Transarterial chemoembolization combined with metformin improves the prognosis of hepatocellular carcinoma patients with type 2 diabetes

Abstract

Objective: The study aims to investigate the effect of metformin on Hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) who received transarterial chemoembolization (TACE) for the first time. Methods:From January 2016 to December 2019, T2DM patients diagnosed with HCC in Shandong Cancer Hospital and treated with TACE were included in this retrospective study. Overall survival (OS) and Progression-free survival (PFS) were compared between patients treated with metformin and other antidiabetics. Univariate and multivariate Cox regression models were used to evaluate the independent risk factors associated with OS and PFS. And subanalysis was performed to investigate whether metformin could give a survival advantage in each Barcelona Clinic Liver Cancer (BCLC) stage of HCC. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted.Results: A total of 123 HCC patients with T2DM underwent TACE, of which 50 (40.65%) received treatment with metformin. For the whole cohort, the median OS (42 vs 32 months, p=0.054) and PFS (12 vs 7 months, P=0.0016) were longer in the metformin group than that in the non-metformin group. Multi-analysis revealed that BCLC stage, BMI (Body Mass Index), and metformin use were independent predictors of OS. Metformin use was independently associated with recurrence. After PSM, 39 matched pairs were identified. The use of metformin was associated with a numerically longer m OS (43 vs 35 months, P=0.183) than the use of other anti-diabetics. And the difference in median PFS (13 vs 7 months, p=0.018) between the metformin group and non-metformin group remained significant.

Antitumor Activity of Metformin Combined with Locoregional Therapy for Liver Cancer: Evidence and Future Directions

“…Following title and abstract screening, there were 154 studies deemed eligible for full-text assessment. Eleven studies were ultimately included in the systematic review [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. One study included both pre-clinical and clinical data and was thus considered two separate studies [ 89 ].…”

“…Both pre-clinical and clinical studies were identified through the literature search process. Of the 11 total studies included in this systematic review, 5 studies were classified as human preclinical studies [ 87 , 88 , 89 , 90 , 91 ] and 6 studies were classified as human clinical studies [ 82 , 83 , 84 , 85 , 86 , 89 ]. All included studies were full-text publications and were published between 2012 and 2022.…”

“…All included studies were full-text publications and were published between 2012 and 2022. Among the 11 studies, 2 studies performed radiofrequency ablation (RFA) [ 82 , 90 ], 3 studies performed transarterial chemoembolization (TACE) [ 83 , 86 , 89 ], and 1 study performed Y90 radioembolization (Y90 RS) [ 84 ]. Four of the eleven studies performed external beam radiation therapies, which included stereotactic body radiotherapy (SBRT)/hypofractionated radiotherapy (HypoRT) (one study) [ 85 ], gamma-ray radiation/neutron radiation (two studies) [ 87 , 91 ], and ionizing radiation (one study) [ 88 ].…”

“…There were four clinical studies reporting outcomes related to overall survival [ 82 , 83 , 85 , 89 ] and four clinical studies reporting outcomes on progression-free survival [ 82 , 83 , 85 , 86 ] ( Table 2 ). Overall survival ranged from 12 months to 75 months, with a mean overall survival of 39.8 months in the locoregional therapy-treated group alone, and overall survival ranged from 12 months to 79 months with a mean overall survival of 39.1 months in the locoregional therapy + metformin-treated group.…”

Targeting Hypoxia-Inducible Factor-1α for the Management of Hepatocellular Carcinoma

“…Indirectly, metformin suppresses HIF-1α translation, and also reduces intracellular oxygen demand, leading to decreased HIF-1α protein levels and decreased stabilization of HIFs under hypoxic conditions [81,82]. Combining metformin with cTACE has shown promise in clinical studies, with improved overall survival and time to progression in metformin users compared to non-users [83,84]. While metformin is a promising adjunct therapy for HCC patients undergoing cTACE, randomized controlled trials are required to elucidate the optimal dosage and timing of metformin in combination with cTACE.…”