Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ analysis
Cohort Studies
Comorbidity
Female
Germany
/ epidemiology
Humans
Intestinal Neoplasms
/ diagnosis
Intestine, Small
/ pathology
Male
Middle Aged
Neoplasm Staging
Neuroendocrine Tumors
/ diagnosis
Prognosis
Retrospective Studies
Risk Factors
Survival Analysis
peptide radionuclide receptor therapy (PRRT)
primary tumour resection
prognosis
stage IV small intestine neuroendocrine neoplasms
survival
Journal
Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
10
10
2021
received:
16
05
2021
accepted:
30
11
2021
pubmed:
30
12
2021
medline:
19
3
2022
entrez:
29
12
2021
Statut:
ppublish
Résumé
There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13076Informations de copyright
© 2021 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.
Références
Niederle B, Pape UF, Costa F, et al. Vienna Consensus Conference participants. ENETS consensus guidelines update for neuroendocrine neoplasms of the jejunum and ileum. Neuroendocrinology. 2016;103(2):125-138.
Eriksson J, Norlén O, Ögren M, Garmo H, Ihre-Lundgren C, Hellman P. Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops. Scand J Surg. 2021;110(1):44-50.
Dasari A, Shen C, Halperin D, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335-1342.
Walsh JC, Schaeffer D F, Kirsch R, et al. Ileal “carcinoid” tumors-small size belies deadly intent: high rate of nodal metastasis in tumors ≤1 cm in size. Hum Pathol. 2016;56:123-127.
Evers M, Rinke A, Rütz J, Ramaswamy A, Maurer E, Bartsch DK. Prognostic factors in curative resected locoregional small intestine neuroendocrine neoplasms. World J Surg. 2021;45(4):1109-1117.
Norlén O, Stålberg P, Öberg K, et al. Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg. 2012;36(6):1419-1431.
Yao JC, Hassan M, Phan A, et al. 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;26(18):3063-3072.
Janson ET, Holmberg L, Stridsberg M, et al. Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol. 1997;8(7):685-690.
Moller JE, Pellikka PA, Bernheim AM, Schaff HV, Rubin J, Connolly HM. Prognosis of carcinoid heart disease: analysis of 200 cases over two decades. Circulation. 2005;112(21):3320-3327.
Strosberg J, Gardner N, Kvols L. Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors of the mid-gut. Neuroendocrinology. 2009;89(4):471-476.
Habbe N, Fendrich V, Heverhagen A, Ramaswamy A, Bartsch DK. Outcome of surgery for ileojejunal neuroendocrine tumors. Surg Today. 2013;43(10):1168-1174.
Watzka FM, Fottner C, Miederer M, et al. Surgical treatment on NEN of small bowel: retrospective analysis. World J Surg. 2016;40(3):749-758.
Jann H, Roll S, Couvelard A, et al. Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome. Cancer. 2011;117(15):3332-3341.
Givi B, Pommier SJ, Thompson AK, Diggs BS, Pommier RF. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery. 2006;140(6):891-897.
Daskalakis K, Karakatsanis A, Hessmann O, et al. Association of a prophylactic surgical approach to stage IV small intestine neuroendocrine tumors with survival. JAMA Oncol. 2018;4(2):183-189.
Howe JR, Cardona K, Fraker DL, et al. The Surgical Management of small bowel neuroendocrine tumors: consensus guideline of the North American Neuroendocrine Tumor Society (NANETS). Pancreas. 2017;46(6):715-731.
Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, et al. Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol. 2010;21(9):1794-1803.
Strosberg JR, Weber JM, Feldman M, Coppola D, Meredith K, Kvols LK. Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors. J Clin Oncol. 2013;31(4):420-425.
Rindi G, Klöppel G, Alhman H, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449(4):395-401.
Brierley JD, Gospodarowicz MK, Wittekind C. Well-differentiated neuroendocrine tumours of the gastrointestinal tract. In: The TNM Classification of Malignant Tumours, 8th ed. Wiley Blackwell; 2016:96-104.
Ohrvall U, Eriksson B, Juhlin C, et al. Method for dissection of mesenteric metastases in mid-gut carcinoid tumors. World J Surg. 2000;24(11):1402-1408.
Partelli S, Bartsch DK, Capdevila J, et al. ENETS consensus guidelines for standard of care in neuroendocrine tumours: surgery for small intestinal and pancreatic neuroendocrine tumours. Neuroendocrinology. 2017;105(3):255-265.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-213.
Knigge U, Capdevila J, Bartsch DK, et al. ENETS consensus recommendations for the standards of care in neuroendocrine tumors: follow-up and documentation. Neuroendocrinology. 2017;105(3):310-319.
Dieckhoff P, Runkel H, Daniel H, et al. Well-differentiated neuroendocrine neoplasia: relapse-free survival and predictors of recurrence after curative intended resections. Digestion. 2014;90(2):89-97.
Søreide O, Berstad T, Bakka A, et al. Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors. Surgery. 1992;111(1):48-54.
National Comprehensive Cancer Network, NCCN. Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors Version 3.2017, NCCN.org.
Ahmed A, Turner G, King B, et al. Midgut neuroendocrine tumors with liver metastases: results of the UKINETS study. Endocr Relat Cancer. 2009;16(3):885-894.
Capurso G, Rinzivillo M, Bettini R, Boninsegna L, Dell Fave G, Falconi M. Systematic review of resection of primary midgut carcinoid tumours in patients with unresectable liver metastases. Br J Surg. 2012;99(11):1480-1486.
Rinke A, Müller HH, Schade-Brittinger C, 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):4656-4663.
Caplin ME, Pavel M, Ćwikła JB, et al. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016;23(3):191-199.
Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135.
Rinke A, Wittenberg M, Schade-Brittinger C, 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 (PROMID): results of long-term survival. Neuroendocrinology. 2017;104:26-32.
Bertani E, Falconi M, Grana C, et al. Small intestine neuroendocrine tumors with liver metastases and resection of the primary: prognostic factors for decision making. Int J Surg. 2015;20:58-64.
Blazevic A, Zandee WT, Franssen GJH, et al. Mesenteric fibrosis and palliative surgery in small intestinal neuroendocrine tumours. Endocr Relat Cancer. 2018;25(3):245-254.
Daskalakis K, Karakatsanis A, Stålberg P, Norlén O, Hellman P. Clinical signs of fibrosis in small intestinal neuroendocrine tumours. Br J Surg. 2017;104(1):69-75.
Lardiere-Deguelte S, de Mestier L, Appere F, et al. Toward a preoperative classification of lymph node metastases in patients with small intestine neuroendocrine tumors in the era of intestinal-sparing surgery. Neuroendocrinology. 2016;103(5):552-559.
Zaidi MY, Lopez-Aguiar AG, Dillhoff M, et al. Prognostic role of lymph node positivity and number of lymph nodes needed for accurately staging small-bowel neuroendocrine tumors. JAMA Surg. 2019;154(2):134-140.
Norlén O, Stålberg P, Zedenius J, Hellmann P. Outcome after resection and radiofrequency ablation of liver metastases from small intestine euroendocrine tumours. Br J Surg. 2013;100(11):1505-1514.
Partelli S, Maurizi A, Tamburrino D, et al. GEP-NEtS update: a review on surgery of gastro-entero-pancreatic neuroendocrine tumors. Eur J Endocrinol. 2014;171(4):R153-R162.