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MO_12_2768 - Impact of Diabetes Mellitus and Metformin on Clinical Outcomes of Brain Metastasis Patients Treated With Stereotactic Radiosurgery

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Impact of Diabetes Mellitus and Metformin on Clinical Outcomes of Brain Metastasis Patients Treated With Stereotactic Radiosurgery
M. C. LeCompte1, E. McTyre1, R. Strowd2, C. M. Lanier1, M. Soike1, R. T. Hughes1, C. K. Cramer1, M. Farris1, J. Ruiz3,4, K. Watabe5, A. Laxton6, S. B. Tatter6, K. M. Winkfield1, and M. D. Chan1; 1Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, 2Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC, 3Department of Medicine (Hematology & Oncology), Wake Forest School of Medicine, Winston-Salem, NC, 4W.G. (Bill) Hefner Veteran Administration Medical Center, Cancer Center, Salisbury, NC, 5Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 6Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC

Purpose/Objective(s): Recent evidence indicates that metformin, the antidiabetic drug, may serve a role in reducing the rate of distant metastasis in some cancer types. It is essentially unknown, however, how the diabetic state and use of metformin affect treatment outcomes and patterns of failure in brain metastasis patients.

Materials/Methods: We conducted a retrospective review of 498 patients with brain metastasis treated at our institution with stereotactic radiosurgery (SRS) between January 2012 and March 2017. We evaluated overall survival (OS), distant brain failure (DBF), local failure (LF), neurologic death, death prior to DBF, and death prior to LF. Time-to-event outcomes were summarized using the Kaplan-Meier estimator and competing risks methodology. Clinicopathologic variables were evaluated using Cox proportional hazards models, and multivariate Cox models were then created using known predictors of survival as well as diabetes status.

Results: Eighty-four patients (16.9%) were identified as having a diagnosis of diabetes mellitus (DM) prior to SRS treatment. Of those diabetics, 49 patients were prescribed metformin prior to SRS treatment. Median follow-up for all patients was 20.5 mo (95% CI: 18.2-23.3 mo). When stratified by DM diagnosis, median OS was 6.0 mo (95% CI: 4.2-10.2 mo) vs. 9.3 mo (95% CI: 7.9-11.5 mo) for diabetics and non-diabetics, respectively (log rank p = 0.15). DM was a significant predictor of OS in multivariate analysis (HR: 1.43, CI: 1.02-2.02, p = 0.04). Rates of neurologic death were similar in diabetics and non-diabetics at 40.4% and 43.5%, respectively (p = 0.55). Median OS was 7.0 mo (CI: 4.8-NA mo) for diabetic metformin users, 4.4 mo (CI: 3.8-15.1 mo) for diabetic non-metformin users, and 9.3 mo (CI: 7.9-11.5 mo) for non-diabetics (log-rank p-value = 0.10). The cumulative incidences of DBF at 6- and 12-months following initial SRS were 18.7% and 21.8% for diabetic metformin users, 36.9% and 45.9% for diabetic non-metformin users, and 30.2% and 39.6% for non-diabetics (Gray’s p-value = 0.04).

Conclusion: Brain metastasis patients with diabetes mellitus had worsened overall survival compared to those without diabetes. Metformin use in diabetics was associated with a significantly lower incidence of distant brain failure in comparison to diabetic patients not using metformin as well as non-diabetics. Further studies are warranted to investigate the effect of metformin on the development of new brain metastases after initial radiosurgical management.

Author Disclosure: M.C. LeCompte: None. E. McTyre: Employee; Wake Forest University Baptist Medical Center. R. Strowd: None. C.M. Lanier: None. M. Soike: None. J. Ruiz: None. K.M. Winkfield: Chair, Health Disparities Committee; American Society of Clinical Oncology. M.D. Chan: Honoraria; Elekta. Advisory Board; Novocure.

Michael LeCompte, MS

Disclosure:
No relationships to disclose.

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