Elsevier

Pancreatology

Volume 19, Issue 2, March 2019, Pages 367-371
Pancreatology

Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study

https://doi.org/10.1016/j.pan.2019.01.007Get rights and content

Abstract

Introduction

Pancreatic neuroendocrine neoplasms (PNEN) are rare tumours and well differentiated PNEN are associated with relatively indolent physiological behaviour. For this reason, only few studies have investigated those factors associated with recurrence in this group of patients. The aim of this study is to analyse whether it is possible to predict tumour recurrence in World Health Organization (WHO) 2017 G1-G2 PNEN patients.

Methods

This is a retrospective multi-institutional study. Patients submitted to pancreatic resection from 7 Spanish centres were reviewed. Only patients with WHO G1-G2 PNEN were included. Demographic and clinicopathological variables were analysed.

Results

Data from 137 patients were reviewed. Median age was 59.2 (25–84) years. Recurrence of disease occurred in 19 (13.9%) patients. Median DFS was 55 months. At multivariate analysis, tumour size >20 mm, lymphnode metastasis and a new tumour grade 2 incorporating Ki-67 labelling index (LI) > 5% and mitotic index (MI) > 2 were independently associated with recurrence. We developed a risk score model with these three factors. High-risk patients had a significantly lower 5-year disease-specific survival compared to low-risk patients (70% vs 100%).

Conclusion

We propose a novel risk score for recurrence based on lymphnode metastasis, tumour size > 20 mm and a new grade 2 based on Ki-67 LI >5% and MI > 2. If 2 factors are present, patients have a higher risk for recurrence and a significantly poorer DSS, and therefore they should be closely monitored during follow-up. The role of adjuvant chemotherapy in these patients needs to be evaluated in clinical trials.

Introduction

Well-differentiated pancreatic neuroendocrine neoplasms (PNEN) are considered a relatively indolent disease. However, the recurrence rate reported after curative surgery can reach 17% of resected patients with consequences on survival [1]. Currently, there is no indication for adjuvant treatment in this group of patients and no surveillance protocols exist.

It has been recently suggested that a Ki-67 Labelling Index (LI) 5% cut-off level is independently associated with recurrence and with poorer disease-specific survival in patients with non-functioning PNEN [[2], [3], [4], [5]] and therefore it might be a useful tool to predict survival. The same authors have reported a novel score to predict disease-specific survival based on World Health Organization (WHO) 2010 tumour grade (G1 and G2), lymph node metastasis, and perineural invasion [1]. However, the 2017 WHO tumour grade classification still utilize a Ki-67 LI < 3% cut-off level to differentiate G1 from G2 PNEN patients [6,7]. Mitotic count (MC) is also considered and the final grade is based on whichever index places the tumour in the higher-grade category.

The aim of our study is to investigate those factors associated with tumour recurrence in a Spanish multi-institutional analysis and the value of a risk score to predict recurrence in WHO G1-G2 PNEN patients.

Section snippets

Methods

All patients referred to 7 Spanish referral centres for PNEN from January 2006 to December 2016 were reviewed. Patients who underwent curative resection of histologically proven PNEN were considered for this study. Those patients with distant metastasis, unresectable PNEN at diagnosis or with PNEN associated with a genetic predisposition were excluded. Both functional and non-functional tumours were included. Tumours were staged according to the 8th edition of AJCC/UICC TNM system. Only G1 and

Results

Data from 137 patients were reviewed (see Flowchart). Patient and tumour characteristics are reported in Table 1. Recurrence of disease occurred in 19 (13.9%) patients. Median time to recurrence was 44 (5–100) months. Median follow-up was 64 months.

At univariate analysis, tumour size, lymphnode metastasis, vascular and perineural invasion, Ki-67 LI, MC and WHO G2 were significantly associated with recurrence (p < 0.05) (Table 2). ROC analysis was used to identify cut-off point for continuous

Discussion

Pancreatic neuroendocrine neoplasms (PNEN) are rare lesions. They include a broad family of tumours that exhibit heterogeneous biologic behaviour [11]. These tumours are increasingly being found in cross sectional imaging performed for other unrelated reasons [12], and surgical resection can be curative in patients with localized PNEN and also it can increase survival in patients with metastatic PNEN [13,14]. Resection in case of non-functioning PNEN < 20 mm is controversial since non-operative

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