BackgroundPre-clinical studies have shown that metformin reduces intratumoral hypoxia, improves T-cell function, and increases sensitivity to PD-1 blockade, and metformin exposure has been associated with improved clinical outcomes in various types of cancer. However, the impact of this drug in diabetic melanoma patients has not yet been fully elucidated.MethodsWe reviewed 4,790 diabetic patients with stage I-IV cutaneous melanoma treated at the UPMC-Hillman Cancer Center and Memorial Sloan Kettering Cancer Center between 1996-2020. The primary endpoints included recurrence rates, progression free survival (PFS), and overall survival (OS) with and without metformin exposure. Tabulated variables included BRAF mutational status, immunotherapy (IMT) by type, and incidence of brain metastases.ResultsThe five-year incidence of recurrence in stage I/II patients was significantly reduced with metformin exposure (32.3% vs 47.7%, p=0.012). The five-year recurrence rate for stage III patients was also significantly reduced (58.3% vs 77.3%, p=0.013) in the metformin cohort. OS was numerically increased in nearly all stages exposed to metformin, though this did not reach statistical significance. The incidence of brain metastases was significantly lower in the metformin cohort (8.9% vs 14.6%, p=0.039).ConclusionThis is the first study to demonstrate significantly improved clinical outcomes in diabetic melanoma patients exposed to metformin. Overall, these results provide further rationale for ongoing clinical trials studying the potential augmentation of checkpoint blockade with metformin in advanced melanoma.
The objective was to evaluate medical comorbidities and surgical variables as independent risk factors for increased health care costs in Medicare patients undergoing lumbar fusion. Care episodes limited to lumbar fusions were retrospectively reviewed on the Centers of Medicare and Medicaid Innovation (CMMI) Bundled Payment for Care Improvement (BPCI) reimbursement database at a single academic institution. Total episode of care cost was also collected. A multivariable linear regression model was developed to identify independent risk factors for increased total episode of care cost, and logistic models for surgical complications and readmission. A total of 500 Medicare patients were included. Risk factors associated with increased total episode of care cost included transforaminal interbody fusion (TLIF) and anterior lumbar interbody fusion (ALIF) (β = $5,399, P < 0.001) and ALIF+PLF (AP) fusions (β = $24,488, P < 0.001), levels fused (β = $3,989, P < 0.001), congestive heart failure (β = $6,161, P = 0.022), hypertension with end-organ damage (β = $10,138, P < 0.001), liver disease (β = $16,682, P < 0.001), inpatient complications (β = $4,548, P = 0.001), 90-day complications (β = $10,012, P = 0.001), and 90-day readmissions (β = $15,677, P < 0.001). The most common surgical complication was postoperative anemia, which was associated with significantly increased costs (β = $18,478, P < 0.001). Female sex (OR = 2.27, P = 0.001), AP fusion (OR = 2.59, P = 0.002), levels fused (OR = 1.45, P = 0.005), cerebrovascular disease (OR = 4.19, P = 0.003), cardiac arrhythmias (OR = 2.32, P = 0.002), and fluid electrolyte disorders (OR = 4.24, P = 0.002) were independent predictors of surgical complications. Body mass index (OR = 1.07, P = 0.029) and AP fusions (OR = 2.87, P = 0.049) were independent predictors of surgical readmission. Among medical comorbidities, congestive heart failure, hypertension with end-organ damage, and liver disease were independently associated with a significant increase in total episode of care cost. Interbody devices were associated with increased admission cost.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.