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Abstract：
BACKGROUND: Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O6-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated.
METHODS: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021.
RESULTS: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13-0.50; p < 0.001; I2: 73%) and risk ratio of 2.29 (95% CI: 1.34-3.91; p < 0.001; I2: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43-0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20-0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs.
CONCLUSIONS: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.
METHODS: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021.
RESULTS: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13-0.50; p < 0.001; I2: 73%) and risk ratio of 2.29 (95% CI: 1.34-3.91; p < 0.001; I2: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43-0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20-0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs.
CONCLUSIONS: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.
摘要：
背景：替莫唑胺（TEM）是转移性神经内分泌肿瘤（NET）的积极治疗方法。接受TEM治疗的多形性胶质母细胞瘤或晚期黑色素瘤患者缺乏O6-甲基鸟嘌呤DNA甲基转移酶（MGMT），具有更好的反应和生存率。然而,MGMT在接受TEM治疗的NETs患者中的预测作用仍存在争议.
方法：我们对文献和荟萃分析进行了系统回顾，基于PRISMA方法，在主要数据库中搜索(PubMed，Embase,Scopus,WebofScience,Cochrane图书馆和临床试验.gov）以及主要国际大会的会议记录，直到2021年4月26日。
结果：在616篇文章中选择了12篇用于我们的分析，关于总共858例接受基于TEM的化疗的NET患者。MGMT的状态已在513（60％）患者中进行了测试，使用各种方法。与MGMT熟练的NETs相比，缺乏MGMT的合并总有效率（ORR）更高，风险差为0.31(95%置信区间，CI：0.13-0.50；p<0.001；I2：73％），风险比为2.29（95％CI：1.34-3.91；p<0.001；I2：55％）。合并无进展生存期(PFS)(风险比，HR=0.56;95％CI：0.43-0.74;p<0.001）和总生存期（OS）（HR=0.41;95％CI：0.20-0.62;p=0.011）在MGMT缺乏的NETs中更长。
结论：我们的荟萃分析表明，MGMT状态可能是TEM疗效的预测指标。然而,由于评价研究的高度异质性,应考虑偏差的风险.在这一假设下，未来的同质前瞻性研究是有必要的。
方法：我们对文献和荟萃分析进行了系统回顾，基于PRISMA方法，在主要数据库中搜索(PubMed，Embase,Scopus,WebofScience,Cochrane图书馆和临床试验.gov）以及主要国际大会的会议记录，直到2021年4月26日。
结果：在616篇文章中选择了12篇用于我们的分析，关于总共858例接受基于TEM的化疗的NET患者。MGMT的状态已在513（60％）患者中进行了测试，使用各种方法。与MGMT熟练的NETs相比，缺乏MGMT的合并总有效率（ORR）更高，风险差为0.31(95%置信区间，CI：0.13-0.50；p<0.001；I2：73％），风险比为2.29（95％CI：1.34-3.91；p<0.001；I2：55％）。合并无进展生存期(PFS)(风险比，HR=0.56;95％CI：0.43-0.74;p<0.001）和总生存期（OS）（HR=0.41;95％CI：0.20-0.62;p=0.011）在MGMT缺乏的NETs中更长。
结论：我们的荟萃分析表明，MGMT状态可能是TEM疗效的预测指标。然而,由于评价研究的高度异质性,应考虑偏差的风险.在这一假设下，未来的同质前瞻性研究是有必要的。
