This study examined the association between statin and beta-blocker (BB) use and outcomes in 130 patients diagnosed with both head and neck cancer and diabetes mellitus. The results showed that use of lipophilic statins and selective BBs was associated with improved overall survival and disease-free survival. However, the small sample sizes of patients using hydrophilic statins and non-selective BBs may have biased these results. The study was limited by its inability to determine medication duration but suggests longer use prior to cancer diagnosis.

1. Introduction
Objectives
Results & Discussion
• Although a small retrospective study, this provides supportive evidence on the benefits of statin
and BB use in DM patients with HNC, according to the presented Cox analysis.
• Lipophilic statins and selective BB use was associated with improved OS and DFS. However, it
is important to note the small hydrophilic statins and non-selective BBs group size (6 and 8
cases, respectively) – a fact that may have significantly biased the observed result.
• One of our limitations was the inability to document the duration of statin or BB use.
Nevertheless, with DM being a risk factor for cancer, it is likely that DM diagnosis occurred long
enough before HNC diagnosis. This suggests that duration of statin and/or BB therapy may
have been rather longer than shorter at the time of cancer diagnosis – this remains, however, a
speculation.
Impact of Statin and Beta-Blocker Type on Head & Neck Cancer Outcomes
Kristin Q. Yin1, Zachary A.P. Wintrob1,2, M.Sc., Lan-Hsi Lin1, George K. Nimako1,2, M.Sc, Pharm.D.,
Sameer Kapoor, Naza Abdelrahman, Alice C. Ceacareanu1,2, Pharm.D., Ph.D.
1Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, 2Department of Pharmacy Services, Roswell Park Cancer Institute, Buffalo, NY
Methods
Approximately 60,000 cases of head and neck cancer
(HNC) are diagnosed every year in the United States, while
HNC mortality reaches roughly 4%.1 Diabetes mellitus (DM) is
a well established cancer risk factor; however, given the
relatively low HNC incidence, studies on the association of DM
and specific HNC occurrence yielded thus far inconsistent
results. To date, a link between DM, periodontal disease and
occurrence of oral and esophageal cancers does exist2-4, but
despite evidence suggesting an association between elevated
low-density lipoprotein cholesterol (LDL-C), periodontal disease
and generally poorer cancer prognosis, the impact of
cholesterol drug use on HNC outcomes remains unclear. While
statins were reported to lower C-reactive protein (CRP) levels
independently of LDL lowering effect5,6, studies evaluating the
impact of statin use on HNC outcomes is still lacking.
Furthermore, pharmaco-epidemiological studies suggest
that β-blockers (BB) could provide a clinical benefit through
inhibition of the pro-metastatic effect of beta-adrenergic
receptor (β-AR) signaling on the tumor microenvironment7,8.
Hence, BB use – pharmacotherapy often prescribed among
statin users with DM - is expected to potentially improve cancer
outcomes.
To evaluate any association between statin or β-AR blocker
use - including the medication type – and HNC outcomes in
patients diagnosed with DM and HNC.
This study was approved by the Institutional Review Board of
the University at Buffalo and Roswell Park Cancer Institute.
• All adult DM patients newly diagnosed with a head or neck
malignancy at Roswell Park Cancer Institute (1/1/2003-
12/31/2010) were included (N=130)
• Baseline demographic, clinical history, and cancer outcomes
were documented.
• Survival data was analyzed by Kaplan-Meier plots with log-
rank statistics and Cox proportional hazards regression.
Presented hazard ratios (HR) were adjusted for the following
variables
 Body mass index (BMI)
 Age
 American Joint Commission on Cancer Stage
References
1. Figueiredo RA, Weiderpass E, Tajara EH, et al. Diabetes mellitus, metformin and head and neck cancer. Oral Oncol. 2016;61:47-54.
2. Migliorati CA. Periodontal diseases and cancer. The Lancet Oncology. 2008;9(6):510-2. doi: 10.1016/S1470-2045(08)70138-4. PubMed PMID: 18510985.
3. Fitzpatrick SG, Katz J. The association between periodontal disease and cancer: a review of the literature. Journal of dentistry. 2010;38(2):83-95.
4. Yang X, So W, Ko GTC, Ma RCW, Kong APS, Chow CC, et al. Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2
diabetes mellitus. Canadian Medical Association Journal. 2008;179(5):427-37
5. MC, Ahn Y, Jang SY, et al. Comparison of clinical outcomes of hydrophilic and lipophilic statins in patients with acute myocardial infarction. Korean J Intern Med.
2011;26(3):294-303.
6. Kruse AL, Luebbers HT, Gratz KW. C-reactive protein levels: a prognostic marker for patients with head and neck cancer? Head Neck Oncol. 2010;2:21.
7. Watkins JL, Thaker PH, Nick AM, et al. Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer. Cancer. 2015;121(19):3444-
3451.
8. Eskander R BL, Chiu C, et al. Beta blocker use and ovarian cancer survival: a retrospective cohort. Gynecol Oncol. 2012;127(1):21.
DM + HNC (N=160)
Included Subjects
(N=130)
MRs Review
BB only
(N=18)
Excluded Subjects
(N=30)
Previous Cancer (N=28)
Incomplete MRs (N=2)
Statin only
(N=32)
Statin and BB
(N=34)
No Statin or BB
(N=46)
Overall Survival Disease-Free Survival
HR 95% CI p1 p2 HR 95% CI p1 p2
No Statin (Reference) 1.00 - -
0.062
1.00 - -
0.048
Hydrophilic Statin 2.44 0.86 to 6.91 0.092 2.47 0.88 to 6.92 0.084
Lipophilic Statin 0.69 0.39 to 1.23 0.208 0.67 0.38 to 1.18 0.168
Hydrophilic vs. Lipophilic 3.55 1.21 to 10.44 0.022 3.68 1.26 to 10.69 0.017
No Beta-Blocker (Reference) 1.00 - -
<0.001
1.00 - -
<0.001
Non-Selective Beta-Blocker 6.86 2.42 to 19.47 <0.001 6.14 2.24 to 16.83 <0.001
Selective Beta-Blocker 0.94 0.51 to 1.72 0.845 0.85 0.47 to 1.55 0.598
Non-Selective vs. Selective 7.28 2.46 to 21.58 <0.001 7.22 2.50 to 20.87 <0.001
p1
is the individual comparison p-value, p2
is the adjusted overall p-value.