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基于糖尿病的慢性高血糖与接受免疫检查点抑制剂治疗的晚期癌症患者生存率降低独立相关。

Chronic hyperglycemia based on diabetes is independently associated with decreased survival in patients with advanced cancer treated with immune checkpoint inhibitors.

作者信息

Yekedüz Emre, Köksoy Elif Berna, Yazgan Sati Coşkun, Karataş Göktürk, Şenler Filiz Çay, Utkan Güngör, Akbulut Hakan, Demirkazik Ahmet, Ürün Yüksel

机构信息

Department of Medical Oncology, Faculty of Medicine.

Cancer Research Institute.

出版信息

Anticancer Drugs. 2022 Nov 1;33(10):1145-1149. doi: 10.1097/CAD.0000000000001354. Epub 2022 Aug 9.

Abstract

Immune checkpoint inhibitors (ICIs) have started a new era in treating patients with cancer. The effect of comorbidities and concomitant drug use on ICIs have become of interest in those patients. Data about the impact of hyperglycemia on response to ICIs in cancer patients are limited. All advanced-stage cancer patients treated with ICIs in Ankara University Medical Oncology Department were retrospectively evaluated. Patients treated in expanded access programs or clinical trials were excluded from the study. A total of 137 patients were included in this study. The most common primary tumor type was malign melanoma (32.8%) and nivolumab (62.3%) was the most common used ICI. More than half of patients (57.7%) had lung metastasis at the initiation of ICIs. Thirty-five patients (25.5%) had diabetes before initiating ICIs. Median baseline fasting glucose level was higher in patients with diabetes than those without diabetes (117 mg/dl vs. 99 mg/dl, P  = 0.002). In all patients, median overall survival and progression-free survival were 11.3 [95% confidence interval (CI), 8.1-14.4) and 5.9 (95% CI, 3.6-8.3) months, respectively. In multivariate analysis, diabetes was found to increase risk of death [hazard ratio (HR), 2.09; 95% CI, 1.27-3.43, P  = 0.004) and disease progression (HR, 2.01, 95% CI, 1.29-3.09, P  = 0.002). Hyperglycemia might decrease response to ICIs in patients with advanced cancer. This research area is still an unmet need in the immunotherapy era. Prospective studies are needed to elucidate the effect of hyperglycemia on the response to ICIs.

摘要

免疫检查点抑制剂(ICIs)开启了癌症治疗的新时代。合并症和同时使用药物对ICIs治疗癌症患者的影响已引起人们的关注。关于高血糖对癌症患者ICIs治疗反应影响的数据有限。对安卡拉大学医学肿瘤学系所有接受ICIs治疗的晚期癌症患者进行了回顾性评估。在扩大准入项目或临床试验中接受治疗的患者被排除在研究之外。本研究共纳入137例患者。最常见的原发性肿瘤类型是恶性黑色素瘤(32.8%),最常用的ICI是纳武单抗(62.3%)。超过一半的患者(57.7%)在开始使用ICIs时发生了肺转移。35例患者(25.5%)在开始使用ICIs之前患有糖尿病。糖尿病患者的基线空腹血糖中位数水平高于无糖尿病患者(117mg/dl对99mg/dl,P = 0.002)。在所有患者中,总生存期和无进展生存期的中位数分别为11.3[95%置信区间(CI),8.1 - 14.4]个月和5.9(95%CI,3.6 - 8.3)个月。在多变量分析中,发现糖尿病会增加死亡风险[风险比(HR),2.09;95%CI,1.27 - 3.43,P = 0.004]和疾病进展风险(HR,2.01,95%CI,1.29 - 3.09,P = 0.002)。高血糖可能会降低晚期癌症患者对ICIs的反应。在免疫治疗时代,这一研究领域仍是未被满足的需求。需要进行前瞻性研究以阐明高血糖对ICIs治疗反应的影响。

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