胰腺神经内分泌肿瘤的预后因素和长期结果：Ki-67 指数对生存的影响大于疾病分期。西班牙国家肿瘤登记处（RGETNE）的丰富经验。

Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE).

机构信息

Department of Surgery, University Hospital La Princesa, Madrid, Spain.

出版信息

Neuroendocrinology. 2013;98(2):156-68. doi: 10.1159/000355152. Epub 2013 Sep 19.

DOI:10.1159/000355152

PMID:23988576

Abstract

INTRODUCTION

Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival.

METHODS

From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses.

RESULTS

Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome.

CONCLUSION

Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.

摘要

简介

胰腺神经内分泌肿瘤（PNENs）是一种少见的具有广泛临床行为的肿瘤。本研究的目的是在一个大的患者队列中评估预后因素对生存的相对影响。

方法

2001 年 6 月至 2010 年 10 月，通过参与中心在西班牙全国胃肠道胰腺神经内分泌肿瘤登记处（RGETNE）的在线网站（www.getne.org）前瞻性注册了 1271 例患者。通过单变量和多变量分析评估临床和组织病理学特征作为潜在的预后因素。

结果

在 483 例 PNENs 中，171 例（35%）为功能性（F），312 例（65%）为非功能性（NF）。NF-PNENs 与更多表示侵袭性疾病的组织学特征相关，例如肿瘤分化差、Ki-67>20%或血管侵犯（NF-与 F-PNENs 相比，分别为 p<0.05）。然而，功能性不是生存的显著预测因素（p=0.19）。诊断时的分期、Ki-67 指数、肿瘤分化和原发性肿瘤的手术切除均为单变量分析中的显著预后因素。然而，Ki-67（>20%与≤2%）（危险比（HR）2.21，p=0.01）和手术切除（是与否）（HR 0.92，p=0.001）是多变量分析中唯一的独立生存预测因素。在接受手术的患者中，高 Ki-67 指数（HR 10.37，p=0.02）和低分化（HR 8.16，p=0.03）是临床结局的唯一独立预测因素。