The Influence of Diabetes Mellitus and Metformin on Distant Metastases in Oropharyngeal Cancer: A Multicenter Study.
The Influence of Diabetes Mellitus and Metformin on Distant Metastases in Oropharyngeal Cancer: A Multicenter Study.
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DOI：
10.1016/j.ijrobp.2015.11.007
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发表时间：
2016-03-01
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影响因子：
--
通讯作者：
Lee NY
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作者：
Spratt DE;Beadle BM;Zumsteg ZS;Rivera A;Skinner HD;Osborne JR;Garden AS;Lee NY
通过综合治疗，口咽癌的局部控制率已经提高到了前所未有的水平，因此，远处转移正成为一个主要的挑战。我们的目的是确定糖尿病和二甲双胍的使用对现代治疗的大量口咽癌患者的临床结果的影响。我们确定了1998-2011年间在两个大型癌症中心接受体外放射治疗的1,745名口咽癌患者。共有184名患者在确诊时患有糖尿病，其中102人正在服用二甲双胍。评估的结果包括局部无失败生存(LFFS)、区域无失败生存(RFFS)、无远处转移生存(DMFS)和总生存(OS)。中位随访时间为4.3年，DMFS的5年精算率非糖尿病患者为89.6%，糖尿病非二甲双胍用户为78.7%(p=0.011)，OS非糖尿病患者为83.0%，糖尿病非二甲双胍用户为70.7%(p=0.048)。糖尿病患者的5年DMFS(90.1%)和OS(89.6%)与非糖尿病患者相似。多变量分析(以糖尿病非二甲双胍为参照)显示，非糖尿病患者的DMF有所改善(0.54[0.32-0.93]，p=0.03)，使用二甲双胍后DMFS有改善的趋势(危险比0.46[95%CI 0.20-1.04]，p=0.06)。LFFS和RFFS在所有组中都很高，并且不同糖尿病状态或二甲双胍的使用没有显著差异。未单独使用二甲双胍的糖尿病患者的远处转移率显著高于非糖尿病患者，而使用二甲双胍的患者的远处转移率与非糖尿病患者相似。有必要进行进一步的前瞻性研究，以证实二甲双胍在口咽癌中的益处。
Local control in oropharyngeal cancer has improved to unprecedented rates with combined modality therapy, and as a result distant metastases are becoming a principle challenge. We aimed to determine the impact of diabetes mellitus and metformin use on clinical outcomes in a large population of oropharyngeal cancer patients treated in the modern era. We identified 1,745 consecutive patients with oropharyngeal cancer treated at two large cancer centers with external beam radiotherapy from 1998-2011. A total of 184 patients had diabetes mellitus at time of diagnosis, of which 102 were taking metformin. Outcomes assessed included local failure-free survival (LFFS), regional failure-free survival (RFFS), distant metastasis-free survival (DMFS), and overall survival (OS). Median follow-up was 4.3 years, and the 5-year actuarial rates of DMFS were 89.6% for non-diabetics and 78.7% for diabetic non-metformin users (p=0.011), and OS were 83.0% for non-diabetics and 70.7% for diabetic non-metformin users (p=0.048). Diabetic metformin users had similar 5-year DMFS (90.1%) and OS (89.6%) to non-diabetics. Multivariate analysis (diabetic non-metformin as reference) demonstrated improved DMFS for non-diabetic patients (0.54 [0.32-0.93], p=0.03) and a trend towards improved DMFS with metformin use (Hazard Ratio 0.46 [95%CI 0.20-1.04], p=0.06). LFFS and RFFS were high in all groups and were not significantly different by diabetic status or metformin use. Diabetic patients not using metformin independently have significantly higher rates of distant metastases than non-diabetic patients, whereas metformin users have similar rates of distant metastases to non-diabetics. Further prospective investigation is warranted to validate metformin's benefit in oropharyngeal cancer.