卡莫司汀结合替莫唑胺通过调节生长因子及其受体水平治疗胶质瘤的作用研究

doi:10.19854/j.cnki.1008-2425.2024.02.0008

摘要/Abstract

摘要： 目的探讨卡莫司汀结合替莫唑胺通过调节生长因子及其受体水平治疗胶质瘤的临床价值。方法回顾性分析选取2018年9月至2020年8月本院收治的122例胶质瘤患者,均行手术切除术,根据化疗方案,将患者分成替莫唑胺组和联合联合组,比较两组患者神经功能、日常生活活动能力、生长因子及其受体水平(VEGF、EGF和EGFR)、生活质量、T淋巴细胞亚群水平、不良反应。随访至2023年7月,比较两组患者总生存期和无进展生存期。结果术后6个月,联合组患者CSS评分(17.05±4.02 vs 26.95±5.30,t=11.742,P=0.000)明显低于替莫唑胺组,联合组患者改良版Barthel指数(75.99±10.05 vs 62.15±9.12, t=7.957, P=0.000)明显高于替莫唑胺组。联合组KPS(84.28±8.41 vs 72.92±7.08, t=19.970, P=0.000)和QOL评分(44.39±4.51 vs 35.81±3.50,t=11.498,P=0.000)明显高于替莫唑胺组。联合组患者CD3+(32.55±3.14vs28.67±3.71, t=6.135, P=0.000)、CD4+(56.49±5.03vs40.84±4.51, t=17.860, P=0.000)和CD4+/CD8+(2.41±0.25vs1.12±0.17, t=33.827, P=0.000) 明显高于替莫唑胺组,联合组患者CD8+(23.48±2.87vs36.71±3.81, t=21.186, P=0.000)明显低于替莫唑胺组。联合组患者VEGF(158.33±19.05 vs235.59 ± 21.61, t=20.962, P=0.000)、 EGF(48.11±4.81vs80.78 ± 6.54, t=30.702,P=0.000)、 EGFR(7.05±1.04vs11.32±3.09, t=9.727, P=0.000) 和VEGFR(2.51±0.38 vs 3.10±0.23, t=10.591, P=0.000) 明显低于替莫唑胺组。治疗期间,两组患者都经历恶心、呕吐、白细胞减少、血小板减少、贫血和肾毒性等副作用,而且Ⅰ~Ⅱ级副作用的发生率超过了Ⅲ~Ⅳ级,两组间的差异并无统计学意义(P＞0.05)。随访3年,替莫唑胺组失访2例,联合组失访3例,联合组的3年总生存率为63.96%,高于替莫唑胺组的48.53%,但差异未见显著性差异(χ²=1.847,P=0.174);联合组的3年无进展生存率为55.56%,明显高于替莫唑胺组的30.88% (χ²=7.771,P=0.005)。结论卡莫司汀联合替莫唑胺应用于胶质瘤可有效改善神经功能,增强日常生活活动能力,并优化生活质量,并恢复T淋巴细胞亚群水平,延长生存期,与降低生长因子及其受体浓度有关,安全性有效,值得临床进一步研究并控制。

关键词: 立体微创术, 卡莫司汀, 替莫唑胺, 生长因子, 胶质瘤, 预后

Abstract: Objective To investigate theresearch on the effect of carmustine combined with temozolomide in the treatment of glioma by regulating the levels of growth factors and their receptors. Methods sA retrospective analysis was conducted to select 122 glioma patients admitted to our hospital from September 2018 to August 2020.All patients underwent surgical resection.According to the chemotherapy regimen, the patients were divided into the temozolomide group and the combination group.The neurological functions of the two groups were compared, ability to carry out activities of daily living, levels of growth factors and their receptors (VEGF, EGF and EGFR), quality of life, levels of T lymphocyte subpopulations, and adverse reactions.Follow-up was conducted until July 2023, and the overall survival and progression-free survival of the two groups of patients were compared. Results Six months post-surgery, patients in the combined therapy group manifested a significantly diminished CSS score (17.05±4.02 vs 26.95±5.30, t=11.742, P=0.000) in contrast to the temozolomide-only group, while their modified Barthel index (75.99±10.05 vs 62.15±9.12, t=7.957, P=0.000) markedly surpassed that of the temozolomide group.The KPS(84.28±8.41 vs 72.92±7.08, t=19.970, P=0.000) and QOL score (44.39±4.51 vs 35.81±3.50, t=11.498, P=0.000) of the combination group were significantly elevated compared to the temozolomide-only group.Further, patients under combined therapy exhibited significantly elevated levels of CD3+ (32.55±3.14 vs 28.67±3.71, t=6.135, P=0.000), CD4+ (56.49±5.03 vs 40.84±4.51, t=17.860, P=0.000), and CD4+/CD8+ ratio (2.41±0.25 vs 1.12±0.17, t=33.827, P=0.000) as opposed to those under temozolomide alone, whereas their CD8+ levels (23.48±2.87 vs 36.71±3.81, t=21.186, P=0.000) were significantly decreased in comparison.Additionally, combined group patients demonstrated significantly reduced levels of VEGF (158.33±19.05 vs 235.59±21.61, t=20.962, P=0.000), EGF (48.11±4.81 vs 80.78±6.54, t=30.702, P=0.000), EGFR (7.05±1.04 vs 11.32±3.09, t=9.727, P=0.000) and VEGFR (2.51±0.38 vs 3.10±0.23, t=10.591, P=0.000) compared to the temozolomide-only group.This denotes a profound augmentation in therapeutic efficacy with the implementation of combined therapy, highlighting the pivotal role of integrated treatment modalities in optimizing clinical outcomes.During treatment, patients in both groups experienced side effects such as nausea, vomiting, leukopenia, thrombocytopenia, anemia, and nephrotoxicity, and the incidence of grade I~ II side effects exceeded grade III~IV, there was no statistical difference between the two groups.significance (P＞0.05).After 3 years of follow-up, 2 cases in the temozolomide group and 3 cases in the combination group were lost to follow-up.The 3-year overall survival rate in the combination group was 63.96%, which was higher than 48.53% in the temozolomide group, but there was no significant difference (χ²=1.847, P=0.174);the 3-year progression-free survival rate of the combination group was 55.56%, which was significantly higher than the 30.88% of the temozolomide group (χ²=7.771, P=0.005). Conclusion The administration of Carmustine in conjunction with Temozolomide post-surgery has demonstrated efficacy in augmenting neurological function, bolstering capabilities for conducting daily activities, and enhancing quality of life for glioma patients.This combined treatment approach also aids in the restoration of T lymphocyte subpopulation levels, extends survival duration, and mitigates the proliferation of growth factors.The effectiveness and safety of this therapeutic combination are correlated with its receptor concentration, warranting further clinical investigation and control to validate its benefits and optimize its application in clinical settings.

Key words: Stereotactic minimally invasive surgery, Carmustine, Temozolomide, Growth factors, Glioma, prognosis

中图分类号:

R739.41

杜蓓, 高凯, 刘常权, 刘英彦. 卡莫司汀结合替莫唑胺通过调节生长因子及其受体水平治疗胶质瘤的作用研究[J]. 立体定向和功能性神经外科杂志, 2024, 37(2): 107-115.

Du Bei, Gao Kai, Liu Changquan, Liu Yingyan. Research on the effect of carmustine combined with temozolomide in the treatment of glioma by regulating the levels of growth factors and their receptors[J]. Chinese Journal of Stereotactic and Functional Neurosurgery, 2024, 37(2): 107-115.

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