scholarly journals Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors

2007 ◽  
Vol 14 (2) ◽  
pp. 221-232 ◽  
Author(s):  
Eduardo Vilar ◽  
Ramón Salazar ◽  
Jose Pérez-García ◽  
Javier Cortes ◽  
Kjell Öberg ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Retrospective Studies ◽  
Response To Treatment ◽  
Biological Behavior ◽  
Endocrine Tumors ◽  
Ki 67 ◽  
Pancreatic Endocrine Tumors ◽  
Poorly Differentiated ◽  
Selection For

Neuroendocrine tumors (NETs) of the digestive tract are a heterogeneous group of rare malignancies. Three major subgroups can be defined: pancreatic endocrine tumors, carcinoid tumors, and poorly differentiated gastroenteropancreatic NETs. Classically, digestive NETS have been considered to have an indolent course characterized for prolonged stabilizations or slow progressions, but there are clear differences in terms of aggressiveness, clinical course, and response to treatment among them. Retrospective studies have identified several clinicopathological and immunohistochemical factors as angioinvasion and proliferative index assessed by Ki-67 expression, which predict biological behavior and correlate with survival. Chemotherapy regimens based on the combination of several active drugs such as streptozocin, doxorubicin, 5-fluorouracil, dacarbazine, and temozolomide show low response rates, which sets the need to improve the results of the medical treatment of these malignancies. This review will analyze the role of Ki-67 in digestive NETs under a clinical perspective and will suggest future fields for development of this approach that enable a better patient selection for chemotherapy. Also a comprehensive review of the literature about chemotherapy in NETs is presented.

Safety and Efficacy of the S-1/Temozolomide Regimen in Patients with Metastatic Neuroendocrine Tumors

2017 ◽  
Vol 106 (4) ◽  
pp. 318-323 ◽  
Author(s):  
Jiuda Zhao ◽  
Hong Zhao ◽  
Yihebali Chi
Keyword(s):  
Neuroendocrine Tumors ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Response To Treatment ◽  
Endocrine Tumors ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Highly Active ◽  
Pancreatic Endocrine Tumors

Purpose: Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods: A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m2 orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival. Results: Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively. Conclusions: The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.

scholarly journals Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review

2018 ◽  
Vol 11 (3) ◽  
pp. 676-681 ◽  
Author(s):  
Kishore Kumar ◽  
Rafeeq Ahmed ◽  
Chime Chukwunonso ◽  
Hassan Tariq ◽  
Masooma Niazi ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Grade ◽  
Small Cell ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Cell Type ◽  
Variable Response ◽  
Ki 67 ◽  
Platinum Based Chemotherapy ◽  
Poorly Differentiated

Neuroendocrine cells are widespread throughout the body and can give rise of neuroendocrine tumors due to abnormal growth of the chromaffin cells. Neuroendocrine tumors divide into many subtypes based on tumor grade (Ki-67 index and mitotic count) and differentiation. These tumors can be further divided into secretory and nonsecretory types based on the production of peptide hormone by tumor cells. Poorly differentiated small-cell-type neuroendocrine tumors are one of the subtypes of neuroendocrine tumors. These tumors are less common; however, they tend to be locally invasive and aggressive in behavior with poor overall median survival. Treatment of the nonsecretory small-cell type is modeled to small-cell lung cancer with a regimen consisting of platinum-based chemotherapy and etoposide with variable response. Here, we present a case of poorly differentiated small-cell neuroendocrine tumor originating from the prostate.

W1678 Will Ki-67 Predict Lymph Node Status in Pancreatic Endocrine Tumors?

2010 ◽  
Vol 138 (5) ◽  
pp. S-901-S-902
Author(s):  
Derick Christian ◽  
Amit S. Khithani ◽  
A. Joe Saad ◽  
Joshua G. Barton ◽  
Jeffrey D. Linder ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Status ◽  
Endocrine Tumors ◽  
Ki 67 ◽  
Node Status ◽  
Pancreatic Endocrine Tumors

scholarly journals Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

2019 ◽  
Vol 37 (28) ◽  
pp. 2571-2580 ◽  
Author(s):  
Alberto Carmona-Bayonas ◽  
Paula Jiménez-Fonseca ◽  
Ángela Lamarca ◽  
Jorge Barriuso ◽  
Ángel Castaño ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Failure Time ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Accelerated Failure Time Model ◽  
Endocrine Tumors ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Well Differentiated

PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

Prognostic Significance of p27, Ki-67, and Topoisomerase IIα Expression in Clinically Nonfunctioning Pancreatic Endocrine Tumors

2000 ◽  
Vol 11 (3) ◽  
pp. 229-242 ◽  
Author(s):  
Hee Jin Chang ◽  
Kenneth P. Batts ◽  
Ricardo V. Lloyd ◽  
Thomas J. Sebo ◽  
Geoffrey B. Thompson ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Endocrine Tumors ◽  
Topoisomerase Iiα ◽  
Ki 67 ◽  
Pancreatic Endocrine Tumors

Canine Neuroendocrine Tumors of the Pancreas: A Study Using Image Analysis Techniques for the Discrimination of Metastatic Versus Nonmetastatic Tumors

1997 ◽  
Vol 34 (2) ◽  
pp. 138-145 ◽  
Author(s):  
G. Minkus ◽  
U. Jütting ◽  
M. Aubele ◽  
K. Rodenacker ◽  
P. Gais ◽  
...  
Keyword(s):  
Image Analysis ◽  
Neuroendocrine Tumors ◽  
Nucleolar Organizer ◽  
Biological Behavior ◽  
Proliferation Index ◽  
Nucleolar Organizer Regions ◽  
Ki 67 ◽  
Analysis Techniques ◽  
Significant Difference ◽  
Image Analysis Techniques

Canine pancreatic neuroendocrine tumors were studied using different image analysis techniques (nuclear image histometry, analysis of argyrophilic proteins of nucleolar organizer regions, determination of the mouse anti-Ki 67 antigen proliferation index, and DNA densitometry) to correlate their biological behavior with objective phenotypic markers. The methods were compared to determine the best method for distinguishing between metastatic and nonmetastatic tumors. Discrimination between the two types of tumor was possible using nuclear image histometry in combination with morphometric analysis of argyrophilic proteins of nucleolar organizer regions. In contrast, the mouse anti-Ki 67 antigen proliferation index, DNA measurement, and immunohistochemical parameters revealed no significant difference between the two types of tumors.

scholarly journals PROGNOSTIC ROLE OF KI - 67 INDEX AND MITOTIC INDEX IN NEUROENDOCRINE TUMORS OF HETEROGENOUS ORIGIN

2014 ◽  
Vol 3 (67) ◽  
pp. 14438-14444
Author(s):  
Triveni B ◽  
Sandeep Kumar ◽  
Sai Mallikarjun S ◽  
Lakshmi Sri
Keyword(s):  
Mitotic Index ◽  
Neuroendocrine Tumors ◽  
Prognostic Role ◽  
Ki 67

New WHO classification for pancreatic endocrine tumors: Is time to leave the previous one?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14647-e14647
Author(s):  
Claudio Ricci ◽  
Davide Campana ◽  
Marina Macchini ◽  
Silvia Vecchiarelli ◽  
Giovanni Taffurelli ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Multivariate Analysis ◽  
Who Classification ◽  
Palliative Surgery ◽  
Tnm Stage ◽  
Endocrine Tumors ◽  
Pancreatic Endocrine Tumors ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Atypical Resection

e14647 Background: In 2010 WHO released a new classification (NWHO) system for endocrine pancreatic tumours (NETs). The aims of this study was to compare the NWHO and previous one (OWHO) in patients affected by NETs. Methods: From January 1980 to December 2010, 89 consecutives patients underwent surgical intervention for PNETs Data regarding sex, age, presence of symptoms, hormonal status, presence of MEN1, surgical procedure, R status, TNM stage, older and new WHO classification and disease specific survival (DSS) were prospectively collected. Multivariate analysis, including OWHO and NWHO, was carried out to evaluate the independent factors related to DSS. A sensitivity analysis was performed to include patients in which NWHO was impossible to be calculated. Results: Mean age of patients was 54.7 ± 14.2 years. There were 46 (51.7%) female and 43 (48.3%) male. Symptoms were present in 68 (76.4%) patients. Fifty-two (58.4%) patients had non-functioning NETs. Left pancreatectomy was performed in 48 (53.9%) cases, atypical resection in 22 (24.7%), pancreaticoduodenectomy in 12 (13.5%), total pancreatectomy in 2 (2.2%) and palliative surgery in 5 (5.6%). R0/1 resection was carried out in 79(88.7%) cases. According TNM stage there were: I, 27 (30.3%); II 29 (32.6%); III, 22 (24.7%); IV, 11 (12.4%). According OWHO 46 (51.7%) patients had a well differentiated tumours (WDT), 32 (36%) well differentiated carcinoma (WDCa), 11(12.4%) poorly differentiated carcinoma (PDCa). The NWHO was available only in 49 (55.1 %) patients: 20 (22.5%) NET G1, 25 (28.1%) NET G2, 4 (4.5%) neuroendocrine carcinomas (NEC) G3. At multivariate analysis OWHO and R2 status were the only independent factors related to DSS (RR=6.7, p<0.001 and RR 2.0, p=0.018 respectively). OWHO stratifies DSS better than NWHO: RR 0.12 (C.I. 95% 0.01-0.99; p=0.049) and RR 0.16 (C.I 95% 0.16-0.05; p=0.002) comparing WDT vs WDCa and WDCa vs PDCa, respectively. The sensitivity analysis confirmed in two model the superiority of OWHO while in others two we did not find any difference. Conclusions: In our experience OWHO still remains the best prognostic factor to predict DSS in patients with NETs .

Biomarkers in pancreatic neuroendocrine tumors.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 166-166
Author(s):  
Angela Tatiana Alistar ◽  
Richard Warner ◽  
Erin Moshier ◽  
Michelle Kim ◽  
Randall F. Holcombe
Keyword(s):  
Neuroendocrine Tumors ◽  
Cytoreductive Surgery ◽  
Response To Treatment ◽  
Serotonin Level ◽  
Pancreatic Neuroendocrine Tumors ◽  
Probability Of Survival ◽  
Post Surgery ◽  
Progression Of Disease ◽  
Early Late

166 Background: This study was designed to determine the role of Chromogranin A (CGA) and serotonin as prognostic biomarkers in relation with cytoreductive surgery for pancreatic neuroendocrine tumors (PNETs).The role of CGA and serotonin as biomarkers for PNETs is not fully established. Clinicians use CGA to monitor progression of disease and response to treatment; however this hasn’t been fully validated. There is no definitive data for serotonin as prognostic biomarker in PNETs. Methods: A retrospective study of patients with PNETs seen at Mount Sinai from 1980 to 2011 was performed. All patients (142) that have had CGA and serotonin concentrations measured at least once were evaluated. Data relating to diagnosis, therapies and survival outcome were noted Results: We evaluated the probability of survival post cytoreductive surgery among patients characterized by their postoperative CGA and serotonin values. 27 patients have had CGA level measured early post-op (0 to 3 months) and 30 patients have had CGA measurement late post-op (3-12 months). We identified no correlation between survival and a normal CGA early post-op (p = 0.5895). We identified a trend (p=0.1369) towards increase in survival for patients with a normal CGA late post-op with a probability in survival of 92.86% vs 65.12% at 3 years and median months to death of 80.265 for normal CGA vs 50.39 months for high CGA late post-op. For the 22 patients that had both a CGA early and late post-op the probability of survival by their change from early to late post- surgery CgA values was not statistically significant (p=0.2903). Serotonin did not correlate with survival in any of the 3 analyses: early post op, late postop or change in serotonin level. Conclusions: The role of CGA as a predictive or prospective biomarker for PNETs is worth prospective investigation. Our study shows that late post-op CGA may predict clinical outocome while CGA early postop and serotonin early, late and change post op did not have value in predicting survival.

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