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Survival Benefit for Metformin Through Better Tumor Response by Neoadjuvant Concurrent Chemoradiotherapy in Rectal Cancer

 Jung Min Kim  ;  Jung Won Park  ;  Jin Ha Lee  ;  Ye Hyun Park  ;  Soo Jung Park  ;  Jae Hee Cheon  ;  Won Ho Kim  ;  Tae Il Kim 
 DISEASES OF THE COLON & RECTUM, Vol.63(6) : 758-768, 2020-06 
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BACKGROUND: Metformin may reduce cancer risk and mortality and improve radiotherapy responses in several malignancies. OBJECTIVE: This study aimed to compare tumor responses and prognoses of metformin and nonmetformin groups of diabetic patients receiving neoadjuvant concurrent chemoradiotherapy for rectal cancer. DESIGN: This is a retrospective study. SETTING: This study was conducted at a single institution in the Republic of Korea. PATIENTS: Between January 2000 and November 2017, 104 patients with rectal cancer who were taking diabetes medication and treated with neoadjuvant concurrent chemoradiotherapy followed by radical surgery were reviewed. Patients were divided into those taking (n = 62) and not taking metformin (n = 42). Tumor responses, survival, and other outcomes were analyzed. MAIN OUTCOME MEASURES: Tumor response, rectal cancer-specific survival, and disease-free survival rates were measured. RESULTS: Tumor regression grade (p = 0.002), pathological complete response (p = 0.037), and N downstaging (p < 0.001) after neoadjuvant concurrent chemoradiotherapy were significantly higher in the metformin group than in the nonmetformin group. In analysis of cancer-specific mortality, metformin use, differentiation (well, moderate vs poor), pathological Union for International Cancer Control stage (3 vs 1–2), ypN stage (1–2 vs 0), and N downstaging (HR, 0.256 (95% CI, 0.082–0.794), p = 0.018; HR, 0.147 (95% CI, 0.031–0.697), p = 0.016; HR, 3.693 (95% CI, 1.283–10.635), p = 0.015; HR, 3.181 (95% CI, 1.155–8.759), p = 0.025, and HR, 0.175 (95% CI, 0.040–0.769), p = 0.021) were significant factors related to mortality in diabetic patients with rectal cancer. In addition, in the multivariate analysis of cancer recurrence, the interaction between metformin use and lymph node downstaging was a significant predictive factor (HR, 0.222 (95% CI, 0.077–0.639); p = 0.005). LIMITATIONS: This was a small retrospective study conducted at a single institution. CONCLUSIONS: Metformin use was associated with better tumor responses and cancer-specific survival, as well as a lower risk of cancer recurrence, in patients with diabetes mellitus who had lymph node downstaging after neoadjuvant concurrent chemoradiotherapy in rectal cancer. See Video
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Soo Jung(박수정)
Park, Yehyun(박예현) ORCID logo https://orcid.org/0000-0001-8811-0631
Park, Jung Won(박정원)
Lee, Jin Ha(이진하)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
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