Krug S, Boch M, Nimphius W, Gress T M, Michl P, Rinke A
Department of Internal Medicine I, Martin Luther University, Halle (Saale), Germany; Department of Gastroenterology and Endocrinology, Philipps-University, Marburg, Germany.
Institute of Pathology, Philipps-University, Marburg, Germany.
Pancreatology. 2017 Jan-Feb;17(1):139-145. doi: 10.1016/j.pan.2016.12.006. Epub 2016 Dec 22.
Chemotherapy with 5-FU and Streptozotocin (STZ) is recommended as first-line treatment in patients with metastatic pancreatic neuroendocrine neoplasms (PNEN). However, data about biomarkers involved in the 5-FU metabolism to predict response are still limited.
Evaluation of clinicopathological features and potential predictive and prognostic markers of patients with PNEN treated with 5-FU based regimens.
We retrospectively analyzed 41 patients with PNEN who were treated at the University Hospital Marburg between 2000 and 2013. Dihydropyrimidine-Dehydrogenase (DPD) and Thymidylate-Synthase (TS) expression was correlated with treatment response in 19 patients who had available tumour tissue and response data. The median overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively.
The median PFS in patients receiving 5-FU/STZ was 17 months with a median OS of 50 months. Objective response rate (ORR) and disease control rate (DCR) were 32% and 73%, respectively. Biochemical response (p = 0.005) and high DPD expression (p = 0.018) were predictive markers of response to 5-FU-based chemotherapy. Univariate analysis identified Ki-67 > 10%, no biochemical response, positive 5-HIAA levels and TS deficiency as independent risk factors for shorter PFS. Moreover, performance status (PS) ≥1 was an independent risk factors for impaired OS.
DPD expression and biochemical response represent promising predictive biomarkers for response to 5-FU based chemotherapy. Moreover, Ki-67, PS and TS are independent prognostic markers of OS and PFS in patients with PNEN.
对于转移性胰腺神经内分泌肿瘤（PNEN）患者，推荐使用5-氟尿嘧啶（5-FU）和链脲佐菌素（STZ）进行化疗作为一线治疗方案。然而，关于参与5-FU代谢以预测反应的生物标志物的数据仍然有限。
评估接受基于5-FU方案治疗的PNEN患者的临床病理特征以及潜在的预测和预后标志物。
我们回顾性分析了2000年至2013年间在马尔堡大学医院接受治疗的41例PNEN患者。对19例有可用肿瘤组织和反应数据的患者，二氢嘧啶脱氢酶（DPD）和胸苷酸合成酶（TS）表达与治疗反应相关。分别使用Kaplan-Meier法和Cox回归法计算中位总生存期（OS）和无进展生存期（PFS）。
接受5-FU/STZ治疗的患者中位PFS为17个月，中位OS为50个月。客观缓解率（ORR）和疾病控制率（DCR）分别为32%和73%。生化反应（p = 0.005）和高DPD表达（p = 0.018）是基于5-FU化疗反应的预测标志物。单因素分析确定Ki-67>10%、无生化反应、5-羟吲哚乙酸（5-HIAA）水平阳性和TS缺乏是PFS较短的独立危险因素。此外，体能状态（PS）≥1是OS受损的独立危险因素。
DPD表达和生化反应是基于5-FU化疗反应的有前景的预测生物标志物。此外，Ki-67、PS和TS是PNEN患者OS和PFS的独立预后标志物。
