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Research Article| Volume 220, ISSUE 2, P284-289, August 2020

Radical intended surgery for highly selected stage IV neuroendocrine neoplasms G3

      Highlights

      • Surgery with radical intent might be considered for selected stage IV GEP-NENs G3.
      • Median OS after radical surgery was 59 months in these patients.
      • All patients recurred, with a median RFS of 8 months.

      Abstract

      Background

      Stage IV gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) G3 are the NENs with the worst prognosis. According to ENETS guidelines, platinum-based chemotherapy is the standard treatment for this population. Surgery is only considered in highly selected “resectable” NENs with usually lower Ki67. However, the role of surgery with curative intent has been poorly investigated.

      Objective

      To describe, in a retrospective series of stage IV GEP-NENs G3, overall survival (OS) and recurrence-free survival (RFS) rates after curatively intended surgery.

      Methods

      Multicenter analysis of stage IV GEP-NENs G3 receiving radical resection (R0/R1) from 2007 to 2017, with minimum post-surgical follow-up time of 3 months.

      Results

      Fifteen patients from 6 NEN referral centers, with median follow-up of 29 months (8-86), were included. Eight cases had a neuroendocrine carcinoma (NEC) and 7 a neuroendocrine tumor G3 (NET G3). Median OS after radical surgery was 59 months. All patients recurred, with a median RFS of 8 months.

      Conclusions

      Radical surgery might be considered for highly selected stage IV GEP-NENs G3. Larger series are needed to confirm these results.

      Keywords

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      References

        • Sorbye H.
        • Welin S.
        • Langer S.W.
        • et al.
        Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.
        Ann Oncol. 2013 Jan; 24 (PubMed PMID: 22967994): 152-160
        • Velayoudom-Cephise F.L.
        • Duvillard P.
        • Foucan L.
        • et al.
        Are G3 ENETS neuroendocrine neoplasms heterogeneous?.
        Endocr Relat Canc. 2013 Oct; 20 (PubMed PMID: 23845449): 649-657
        • Heetfeld M.
        • Chougnet C.N.
        • Olsen I.H.
        • et al.
        Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms.
        Endocr Relat Canc. 2015 Aug; 22 (PubMed PMID: 26113608): 657-664
        • Basturk O.
        • Yang Z.
        • Tang L.H.
        • et al.
        The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms.
        Am J Surg Pathol. 2015 May; 39 (PubMed PMID: 25723112. Pubmed Central PMCID: PMC4398606): 683-690
        • Tang L.H.
        • Untch B.R.
        • Reidy D.L.
        • et al.
        Well-differentiated neuroendocrine tumors with a morphologically apparent high-grade component: a pathway distinct from poorly differentiated neuroendocrine carcinomas.
        Clin Canc Res. 2016 Feb 15; 22 (PubMed PMID: 26482044. Pubmed Central PMCID: PMC4988130): 1011-1017
        • Crippa S.
        • Partelli S.
        • Bassi C.
        • et al.
        Long-term outcomes and prognostic factors in neuroendocrine carcinomas of the pancreas: morphology matters.
        Surgery. 2016 Mar; 159 (PubMed PMID: 26602841): 862-871
      1. WHO Classification of Tumors Editorial Board: Digestive System Tumors. fifth ed. 2019
        • Garcia-Carbonero R.
        • Rinke A.
        • Valle J.W.
        • et al.
        ENETS consensus guidelines for the standards of care in neuroendocrine neoplasms. Systemic therapy 2: chemotherapy.
        Neuroendocrinology. 2017; 105 (PubMed PMID: 28380493): 281-294
        • Garcia-Carbonero R.
        • Sorbye H.
        • Baudin E.
        • et al.
        ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas.
        Neuroendocrinology. 2016; 103 (PubMed PMID: 26731334): 186-194
        • Fischer L.
        • Bergmann F.
        • Schimmack S.
        • et al.
        Outcome of surgery for pancreatic neuroendocrine neoplasms.
        Br J Surg. 2014 Oct; 101 (PubMed PMID: 25132004): 1405-1412
        • Yang M.
        • Ke N.W.
        • Zeng L.
        • et al.
        Survival analyses for patients with surgically resected pancreatic neuroendocrine tumors by World Health organization 2010 grading classifications and American joint committee on cancer 2010 staging systems.
        Medicine (Baltim). 2015 Dec; 94 (PubMed PMID: 26632896. Pubmed Central PMCID: PMC4674199)e2156
        • Shen C.
        • Chen H.
        • Chen H.
        • et al.
        Surgical treatment and prognosis of gastric neuroendocrine neoplasms: a single-center experience.
        BMC Gastroenterol. 2016 Sep 9; 16 (PubMed PMID: 27613657. Pubmed Central PMCID: PMC5016962): 111
        • Partelli S.
        • Inama M.
        • Rinke A.
        • et al.
        Long-term outcomes of surgical management of pancreatic neuroendocrine tumors with synchronous liver metastases.
        Neuroendocrinology. 2015; 102 (PubMed PMID: 26043944): 68-76
        • Yoshida T.
        • Hijioka S.
        • Hosoda W.
        • et al.
        Surgery for pancreatic neuroendocrine tumor G3 and carcinoma G3 should be considered separately.
        Ann Surg Oncol. 2019 Mar 12; 26 (PubMed PMID: 30863939): 1385-1393
        • Yang M.
        • Zhang Y.
        • Zeng L.
        • et al.
        Survivals of patients with surgically treated and High-grade pancreatic neuroendocrine carcinomas: a comparative study between two American Joint Committee on Cancer 8th tumor-node-metastasis staging systems.
        Eur J Surg Oncol. 2019 Jan 11; 45 (PubMed PMID: 30661921): 1054-1060
        • Partelli S.
        • Javed A.A.
        • Andreasi V.
        • et al.
        The number of positive nodes accurately predicts recurrence after pancreaticoduodenectomy for nonfunctioning neuroendocrine neoplasms.
        Eur J Surg Oncol. 2018 Jun; 44 (PubMed PMID: 29610023): 778-783
        • Yamaguchi T.
        • Machida N.
        • Morizane C.
        • et al.
        Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.
        Canc Sci. 2014 Sep; 105 (PubMed PMID: 24975505. Pubmed Central PMCID: PMC4462387): 1176-1181
        • Iwasa S.
        • Morizane C.
        • Okusaka T.
        • et al.
        Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas.
        Jpn J Clin Oncol. 2010 Apr; 40 (PubMed PMID: 20047862): 313-318
        • Patta A.
        • Fakih M.
        First-line cisplatin plus etoposide in high-grade metastatic neuroendocrine tumors of colon and rectum (MCRC NET): review of 8 cases.
        Anticancer Res. 2011 Mar; 31 (PubMed PMID: 21498724): 975-978
        • Okita N.T.
        • Kato K.
        • Takahari D.
        • et al.
        Neuroendocrine tumors of the stomach: chemotherapy with cisplatin plus irinotecan is effective for gastric poorly-differentiated neuroendocrine carcinoma.
        Gastric Cancer. 2011 Jun; 14 (PubMed PMID: 21327441): 161-165
        • Lu Z.H.
        • Li J.
        • Lu M.
        • et al.
        Feasibility and efficacy of combined cisplatin plus irinotecan chemotherapy for gastroenteropancreatic neuroendocrine carcinomas.
        Med Oncol. 2013; 30 (PubMed PMID: 23864251): 664
        • Okuma H.S.
        • Iwasa S.
        • Shoji H.
        • et al.
        Irinotecan plus cisplatin in patients with extensive-disease poorly differentiated neuroendocrine carcinoma of the esophagus.
        Anticancer Res. 2014 Sep; 34 (PubMed PMID: 25202088): 5037-5041
        • Rogowski W.
        • Wachula E.
        • Gorzelak A.
        • et al.
        Capecitabine and temozolomide combination for treatment of high-grade well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma.
        Retrosp. Anal Endokrynol Pol. 2019 Mar 7; 70 (PubMed PMID: 30843182): 313-317
        • Pellat A.
        • Dreyer C.
        • Couffignal C.
        • et al.
        Clinical and biomarker evaluations of sunitinib in patients with grade 3 digestive neuroendocrine neoplasms.
        Neuroendocrinology. 2018; 107 (PubMed PMID: 29518779): 24-31
        • Panzuto F.
        • Rinzivillo M.
        • Spada F.
        • et al.
        Everolimus in pancreatic neuroendocrine carcinomas G3.
        Pancreas. 2017 Mar; 46 (PubMed PMID: 28099254): 302-305
        • Zhang J.
        • Kulkarni H.R.
        • Singh A.
        • et al.
        Peptide receptor radionuclide therapy in grade 3 neuroendocrine neoplasms: safety and survival analysis in 69 patients.
        J Nucl Med. 2019 Mar; 60 (PubMed PMID: 30115686): 377-385
        • Carlsen E.A.
        • Fazio N.
        • Granberg D.
        • et al.
        Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study.
        Endocr Relat Canc. 2019 Feb 1; 26 (PubMed PMID: 30540557): 227-239
        • Collot T.
        • Fumet J.D.
        • Klopfenstein Q.
        • et al.
        Bevacizumab-based chemotherapy for poorly-differentiated neuroendocrine tumors.
        Anticancer Res. 2018 Oct; 38 (PubMed PMID: 30275226): 5963-5968
        • Klöppel G ea
        fourth ed. WHO Classification of Tumours of Endocrine Organs: WHO/IARC Classification of Tumours. vol. 10. 2017 (2017)
        • Galleberg R.B.
        • Knigge U.
        • Tiensuu Janson E.
        • et al.
        Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas.
        Eur J Surg Oncol. 2017 Sep; 43 (PubMed PMID: 28522174): 1682-1689
        • Deng H.Y.
        • Li G.
        • Luo J.
        • et al.
        The role of surgery in treating resectable limited disease of esophageal neuroendocrine carcinoma.
        World J Surg. 2018 Jan 16; 42 (PubMed PMID: 29340724): 2428-2436
        • Maire F.
        • Hammel P.
        • Kianmanesh R.
        • et al.
        Is adjuvant therapy with streptozotocin and 5-fluorouracil useful after resection of liver metastases from digestive endocrine tumors?.
        Surgery. 2009 Jan; 145 (PubMed PMID: 19081477): 69-75
        • Ramella Munhoz R1 dMRJ.
        • de Celis Ferrari A.R.
        • Ignez Braghiroli M.
        • et al.
        Combination of irinotecan and a platinum agent for poorly differentiated neuroendocrine carcinomas.
        Rare Tumors. 2013; 5: e39