神经内分泌肿瘤患者骨转移的已知和未知因素：系统评价和荟萃分析。

Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis.

机构信息

Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom; Department of Haematology and Medical Oncology, Hospital Morales Meseguer, Murcia, Spain.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.

出版信息

Cancer Treat Rev. 2021 Mar;94:102168. doi: 10.1016/j.ctrv.2021.102168. Epub 2021 Feb 19.

DOI:10.1016/j.ctrv.2021.102168

PMID:33730627

Abstract

OBJECTIVE

This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.

METHODS

PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .

RESULTS

A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.

CONCLUSIONS

BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.

摘要

目的

本系统评价和荟萃分析旨在对神经内分泌肿瘤（NEN）中骨转移（BMs）的现有知识进行循证总结，为诊断和治疗提供信息，并在各机构之间实现规范化管理。

方法

检索 PubMed、Medline、EMBASE 和会议记录，以获取报告任何分化程度和部位的 NEN 患者 BMs 数据的合格研究；排除分化差的大/小细胞肺癌。使用 STATA v.12 提取和分析数据。对比例进行荟萃分析以计算 BM 的估计汇总患病率，并计算其他感兴趣变量的加权汇总频率和加权汇总平均值。

结果

共有 149 项研究符合入选标准。BMs 的汇总患病率为 18.4%（95%CI 15.4-21.5）。BMs 主要与 NEN 的初始诊断呈亚同步性（61.2%），主要为成骨性；约 61%为多灶性，轴向骨骼易受累。PET/CT 似乎与 MRI 一起为 BM 检测提供了最高的灵敏度和特异性。近一半的患者（46.4%）报告了与 BM 相关的症状：疼痛（66%）和骨骼相关事件（SREs，骨折/脊髓压迫）（26.2%；加权平均 SRE 时间为 9.9 个月）。BMs 的治疗是多模式的[双膦酸盐和骨修饰剂（45.2%）、外照射放疗（34.9%）、手术（14.8%）]，但证据不足。从诊断为 BMs 开始的总生存期（OS）较长[加权平均 50.9 个月（95%CI 40.0-61.9）]。与没有 BMs 的患者相比，有 BMs 的患者的 OS 更短[48.8 个月（95%CI 37.9-59.6）]；p=0.001）。较差的表现状态和 BM 相关症状也与较差的 OS 相关。