手术切除的高分化胰腺神经内分泌肿瘤的预后特征：对904例患者进行7882人年随访的分析

Prognostic Features in Surgically Resected Well-Differentiated Pancreatic Neuroendocrine Tumors: An Analysis of 904 Patients with 7882 Person-Years of Follow-Up.

作者信息

Kiemen Ashley L, Young Eric D, Blackford Amanda L, Wu Pengfei, Burkhart Richard A, Burns William R, Cameron John L, Lafaro Kelly, Shubert Christopher, Gaillard Zoe, Ebong Uwakmfon-Abasi, Reucroft Ian, Shen Yu, Dequiedt Lucie, Matos Valentina, Klöppel Günter, Kasajima Atsuko, He Jin, Hruban Ralph H

机构信息

Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.

出版信息

medRxiv. 2025 Apr 3:2025.04.01.25325055. doi: 10.1101/2025.04.01.25325055.

DOI:10.1101/2025.04.01.25325055

PMID:40236435

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11998843/

Abstract

IMPORTANCE

The clinical behavior of well-differentiated pancreatic neuroendocrine tumors (PanNETs) is difficult to predict.

OBJECTIVE

To define more accurately prognosticators for patients with a surgically resected PanNET.

DESIGN

The pathology and Ki-67 immunolabeling index of PanNETs resected from 904 patients was correlated with patient outcome.

SETTING

Academic tertiary care hospital.

PARTICIPANTS

Consecutive patients who had a PanNET resected between 1985 and 2025.

RESULTS

The mean patient age at surgery was 56.6 years (SD 14.0), 477 were male (52.8%), and 7882 person-years of follow-up were obtained (mean 8.8 years, SD 6.5). The 10-year survival was 81% (95% CI: 77,86%) for patients with G1 PanNETs (Ki-67 <3%), 68% (95% CI: 61,76%) for patients with G2a PanNETs (Ki-67 3- <10%), 44% (95% CI: 29,66%) for patients with G2b PanNETs (Ki-67 of 10%- ≤20%), and 23% (95% CI: 8,61%) for patients with G3 PanNETs. Metastases (HR 4.7, p <0.0001), vascular invasion (HR 3.0, p <0.0001), tumor size ≥ 2 cm (HR 2.88, p <0.0001), perineural invasion (HR 2.42, p<0.0001), and positive margins (HR 2.18, p <0.0001) were associated with worse overall survival. Insulinoma (HR 0.34, p=3e-04), sclerosing variant (HR 0.47, p=0.05), and cystic variant (HR 0.61, p=0.05) were associated with improved overall survival. T stage and N stage were all statistically significant classifiers of overall survival. Similar associations were found with respect to disease relapse. There was a significant (P<0.001) increase in the proportion of patients diagnosed with stage I vs stage IV disease over time.

CONCLUSIONS AND RELEVANCE

This study supports the classification of PanNETs into four grades (G1, G2a, G2b, and G3) based on Ki-67 labeling, which allows a more accurate prognostic assessments of patients.

摘要

重要性

高分化胰腺神经内分泌肿瘤（PanNETs）的临床行为难以预测。

目的

更准确地确定接受手术切除的PanNETs患者的预后因素。

设计

对904例患者切除的PanNETs的病理及Ki-67免疫标记指数与患者预后进行相关性分析。

地点

学术性三级医疗中心。

参与者

1985年至2025年间连续接受PanNETs切除手术的患者。

结果

手术时患者的平均年龄为56.6岁（标准差14.0），男性477例（52.8%），共获得7882人年的随访（平均8.8年，标准差6.5）。G1级PanNETs（Ki-67<3%）患者的10年生存率为81%（95%CI：77,86%），G2a级PanNETs（Ki-67 3-<10%）患者为68%（95%CI：61,76%），G2b级PanNETs（Ki-67为10%-≤20%）患者为44%（95%CI：29,66%），G3级PanNETs患者为23%（95%CI：8,61%）。转移（HR 4.7，p<0.0001）、血管侵犯（HR 3.0，p<0.0001）、肿瘤大小≥2 cm（HR 2.88，p<0.0001）、神经周围侵犯（HR 2.42，p<0.0001）和切缘阳性（HR 2.18，p<0.0001）与较差的总生存期相关。胰岛素瘤（HR 0.34，p=3×10⁻⁴）、硬化型（HR 0.47，p=0.05）和囊性型（HR 0.61，p=0.05）与总生存期改善相关。T分期和N分期均为总生存期的统计学显著分类因素。在疾病复发方面也发现了类似的关联。随着时间的推移，诊断为I期与IV期疾病的患者比例有显著（P<0.001）增加。