scholarly journals Well differentiated grade 3 pancreatic neuroendocrine tumors compared with related neoplasms: A morphologic study

2018 ◽  
Vol 126 (5) ◽  
pp. 326-335 ◽  
Author(s):  
Carlie S. Sigel ◽  
Vitor Werneck Krauss Silva ◽  
Michelle D. Reid ◽  
David Chhieng ◽  
Olca Basturk ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Morphologic Study ◽  
Well Differentiated ◽  
Grade 3

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

Prognostic transcriptome classes of duodenopancreatic neuroendocrine tumors

2021 ◽  
Author(s):  
Marc Diedisheim ◽  
Solène Dermine ◽  
Anne Jouinot ◽  
Amandine Septier ◽  
Sébastien Gaujoux ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Beta Cell ◽  
Tumor Biology ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Pancreatic Alpha Cell ◽  
Liver Gene ◽  
Well Differentiated ◽  
Grade 3 ◽  
Definition Of

Duodenopancreatic neuroendocrine tumors (DPNETs) aggressiveness is heterogeneous. Tumor grade and extension are commonly used for prognostic determination. Yet, grade classes are empirically defined, with regular up-dates changing the definition of classes. Genomic screening may provide more objective classes, and reflect tumor biology. The aim of this study was to provide a transcriptome classification of DPNETs. We included 66 DPNETs, covering the entire clinical spectrum of the disease in terms of secretion, grade, and stage. Three distinct molecular groups were identified, associated with distinct outcome (log-rank p<0.01): (i) better-outcome DPNETs with pancreatic beta-cell signature. This group was mainly composed of well-differentiated, grade 1 insulinomas; (ii) poor-outcome DPNETs with pancreatic alpha-cell and hepatic signature. This group included all neuroendocrine carcinomas and grade 3 DPNETs, but also some grade 1 and grade 2 DPNETs; and (iii) intermediate-outcome DPNETs with pancreatic exocrine and progenitor signature. This group included grade 1 and grade 2 DPNETs, with some insulinomas. Fibrinogen gene FGA expression was one of the top most expressed liver gene. FGA expression was associated with disease-free survival (HR=1.13, p=0.005), and could be validated on two independent cohorts. This original pathophysiologic insight provides new prognostic classification perspectives.

Erratum to: KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

Endocrine ◽  
2017 ◽  
Vol 57 (3) ◽  
pp. 503-503
Author(s):  
Federica Grillo ◽  
Luca Valle ◽  
Diego Ferone ◽  
Manuela Albertelli ◽  
Maria Pia Brisigotti ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Well Differentiated ◽  
Grade Assessment

scholarly journals Expression of the phosphorylated variant of the AKT1-kinase (p-AKT1) in well-differentiated pancreatic neuroendocrine tumors: immunohistochemical evaluation

2018 ◽  
Vol 46 (4) ◽  
pp. 314-322
Author(s):  
V. V. Delektorskaya ◽  
O. N. Solov'eva ◽  
G. Yu. Chemeris ◽  
Yu. I. Patyutko
Keyword(s):  
Liver Metastases ◽  
Neuroendocrine Tumors ◽  
Treatment Effectiveness ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
New Treatment ◽  
Well Differentiated ◽  
High Level

Background:Well-differentiated pancreatic neuroendocrine tumors (pNETs) represent a group of rare epithelial neoplasms with a highly variable clinical course. AKT1 is one of the most frequently activated protein kinases in pNETs, which promotes the tumor growth and is of interest as a prognostic factor and a target for new treatment approaches.Aim:To study the expression of the phosphorylated variant of AKT1-kinase (p-AKT1) in primary pNETs and their liver metastases and to correlate the results with various clinical and pathological parameters and the disease prognosis.Materials and methods:P-AKT1 expression was studied by the immunohistochemical analysis of the primary lesions and liver metastases in 52 pNETs patients.Results:A high level of cytoplasmic and/or nuclear immunoreactivity was detected in 24/52 of the primary pNETs (46.2%) and in 16/27 of their liver metastases (59.3%). p-AKT1 expression was observed in 3 (21.4%) of NET grade (G) 1, in 14 (46.7%) of NET G2, and in 7 (87.5%) of NET G3. p-AKT1 expression was more frequently identified in pNET G3 category and increased during the tumor progression in metachronous liver metastases, as compared to the corresponding primary tumor. In addition, p-AKT1 positivity was significantly associated with an increase of grade from G1 to G3 (p = 0.004), the Ki-67 index (p = 0.029), the pTNM stage (p = 0.0008), perineural invasion (p = 0.031) and a decrease in disease-free survival (p = 0.05).Conclusion:The results suggest that p-АКТ1 plays an important role in the pathogenesis of pNETs and may be an additional criterion for assessment of the prognosis and treatment effectiveness in this type of tumors.

scholarly journals Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors

Oncogenesis ◽  
2021 ◽  
Vol 10 (12) ◽  
Author(s):  
Angela M. Carter ◽  
Nilesh Kumar ◽  
Brendon Herring ◽  
Chunfeng Tan ◽  
Rachael Guenter ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Islet Cells ◽  
Tumor Development ◽  
Heterogeneous Population ◽  
Targeted Therapeutics ◽  
Pancreatic Neuroendocrine Tumors ◽  
The Past ◽  
Regulated Expression ◽  
Well Differentiated ◽  
Conditional Mouse Model

AbstractPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in β-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Are Cystic Pancreatic Neuroendocrine Tumors an Indolent Entity Results from a Single-Center Surgical Series

2017 ◽  
Vol 106 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Salvatore Paiella ◽  
Giovanni Marchegiani ◽  
Marco Miotto ◽  
Anna Malpaga ◽  
Harmony Impellizzeri ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Postoperative Outcome ◽  
Tumor Diameter ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Excellent Outcome ◽  
Comparison Results ◽  
Well Differentiated

Introduction: Cystic pancreatic neuroendocrine tumors (CPanNETs) represent an uncommon variant of pancreatic neuroendocrine tumors (PanNETs). Due to their rarity, there is a lack of knowledge with regard to clinical features and postoperative outcome. Methods: The prospectively maintained surgical database of a high-volume institution was queried, and 46 resected CPanNETs were detected from 1988 to 2015. Clinical, demographic, and pathological features and survival outcomes of CPanNETs were described and matched with a population of 92 solid PanNETs (SPanNETs) for comparison. Results: CPanNETs accounted for 7.8% of the overall number of resected PanNETs (46/587). CPanNETs were mostly sporadic (n = 42, 91%) and nonfunctioning (39%). Two functioning CPanNETs were detected (4.3%), and they were 2 gastrinomas. The median tumor diameter was 30 mm (range 10-120). All tumors were well differentiated, with 38 (82.6%) G1 and 8 (17.4%) G2 tumors. Overall, no CPanNET showed a Ki-67 >5%. A correct preoperative diagnosis of a CPanNET was made in half of the cases. After a median follow-up of >70 months, the 5- and 10-year overall survival of resected CPanNETs was 93.8 and 62.5%, respectively, compared to 92.7 and 84.6% for SPanNETs (p > 0.05). The 5- and 10-year disease-free survival rates were 94.5 and 88.2% for CPanNETs and 81.8 and 78.9% for SPanNETs, respectively (p > 0.05). Conclusion: In the setting of a surgical cohort, CPanNETs are rare, nonfunctional, and well-differentiated neoplasms. After surgical resection, they share the excellent outcome of their well-differentiated solid counterparts for both survival and recurrence.

A phase II study of temozolomide and bevacizumab in patients with advanced neuroendocrine tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4044-4044 ◽  
Author(s):  
M. H. Kulke ◽  
K. Stuart ◽  
C. C. Earle ◽  
P. Bhargava ◽  
J. W. Clark ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Response Table ◽  
Pancreatic Net ◽  
Prospective Phase ◽  
Vegf Pathway ◽  
Well Differentiated ◽  
Grade 3 ◽  
Ecog Ps

4044 Background: Inhibitors of the VEGF pathway have been shown to have activity in neuroendocrine tumors (NETs). Temozolomide (TMZ), an oral analog of dacarbazine is also active in this setting. We performed a prospective, phase II study to assess the safety and efficacy of TMZ, administered in combination with bevacizuamb, in patients (pts) with advanced NETs. Methods: Pts received TMZ, 150 mg/m2/day po for 7 days every other week, and bevacizumab, 5 mg/kg IV every other week. Due to anticipated lymphopenia, pts received prophylaxis with trimethoprim/sulfamethoxazole (1 DS tablet q MWF) and acyclovir (400 mg po TID). Pts were followed for toxicity, response, and survival. Results: Enrolled patients (n=34) had the following characteristics: M:F = 19:15; median age 61 (range 37–75); ECOG PS 0/1/2 = 12/20/2; carcinoid/pancreatic NET = 16/18. Prior treatments included chemoembolization (n=7) chemotherapy (n=12); and octreotide (n=17); pts on octreotide remained on octreotide at stable doses for the duration of the study. Pts had either well-differentiated tumors (n=27) or moderately/poorly-differentiated NETs (n=7); pts with small cell carcinoma were not eligible for the study. Pts have received treatment for a median of 22 weeks. Grade 3–4 toxicities included: lymphopenia (n=21, 62%), leukopenia (n=2, 6%), thrombocytopenia (n=7, 21%), neutropenia (n=2, 6%), hyponatremia (n=1, 3%), vomiting (n=3, 9%), nausea (n=2, 6%), dehydration (n=1, 3%), fatigue (n=2, 6%), constipation (n=1, 3%), and hypertension (n=1, 3%). 20 pts had elevated CGA levels (>36.4 ng/ml) at baseline; 0/9 (0%) carcinoid and 4/11 (36%) pancreatic NET experienced CGA decreases of >50% from baseline on two consecutive assessments. 29 pts are currently evaluable for radiologic response ( Table ). Conclusions: The combination of TMZ and bevacizumab can be safely administered and shows promising activity in pts with advanced pancreatic NETs. Additional studies with this combination are warranted. [Table: see text] [Table: see text]

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