Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Acta Oncol. 2013 Jun;52(5):1002-9. doi: 10.3109/0284186X.2012.718096. Epub 2012 Sep 5.
We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin.
Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ(2) statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT.
The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥ 1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05).
Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy.
我们研究了接受新辅助放化疗的服用二甲双胍的食管腺癌患者的放射学和病理学缓解率。
本研究纳入了 1997 年至 2012 年间接受同步放化疗（CRT）后行食管切除术的 285 例食管腺癌患者，其中包括 29 例服用二甲双胍的糖尿病患者、21 例未服用二甲双胍的糖尿病患者和 235 例非糖尿病患者。204 例患者有治疗前后的正电子发射断层扫描（PET）扫描。在手术时对病理学反应进行分级。使用 χ(2)统计和 ANOVA 进行比较，并进行事后 LSD 分析。采用多变量逻辑回归分析来控制 CRT 后病理学完全缓解（CR）的预测因素。
研究人群的总体病理学 CR 率为 20%。服用二甲双胍的患者（34.5%）的病理学 CR 率高于未服用二甲双胍的糖尿病患者（4.8%，p=0.01）和非糖尿病患者（19.6%，p=0.05）。病理学 CR 与二甲双胍剂量有关，剂量≥1500mg/d 与更高的 CR 率相关。未发现治疗前最大肿瘤 SUV（p=0.93）有显著差异，但服用二甲双胍的患者治疗后最大 SUV 显著降低（p=0.05）。多变量逻辑回归分析显示，二甲双胍的使用与病理学 CR 独立相关（p=0.04）。二甲双胍的使用还与放疗后局部区域失败的发生率降低有关（p=0.05）。
二甲双胍的使用与食管癌对 CRT 的剂量依赖性反应增加有关，可能是该治疗的增敏剂。
