scholarly journals Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Su-Jung Kim ◽  
Jin Won Kim ◽  
Sae-Won Han ◽  
Do-Youn Oh ◽  
Se-Hoon Lee ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Neuroendocrine Tumors ◽  
Treatment Strategy ◽  
Tumor Grade ◽  
Biological Characteristics ◽  
Metastatic Site

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.

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.

Real-world efficacy and safety of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 364-364
Author(s):  
Estephany Abou Jokh Casas ◽  
Nieves Purificacion Martinez ◽  
Urbano Anido Herranz ◽  
Jose Manuel Cabezas Agricola ◽  
Silvia Varela Ferreiro ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Real World ◽  
Primary Tumor ◽  
Premature Death ◽  
Tumor Grade ◽  
Tumor Surgery ◽  
Efficacy And Safety ◽  
Ki 67 ◽  
Multicentric Study ◽  
Systemic Treatments

364 Background: PRRT with 177Lu-Dotatate (Lutathera) is a radiolabeled somatostatin analog indicated treatment of somatostatin receptor (STTR) positive GEP-NETs. The study aims to establish the efficacy and safety of PRRT in GEP-NETs in a real-world setting. Methods: We conducted an observational, retrospective, multicentric study of 40 patients with GEP-NET treated with PRRT belonging to GGNET (Galician Research Group on Neuroendocrine Tumors) network at Nuclear Medicine Department of Santiago de Compostela University Hospital (Spain). Patients characteristics, overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity data were retrospectively collected and analyzed. Results: Data from 40 patients (pts) treated between 2016 and 2020 were recorded in this study. Median age was 63.5 years (range 41-85) and 55% were male. The baseline ECOG PS 0/1/2 was 15 (37.5%)/16 (40%)/9 (22.5%). Tumor location was intestinal 26 pts (65%), pancreas in 11 pts (27.5%) and unknown origin in 3 pts (7.5%). 25 pts (62.5%) were none functioning. Tumor grade G1/G2/G3 were 17 pts (42.5%)/ 20 pts (50%)/ 3 pts (7.5%), and Ki 67 < 2/3-20/ > 20%/unknown was 11 pts (27.5%)/ 21 pts (52.5%)/ 3 pts (7.5%)/ 5 pts (12.5%), respectively. The most frequent site of metastasis was liver in 32 pts (80%), lymph nodes in 19 pts (47.5%), peritoneum 11 pts (27.5%) and bone 10 pts (25%). Surgery: 22 pts (55%) primary tumor surgery and 8 pts (20%) metastasectomy. Previous systemic treatments included somatostatin analogs (SSA) in 40 pts (100%), everolimus in 26 pts (65%) and sunitnib in 11 pts (27.5%), others 7 pts (17.5%). 34 pts (85%) completed 4 cycles of treatment (6 pts (15%) non-complete due to premature death). 35 pts were evaluable for early response (after 2 cycles of treatment). Early ORR and DCR were 2.8% and 74.2%, respectively. 26 pts were evaluable after finishing treatment (6 pts premature death and 8 pending evaluation). ORR and DCR were 19.2% and 92.3%. With a median follow up of 21 months, 14 pts (35%) had died. Median OS was not reached (NR) and median PFS was 27.2 m (95% CI 16.0-38.4m). Tumor grade G1-2 (p < 0.001), Ki 67 <20% (p = 0.002), primary tumor surgery (p = 0.039) and metastasectomy (p = 0.030) were associated with prolonged PFS. Mild adverse events were most frequent after the 1º doses in 27.5% patients, and medium-term toxicity was present in 25.6%, mainly hematological, G1-G2 25.6%, and G3 5%. Conclusions: 177Lu-Dotatate is a safe and effective treatment for those patients diagnosed with metastatic GEP-NET and positive somatostatin receptors, with an excellent clinical and radiological response. Furthermore, we have identified some predictive factors to OS that should be taken into consideration.

Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors

2019 ◽  
Vol 110 (5) ◽  
pp. 384-392 ◽  
Author(s):  
Andrew M. Blakely ◽  
Kelly J. Lafaro ◽  
Daneng Li ◽  
Jonathan Kessler ◽  
Sue Chang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Neuroendocrine Tumors ◽  
Lymphovascular Invasion ◽  
Pancreatic Head ◽  
Tumor Grade ◽  
Mitotic Rate ◽  
Endoscopic Biopsy ◽  
Pancreatic Neuroendocrine Tumors ◽  
Regional Lymphadenectomy ◽  
Node Involvement

Introduction: Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. Methods: The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004–2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. Results: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1–2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. Conclusions: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.

scholarly journals Combined test of serum CgA and NSE improved the power of prognosis prediction of NF-pNETs

2018 ◽  
Vol 7 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Yang Lv ◽  
Xu Han ◽  
Chunyan Zhang ◽  
Yuan Fang ◽  
Ning Pu ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Statistical Significance ◽  
Neuron Specific Enolase ◽  
Tumor Grade ◽  
Clinical Value ◽  
Serum Samples ◽  
Individual Values ◽  
Predictive Values ◽  
Combined Test ◽  
The Mean

Purpose Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs). Patients and Methods In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05. Results Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001). Conclusion CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.

Systemic immune-inflammation index and neutrophil to lymphocyte ratio for predicting tumor grade in neuroendocrine tumors.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16179-e16179
Author(s):  
Idris Yucel ◽  
Yasemin Kemal ◽  
Seda Gun ◽  
Guzin Demirag ◽  
Murat Derebey
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Grade ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Immune Inflammation

Predictors of recurrence in patients with surgically resected pancreatic neuroendocrine tumors.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 408-408
Author(s):  
Cynthia Harris ◽  
Michelle Kang Kim ◽  
Kiwoon Joshua Baeg ◽  
Mi Ri Lee ◽  
Julie Starr ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Disease Recurrence ◽  
Stage Ii ◽  
Pancreatic Neuroendocrine Tumors ◽  
Cox Regression Analysis ◽  
Grade 3

408 Background: Current surveillance guidelines regarding follow up of patients with resected pancreatic neuroendocrine tumors (PNETs) are based on limited data, and there have been few studies evaluating recurrence risk in such patients. We assessed disease-free survival (DFS) in a large, multi-institutional cohort of patients with resected PNETs. Methods: Patients with surgically resected, non-metastatic PNETs between 1990-2017 were identified using institutional databases at three institutions: Mount Sinai Hospital, Dana-Farber Cancer Institute, and University of Pennsylvania. Recurrence date was defined as the imaging date documenting first recurrence (n = 56); if an imaging date was not available, then July 1 of that year was used in calculations (n = 9). Kaplan-Meier analysis was used to estimate DFS; multivariate Cox regression analysis was used to assess DFS adjusted for patient and disease-related characteristics, including tumor stage and grade. Results: We identified a total of 418 patients with surgically resected, non-metastatic PNETs between 1990-2017. Of these patients, 299 patients had complete stage and tumor grade information and were used for subsequent analysis. Patients were 48.6% male with a median age of 57.5 years at time of surgery. The distribution of AJCC stage and grade was as follows: 170 (56.9%) patients were stage I, 129 (43.1%) were stage II; 167 (55.9%) had grade 1, 121 (40.5%) had grade 2, and 11 (3.7%) had grade 3 tumors. Median follow-up was 2.6 years (interquartile range = 4.2); during this time, 65 (21.7%) patients developed disease recurrence. After adjusting for potential confounders, patients with more advanced stage and higher tumor grade were significantly more likely to develop disease recurrence (Hazard Ratio (HR): 6.9, 95% CI: 2.5-19.1 for stage II; HR 4.0 (1.7-9.5) for grade 2; HR 2.6 (0.4-17.8) for grade 3). Both higher stage and tumor grade were associated with decreased DFS (p < 0.0001 for both). Conclusions: In surgically resected PNETs, with a median follow-up time of 2.6 years, both higher stage and higher grade are associated with decreased DFS. Further follow up of this cohort is planned.

Circulating Tumor Cells As Prognostic Markers in Neuroendocrine Tumors

2013 ◽  
Vol 31 (3) ◽  
pp. 365-372 ◽  
Author(s):  
Mohid S. Khan ◽  
Amy Kirkwood ◽  
Theodora Tsigani ◽  
Jorge Garcia-Hernandez ◽  
John A. Hartley ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Immunomagnetic Separation ◽  
Tumor Burden

Purpose To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer. Patients and Methods In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule–expressing cells. Results Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of ≥ one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P < .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036). Conclusion CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy.

scholarly journals Short and long-term outcomes of video observed treatment in tuberculosis patients, the Republic of Moldova

2021 ◽  
Vol 15 (09.1) ◽  
pp. 17S-24S
Author(s):  
Svetlana Doltu ◽  
Ana Ciobanu ◽  
Yuliia Sereda ◽  
Ruth Persian ◽  
Luke Ravenscroft ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Strategy ◽  
Term Outcome ◽  
Operational Conditions ◽  
Republic Of Moldova ◽  
Tb Treatment ◽  
Long Term Treatment ◽  
Short And Long Term ◽  
The Republic

Introduction: The Republic of Moldova is among the 18 high priority countries for tuberculosis (TB) in Europe. This study compared adherence and short and long-term TB treatment outcomes for TB patients who experienced asynchronous Video Observed Treatment (aVOT) during three months of outpatient treatment versus Directly Observed Treatment (DOT) in operational conditions in 2016-2017 in Chisinau. Methodology: We used secondary data from the 2016-2017 Randomized Clinical Trial (RCT) that piloted the aVOT Strategy in Chisinau and data from the national TB register. Relative risk was selected as a measure of association in analysis of treatment strategies (aVOT and DOT under operational conditions) and short and long-term treatment outcomes. Results: From 647 TB patients included in the study, 169 followed the treatment strategy in the RCT (83 in aVOT and 86 in DOT) and 478 were on DOT in operational conditions. Those in aVOT were more likely to have favourable short-term outcome than patients with DOT in operational conditions (RR 0.07; p < 0.001). TB recurrence as an indicator for the long-term outcome, was observed in group with DOT in operational conditions (40 cases, p = 0.006). Conclusions: This study demonstrated that the aVOT treatment strategy was associated with better adherence and both short and long-term TB treatment favourable outcomes. aVOT as a new patient-centred approach supporting TB patients on improving treatment adherence and outcomes might be recommended as an alternative to DOT strategy in the Republic of Moldova.

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