脊柱转移患者12个月、24个月和36个月预期生存率的曲线下面积（area under curve，AUC）分别为0.771（95%CI：0.585~0.958，P<0.001）、0.796（95%CI：0.679~0.913，P<0.001）、0.810（95%CI：0.695~0.924，P<0.001）。决策曲线分析显示风险阈值依次为（0.0~0.12，0.02~0.61）、（0.0~0.25，0.06~0.64）、（0.0~0.5，0.20~0.83）时，该模型对肝细胞癌术后脊柱转移患者12个月、24个月和36个月预后的临床预测效能最好。结论：脊柱转移瘤手术、高敏感C反应蛋白和血红蛋白水平是肝细胞癌术后脊柱转移患者预后的独立影响因素；基于上述影响因素构建的列线图预测模型对这类患者预后具有良好的预测能力，有助于进行临床决策和早期干预。

英文摘要:

  【Abstract】 Objectives: To explore the factors influencing the prognosis of patients with spinal metastasis after hepatocellular carcinoma surgery and construct a nomogram prediction model. Methods: A retrospective analysis was conducted on the clinical data of 50 patients with spinal metastasis after hepatocellular carcinoma surgery admitted to Zhongshan Hospital, Fudan University, from April 2011 to October 2020. There were 39 males and 11 females. Baseline data were collected, including patient age, general condition[Karnofsky performance scale(KPS)], laboratory indicators(albumin, hemoglobin, white blood cell count, liver function indicators, and high-sensitivity C-reactive protein), spinal neurological impairment(Frankel grade), tumor marker levels(alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 199), distribution and number of bone metastases, presence of visceral metastases, spinal stability[spinal instability neoplastic score(SINS)], degree of dural and spinal cord compression[epidural spinal cord compression(ESCC) score], modified Tokuhashi score, Tomita score, New England Spinal Metastasis Score, and treatment condition for spinal metastasis. Survival analysis was performed based on clinical characteristics and prognosis. Univariate and multivariate Cox regression analyses were used to screen prognostic factors in patients with spinal metastasis after hepatocellular carcinoma surgery. Based on the analysis results of influencing factors, a nomogram prediction model was constructed and internally validated using the Bootstrap method. The nomogram prediction model was compared with the prediction models of spinal metastasis-related scoring systems to validate its prognostic prediction value for patients with spinal metastasis after hepatocellular carcinoma surgery. Results: The age of the 50 patients ranged from 32 to 85 years(54.3±10.9 years), with a median survival time of 33 months(95%CI: 27-39 months). Univariate and multivariate Cox regression analyses showed that surgical treatment of spinal metastasis, high-sensitivity C-reactive protein, and hemoglobin were independent predictors of prognosis in patients with spinal metastasis after hepatocellular carcinoma surgery(P<0.05). The nomogram prediction model, constructed based on the analysis results of influencing factors and validated internally using the Bootstrap method, showed that its calibration curve was close to the standard curve, with a concordance index of 0.697. Receiver operating characteristic(ROC) curves were plotted, and the results showed that the area under the curve(AUC) of the nomogram prediction model for predicting the expected survival rates at 12, 24, and 36 months in patients with spinal metastasis after hepatocellular carcinoma surgery was 0.771(95%CI: 0.585-0.958, P<0.001), 0.796(95%CI: 0.679-0.913, P<0.001), and 0.810(95%CI: 0.695-0.924, P<0.001), respectively. Decision curve analysis indicated that the model demonstrated the best clinical prediction performance for the 12-month, 24-month, and 36-month prognosis of patients with spinal metastasis after hepatocellular carcinoma surgery when the risk thresholds were(0.0-0.12, 0.02-0.61), (0.0-0.25, 0.06-0.64), and(0.0-0.5, 0.20-0.83), respectively. Conclusions: Spine metastasis surgery, high-sensitivity C-reactive protein levels, and hemoglobin levels are independent prognostic factors for patients with hepatocellular carcinoma who develop spinal metastases after surgery. The nomogram prediction model constructed based on these factors demonstrates strong predictive capability for the prognosis of such patients, therefore is conducive to clinical decision-making and early intervention.