Matsuda S, Takeuchi H, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Saikawa Y, Omori T, Kitagawa Y
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Dis Esophagus. 2014 Sep-Oct;27(7):654-61. doi: 10.1111/dote.12115. Epub 2013 Aug 27.
Among multidisciplinary therapies developed for advanced esophageal cancer, neoadjuvant chemotherapy and chemoradiotherapy have been established as standard treatments. To deliver cautious follow up and intense treatment for high-risk patients, a simple and instructive biomarker for the postoperative recurrence needs to be identified. Fibrinogen, a common component of hemostasis, has been suggested to not only play an important role in cancer metastasis, but also correlate with tumor recurrence. We aim to clarify the validity of plasma fibrinogen as a marker for predicting the postoperative recurrence of esophageal squamous cell carcinoma patients who received neoadjuvant treatment. We reviewed 72 consecutive patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy at the Keio University Hospital from 2001 to 2010. Of them, we retrospectively examined 68 patients who underwent plasma fibrinogen examination before and after neoadjuvant treatment and underwent transthoracic radical esophagectomy. We investigated patient characteristics, clinicopathological factors, neoadjuvant treatment effects, postoperative course, and plasma fibrinogen levels. We investigated pretreatment and preoperative (postneoadjuvant treatment) plasma fibrinogen levels, as well as changes in fibrinogen levels before and after neoadjuvant treatment. Patients with preoperative hyperfibrinogenemia (>350 mg/dL) and patients with increased plasma fibrinogen levels during neoadjuvant treatment showed significantly shorter postoperative disease-free survival (DFS) (P = 0.002 and P = 0.037, respectively). Moreover, we classified these patients into three classes on the basis of their preoperative fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment. Patients who had both high preoperative plasma fibrinogen and increased fibrinogen levels showed significantly shorter DFS than others. In contrast, patients who had normal preoperative plasma fibrinogen and decreased fibrinogen levels showed significantly longer DFS. Based on this fibrinogen classification, we could differentiate between significantly favorable and poor prognosis patients group. Overall, this classification (hazard ratio = 1.812, P = 0.013) and the response to neoadjuvant treatment (hazard ratio = 0.350, P = 0.007) were found to be significant determining factors for postoperative DFS. With the validity of preoperative plasma fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment, the plasma fibrinogen level was found to be a possible biomarker for postoperative recurrence in advanced esophageal cancer patients who received neoadjuvant treatment. Moreover, plasma fibrinogen classification could be a simple and valuable predictive marker for postoperative follow up.
在为晚期食管癌开发的多学科治疗方法中，新辅助化疗和放化疗已被确立为标准治疗方法。为了对高危患者进行谨慎的随访和强化治疗，需要确定一种简单且具有指导意义的术后复发生物标志物。纤维蛋白原是止血的常见成分，不仅被认为在癌症转移中起重要作用，还与肿瘤复发相关。我们旨在阐明血浆纤维蛋白原作为预测接受新辅助治疗的食管鳞状细胞癌患者术后复发标志物的有效性。我们回顾了2001年至2010年在庆应义塾大学医院连续接受新辅助化疗或放化疗，随后行食管切除术的72例食管鳞状细胞癌患者。其中，我们回顾性研究了68例在新辅助治疗前后接受血浆纤维蛋白原检查并接受经胸根治性食管切除术的患者。我们调查了患者特征、临床病理因素、新辅助治疗效果、术后病程和血浆纤维蛋白原水平。我们研究了治疗前和术前（新辅助治疗后）的血浆纤维蛋白原水平，以及新辅助治疗前后纤维蛋白原水平的变化。术前高纤维蛋白原血症（>350mg/dL）患者和新辅助治疗期间血浆纤维蛋白原水平升高的患者术后无病生存期（DFS）明显缩短（分别为P = 0.002和P = 0.037）。此外，我们根据患者术前纤维蛋白原水平和新辅助治疗期间纤维蛋白原水平的变化将这些患者分为三类。术前血浆纤维蛋白原水平高且纤维蛋白原水平升高的患者DFS明显短于其他患者。相比之下，术前血浆纤维蛋白原水平正常且纤维蛋白原水平降低的患者DFS明显更长。基于这种纤维蛋白原分类，我们可以区分预后明显良好和不良的患者组。总体而言，这种分类（风险比=1.812，P = 0.013）和对新辅助治疗的反应（风险比=0.350，P = 0.007）被发现是术后DFS的重要决定因素。鉴于术前血浆纤维蛋白原水平和新辅助治疗期间纤维蛋白原水平变化的有效性，血浆纤维蛋白原水平被发现可能是接受新辅助治疗的晚期食管癌患者术后复发的生物标志物。此外，血浆纤维蛋白原分类可能是一种简单且有价值的术后随访预测标志物。
