Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis.
Early Detection of Cancer
/ methods
Female
Fluorodeoxyglucose F18
/ pharmacology
Humans
Immunohistochemistry
Intestinal Neoplasms
/ diagnosis
Italy
/ epidemiology
Ki-67 Antigen
/ analysis
Male
Middle Aged
Neoplasm Grading
Neuroendocrine Tumors
/ diagnosis
Organometallic Compounds
/ pharmacology
Pancreatic Neoplasms
/ diagnosis
Patient Selection
Positron Emission Tomography Computed Tomography
/ methods
Prognosis
Radiopharmaceuticals
/ pharmacology
Retrospective Studies
Stomach Neoplasms
/ diagnosis
Survival Analysis
G3
NENs
NETs
Neuroendocrine
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
18
05
2021
accepted:
14
07
2021
pubmed:
21
7
2021
medline:
16
3
2022
entrez:
20
7
2021
Statut:
ppublish
Résumé
Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.
Identifiants
pubmed: 34282554
doi: 10.1007/s40618-021-01642-0
pii: 10.1007/s40618-021-01642-0
doi:
Substances chimiques
Ki-67 Antigen
0
Organometallic Compounds
0
Radiopharmaceuticals
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
gallium Ga 68 dotatate
9L17Y0H71P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-325Informations de copyright
© 2021. Italian Society of Endocrinology (SIE).
Références
Basturk O, Yang Z, Tang Lh, Hruban Rh, Adsay V, Cm M et al (2015) 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 39(5):683–690
doi: 10.1097/PAS.0000000000000408
Heetfeld M, Chougnet CN, Olsen IH, Rinke A, Borbath I, Crespo G et al (2015) Characteristics and treatment of patients with g3 gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 22(4):657–664
doi: 10.1530/ERC-15-0119
Velayoudom-Cephise Fl, Duvillard P, Foucan L, Hadoux J, Chougnet Cn, Leboulleux S et al (2013) Are G3 enets neuroendocrine neoplasms heterogeneous? Endocr Relat Cancer. 20(5):649–657
doi: 10.1530/ERC-13-0027
Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P et al (2013) Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (who g3): the nordic nec study. Ann Oncol. 24(1):152–160
doi: 10.1093/annonc/mds276
Milione M, Maisonneuve P, Spada F, Pellegrinelli A, Spaggiari P, Albarello L et al (2017) The clinicopathologic heterogeneity of grade 3 gastroenteropancreatic neuroendocrine neoplasms: morphological differentiation and proliferation identify different prognostic categories. Neuroendocrinology 104(1):85–93
doi: 10.1159/000445165
Or LR, Kloppel G, Rosai J et al (2017) Who classification of tumours of endocrine organs (World Health Organization Classification Of Tumors), 4th edn. Iarc Press, Lyons France
Or NI, Klimstra D, Paradis V, Rugge M, Schirmacher P, Washington M, Carneiro F, Cree I (2019) Who classification of tumor editorial board; digestive system tumours, who classification of tumours, 5th edn. Iarc Press, France
Konukiewitz B, Am S, Jesinghaus M, Pfister D, Steiger K, Segler A et al (2017) Somatostatin receptor expression related to Tp53 and Rb1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with A Ki67-index above 20. Mod Pathol 30(4):587–598
doi: 10.1038/modpathol.2016.217
Yachida S, Vakiani E, Cm W, Zhong Y, Saunders T, Morgan R et al (2012) Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am J Surg Pathol 36(2):173–184
doi: 10.1097/PAS.0b013e3182417d36
Dr S, Fc R, Ej S (2012) Molecular and cellular biology of neuroendocrine lung tumors: evidence for separate biological entities. Biochim Biophys Acta 1826(2):255–271
Ao V, Ia L, Mj M, Cy W, Pham T, Ee F et al (1997) Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. J Natl Cancer Inst 89(19):1448–1453
doi: 10.1093/jnci/89.19.1448
Kloppel G (2019) Neuroendocrine neoplasms: two families with distinct features unified in one classification (German version). Pathologe 40(3):211–219
doi: 10.1007/s00292-019-0594-3
Gm BJ, Wittekind C (2016) Tnm classification of malignant tumours, 8th edn. Wiley
Dy L, Yi K (2019) Prognostic value of maximum standardized uptake value in 68ga-somatostatin receptor positron emission tomography for neuroendocrine tumors: a systematic review and meta-analysis. Clin Nucl Med 44(10):777–783
doi: 10.1097/RLU.0000000000002694
Zhang P, Yu J, Li J, Shen L, Li N, Zhu H et al (2018) Clinical and prognostic value of pet/ct imaging with combination of (68)Ga-Dotatate and (18)F-Fdg in gastroenteropancreatic neuroendocrine neoplasms. Contrast Media Mol Imaging 2018:2340389
pubmed: 29681780
pmcid: 5846381
Karfis I, Marin G, Levillain H, Drisis S, Muteganya R, Critchi G et al (2020) Prognostic value of a three-scale grading system based on combining molecular imaging with (68)ga-dotatate and (18)f-fdg pet/ct in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias. Oncotarget 11(6):589–599
doi: 10.18632/oncotarget.27460
Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B et al (2017) Phase 3 trial of (177)lu-dotatate for midgut neuroendocrine tumors. N Engl J Med 376(2):125–135
doi: 10.1056/NEJMoa1607427
Severi S, Nanni O, Bodei L, Sansovini M, Ianniello A, Nicoletti S et al (2013) Role of 18fdg pet/ct in patients treated with 177lu-Dotatate for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging 40(6):881–888
doi: 10.1007/s00259-013-2369-z
Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A (2010) 18f-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res 16(3):978–985
doi: 10.1158/1078-0432.CCR-09-1759
Sorbye H, Baudin E, Borbath I, Caplin M, Chen J, Cwikla JB et al (2019) Unmet needs in high-grade gastroenteropancreatic neuroendocrine neoplasms (Who G3). Neuroendocrinology 108(1):54–62
doi: 10.1159/000493318