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

Nuñez‐Valdovinos, Barbara; Carmona‐Bayonas, Alberto; Jiménez‐Fonseca, Paula; Capdevila, Jaume; Castaño‐Pascual, Ángel; Benavent, Marta; Barrio, Jose Javier Pi; Teulé, Alexandre; Alonso, Vicente; Custodio, Ana; Marazuela, Mónica; Segura, Ángel; Beguiristain, Adolfo; Llanos, Marta; Prado, María Purificación Martínez del; Díaz-Pérez, Jose; Castellano, Daniel; Sevilla, Isabel; López, Carlos; Alonso, Teresa; García‐Carbonero, Rocío

doi:10.1634/theoncologist.2017-0364

Cited by 71 publications

(55 citation statements)

References 24 publications

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“…Regarding the tumor characteristics, the grading defined by Ki-67 proliferation index is considered an established strong prognostic factor in numerous series (21,22,23). Our paper demonstrates how tumor grading significantly correlates with overall survival in malignant insulinomas.…”

Section: Discussionmentioning

confidence: 67%

Clinico–pathological features, treatments and survival of malignant insulinomas: a multicenter study

Veltroni

Cosaro

Spada

et al. 2020

European Journal of Endocrinology

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Introduction Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. Aim of the study To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. Materials and methods Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. Results The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. Conclusions Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.

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Section: Discussionmentioning

confidence: 67%

Clinico–pathological features, treatments and survival of malignant insulinomas: a multicenter study

Veltroni

Cosaro

Spada

et al. 2020

European Journal of Endocrinology

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“…Research so far has identified stage, site of origin [4] and differentiation [5 6], as well as proliferative indices (Ki-67, mitotic count) as important prognostic factors and multiple scores have been published, trying to predict survival in metastatic disease or recurrence after curative surgery [5][6][7][8][9][10][11]. In general, well-differentiated tumors progress slowly and surveillance may be the best approach in some cases, whereas poorly differentiated neoplasms require urgent aggressive chemotherapy and are associated with markedly shorter survivals [12]. Tumors of small bowel origin tend to have a better prognosis [13] compared to NENs originating in the pancreas.…”

Section: Introductionmentioning

confidence: 99%

Effect of metastatic site on survival in patients with neuroendocrine neoplasms (NENs). An analysis of SEER data from 2010 to 2014

et al. 2020

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Background: Neuroendocrine neoplasms (NENs) display variable behaviors based on origin and grade. We assumed that both tumor origin and the location of metastasis may play a role in survival. Methods: We queried the SEER database (2010-2014) for patients with an established diagnosis of NENs and documented site of metastasis and identified 2005 patients. Overall survival (OS) at the time points were estimated by the Kaplan-Meier method Cox proportional-hazards models were used to evaluate the relationship of the interested variables and OS. Results: Lung, liver, bone and brain metastases were observed in 9, 77, 7 and 6% of metastatic patients respectively. In the multivariate model, metastasis locations were significantly associated with worse survival (liver HR: 1.677 (1.226-2.294); (bone metastasis HR: 1.412 (0.965-2.065); brain HR: 1.666 (1.177-2.357)). We produced a scoring system based on site of origin, metastasis location, age, gender, histology and tumor size that can stratify metastatic NEN patients in low, intermediate and high-risk categories to help physicians with decision making. Conclusion: Site of metastasis plays an important role in survival of metastatic NEN patients independent of commonly described prognostic factors and should be considered in survival estimates.

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“…In clinical practice, grade 2 NETs form a very heterogeneous group and survival in this group can be very different between a "low" grade 2 with a Ki67 close to 2% or a "high" grade 2 with a Ki67 close to 20%. In our study, a cut off of 5% turned out to be more relevant than a cut off of 2% for Ki67, which has already been suggested (3,6,23). The WHO classification of NET should therefore probably be revised.…”

Section: Discussionmentioning

confidence: 57%

Survival and prognostic factors analysis of 151 intestinal and pancreatic neuroendocrine tumors: a single center experience

Foubert

Salimon

Dumars

et al. 2018

J. Gastrointest. Oncol

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Background: Intestinal and pancreatic neuroendocrine tumors (IP-NETs) are rare tumors with heterogeneous outcomes. The aim of our study was to determine the clinical, therapeutic and pathological factors which impact the overall survival (OS) in IP-NETs. Methods: All the patients diagnosed with IP-NETs at the Nantes University Hospital between October 1994 and October 2013 were retrospectively analysed. Patients with MEN-1 (Type 1 Multiple Endocrine Neoplasia) or Von Hippel-Lindau syndrome were excluded. Additionally, a prospective analysis of tumor grade (mitotic index and Ki67 index) was performed on tumor samples. OS was evaluated by Kaplan-Meier method and prognostic factors by log-rank test and Cox model. Results: The study included 151 patients. Median age was 60 (range, 14-81). Primary tumor was pancreatic in 86 patients (56.95%) and intestinal in 65 patients (43.05%). Tumors were metastatic (synchronous or metachronous) in 72 patients (47.7%). The median OS was 157 months. For all IP-NETs, age >65 years (P<0.0001), Ki67 >5% (P=0.03), synchronous metastases (P=0.016), primary tumor size >25 mm (P=0.03) and emergency surgery (P=0.007) were independent poor prognostic factors. Conclusions: In this large series of patients with IP-NET, age >65 years, Ki67 >5%, primary tumor size >25 mm, synchronous metastases and emergency surgery for acute complications have been identified as independent poor prognostic factors.

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

Cited by 71 publications

References 24 publications

Clinico–pathological features, treatments and survival of malignant insulinomas: a multicenter study

Clinico–pathological features, treatments and survival of malignant insulinomas: a multicenter study

Effect of metastatic site on survival in patients with neuroendocrine neoplasms (NENs). An analysis of SEER data from 2010 to 2014

Survival and prognostic factors analysis of 151 intestinal and pancreatic neuroendocrine tumors: a single center experience

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