Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Ann Palliat Med. 2021 Oct;10(10):10276-10292. doi: 10.21037/apm-21-584. Epub 2021 Sep 17.
This study sought to evaluate the effects of pre-neoadjuvant chemotherapy lactate dehydrogenase (pre-NAC LDH) levels, preoperative LDH levels, and changes in LDH levels on the pathological response and outcomes of colorectal liver metastases (CRLM) patients treated with liver resection after NAC.
This study included 152 colorectal CRLM patients, who underwent NAC followed by liver resection. Patients were excluded if they were diagnosed with other malignancies or lacked follow-up and clinical data. Demographic and clinicopathological data were collected from hospital records. Pathological response and postoperative complications were measured according to the tumor regression grade (TRG) and Clavien-Dindo classification system, respectively. The optimal cutoff values were determined by the receiver operating characteristic curve and the X-tile analysis. Changes in LDH levels were graded as 0, 1, and 2. A logistic regression analysis was conducted to identify the independent predictors of pathological response and postoperative major complications. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors of progression-free survival (PFS) and overall survival (OS).
The multivariate analysis indicated that a grade 2 LDH level change was a risk factor of an unfavorable histological response [odds ratio (OR) 0.249, 95% confidence interval (CI): 0.066-0.942; P=0.041] and major postoperative complications (OR 2.523, 95% CI: 1.179-10.530; P=0.024), which were independent of other clinical covariates. A pre-NAC LDH level ≥145 IU/L [hazards ratio (HR) 0.584, 95% CI: 0.359-0.950; P=0.030], a grade 1 LDH level change (HR 0.584, 95% CI: 0.359-0.950; P=0.030) and a grade 2 LDH level change (HR 0.447, 95% CI: 0.231-0.864; P=0.017) were independent prognostic predictors of PFS. A preoperative a LDH level ≥231 IU/L (HR 0.405, 95% CI: 0.192-0.852; P=0.017) and a grade 2 LDH level change (HR 0.362, 95% CI: 0.157-0.834; P=0.017) were independent prognostic factors of OS, which were independent of other clinical covariates.
LDH levels and changes in LDH levels are potentially useful biomarkers for predicting the pathological response and prognosis of CRLM patients receiving NAC followed by liver resection.
本研究旨在评估新辅助化疗前乳酸脱氢酶（pre-NAC LDH）水平、术前 LDH 水平以及 LDH 水平变化对接受新辅助化疗后行肝切除术的结直肠癌肝转移（CRLM）患者的病理应答和结局的影响。
本研究纳入了 152 例接受新辅助化疗后行肝切除术的结直肠癌 CRLM 患者。排除标准为合并其他恶性肿瘤或缺乏随访和临床资料的患者。从病历中收集人口统计学和临床病理数据。根据肿瘤退缩分级（TRG）和 Clavien-Dindo 分类系统分别测量病理应答和术后并发症。通过受试者工作特征曲线和 X-tile 分析确定最佳截断值。LDH 水平变化分为 0、1 和 2 级。采用 logistic 回归分析确定病理应答和术后主要并发症的独立预测因子。采用单因素和多因素 Cox 回归分析确定无进展生存期（PFS）和总生存期（OS）的独立风险因素。
多因素分析表明，LDH 水平变化 2 级是组织学应答不良的危险因素[比值比（OR）0.249，95%置信区间（CI）：0.066-0.942；P=0.041]和主要术后并发症（OR 2.523，95%CI：1.179-10.530；P=0.024）的独立预测因子，不受其他临床协变量的影响。新辅助化疗前 LDH 水平≥145IU/L[风险比（HR）0.584，95%CI：0.359-0.950；P=0.030]、LDH 水平变化 1 级（HR 0.584，95%CI：0.359-0.950；P=0.030）和 LDH 水平变化 2 级（HR 0.447，95%CI：0.231-0.864；P=0.017）是 PFS 的独立预后预测因子。术前 LDH 水平≥231IU/L（HR 0.405，95%CI：0.192-0.852；P=0.017）和 LDH 水平变化 2 级（HR 0.362，95%CI：0.157-0.834；P=0.017）是 OS 的独立预后因素，不受其他临床协变量的影响。
LDH 水平及其变化可能是预测接受新辅助化疗后行肝切除术的 CRLM 患者病理应答和预后的有用生物标志物。
