Panzuto Francesco, Ricci Claudio, Rinzivillo Maria, Magi Ludovica, Marasco Matteo, Lamberti Giuseppe, Casadei Riccardo, Campana Davide
ENETS Center of Excellence, Disease Unit, Sant'Andrea University Hospital, 00189 Rome, Italy.
Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy.
J Clin Med. 2022 Oct 18;11(20):6127. doi: 10.3390/jcm11206127.
Background: The antiproliferative activity of a high dose of somatostatin analogs (HD-SSA) in treating gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) remains under debate. Methods: A systematic review and proportion meta-analysis were made. The primary endpoint was the efficacy measured as incidence density ratio (IDR) at one year. The secondary endpoints were the disease control rate (DCR) and severe adverse events (SAEs). The heterogeneity (I2), when high (>50%), was interpreted by performing a univariate metaregression analysis, analyzing as covariates: type and design of the study, location (Europe or USA), sample size, grading according to 2017 WHO, the metastatic disease rate, previous therapy including surgery, and quality of the study. Results: A total of 11 studies with 783 patients were included. The IDR was 62 new progressions of 100 patients treated with HD-SSA every one year. The heterogeneity was high. The study’s year, type and design, primary tumor, grading, previous treatments, and quality of the studies did not influence the IDR. The IDR was significantly higher in USA centers and studies with more than 50 patients. The IDR was lower when a high rate of metastatic patients was present in the studies. The DCR was 45%. The heterogeneity was high. The DCR was lower in USA studies and in prospective trials. Conclusion: Given the limited efficacy of HD-SSA in preventing the disease progression in unresectable GEP-NENs after failure of standard dose SSA, the use of this therapeutic approach is advisable in selected cases when other antiproliferative treatments are not feasible.
高剂量生长抑素类似物（HD - SSA）治疗胃肠胰神经内分泌肿瘤（GEP - NENs）的抗增殖活性仍存在争议。方法：进行系统评价和比例Meta分析。主要终点是以一年时的发病密度比（IDR）衡量的疗效。次要终点是疾病控制率（DCR）和严重不良事件（SAE）。当异质性高（>50%）时，通过进行单变量Meta回归分析来解释，将以下因素作为协变量进行分析：研究的类型和设计、地点（欧洲或美国）、样本量、根据2017年世界卫生组织的分级、转移性疾病发生率、包括手术在内的既往治疗以及研究质量。结果：共纳入11项研究，783例患者。HD - SSA治疗的100例患者中，每年有62例出现新进展，即IDR为62。异质性高。研究年份、类型和设计、原发肿瘤、分级、既往治疗以及研究质量均未影响IDR。在美国的研究中心以及样本量超过50例的研究中，IDR显著更高。研究中转移性患者比例高时，IDR较低。DCR为45%。异质性高。在美国的研究以及前瞻性试验中，DCR较低。结论：鉴于在标准剂量SSA治疗失败后，HD - SSA在预防不可切除GEP - NENs疾病进展方面疗效有限，当其他抗增殖治疗不可行时，在特定病例中采用这种治疗方法是可取的。
