Fransgaard Tina, Hallas Jesper, Thygesen Lau Caspar, Gögenur Ismail
Zealand University Hospital, Department of Surgery, Lykkebækvej 1, 4600, Køge, Denmark.
Clinical Pharmacology and Pharmacy, University of Southern Denmark, J. B. Winsløws Vej 19, 2, 5000, Odense C, Denmark.
Surg Oncol. 2019 Mar;28:62-66. doi: 10.1016/j.suronc.2018.11.007. Epub 2018 Nov 8.
The aim of the study was to investigate, in a nationwide study, if diabetes and especially metformin exposure during neoadjuvant chemo-radiotherapy improves the oncological outcomes in patients with rectal cancer.
Patients undergoing neoadjuvant chemo-radiotherapy and curative intended resection for rectal cancer in Denmark between January 1, 2003 and July 1, 2015 were identified. Diabetes was defined as medically treated diabetes. Only patients who were either active users of antidiabetic medication at the beginning of the radiotherapy or never-users were included. Active users were matched with never-users 1:2 by propensity score. Subgroup analyses concerning metformin treatment were performed. The primary outcome of the study was disease-free survival and the secondary outcomes were recurrence free survival and all-cause mortality.
A total of 9799 patients were undergoing rectal cancer surgery with curative intend in the period. Of those, 2379 received neoadjuvant treatment up to one year preceding surgery. In total 459 patients were included in the study 154 patients with diabetes and 305 not diagnosed with diabetes. In the diabetes group, 53 were in active treatment with metformin. No statistical difference between the diabetes group and the non-diabetes group was shown with respect to disease free survival (HR 0.96, 95%CI 0.73-1.26, p = 0.77), recurrence-free survival (HR = 1.11, 95% CI 0.78-1.58, p = 0.56) or all-cause mortality (HR = 0.94, 95% CI 0.69-1.28, p = 0.69). Metformin treatment did not influence any of the outcomes.
Our study does not support that diabetes or metformin use are associated with response to neoadjuvant chemo-radiotherapy in terms of disease-free survival, recurrence-free survival or all-cause mortality.
本研究旨在通过一项全国性研究，调查糖尿病尤其是在新辅助放化疗期间使用二甲双胍是否能改善直肠癌患者的肿瘤学结局。
确定2003年1月1日至2015年7月1日期间在丹麦接受新辅助放化疗并计划进行直肠癌根治性切除术的患者。糖尿病定义为接受药物治疗的糖尿病。仅纳入放疗开始时为抗糖尿病药物的活跃使用者或从未使用者的患者。活跃使用者与从未使用者按倾向评分1:2进行匹配。进行了关于二甲双胍治疗的亚组分析。研究的主要结局是无病生存期，次要结局是无复发生存期和全因死亡率。
在此期间，共有9799例患者接受了直肠癌根治性手术。其中，2379例在手术前一年接受了新辅助治疗。总共有459例患者纳入研究，154例患有糖尿病，305例未被诊断为糖尿病。在糖尿病组中，53例正在接受二甲双胍治疗。糖尿病组和非糖尿病组在无病生存期（风险比0.96，95%置信区间0.73 - 1.26，p = 0.77）、无复发生存期（风险比 = 1.11，95%置信区间0.78 - 1.58，p = 0.56）或全因死亡率（风险比 = 0.94，95%置信区间0.69 - 1.28，p = 0.69）方面均未显示出统计学差异。二甲双胍治疗对任何结局均无影响。
我们的研究不支持糖尿病或使用二甲双胍与新辅助放化疗在无病生存期、无复发生存期或全因死亡率方面的反应相关。
