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.

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.

Liver Needle Biopsies are Poor Predictors of Histologic Tumor Grade for Midgut Neuroendocrine Tumors

2020 ◽  
pp. 1-4
Author(s):  
Robert A. Ramirez ◽  
Yi-Zarn Wang ◽  
Brianne Voros ◽  
David T. Beyer ◽  
Eugene A. Woltering ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Hepatic Metastasis ◽  
Error Rate ◽  
Needle Biopsy ◽  
Hepatic Metastases ◽  
Tumor Grade ◽  
Histologic Grade ◽  
Ki 67 ◽  
Core Needle ◽  
Fine Needle

Background: Our group has previously shown than neuroendocrine tumors (NETs) are heterogeneous neoplasms having histologic and functional differences between their primary tumor, lymph node, and hepatic metastases. Due to the heterogeneity of these malignancies, we hypothesized that there would be discordance between the histologic grade of surgical specimens and that predicted by preoperative biopsies. Methods: Twenty consecutive patients diagnosed with NETs of the ileum and hepatic metastasis were included. Ki-67 proliferative index and WHO 2010 histologic grade were recorded for preoperative hepatic needle biopsy and subsequent tissue-matched surgical specimens. Concordance between sample values was determined. Results: Ten males and 10 females were included in this analysis. Five and 15 patients had fine-needle aspirate (FNA) and core needle biopsies, respectively. Preoperative biopsies predicted the histologic grade of subsequent tissue-matched surgical specimens in only 65% of samples (13/20). Of the 7 values that changed grade (7/20, 35%), 4 went from intermediate (G2) to low (G1) grade [1 FNA and 3 core biopsies] and 3 went from low (G1) to intermediate (G2) grade [1 FNA and 2 core biopsies]. The corresponding interrater agreement statistic (K) was 0.251±0.230 (95% CI: -0.199-0.702), with 0.21<K<0.40 indicating fair strength of agreement. Conclusion: Preoperative fine-needle aspirates and core needle biopsies of hepatic metastasis have a 35% error rate in predicting the histologic grade from subsequent tissue-matched surgical NET specimens. Clinicians should be cognizant of this error rate when making decisions on systemic treatment and consider repeat needle biopsy or open biopsy if the actual clinical course does not match predicted behaviour.

High-Grade Progression Confers Poor Survival in Pancreatic Neuroendocrine Tumors

2019 ◽  
Vol 110 (11-12) ◽  
pp. 891-898 ◽  
Author(s):  
Johan Botling ◽  
Angela Lamarca ◽  
Duska Bajic ◽  
Olov Norlén ◽  
Vincent Lönngren ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Grade ◽  
University Hospital ◽  
High Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Grade 3 ◽  
Over Time ◽  
Grade Progression

Introduction: Little is known about how pancreatic neuroendocrine tumors (PanNETs) evolve over time and if changes toward a more aggressive biology correlate with prognosis. The purpose of this study was to characterize changes in PanNET differentiation and proliferation over time and to correlate findings to overall survival (OS). Patients and Methods: In this retrospective cohort study, we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were reevaluated with regard to tumor histopathology and Ki-67 index. Results: Forty-six patients with 106 tumor samples (56 available for pathology reevaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1–38%), grade 1 n = 8, grade 2 n = 36, and grade 3 n = 2. The median change in Ki-67 index (absolute value; follow-up – baseline) was +14% (range –11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n = 24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (hazard ratio 3.89, 95% CI 1.91–7.94, p < 0.001). Conclusions: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET.

The role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 371-371
Author(s):  
Estephany Abou Jokh Casas ◽  
Nieves Martinez Lago ◽  
Jose Manuel Cabezas Agricola ◽  
Urbano Anido Herranz ◽  
Francisco Baron ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Systemic Inflammation ◽  
Neutrophil Count ◽  
Lymphocyte Count ◽  
Inflammatory Factors ◽  
Prognostic Impact ◽  
Monocyte Count ◽  
Multicentric Study ◽  
Cutoff Values ◽  
Systemic Treatments

371 Background: Inflammation plays a key role in the pathophysiology of many diseases, including cancer. Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, it is unknown the prognostic impact of systemic inflammation markers in patients with GEP-NETs treated with PRRT. 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). The systemic inflammatory markers were calculated as follows: NLR = neutrophil count/lymphocyte count, PLR = platelet count/lymphocyte count, MLR= monocyte count/lymphocyte count, ALB= albumin levels and dNLR = neutrophil count/ (leucocytes count – neutrophils count). For the calculation of the different ratios, baseline analysis and after the second dose were used. The cut-off values were determined as the median of each values, correlating them with progression-free survival (PFS). Results: Data from 40 patients (pts) treated between 2016 and 2020 were recorded. Median age was 63.5 years (range 41-85) and 55% were male. Baseline ECOG PS 0/1/2 was 15 (37.5%)/16 (40%)/9 (22.5%). Tumor location was intestinal 26 pts (65%), pancreas 11 pts (27.5%) and unknown origin 3 pts (7.5%). 15 pts (37.5%) were 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 were 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 32 pts (80%), lymph nodes 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) 40 pts (100%), everolimus 26 pts (65%) and sunitnib 11 pts (27.5%), others 7 pts (17.5%). The baseline cutoff-values for NLR was 2.61, for PLR 110.14, for MLR 0.31, for ALB 4.2. and for dNLR 1.71. The cutoff-values after the 2nd dose for NLR was 2.3, for PLR 2.15, for MLR 0.3, for ALB 4.2 and for dNLR 1.48. With a median follow up of 21 months, 14 pts (35%) had died. Median PFS was 27.2 m (95% CI 16.0-38.4m) and OS was not reached (NR). Pts with baseline higher NLR (>2.61 vs. <2.61) had a significantly lower PFS: 15.8 m vs. NR (HR 0.181; 95% CI 0.051-0.638, p=0.03), which was also true for pts with elevated dNLR (>1.71 vs. <1.71): PFS 15.8 m vs. NR (HR 0.174; 0.049-0.614, p=0.03). Baseline PLR, ALB, MLR and NLR, PLR, ALB, dNLR and MLR values after the 2nd dose was not statistically significant for PFS. Conclusions: We have identified that baseline NLR and dNRL are significant predictive factors in patients with GEP-NETs treated with PRRT.

scholarly journals Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E-Mutant NSCLC in Real-World Setting: GFPC 01-2019

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3608
Author(s):  
Jean-Bernard Auliac ◽  
Sophie Bayle ◽  
Pascal Do ◽  
Gwenaëlle Le Garff ◽  
Magali Roa ◽  
...  
Keyword(s):  
Real World ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Braf V600e ◽  
Efficacy And Safety ◽  
First Line ◽  
Multicentric Study ◽  
Free Survival ◽  
Entire Cohort ◽  
Real World Setting

Dabrafenib plus trametinib combination is approved in Europe for BRAF V600E-mutant metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to assess efficacy and safety of this combination in a real-world setting. This retrospective multicentric study included 40 patients with advanced NSCLC harboring BRAF V600E mutation and receiving dabrafenib plus trametinib. The median progression-free survival (PFS) and overall survival (OS) were 17.5 (95% CI 7.1–23.0) months and 25.5 (95% CI 16.6–not reached) months in the entire cohort, respectively. For the 9 patients with first-line treatment, median PFS was 16.8 (95% CI 6.1–23.2) months and median OS was 21.8 (95% CI 1.0–not reached) months; for the 31 patients with second-line or more treatments, median PFS and OS were 16.8 (95% CI 6.1–23.2) months and 25.5 (95% CI 16.6–not reached) months, respectively. Adverse events led to permanent discontinuation in 7 (18%) patients, treatment interruption in 8 (20%) and dose reduction in 12 (30%). In conclusion, these results suggest that efficacy and safety of dabrafenib plus trametinib combination in patients with BRAF V600E metastatic NSCLC are comparable in a real-world setting and in clinical trials for both previously untreated and treated patients.

Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 134-147 ◽  
Author(s):  
Mirko Hirschl ◽  
Michael Kundi
Keyword(s):  
Real World ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Nonvalvular Atrial Fibrillation ◽  
Real World Data ◽  
Hazard Ratios ◽  
Direct Acting ◽  
Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

The Role of Wireless Capsule Endoscopy (WCE) in the Detection of Occult Primary Neuroendocrine Tumors

2017 ◽  
Vol 26 (2) ◽  
pp. 151-156
Author(s):  
Manuele Furnari ◽  
Andrea Buda ◽  
Gabriele Delconte ◽  
Davide Citterio ◽  
Theodor Voiosu ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Capsule Endoscopy ◽  
Primary Tumor ◽  
Diagnostic Yield ◽  
Somatostatin Receptor ◽  
Tertiary Care ◽  
Wireless Capsule Endoscopy ◽  
First Line ◽  
Wireless Capsule

Background & Aims: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumor in patients showing liver NET metastases when first-line investigations are inconclusive.Method: Twenty-four patients with histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration.Results: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded.Conclusions: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.Abbreviations: DBE: double balloon enteroscopy; GEP-NET: gastro-entero-pancreatic neuroendocrine tumor; GI: gastrointestinal; ENETS: European Neuroendocrine Tumor Society; NET: neuroendocrine tumor; SSRS: somatostatin receptor scintigraphy; WCE: wireless capsule endoscopy.

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