Weixler Benjamin, Viehl Carsten T, Warschkow Rene, Guller Ulrich, Ramser Michaela, Sauter Guido, Zuber Markus
Department of Surgery, University Hospital Basel, Basel, Switzerland.
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
JAMA Surg. 2017 Oct 1;152(10):912-920. doi: 10.1001/jamasurg.2017.1514.
Small nodal tumor infiltrates (SNTI; isolated tumor cells and micrometastases) in sentinel lymph nodes and bone marrow micrometastases (BMM) were independently described as prognostic factors in patients with colon cancer.
To examine the association between the occurrence of SNTI and BMM as well as their prognostic relevance.
DESIGN, SETTING, AND PARTICIPANTS: This prospective study was conducted at 3 university-affiliated institutions in Switzerland between May 2000 and December 2006. Statistical analyses were performed in October 2016. A total of 122 patients with stage I to III colon cancer were included. Follow-up time exceeded 6 years, with no patients lost to follow-up.
Bone marrow aspiration from the iliac crests and in vivo sentinel lymph node mapping were performed during open standard oncological resection. Bone marrow aspirates were stained with the pancytokeratin marker A45-B/B3. All sentinel lymph nodes underwent multilevel sectioning and were stained with hematoxylin-eosin and the pancytokeratin marker AE1/AE3.
Association of SNTI in sentinel lymph nodes and BMM in patients with stage I to III colon cancer and the prognostic effect on disease-free survival (DFS) and overall survival (OS).
Of the 122 patients, 63 (51.6%) were female, with a mean (SD) age of 71.2 (11.7) years. Small nodal tumor infiltrates and BMM were found in a total of 21 patients (17.2%) and 46 patients (37.7%), respectively. The occurrence of BMM was not associated with the presence of SNTI by standard correlation (κ, -0.07; 95% CI, -0.29 to 0.14; P = .49) nor by univariate logistic regression analysis (odds ratio, 0.64; 95% CI, 0.22-1.67; P = .37) or multivariate logistic regression analysis (odds ratio, 1.09; 95% CI, 0.34-3.28; P = .88). The presence of SNTI was an independent negative prognostic factor for DFS (hazard ratio [HR], 2.93; 95% CI, 1.24-6.93; P = .02) and OS (HR, 4.04; 95% CI, 1.56-10.45; P = .005), as was BMM (HR, 2.07; 95% CI, 1.06-4.06; P = .04; and HR, 2.68; 95% CI, 1.26-5.70; P = .01; respectively). The combined detection of BMM and SNTI demonstrated the poorest DFS (HR, 6.73; 95% CI, 2.29-19.76; P = .006) and OS (HR, 5.96; 95% CI, 1.66-21.49; P = .03).
This study demonstrates no association between the occurrence of SNTI and BMM in patients with stage I to III colon cancer. However, both SNTI and BMM are independent negative prognostic factors regarding DFS and OS, and the occurrence of both is associated with significantly worse prognosis compared with either one of them.
clinicaltrials.gov Identifier: NCT00826579.
前哨淋巴结中的微小肿瘤浸润（SNTI；孤立肿瘤细胞和微转移灶）以及骨髓微转移（BMM）已被分别描述为结肠癌患者的预后因素。
研究SNTI和BMM的发生之间的关联及其预后相关性。
设计、地点和参与者：这项前瞻性研究于2000年5月至2006年12月在瑞士的3家大学附属医院进行。2016年10月进行统计分析。共纳入122例I至III期结肠癌患者。随访时间超过6年，无患者失访。
在开放式标准肿瘤切除术中进行髂嵴骨髓穿刺和体内前哨淋巴结定位。骨髓穿刺物用全细胞角蛋白标志物A45-B/B3染色。所有前哨淋巴结均进行多层切片，并分别用苏木精-伊红和全细胞角蛋白标志物AE1/AE3染色。
I至III期结肠癌患者前哨淋巴结中的SNTI与BMM之间的关联以及对无病生存期（DFS）和总生存期（OS）的预后影响。
122例患者中，63例（51.6%）为女性，平均（标准差）年龄为71.2（11.7）岁。分别在21例（17.2%）和46例（37.7%）患者中发现微小肿瘤浸润和BMM。通过标准相关性分析（κ，-0.07；95%CI，-0.29至0.14；P = 0.49）、单因素逻辑回归分析（比值比，0.64；95%CI，0.22 - 1.67；P = 0.37）或多因素逻辑回归分析（比值比，1.09；95%CI，0.34 - 3.28；P = 0.88），BMM的发生与SNTI的存在均无关联。SNTI的存在是DFS（风险比[HR]，2.93；95%CI，1.24 - 6.93；P = 0.02）和OS（HR，4.04；95%CI，1.56 - 10.45；P = 0.005）的独立阴性预后因素，BMM也是如此（HR分别为2.07；95%CI，1.06 - 4.06；P = 0.04；以及HR，2.68；95%CI，1.26 - 5.70；P = 0.01）。BMM和SNTI的联合检测显示DFS最差（HR，6.73；95%CI，2.29 - 19.76；P = 0.006），OS也是如此（HR，5.96；95%CI，1.66 - 21.49；P = 0.03）。
本研究表明，I至III期结肠癌患者中SNTI和BMM的发生之间无关联。然而，SNTI和BMM都是DFS和OS的独立阴性预后因素，与其中任何一个因素相比，两者同时出现与更差的预后相关。
clinicaltrials.gov标识符：NCT00826579。
