The influence of diabetes mellitus and metformin on distant metastases in oropharyngeal cancer: A multicenter study Journal Article


Authors: Spratt, D. E.; Beadle, B. M.; Zumsteg, Z. S.; Rivera, A.; Skinner, H. D.; Osborne, J. R.; Garden, A. S.; Lee, N. Y.
Article Title: The influence of diabetes mellitus and metformin on distant metastases in oropharyngeal cancer: A multicenter study
Abstract: Purpose Local control in oropharyngeal cancer has improved to unprecedented rates with combined modality therapy; as a result, distant metastases are becoming a principal 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. Methods and Materials We identified 1745 consecutive patients with oropharyngeal cancer treated at 2 large cancer centers with external beam radiation therapy from 1998 to 2011. A total of 184 patients had diabetes mellitus at the time of diagnosis, of whom 102 were taking metformin. The outcomes assessed included local failure-free survival (LFFS), regional failure-free survival (RFFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results The median follow-up time was 4.3 years. The 5-year actuarial rates of DMFS were 89.6% for nondiabetic patients and 78.7% for diabetic nonmetformin users (P=.011) and of OS were 83.0% for nondiabetic patients and 70.7% for diabetic nonmetformin users (P=.048). Diabetic metformin users had 5-year DMFS (90.1%) and OS (89.6%) similar to those of nondiabetic patients. Multivariate analysis (diabetic nonmetformin users as reference) demonstrated improved DMFS for nondiabetic patients (adjusted hazard ratio 0.54; 95% confidence interval 0.32-0.93; P=.03) and a trend toward improved DMFS with metformin use (adjusted hazard ratio 0.46; 95% confidence interval 0.20-1.04; P=.06). LFFS and RFFS were high in all groups and were not significantly different by diabetic status or metformin use. Conclusions Diabetic patients not using metformin independently have significantly higher rates of distant metastases than do nondiabetic patients, whereas metformin users have rates of distant metastases similar to those of nondiabetic patients. Further prospective investigation is warranted to validate the benefit of metformin in oropharyngeal cancer. © 2016 Elsevier Inc.
Keywords: combined modality therapy; radiotherapy; patient monitoring; pathology; distant metastasis; confidence interval; multicenter study; diagnosis; patient treatment; multi variate analysis; multivariant analysis; diseases; external beam radiation therapy; hazards; oropharyngeal cancer; methods and materials
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 94
Issue: 3
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2016-03-01
Start Page: 523
End Page: 531
Language: English
DOI: 10.1016/j.ijrobp.2015.11.007
PROVIDER: scopus
PUBMED: 26867881
PMCID: PMC4993040
DOI/URL:
Notes: Article -- Export Date: 2 May 2016 -- Source: Scopus
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MSK Authors
  1. Joseph R Osborne
    56 Osborne
  2. Nancy Y. Lee
    542 Lee
  3. Zachary Stephan Zumsteg
    34 Zumsteg
  4. Daniel Eidelberg Spratt
    83 Spratt
  5. Andrew   Rivera
    2 Rivera