Table_2_Glycemic Control as an Early Prognostic Marker in Advanced Pancreatic Cancer.xlsx

PurposeImpaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting.
Patients and MethodsSeventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables.
ResultsOne thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (P=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to >120 mg/dl (19 vs. 9 months; HR=0.37, P=0.002). In contrast, an early decline in CA 19-9 could not predict OS.
ConclusionLower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.

研究目的：多数胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）患者存在葡萄糖代谢受损。既往研究多聚焦于合并糖尿病的胰腺导管腺癌患者的治疗前血糖指标与预后的关联，但尚未明确化疗期间的血糖控制对伴/不伴糖尿病患者预后的影响。本研究针对社区诊疗环境下接受治疗的晚期胰腺导管腺癌患者队列，探讨早期血糖控制与总生存期（overall survival, OS）之间的关联。

患者与方法：本研究纳入73例晚期胰腺导管腺癌患者，其中38%合并糖尿病，所有患者均在接受化疗的同时参与生物样本库临床试验。研究人员从患者的电子病历中提取了其1年内的临床特征与实验室检测结果。采用Kaplan-Meier法绘制生存曲线、Log-rank检验及计算风险比，以评估血糖控制对总生存期的影响；同时运用Cox比例风险回归模型，明确血糖控制与其他生存相关变量的关联显著性。

研究结果：本研究共分析了1418份随机血糖（random blood glucose, RBG）检测值。与既往研究结果一致，血清肿瘤标志物CA 19-9任意时点下降50%可预测患者生存（P=0.0002）。单因素分析显示，治疗前平均随机血糖、3个月平均随机血糖（3-month average random blood glucose, RBG-3）以及FOLFIRINOX化疗方案与更长的生存期显著相关。通过受试者工作特征（Receiver Operating Characteristic, ROC）曲线分析（曲线下面积AUC=0.82），确定120mg/dl为RBG-3预测12个月生存期的最佳截断值。在纳入年龄、肿瘤分期、身体质量指数（body mass index, BMI）、体力状况评分、糖尿病患病情况及化疗方案的多因素分析中，仅RBG-3仍具有统计学显著性：与RBG-3＞120mg/dl的患者相比，RBG-3≤120mg/dl的患者总生存期更优（19个月 vs 9个月；风险比HR=0.37，P=0.002）。与之相反，早期CA 19-9水平下降无法预测患者总生存期。

结论：晚期胰腺导管腺癌患者接受治疗的前3个月内血糖水平越低，无论是否合并糖尿病，其总生存期均更优。本研究结果提示，RBG-3或可成为一种新型预后生物标志物，有待在更大规模的患者队列中进一步验证；同时，针对这一与生存期相关的新型关联的因果机制开展相关研究具有重要意义。