早期默克尔细胞癌治疗的有效性和安全性：一项关于随机和非随机研究的系统评价与荟萃分析

Effectiveness and Safety of Treatments for Early-Stage Merkel Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized and Non-Randomized Studies.

作者信息

Mbous Yves Paul Vincent, Mohamed Rowida, Sambamoorthi Usha, Bharmal Murtuza, Kamal Khalid M, LeMasters Traci, Kolodney Joanna, Kelley George A

机构信息

School of Pharmacy, Department of Pharmaceutical Systems and Policy, Robert C. Byrd Health Sciences Center [North], West Virginia University, Morgantown, West Virginia, USA.

Department of Obstetrics and Gynecology, Biological Sciences Division, The University of Chicago, Chicago, Illinois, USA.

出版信息

Cancer Med. 2025 Jan;14(1):e70553. doi: 10.1002/cam4.70553.

DOI:10.1002/cam4.70553

PMID:39749718

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696246/

Abstract

OBJECTIVE

The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study.

METHODS

A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.

RESULTS

Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.

CONCLUSIONS

Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.

摘要

目的

包括手术（SRx）、放疗（RTx）、化疗（CTx）及其联合治疗在内的标准疗法在早期皮肤 Merkel 细胞癌（MCC）的获益和危害方面缺乏共识，促使开展本研究。

方法

对 1972 年 1 月 1 日至 2023 年 1 月 31 日期间发表的、以总生存期（OS）、局部复发（LR）、区域复发（RR）、疾病特异性生存期（DSS）和/或无病生存期（DFS）为结局的随机和非随机研究进行系统评价和荟萃分析，使用Cochrane 对照试验中心注册库（CENTRAL）、PubMed（NCBI）、Scopus（爱思唯尔）和科学引文索引（科睿唯安）数据库。采用逆方差异质性模型汇总风险比（HRs）及其方差。

结果

荟萃分析纳入了代表 46,215 名参与者的 49 项研究。与单纯 SRx 相比，接受辅助 RTx（SRx + RTx）的组在 OS 方面观察到有统计学意义的改善（HR = 0.78，95%CI，0.62 - 0.99），尽管存在统计学意义的异质性（Q = 532.30，p < 0.001）和大量不一致性（I = 94%，95%CI，93.0 - 95.5）。LR（HR = 1.52，95%CI，0.37 - 6.19）和 RR（HR = 0.41，95%CI，0.09 - 1.78）均无统计学意义。此外，DSS（HR = 0.58，95%CI，0.24 - 1.40）无统计学意义，但 DFS 有统计学意义（HR = 0.35，95%CI，0.13 - 0.93）。亚组分析显示，辅助放疗在局部 MCC 中比区域 MCC 更有效。E 值表明 RTx 剂量是辅助 RTx 观察到的有效性的一个混杂因素；而且，辅助 RTx 后使用 CTx 并不影响 OS 证据的强度。