Management of Ileal Neuroendocrine Tumors with Liver Metastases
Assessment of treating metastatic ileal neuroendocrine tumors (NETs) with complete resection of primary tumor, nodal and liver metastases, plus administration of long-acting somatostatin analogues (SSAs).
A prospective database was queried for patients with ileal or pancreatic NETs with pathology-confirmed liver metastases and tumor somatostatin receptors. Patients did not have MEN-1 and had no previous treatment. The impacts of SSA treatment on the primary outcome of survival and secondary outcome of progression-free survival were assessed with Kaplan–Meier analysis. Log rank test was used to compare overall and progression-free survival among groups.
Seventeen ileal NET patients and 36 pancreatic NET patients who underwent surgical resection between 2001 and 2018, who had pathology-confirmed liver metastases and confirmed tumor somatostatin receptors, did not have MEN-1, and had no previous treatment were identified. Median follow-up for patients with ileal NETs was 80 months (range 0–197 months) and 32 months (range 1–182 months) for pancreatic NETs. Five-year survival was 93% and 72% for ileal and pancreatic NET, respectively. Progression-free 5-year survival was 70% and 36% for ileal and pancreatic NET, respectively. Overall 5-year survival for pNETs was greater in those patients treated with SSA (79%) compared to those who underwent surgery alone (34%, p < 0.01). The average ECOG score was low for surviving patients with ileal (0.15) and pancreatic NET (0.73) indicating a good quality of life.
Resection of primary lymph node and liver metastatic ileal or pancreatic NETs followed with continued SSAs is associated with an excellent progression-free and overall survival and minimal side effects.
KeywordsCarcinoid NET Octreotide
Dr. Jeffrey Norton surgically treated the participants, devised the research plan, and revised the manuscript.
Andrea Fisher collected data from ileal patient records, performed analysis, developed figures for ileal patients, and drafted the manuscript.
Dr. Ashley Titan performed analysis of patient records, developed figures for pancreatic patients, and revised the manuscript.
Dr. Deshka Foster facilitated data analysis and figure creation for the ileal patients.
Dr. Patrick Worth collected data from pancreatic patient records.
Dr. George Poultsides surgically treated the participants, facilitated with devising the research plan, and revised the manuscript.
Dr. Brendan Visser surgically treated the participants and revised the manuscript.
Dr. Monica Dua surgically treated the participants and revised the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 1.Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker R V., et al. Gastroenteropancreatic neuroendocrine tumours. The Lancet Oncology. 2008. p. 61–72.Google Scholar
- 4.Frilling A, Sotiropoulos GC, Li J, Kornasiewicz O, Plöckinger U. Multimodal management of neuroendocrine liver metastases. HPB (Oxford) [Internet]. 2010;12(6):361–79.Google Scholar
- 9.Frilling A, Modlin IM, Kidd M, Russell C, Breitenstein S, Salem R, et al. Recommendations for management of patients with neuroendocrine liver metastases. The Lancet Oncology. 2014. p. E8–21.Google Scholar
- 14.Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: A report from the PROMID study group. J Clin Oncol. 2009;27(28):4656–63.CrossRefPubMedGoogle Scholar
- 18.Norton JA, Warren RS, Kelly MG, Zuraek MB, Jensen RT, Fahey TJ, et al. Aggressive surgery for metastatic liver neuroendocrine tumors. Surgery. 2003. p. 1057–63.Google Scholar
- 20.Elias D, Lasser P, Ducreux M, Duvillard P, Ouellet JF, Dromain C, et al. Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: A 15-year single center prospective study. Surgery. 2003;Google Scholar
- 21.Sowa-Staszczak A, Pach D, Chrzan R, Trofimiuk M, Stefanska A, Tomaszuk M, et al. Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur J Nucl Med Mol Imaging. 2011;38(9):1669–74.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med [Internet]. 2017 Jan 11;376(2):125–35. Available from: https://doi.org/10.1056/NEJMoa1607427
- 23.Fiore F, Del Prete M, Franco R, Marotta V, Ramundo V, Marciello F, et al. Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine. 2014;47(1):177–182.CrossRefPubMedGoogle Scholar
- 26.Yang TX, Chua TC, Morris DL. Radioembolization and chemoembolization for unresectable neuroendocrine liver metastases - A systematic review. Surgical Oncology. 2012. p. 299–308.Google Scholar
- 27.Pusceddu S, Verzoni E, Prinzi N, Mennitto A, Femia D, Grassi P, et al. Everolimus treatment for neuroendocrine tumors: Latest results and clinical potential. Therapeutic Advances in Medical Oncology. 2017. p. 183–188.Google Scholar
- 28.Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): A randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968–77.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Boudreaux JP, Klimstra DS, Hassan MM, Woltering EA, Jensen RT, Goldsmith SJ, et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: Well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Pancreas. 2010. p. 753–66.Google Scholar