Adeberg Sebastian, Bernhardt Denise, Ben Harrabi Semi, Bostel Tilman, Mohr Angela, Koelsche Christian, Diehl Christian, Rieken Stefan, Debus Juergen
Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Strahlenther Onkol. 2015 Dec;191(12):928-35. doi: 10.1007/s00066-015-0884-5. Epub 2015 Sep 2.
Changes in metabolism, including high glucose serum levels, seem to influence the initiation of malignancy as well as recurrence. Therefore, limiting the energy supply in tumor cells with the antidiabetic drug metformin might be a useful approach to inhibit glioma cell progression. However, little is known about the effects of endocrine disorders (e.g., diabetes mellitus, corticosteroid therapy, and metformin therapy) on progression and survival in primary glioblastoma patients.
Between 2006 and 2013, 276 patients with primary glioblastoma underwent radiation therapy at Heidelberg University Hospital and German Cancer Research Center. Clinical records as well as pretherapeutic and follow-up magnetic resonance (MR) images were assessed. Forty patients (14.5 %) were identified with a pretherapeutic history of diabetes, and 20 (50 %) of them were treated with metformin. Survival and correlations were calculated using t-test and log-rank, univariate and multivariate Cox proportional hazards ratio analyses.
Persistent mild and excessive hyperglycemia were correlated with decreased survival. Corticosteroid therapy was associated with decreased progression-free and overall survival in the multivariate analysis. No negative influence of diabetes on progression and survival could be detected. Interestingly, diabetic patients with metformin therapy demonstrated prolonged progression-free intervals.
Corticosteroid therapy and hyperglycemia were strongly associated with impaired survival rates and serves as negative prognostic factors. Diabetes did not influence survival. Interestingly, our findings showed an association of metformin therapy and prolonged progression-free survival in glioblastoma patients with diabetes and therefore serve as a foundation for further preclinical and clinical investigations.
包括高血糖血清水平在内的代谢变化似乎会影响恶性肿瘤的发生以及复发。因此，使用抗糖尿病药物二甲双胍限制肿瘤细胞的能量供应可能是抑制胶质瘤细胞进展的一种有用方法。然而，关于内分泌紊乱（如糖尿病、皮质类固醇治疗和二甲双胍治疗）对原发性胶质母细胞瘤患者的进展和生存的影响知之甚少。
2006年至2013年间，276例原发性胶质母细胞瘤患者在海德堡大学医院和德国癌症研究中心接受了放射治疗。评估了临床记录以及治疗前和随访的磁共振（MR）图像。40例患者（14.5%）有治疗前糖尿病病史，其中20例（50%）接受了二甲双胍治疗。使用t检验和对数秩检验、单变量和多变量Cox比例风险比分析计算生存率和相关性。
持续性轻度和重度高血糖与生存率降低相关。在多变量分析中，皮质类固醇治疗与无进展生存期和总生存期降低相关。未检测到糖尿病对进展和生存的负面影响。有趣的是，接受二甲双胍治疗的糖尿病患者无进展生存期延长。
皮质类固醇治疗和高血糖与生存率受损密切相关，是不良预后因素。糖尿病不影响生存。有趣的是，我们的研究结果显示二甲双胍治疗与糖尿病胶质母细胞瘤患者无进展生存期延长有关，因此可为进一步的临床前和临床研究奠定基础。
