Connell Louise C, Boucher Taryn M, Chou Joanne F, Capanu Marinela, Maldonado Stephanie, Kemeny Nancy E
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
J Surg Oncol. 2017 Mar;115(4):480-487. doi: 10.1002/jso.24536. Epub 2016 Dec 23.
While the significance of carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and Kirsten rat sarcoma (KRAS) status as individual prognostic factors for patients with metastatic colorectal cancer has been addressed, the relationship and interdependence between these prognostic factors on survival is limited.
Patients with unresectable colorectal liver metastases with known KRAS status, and with baseline CEA and LDH levels who were treated with hepatic arterial infusion and systemic chemotherapy were identified. Patients were divided into two groups: hepatic-only disease and extra-hepatic disease.
A total of 193 patients were included: 121 with hepatic-only and 72 with extra-hepatic disease. In the hepatic-only group, median overall survival (OS) was 55 months. On multivariate analysis, KRAS mutated tumors (HR 1.7, P < 0.05), LDH >200 U/L (HR 2.0, P < 0.05), and prior chemotherapy (HR 2.1, P < 0.05) had lower OS. In patients with extra-hepatic disease, median OS was 32 months. On multivariate analysis, baseline CEA >200 ng/mL (HR 2.1, P = 0.051), LDH >200 U/L (HR 3.8, P < 0.05), and right-sided tumors (HR 2.8, P < 0.05) had lower OS.
This analysis verifies two distinct patterns in terms of biomarkers in patients with unresectable colorectal liver metastases. In patients with hepatic-only disease, KRAS mutation and elevated LDH negatively influenced survival. In patients with extra-hepatic disease, elevated LDH negatively impacted survival.
虽然癌胚抗原(CEA)、乳酸脱氢酶(LDH)和 Kirsten 大鼠肉瘤(KRAS)状态作为转移性结直肠癌患者个体预后因素的意义已得到探讨,但这些预后因素对生存的关系和相互依赖性尚不明确。
确定接受肝动脉灌注和全身化疗的不可切除结直肠癌肝转移患者,其 KRAS 状态已知,且有基线 CEA 和 LDH 水平。患者分为两组:仅肝内疾病组和肝外疾病组。
共纳入 193 例患者:121 例为仅肝内疾病,72 例为肝外疾病。在仅肝内疾病组中,中位总生存期(OS)为 55 个月。多因素分析显示,KRAS 突变肿瘤(HR 1.7,P < 0.05)、LDH>200 U/L(HR 2.0,P < 0.05)和既往化疗(HR 2.1,P < 0.05)的 OS 较低。在肝外疾病患者中,中位 OS 为 32 个月。多因素分析显示,基线 CEA>200 ng/mL(HR 2.1,P = 0.051)、LDH>200 U/L(HR 3.8,P < 0.05)和右侧肿瘤(HR 2.8,P < 0.05)的 OS 较低。
该分析验证了不可切除结直肠癌肝转移患者生物标志物方面的两种不同模式。在仅肝内疾病患者中,KRAS 突变和 LDH 升高对生存有负面影响。在肝外疾病患者中,LDH 升高对生存有负面影响。