Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE)

Autor: Jose Javier Pi Barrio, Carlos F. Lopez, Daniel Castellano, Vicente Alonso, Ángel Castaño‐Pascual, Ángel Segura, Paula Jiménez-Fonseca, Alex Teulé, Barbara Nuñez‐Valdovinos, Alberto Carmona-Bayonas, Ana Custodio, Jose Angel Diaz‐Perez, Mónica Marazuela, Isabel Sevilla, Marta Llanos, Adolfo Beguiristain, Teresa Alonso, Marta Benavent, Rocio Garcia-Carbonero, Maria Purificacion Martinez del Prado, Jaume Capdevila
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Oncology
Male
Cancer Research
Proliferation index
Neuroendocrine tumors
0302 clinical medicine
Gastrointestinal Cancer
Registries
Child
Aged
80 and over
biology
Cell Differentiation
Middle Aged
Prognosis
Survival Rate
Neuroendocrine Tumors
030220 oncology & carcinogenesis
Ki-67
Female
Adult
medicine.medical_specialty
Registry
Adolescent
030209 endocrinology & metabolism
Tumor differentiation
World Health Organization 2010
World Health Organization
Tumor heterogeneity
World health
Gastroenteropancreatic
03 medical and health sciences
Young Adult
Stomach Neoplasms
Internal medicine
Intestinal Neoplasms
medicine
Humans
Grading (tumors)
Ki‐67
Aged
Neoplasm Staging
Proportional Hazards Models
business.industry
medicine.disease
Tumor registry
Carcinoma
Neuroendocrine
Clinical trial
Pancreatic Neoplasms
Ki-67 Antigen
Spain
Neuroendocrine neoplasms
biology.protein
Heterogeneity
Neoplasm Grading
business
Zdroj: Oncologist
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
ISSN: 1083-7159
Popis: BackgroundGastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs.Subjects, Materials, and MethodsA total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3.ResultsFive-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%–5%], 72% [Ki-67 6%–10%], 52% [Ki-67 11%–20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%–50%], 22% [Ki-67 51%–100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%).ConclusionSubstantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index.Implications for PracticeGastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.
Databáze: OpenAIRE
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