Elsevier

Pancreatology

Volume 18, Issue 3, April 2018, Pages 304-312
Pancreatology

Proactive multi-modality treatment of Pancreatic Neuroendocrine Tumours (PNETs): Potential survival benefits

https://doi.org/10.1016/j.pan.2017.12.006Get rights and content

Abstract

Background/objectives

Primary and metastatic pancreatic neuroendocrine tumours (PNET) can be treated with combination of surgery, locoregional and systemic therapy. Survival benefits from individual treatments have been well reported, however, the combined outcome from multimodal treatments are not well described in the literature. We report outcomes in a cohort of PNET patients treated with proactive, multimodality therapy.

Methods

106 patients were identified from a single tertiary referral centre prospective database. Outcomes of treatment were studied, with the primary end point being death from any cause.

Results

Median follow-up was 71 months and overall 5-year survival of 62%. In patients with stage I-III disease (51 patients) estimated 5-year survival was 90%. Median survival in patients with stage IV disease was 51 months with an estimated 5-year survival of 40% in this group. A total of 80 patients (75%) had surgery of which 16% suffered complications requiring intervention. There was no perioperative mortality.

Conclusions

This study demonstrates that proactive multimodal treatment is safe and may confer a survival benefit to patients in this cohort compared to historical data.

Introduction

The incidence of pancreatic neuroendocrine tumours has been steadily increasing in the recent years [1]. This has partly been attributed to the rise in the identification of incidental neuroendocrine tumours by better diagnostic imaging but also an increase in awareness of the disease [2]. Compared to other gastrointestinal and bronchial neuroendocrine tumours (NETs), PNETs carry a relatively poor prognosis [3,4]. Functioning PNETs are generally diagnosed early due to the presence of endocrine syndromes. However, the more common non-functioning PNETs tend to present late due to lack of symptoms early in the disease [4]. Around half of the patients with PNETs present with liver metastases [1,2]. Furthermore, the majority of patients will develop liver metastases during the course of their disease [7]. Overall survival of 24–34 months have been reported in patients with liver metastases without treatment [8,9]. Even in the presence of distant metastases, grade of a tumour plays a significant role in predicting survival [10]. However, recent studies demonstrate an improvement in 5-year median survival of up to 59–88% with hepatic resection in selected patients with liver metastases[4,11,12]. This large variation in 5-year survival is attributed largely to the heterogeneity of PNET [10,12] but also reflects non-conformity in management strategies.

Surgery is the mainstay of curative treatment and a key modality in the cytoreduction of PNETs. Locoregional liver directed therapy is also usefully employed in the treatment of PNETs: trans-arterial chemo-embolisation (TACE), transarterial embolisation (TAE), radiofrequency ablation (RFA) or microwave ablation (MWA), selective internal radiation therapy (SIRT) and cryotherapy. Systemic therapies offer other treatment options: cytotoxic chemotherapy, biological therapy (Everolimus/Sunitinib), somatostatin receptor inhibition (SSRI), and peptide receptor radiotherapy (PRRT). The choice of modality is guided by the site of disease, Ki67 index, somatostatin receptor status, clinician and patient choice amongst other factors [7,19]. There is little by way of randomised controlled studies to guide management, particularly the order in which treatment is given.

Our multidisciplinary team has a proactive management philosophy. We define treatment as proactive because it is employed at the time of diagnosis, rather than being reserved for when symptoms occur or there is radiological disease progression. In this paper, we report our short and long-term outcomes of this approach in a large cohort of patients with both early and advanced disease.

Section snippets

Methods

We reviewed a prospectively collected database of all patients referred with PNETs in a tertiary referral centre (Southampton University Hospitals NHS Trust) between January 2000 and December 2014. The centre receives referrals from 13 hospitals across the South of England. All patients were included in the analysis whether they received active treatment with either curative or palliative intent or no active treatment. The study was retrospectively registered on August 2017 (registration number

Results

From the NET database of which 127 (29.7%) patients with a diagnosis of PNET were identified. A total of 21 patients were excluded from analysis: 17 had incomplete clinical data or no histology/Ki67 index, 2 were lost to follow up and 2 patients treated elsewhere. An increase in the number of referrals to the NET service year on year was observed but the overall proportion with PNETs remained the same.

106 patients with histologically proven PNETs were analysed. Median follow up was 67 months

Discussion

In this study, we report the outcome of a large cohort of patients presenting with PNETS who were treated with a proactive management strategy. The survival for all stages of disease were 92.5%, and 62% at 1, and 5 years respectively. This data compares very favourably with historical data from USA, Norway and UK, which reports 5-year survival of 17–43% [22]. Like this data, our cohort includes all patients including those who did not have treatment. Indeed, the outcomes we see in our stage 4

Acknowledgements

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interests.

References (50)

  • E. Bertani

    Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation

    Eur J Surg Oncol

    (2017)
  • A.S. Kennedy

    Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors

    Int J Radiat Oncol

    (2009)
  • M. Abu Hilal

    Implementation of enhanced recovery programme after pancreatoduodenectomy: a single-centre UK pilot study

    Pancreatology

    (2013)
  • A. Dasari

    Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States

    JAMA Oncol

    (2017)
  • T. Ito et al.

    Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

    J Gastroenterol

    (2012)
  • L.R. McKenna et al.

    Update on pancreatic neuroendocrine tumors

    Gland Surg

    (2014)
  • J.C. Yao

    One hundred years after “Carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States

    J Clin Oncol

    (2008)
  • J. Strosberg et al.

    Survival and prognostic factor analysis in patients with metastatic pancreatic endocrine carcinomas

    Pancreas

    (2009)
  • S.C. Mayo

    Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis

    Ann Surg Oncol

    (2010)
  • D.J. Birnbaum

    Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study

    Ann Surg Oncol

    (2015)
  • American Joint Committee on Cancer

    AJCC cancer staging handbook. Cancer

    (2010)
  • G. Rindi et al.
  • M. Pavel

    ENETS consensus guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary

    Neuroendocrinology

    (2012)
  • J.C. Yao

    Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study

    J Clin Oncol

    (2008)
  • E. Raymond

    Sunitinib malate for the treatment of pancreatic neuroendocrine tumors

    N Engl J Med

    (2011)
  • Cited by (3)

    • The role of oncologic resection and enucleation for small pancreatic neuroendocrine tumors

      2021, HPB
      Citation Excerpt :

      The treatment of pancreatic neuroendocrine tumors (PNETs) varies with regards to size, function, and lymph node involvement.1

    View full text