Treatment tactics of new NET G3 subgroup in first line of therapy

2022 ◽  
pp. 20-24
Author(s):  
E. V. Evdokimova ◽  
E. V. Artamonova ◽  
V. V. Delectorskaya ◽  
G. Yu. Chemeris ◽  
G. S. Emelyanova ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Receptors ◽  
Prospective Trial ◽  
Neuroendocrine Neoplasm ◽  
Cytostatic Drug ◽  
Ki 67 ◽  
P53 Expression ◽  
Treatment Standard ◽  
Platinum Based Chemotherapy ◽  
Grade 3

Considering the fact that the group of neuroendocrine carcinomas (NECs) grade 3 is heterogenous, in the year of 2017 a new subgroup of welldifferentiated neuroendocrine tumors grade 3 (NETs G3) was described. NETs G3 are tumors with more favorable prognosis and less sensitive to platinum-based chemotherapy regimens than NECs, they also have peculiar morphogenetical qualities: lower ki‑67 index (mean 35.0 %), higher somatostatin receptors expression, absence of DAXX/ATRX/MEN 1 genes mutation, p53 expression in the absence of TP53 mutation. Nowadays treatment standard for NETs G3 subgroup is still remain unclear due to lack of prospective clinical trials. At the same time taking in note historical retrospective data, NETs G3 should be treated in line with NETs G1/G2 and only patients with higher ki‑67 index can be treated as NECs with platinum-based chemotherapy. In our non-randomised phase II prospective trial, we accessed the efficacy of different chemotherapy regimens in combination with somatostatin analogues in new NETs G3 subgroup. 153 patients with IHC-confirmed neuroendocrine neoplasm diagnose were included: NETs G3 n = 53 mean ki‑67 36.4 % [21.0–60.0 %], NETs G2 n = 50 mean ki‑67 15.7 % [2.1–20.0 %], NECs n = 50 mean ki‑67 69.0 % [38.0–96.0 %]). Patients from NETs G3 subgroup received 4 chemotherapy regimens: Aranose (n = 19), Aranose (arabinopiranosilmethyl nitrosocarbamide, ALK, – cytostatic drug with a chemical structure similar to Streptozotocin and Nitrosomethylurea, approved in Russian Federation for melanoma and welldifferentiated neuroendocrine tumors treatment), XELOX (n = 8), TemCAP (n = 11), EP/EC (n = 10). mPFS in Aranose-subgroup was 19.3 ± 5.9 months (95 % CI: 7.7–30.8), in XELOX – 10.8 ± 3.6 months (3.7–17.8), in TemCAP – 14.8 ± 4.2 months (6.6–23.1) and in platinum-based regimens – 4.4 ± 1.9 months (0.6–8.2) (p = 0.01). DCR in Aranose subgroup was 73.6 % and ORR – 36.8 %, PDR – 21.1 %, in XELOX subgroup ORR was 62.5 %, SDR was 50.0 % and PDR – 25.0 %, in TemCAP subgroup DCR was 63.6 %, ORR – 9.1 %, PDR – 18.2 % and in platinum-based regimens SDR was 40.0 %, PDR – 50.0 % (p = 0.05).

scholarly journals Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung

2020 ◽  
Vol 8 (2) ◽  
pp. e000980
Author(s):  
Chul Kim ◽  
Stephen V Liu ◽  
Deepa S Subramaniam ◽  
Tisdrey Torres ◽  
Massimo Loda ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Neuroendocrine Tumors ◽  
Phase I Study ◽  
Somatostatin Receptors ◽  
Atypical Carcinoid ◽  
Platinum Based Chemotherapy ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

BackgroundLutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.MethodsPatients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).ResultsNine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.ConclusionsLutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.Trial registration numberNCT03325816

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.

Evaluating the Effectiveness of Somatostatin Receptors Scintigraphy with 111In-Octreotide in the Diagnosis of Neuroendocrine Tumors

2018 ◽  
pp. 44-51
Author(s):  
А. Маркович ◽  
A. Markovich ◽  
С. Ширяев ◽  
S. Shiryaev ◽  
М. Гончаров ◽  
...  
Keyword(s):  
Positive Result ◽  
Neuroendocrine Tumors ◽  
Predictive Value ◽  
Single Photon ◽  
Somatostatin Receptors ◽  
Photon Emission ◽  
Neuroendocrine Neoplasm ◽  
Characteristic Parameters ◽  
Single Photon Emission ◽  
Negative Results

Purpose: Exploring methods to improve diagnosis of neuroendocrine tumors (NET) in different locations using somatostatin receptors scintigraphy with 111In-octreotide. Material and methods: The study included 125 patients with NET in different locations. Activity of injected 111In-octreotide was 200–250 MBq (effective dose – 0.054 mSv/MBq), which allows to carry out a planar study as and single photon emission computed tomography. The study was performed after 24 hours on intravenous injection of indicator on the combined SPECT/CT machine Symbia T2 (Siemens, Germany). Results: In the sample of patients, NET distribution by localization is indicated in Fig. 1. The results of the study with 111In-octreotide are presented in the form of scintigrams in the whole body scanning mode and in the form of single-photon emission computer tomograms combined with CT. To determine the effectiveness of scintigraphy with 111In-octreotide, after a visual evaluation of the scintigrams obtained, the number of positive and negative results of the study was calculated. A comparison was made with the data of other methods and the number of TP, TN, FP, and FN results was determined. Further, the characteristic parameters of the method studied were calculated to determine its effectiveness. The study of values of characteristic parameters showed that the sensitivity was 73 % (95 % CI: 63–83 %), specificity – 97 % (95 % CI: 88–100 %) accuracy is 79 % (95 % CI: 71–87 %). The value of the positive predictive value of 99 % (95 % CI: 94–100 %), the predictive value of negative results – 55 % (95 % CI: 40–70 %). While the study shows a high frequency of TP results, while the frequencies of the TN and FN results are not significantly different (the average frequency of the FN results falls within the confidence interval for the frequency of the TN results). The method has a high value of the prognostic value of the positive result, which gives the right to assert about the high probability of the presence of a neuroendocrine neoplasm in obtaining a positive result. In the present study, no FP results were obtained due to the presence of concomitant diseases, in which accumulation of used radiopharmaceutical is possible, since the data on the presence of such diseases were taken into account in the analysis of scintigrams. The data obtained in this paper are in good agreement with the data obtained by other authors, as well as early Russian publications. It is worth noting that the data of domestic authors were obtained on a small sample, without specifying confidence intervals; the injected activity was less than in this study. In addition, the possibility of obtaining more information than using classical imaging methods (for SPECT/CT, the tissue with the pathological accumulation of 111In-octreotide appeared to be intact on CT), allows us to recommend the method as a method of choice in the diagnosis of NET of different localization. Conclusions: The method of somatostatin receptors scintigraphy using domestic analogue of somatostatin in the diagnosis of NET has a high efficiency (efficiency of the method, calculated as the average value of the parameters of sensitivity and specificity of 85 % (95 % CI: 66–100 %).

scholarly journals Mixed Neuroendocrine Carcinoma and Hepatocellular Carcinoma: A Case Report and Literature Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwei Lan ◽  
Deliang Guo ◽  
Xian Qin ◽  
Baiyang Chen ◽  
Quanyan Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Neuroendocrine Tumors ◽  
Disease Recurrence ◽  
Carcinoma Cells ◽  
Neuroendocrine Neoplasm ◽  
Cancer Type ◽  
Case Presentation ◽  
Platinum Based Chemotherapy ◽  
Undifferentiated Cells

Background: Neuroendocrine tumors are heterogeneous malignancies that originate from the neuroendocrine system. Previous studies show that this cancer type mainly localizes in the gastrointestinal tract and often metastasizes to the liver. Primary liver neuroendocrine tumors are very rare and primary hepatic neuroendocrine tumors (PHNET) with concurrent hepatocellular carcinoma (HCC) are extremely rare. To the best of our knowledge, only few PHNET cases have been identified, making their diagnosis difficult. Here, we report the biggest ever reported and “deceiving” lesion of a mixed neuroendocrine-non-neuroendocrine neoplasm in the liver, aiming to raise awareness and improve treatment of the disease.Case Presentation: Here, we report a preoperative misdiagnosed case that presented with hepatocellular carcinoma clinical features and no extrahepatic tumors. Postoperative pathology confirmed that it was a mixed neuroendocrine-non-neuroendocrine neoplasm. The patient was then referred for etoposide and cisplatin-based chemotherapy. No disease recurrence was observed at the 6-month follow-up.Conclusion: We report a very rare and easily misdiagnosed case and we speculate that there were “undifferentiated cells” undergoing neuroendocrine and hepatocellular carcinoma differentiation, during which some hepatocellular carcinoma cells express neuroendocrine features. We recommend proper surgery and postoperative platinum-based chemotherapy in the management of this disease.

The Spectrum of Neuroendocrine Tumors: Histologic Classification, Unique Features and Areas of Overlap

2015 ◽  
pp. 92-103 ◽  
Author(s):  
David S. Klimstra ◽  
Himisha Beltran ◽  
Rogerio Lilenbaum ◽  
Emily Bergsland
Keyword(s):  
Neuroendocrine Tumors ◽  
Prostate Gland ◽  
Neuroendocrine Differentiation ◽  
Large Cell ◽  
Genetic Alterations ◽  
Neuroendocrine Cells ◽  
Neuroendocrine Neoplasms ◽  
Platinum Based Chemotherapy ◽  
Well Differentiated ◽  
Grade 3

Neuroendocrine neoplasms are diverse in terms of sites of origin, functional status, and degrees of aggressiveness. This review will introduce some of the common features of neuroendocrine neoplasms and will explore the differences in pathology, classification, biology, and clinical management between tumors of different anatomic sites, specifically, the lung, pancreas, and prostate. Despite sharing neuroendocrine differentiation and histologic evidence of the neuroendocrine phenotype in most organs, well-differentiated neuroendocrine tumors (WD-NETs) and poorly differentiated neuroendocrine carcinomas (PD-NECs) are two very different families of neoplasms. WD-NETs (grade 1 and 2) are relatively indolent (with a natural history that can evolve over many years or decades), closely resemble non-neoplastic neuroendocrine cells, and demonstrate production of neurosecretory proteins, such as chromogranin A. They arise in the lungs and throughout the gastrointestinal tract and pancreas, but WD-NETs of the prostate gland are uncommon. Surgical resection is the mainstay of therapy, but treatment of unresectable disease depends on the site of origin. In contrast, PD-NECs (grade 3, small cell or large cell) of all sites often demonstrate alterations in P53 and Rb, exhibit an aggressive clinical course, and are treated with platinum-based chemotherapy. Only WD-NETs arise in patients with inherited neuroendocrine neoplasia syndromes (e.g., multiple endocrine neoplasia type 1), and some common genetic alterations are site-specific (e.g., TMPRSS2-ERG gene rearrangement in PD-NECs arising in the prostate gland). Advances in our understanding of the molecular basis of NETs should lead to new diagnostic and therapeutic strategies and is an area of active investigation.

The efficacy and safety of the capecitabine/temozolomide (CAPTEM) regimen in the treatment of well-differentiated neuroendocrine tumors with liver metastasis after failure of previous therapy: Columbia University Medical Center experience.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 308-308
Author(s):  
Paul Eliezer Oberstein ◽  
Anthony Paul Gulati ◽  
Benjamin A Krantz ◽  
Rebecca Anne Moss ◽  
Stephen M. Schreibman ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Neuroendocrine Tumors ◽  
Medical Center ◽  
Performance Status ◽  
Columbia University ◽  
Ki 67 ◽  
Contrast Enhanced Ct ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Long Acting

308 Background: We have observed efficacy and tolerability of the CAPTEM regimen in pNET. We conducted a retrospective review of patients with liver metastasis from any NET, including carcinoid, who were treated with this regimen at our institution between 2002-2008. Methods: We identified patients with neuroendocrine tumors who demonstrated progressive liver metastasis while on treatment with long-acting octreotide (up to 60mg/month) and were then treated with CAPTEM as per our institutional protocol. Patients received capecitabine for 14 days at 1000mg PO bid with temozolomide at 150 or 200mg/m2 in bid dosing on days 10-14 of each 28 day cycle. All patients had contrast enhanced CT or MRI, response was assessed by a radiologist utilizing RECIST 1.0 criteria. Results: We identified 18 patients (50% female, median age- 55), 9 had pNET (2 functional, 7 non-functional), 2 had MEN1, 4 had carcinoid (1 functional), 2 with gastrinoma and 1 with glucagonoma. All patients had Ki-67 <10%, 11 patients (61%) had received previous chemotherapy (median of 2 regimens), and 50% had previous chemoembolization. Performance status at time of enrollment was 0-2 (5 patients, 28% with PS-2.)The response rate in the population was 61% (11/18) with 1 CR and 10 PR by RECIST 1.0 criteria. Stable disease was seen in 4 (22%) patients and clinical benefit (CR+PR+SD) in 83%. Response was noted in carcinoid patients (2 of 4, with 1 CR and 1 PR in this group) and in MEN1 patients (1 of 2 with PR). Median PFS was 14.0 months (range 4.2-18 months). Treatment was well tolerated; the most common grade 1/2 toxicities were lymphopenia (50%) and neutropenia (44%), 1 patient had hand-foot syndrome. Grade 3 thrombocytopenia was observed in 2 patients (11%), there was no other grade 3 or 4 toxicities. Conclusions: The CAPTEM regimen is well tolerated and is associated with a significant response in patients with liver metastasis from NET including the difficult to treat cases of carcinoid and MEN1. A prospective Phase II trial of this regimen is ongoing.

scholarly journals Amrubicin Monotherapy for Patients with Platinum-Refractory Gastroenteropancreatic Neuroendocrine Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Takayuki Ando ◽  
Ayumu Hosokawa ◽  
Hiroki Yoshita ◽  
Akira Ueda ◽  
Shinya Kajiura ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Platinum Refractory ◽  
Grade 3

Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, the role of salvage chemotherapy remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC.Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2007 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively.Results. Eight males and two females (median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n=7, 70%), cisplatin plus etoposide (n=2, 20%), and carboplatin plus etoposide (n=1, 10%) before amrubicin therapy. Median progression-free survival and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore, NEC with response for amrubicin had characteristics with a high Ki-67 index and receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4 neutropenia and anemia were observed in four and five patients, respectively.Conclusion. Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.

scholarly journals Immunophenotyping in incidental gastrointestinal neuroendocrine tumors: study at tertiary care centre

2020 ◽  
Vol 10 (2) ◽  
pp. 1751-1755
Author(s):  
Rachana R Lakhe ◽  
Ravi M Swami ◽  
Purva Kulkarni ◽  
Preeti Rajeev Doshi ◽  
Narayanan Subramanian Mani
Keyword(s):  
Neuroendocrine Tumors ◽  
Tertiary Care ◽  
Gastrointestinal Tumors ◽  
Common Site ◽  
Tertiary Care Centre ◽  
Ki 67 ◽  
Hematoxylin And Eosin ◽  
Diagnostic Modalities ◽  
Grade 3 ◽  
Slow Growing

Background: Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological, biological, and clinical characteristics that have increased in incidence and prevalence in the last few decades. This study is aimed to find out the incidence of neuroendocrine tumors among the gastrointestinal tumors and to grade gastrointestinal neuroendocrine tumors. Materials and Methods: A total of 119 cases of gastrointestinal tumors of gastrointestinal neuroendocrine was included in the study. The paraffin blocks were retrieved and slides were stained with routine Hematoxylin and Eosin, synaptophysin, chromogranin, and Ki67. The histologic grading was done based on mitosis and Ki-67 index as per WHO 2017 classification. Results: Out of 119 cases of Gastrointestinal Tract tumor, 13 (10.92%) constituted neuroendocrine tumors. Duodenum was the most common site (38%) followed by the appendix (23%). The majority (1.9%) of the cases were categorized as of grade 1 followed by 2.3% of grade 2 and 1.19% of grade 3.  Immunohistochemically, chromogranin, and synaptophysin were strongly expressed in all ten cases of neuroendocrine tumors. The Ki67 labeling index was <3 % in 10 cases, while it was in the range of 3 – 20 % in 2 cases and >20 % in one case. Conclusions: The incidence of gastrointestinal neuroendocrine tumors is on the rise. They should be considered in developing a differential diagnosis. Hence use of diagnostic modalities such as immunohistochemistry should be implemented for better treatment.

scholarly journals Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

2020 ◽  
Vol 9 (6) ◽  
pp. 1677
Author(s):  
Anna Pellat ◽  
Romain Coriat
Keyword(s):  
Digestive Tract ◽  
Neuroendocrine Tumors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Small Sample ◽  
World Health ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Metastatic Setting ◽  
Well Differentiated ◽  
Grade 3

The 2017 World Health Organization (WHO) classification of neuroendocrine neoplasms (NEN) of the digestive tract introduced a new category of tumors named well-differentiated grade 3 neuroendocrine tumors (NET G−3). These lesions show a number of mitosis, or a Ki−67 index higher than 20% with a well-differentiated morphology, therefore separating them from neuroendocrine carcinomas (NEC) which are poorly differentiated. It has become clear that NET G−3 show differences not only in morphology but also in genotype, clinical presentation, and treatment response. The incidence of digestive NET G−3 represents about one third of NEN G−3 with main tumor sites being the pancreas, the stomach and the colon. Treatment for NET G−3 is not yet standardized because of lack of data. In a non-metastatic setting, international guidelines recommend surgical resection, regardless of tumor grading. For metastatic lesion, chemotherapy is the main treatment with similar regimen as NET G−2. Sunitinib has also shown some positive results in a small sample of patients but this needs confirmation. Peptide receptor radionuclide therapy (PRRT) and immunotherapy could be future available treatments after ongoing studies. The goal of this review was to sum up the latest data on the epidemiology and management of digestive NET G−3.

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