Clinical study on preoperative radiotherapy before hepatectomy for reducing postoperative recurrence risk in patients with central hepatocellular carcinoma
Clinical study on preoperative radiotherapy before hepatectomy for reducing postoperative recurrence risk in patients with central hepatocellular carcinoma
目的 探讨术前放疗对肝切除术治疗的中央型肝细胞癌患者术后复发的影响。 方法 回顾性队列研究。回顾性收集2016年1月至2019年1月中国医学科学院北京协和医学院肿瘤医院接受手术治疗的142例中央型肝细胞癌患者临床病理资料。根据术前是否接受放疗，将患者分为术前放疗组（30例）和单纯手术组（112例）。主要观察指标为无复发生存（RFS）及术中出血量、手术时间和术后并发症发生情况。采用Kaplan-Meier法进行生存分析，组间比较采用log-rank检验；通过标准化均数差（SMD）评价各因素两组间是否存在差异；采用Cox比例风险模型分析行肝切除术的中央型肝细胞癌患者RFS的影响因素；采用倾向得分匹配（PSM）、回归模型调整倾向得分（CAPS）以及逆概率加权（IPTW）方法研究暴露因素及混杂变量与RFS的关系；敏感性分析采用E值评估未测量混杂因素对结果的潜在影响。 结果 术前放疗组和单纯手术组中男性分别占96.7%（29/30）、87.5%（98/112），年龄分别为（55±10）岁和（54±12）岁。PSM法匹配前，两组间性别、丙型肝炎患者比例、丙氨酸氨基转移酶、血清清蛋白、甲胎蛋白、术后病理卫星结节、肿瘤数量均存在差异（均SMD>0.1）。共26对患者匹配成功，术前放疗组和单纯手术组匹配后基线特征均无差异（均SMD<0.1）。单因素Cox回归分析示术前放疗、肿瘤数量、肿瘤长径以及术后病理卫星结节是RFS的影响因素（均P<0.05）；多因素Cox回归分析示术前放疗是行肝切除术的中央型肝细胞癌患者RFS的独立保护因素（HR＝0.55，95% CI：0.31～0.97，P＝0.038），肿瘤长径（HR＝1.08，95% CI：1.02～1.15，P＝0.008）、有术后病理卫星结节（HR＝1.97，95% CI：1.21～3.19，P＝0.006）为RFS的独立危险因素。术前放疗与中央型肝细胞癌患者较优的RFS相关（PSM，HR＝0.41，95% CI：0.20～0.86，P＝0.018；CAPS，HR＝0.42，95% CI：0.20～0.87，P＝0.019；IPTW，HR＝0.41，95% CI：0.22～0.76，P＝0.005）。匹配前，术前放疗组术后1、3、5年RFS率分别为77%、56%和45%，单纯手术组分别为48%、32%和28%；匹配前后术前放疗组RFS均优于单纯手术组（χ2＝5.65，P＝0.017；χ2＝6.00，P＝0.014）。未测量混杂因素改变结论的E值为2.39，提示结果可靠、稳定。匹配后，术前放疗组和单纯手术组患者术中出血量[M（Q1，Q3）]分别为300 ml（125 ml，600 ml）和400 ml（200 ml，600 ml）（U＝0.51，P＝0.611），手术时间>180 min患者比例分别为92.3%（24/26）和84.6%（22/26）（χ2＝0.75，P＝0.385），术后轻度并发症发生率分别为100.0%（26/26）和92.3%（24/26）（χ2＝2.08，P＝0.149），差异均无统计学意义。 结论 中央型肝细胞癌患者肝切除术前放疗安全、有效，具有减少术后复发的优势。 Objective To investigate the effect of preoperative radiotherapy on postoperative recurrence in central hepatocellular carcinoma patients treated by hepatectomy. Methods A retrospective cohort study was conducted. Clinicopathological data of 142 patients with central hepatocellular carcinoma who underwent surgical treatment at the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from January 2016 to January 2019 were retrospectively collected. According to whether they received preoperative radiotherapy or not, the patients were divided into preoperative radiotherapy group (30 cases) and surgery-only group (112 cases). The main observation indexes were recurrence-free survival (RFS), intraoperative bleeding amount, operation time and the occurrence of postoperative complications. Kaplan-Meier method was used for survival analysis, and log-rank test was used for intergroup comparisons the differences between the two groups for each factor were evaluated by standardized mean difference (SMD) Cox proportional hazards model was used to analyze the influencing factors of RFS in central hepatocellular carcinoma patients with hepatectomy. Propensity score matching (PSM), regression model-adjusted propensity score (CAPS) and inverse probability of treatment weighting (IPTW) methods were used to investigate the relationship between exposure factors and confounding variables and RFS. Sensitivity analysis was performed using E-value to assess the potential impact of unmeasured confounders on outcomes. Results Men comprised 96.7% (29/30) and 87.5% (98/112) of the preoperative radiotherapy and surgery-only groups, with ages of (55±10) years old and (54±12) years old, respectively. Before matching by the PSM method, there were differences in gender, proportion of patients with hepatitis C, alanine aminotransferase, serum albumin, alpha-fetoprotein, satellite nodules by postoperative pathology, and number of tumors between the two groups (all SMD > 0.1). A total of 26 pairs of patients were successfully matched, and there was no difference in baseline characteristics between the preoperative radiotherapy group and the surgery-only group after matching (all SMD < 0.1). Univariate Cox regression analysis showed that preoperative radiotherapy, number of tumors, maximum diameter of tumor, and satellite nodules by postoperative pathology were the influencing factors of RFS (all P < 0.05) multivariate Cox regression analysis showed that preoperative radiotherapy was an independent protective factor of RFS in central hepatocellular carcinoma patients with hepatectomy ( HR = 0.55, 95% CI: 0.31-0.97, P = 0.038), and maximum diameter of tumor (HR = 1.08, 95% CI: 1.02-1.15, P = 0.005) and satellite nodules by postoperative pathology (HR = 1.97, 95% CI: 1.21-3.19, P = 0.006) were independent risk factors of RFS. Preoperative radiotherapy was associated with superior RFS in patients with central hepatocellular carcinoma (PSM, HR = 0.41, 95% CI: 0.20-0.86, P = 0.018 CAPS, HR = 0.42, 95% CI: 0.20-0.87, P = 0.019 IPTW, HR = 0.41, 95% CI: 0.22-0.76, P = 0.005). Before matching, the 1-, 3-, and 5-year postoperative RFS rates in the preoperative radiotherapy group were 77%, 56% and 45%, respectively, and the surgery-only group were 48%, 32% and 28%, respectively. RFS in the preoperative radiotherapy group was superior to that in the surgery-only group before and after matching (χ2 = 5.65, P = 0.017 χ2 = 6.00, P = 0.014). The E-value for unmeasured confounders altering the conclusions was 2.39, suggesting reliable and stable results. After matching, intraoperative bleeding [M (Q1, Q3)] for patients in the preoperative radiotherapy group and the surgery-only group was 300 ml (125 ml, 600 ml) and 400 ml (200 ml, 600 ml), respectively (U = 0.51, P = 0.611), and the proportions of patients with the operation time >180 min were 92.3% (24/26) and 84.6% (22/ 26), respectively ( χ2 = 0.75, P = 0.385), and the rates of mild postoperative complications were 100.0% (26/26) and 92.3% (24/26), respectively (χ2 = 2.08, P = 0.149), the differences were not statistically significant. Conclusions Preoperative radiotherapy for hepatectomy in patients with central hepatocellular carcinoma is safe and effective, and has the advantage of reducing postoperative recurrence.
Abstract
Objective To investigate the effect of preoperative radiotherapy on postoperative recurrence in central hepatocellular carcinoma patients treated by hepatectomy. Methods A retrospective cohort study was conducted. Clinicopathological data of 142 patients with central hepatocellular carcinoma who underwent surgical treatment at the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from January 2016 to January 2019 were retrospectively collected. According to whether they received preoperative radiotherapy or not, the patients were divided into preoperative radiotherapy group (30 cases) and surgery-only group (112 cases). The main observation indexes were recurrence-free survival (RFS), intraoperative bleeding amount, operation time and the occurrence of postoperative complications. Kaplan-Meier method was used for survival analysis, and log-rank test was used for intergroup comparisons the differences between the two groups for each factor were evaluated by standardized mean difference (SMD) Cox proportional hazards model was used to analyze the influencing factors of RFS in central hepatocellular carcinoma patients with hepatectomy. Propensity score matching (PSM), regression model-adjusted propensity score (CAPS) and inverse probability of treatment weighting (IPTW) methods were used to investigate the relationship between exposure factors and confounding variables and RFS. Sensitivity analysis was performed using E-value to assess the potential impact of unmeasured confounders on outcomes. Results Men comprised 96.7% (29/30) and 87.5% (98/112) of the preoperative radiotherapy and surgery-only groups, with ages of (55±10) years old and (54±12) years old, respectively. Before matching by the PSM method, there were differences in gender, proportion of patients with hepatitis C, alanine aminotransferase, serum albumin, alpha-fetoprotein, satellite nodules by postoperative pathology, and number of tumors between the two groups (all SMD > 0.1). A total of 26 pairs of patients were successfully matched, and there was no difference in baseline characteristics between the preoperative radiotherapy group and the surgery-only group after matching (all SMD < 0.1). Univariate Cox regression analysis showed that preoperative radiotherapy, number of tumors, maximum diameter of tumor, and satellite nodules by postoperative pathology were the influencing factors of RFS (all P < 0.05) multivariate Cox regression analysis showed that preoperative radiotherapy was an independent protective factor of RFS in central hepatocellular carcinoma patients with hepatectomy ( HR = 0.55, 95% CI: 0.31-0.97, P = 0.038), and maximum diameter of tumor (HR = 1.08, 95% CI: 1.02-1.15, P = 0.005) and satellite nodules by postoperative pathology (HR = 1.97, 95% CI: 1.21-3.19, P = 0.006) were independent risk factors of RFS. Preoperative radiotherapy was associated with superior RFS in patients with central hepatocellular carcinoma (PSM, HR = 0.41, 95% CI: 0.20-0.86, P = 0.018 CAPS, HR = 0.42, 95% CI: 0.20-0.87, P = 0.019 IPTW, HR = 0.41, 95% CI: 0.22-0.76, P = 0.005). Before matching, the 1-, 3-, and 5-year postoperative RFS rates in the preoperative radiotherapy group were 77%, 56% and 45%, respectively, and the surgery-only group were 48%, 32% and 28%, respectively. RFS in the preoperative radiotherapy group was superior to that in the surgery-only group before and after matching (χ2 = 5.65, P = 0.017 χ2 = 6.00, P = 0.014). The E-value for unmeasured confounders altering the conclusions was 2.39, suggesting reliable and stable results. After matching, intraoperative bleeding [M (Q1, Q3)] for patients in the preoperative radiotherapy group and the surgery-only group was 300 ml (125 ml, 600 ml) and 400 ml (200 ml, 600 ml), respectively (U = 0.51, P = 0.611), and the proportions of patients with the operation time >180 min were 92.3% (24/26) and 84.6% (22/ 26), respectively ( χ2 = 0.75, P = 0.385), and the rates of mild postoperative complications were 100.0% (26/26) and 92.3% (24/26), respectively (χ2 = 2.08, P = 0.149), the differences were not statistically significant. Conclusions Preoperative radiotherapy for hepatectomy in patients with central hepatocellular carcinoma is safe and effective, and has the advantage of reducing postoperative recurrence.
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