scholarly journals Management of Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEPNETs): A Review

2017 ◽  
Vol 39 (11) ◽  
pp. 2146-2157 ◽  
Author(s):  
Gurleen Pasricha ◽  
Parikshit Padhi ◽  
Nour Daboul ◽  
Dulabh K. Monga
Keyword(s):  
Neuroendocrine Tumors ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Well Differentiated

Gastroenteropancreatic neuroendocrine tumors: clinicopathological evaluation at Shifa International Hospital, Islamabad. A single centre experience

2020 ◽  
pp. 1-14
Author(s):  
Nadira Mamoon ◽  
Hania Naveed ◽  
Mariam Abid ◽  
Humaira Nasir ◽  
Imran Nazir Ahmad ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Neuroendocrine Carcinoma ◽  
World Health ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Single Centre Experience ◽  
Who 2010 Classification ◽  
Well Differentiated ◽  
Grade 3 ◽  
Health Organization

Abstract Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have rarely been studied in the Pakistani population. We investigated the clinical characteristics of these tumors according to the updated World Health Organization (WHO) 2010 classification. Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018. Results: One hundred and eighteen patients (mean age, 52.2 years; male, 55.1%) were identified. 83.1% of the patients were symptomatic including5.1% functional tumors. Pancreas (28%) was the most frequent primary site noted. The most common histologic type was well differentiated neuroendocrine tumor (WDNET) in 81.4% followed by neuroendocrine carcinoma (NEC) in 16.1%. 45.8% cases of WDNET were grade 1, 27.1% were grade 2, and 8.5% were grade 3.15.3% had distant metastasis at the time of diagnosis with liver (77.7%) as the most common metastatic site. Synaptophysin positivity was seen in 96.8% of grade 1 & grade 2 WDNET, 100% of grade 3 WDNET and 92.3% of NEC and chromogranin was positive in 94.2% of grade 1 &grade 2 WDNET, 83.3% of grade 3 WDNET and 45.4% of NEC. Conclusion: GEP-NETs showed a wide clinicopathological spectrum. Pancreas is the most site of involvement by the GEP-NET however grade 3 WDNET had a predilection for the colon. Small cell carcinomas were commonly observed in esophagus. Keywords: Gastroenteropancreatic neuroendocrine tu­mor, well differentiated neuroendocrine tumor, neuroendocrine carcinoma. Continuous...

Treatment response and clinical outcomes of well-differentiated high-grade neuroendocrine tumors to 177Lu-DOTATATE.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 368-368
Author(s):  
Kelley Lauren Coffman ◽  
Lisa Bodei ◽  
Tiffany Le ◽  
Ye Choi ◽  
Joanne F. Chou ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Stable Disease ◽  
Tumor Tissue ◽  
Somatostatin Receptor ◽  
Response To Treatment ◽  
High Grade ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Best Response ◽  
Well Differentiated

368 Background: 177Lu-DOTATATE is an approved therapy for somatostatin receptor (sstr) positive gastroenteropancreatic neuroendocrine tumors (NETs). There are little data available on response and outcomes for well differentiated (WD) high grade (HG) NETs treated with 177Lu-DOTATATE. Methods: Pts with WD HGNETs treated with 177Lu-DOTATATE at MSK from 2018-2020 were identified. Demographics, response to treatment, and progression-free survival (PFS) were determined. In pts with archival tumor tissue, next-generation sequencing (NGS) was performed through an institutional platform (MSK-IMPACT). Results: 19 pts were identified (mean age 54, 63% female). Site of tumor origin included: pancreas (14/19, 74%), small bowel (2/19, 10.5%), rectal (2/19, 10.5%), lung (1/19, 5%). Average tumor Ki-67 was 34.8 (range 22-56). All tumors were sstr avid on pre-treatment Ga68-DOTATATE PET/CT; none of the patients had sstr negative lesions detected. Median number of prior treatments (systemic and/or liver-directed) was 4 (range 2-7). All pts had progressive disease prior to initiation of 177Lu-DOTATATE. 13 pts (68%) completed all four treatment cycles; treatment was incomplete in 6 pts due to treatment-related toxicities (n = 3) and clinical progression (n = 3). Best response by radiographic report was available in 16 patients (84%):10/16 (63%) with partial response, 1/16 (6%) with stable disease, 5/16 (31%) with disease progression. One pt with stable disease as best response received two additional cycles of 177Lu-DOTATATE at progression. Median PFS (from date of first treatment with 177Lu-DOTATATE until progression/death) was 11.1 months (95% CI 10.6 to NA). Five pts (26%) experienced dose modifying toxicity with 177Lu-DOTATATE. The most common treatment-related toxicities were thrombocytopenia (9 pts, 47%; G3/4 in 1 pt, 5%), anemia (7 pts, 37%; G3/4 in 2 pts, 10.5%), leukopenia (6 pts, 32%; G3/4 in 0 pts), and AST/ALT elevation (4 pts, 21%; G3/4 in 0 pts). NGS results were available in the tumor tissue of 13 pts (68%). The most commonly observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations were identified. Conclusions: We observed a meaningful disease control rate of 69% during treatment of WD HGNETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of pts received all four treatment cycles with treatment-related toxicities largely bone-marrow related, as expected, based on historical data. As would be expected in sstr avid tumors, the vast majority had alterations in chromatin remodeling genes (MEN1, DAXX) consistent with WD NETs, with no RB1 alterations identified.

Somatostatin analogs in association with peptide receptor radionucleotide therapy in advanced well-differentiated NETs

2019 ◽  
Vol 15 (26) ◽  
pp. 3015-3024
Author(s):  
Natalie Prinzi ◽  
Alessandra Raimondi ◽  
Marco Maccauro ◽  
Massimo Milione ◽  
Enrico Garanzini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Peptide Receptor ◽  
Treatment Beyond Progression ◽  
Well Differentiated

Aim: Data from 69 well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy + somatostatin analogs (SSAs) after SSA treatment failure were evaluated. Methods: We identified two groups: S1 – patients who kept the same SSA treatment beyond progression; S2 – patients who switched the SSA with another SSA after progression. Results: Median progression-free survival was 53 and 127 months in S1 and S2, respectively (p = 0.001; hazard ratio: 0.31; 95% CI: 0.15–0.63). Median overall survival was 69 versus 150 months in S1 and S2, respectively (p = 0.004; hazard ratio: 0.32; 95% CI: 0.14–0.71). Conclusion: In patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy plus SSA after SSA failure, the ‘switch’ strategy of SSA after progression improve progression-free survival and overall survival.

scholarly journals Novel therapeutics for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors

2021 ◽  
Vol 13 ◽  
pp. 175883592110180
Author(s):  
Satya Das ◽  
Arvind Dasari
Keyword(s):  
Dna Damage ◽  
Neuroendocrine Tumors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Somatostatin Receptor ◽  
Single Agent ◽  
Development Spectrum ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Alpha Emitter ◽  
Well Differentiated

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) represent the most common subtype of NETs. The incidence of all NETs, and specifically GEP NETs, has risen exponentially over the last three decades. Only within the past several years have these tumors been appropriately classified, allowing for meaningful drug development. Broadly, some of the most exciting drug classes being developed for patients with well-differentiated GEP NETs include newer types of peptide receptor radionuclide therapy (PRRT) or combinations which increase the potency of lutetium-177 (177Lu)-Dotatate, novel multi-target receptor tyrosine kinase inhibitors (RTKIs) and immunotherapy modalities, beyond checkpoint inhibitors, which seek to unleash the immune system against NETs. Specifically looking at newer types of PRRT, somatostatin receptor antagonists and alpha-emitter radionuclides each have demonstrated the ability to elicit greater DNA damage than 177Lu-Dotatate in preclinical models. Early clinical experiences with each of these agents suggest they may be more cytotoxic than 177Lu-Dotatate. Other approaches seeking to build upon the DNA damage created by 177Lu-Dotatate include combinations of PRRT with radiosensitizers such as heat shock protein 90 inhibitors, hedgehog inhibitors, chemotherapy combinations, and triapine. Many of these combinations have just begun to be tested clinically. With regards to novel RTKIs, some of the ones which have demonstrated potent cytoreductive potential include cabozantinib and lenvatinib. Other RTKIs which are further along the clinical development spectrum and have demonstrated benefit in randomized trials include surufatinib and pazopanib. And though single-agent immune checkpoint inhibitors have not demonstrated significant anti-tumor activity in patients with GEP NETs, outside of certain biomarker selected subsets, somatostatin receptor-directed chimeric antigen receptor (CAR) T cells and vaccines such as SurVaxM, which targets survivin, represent two means through which NET-directed immunity may be modulated. The potential of these agents, if clinically realized, will likely improve outcomes for patients with well-differentiated GEP NETs.

scholarly journals Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayank Patel ◽  
Isabel Tena ◽  
Abhishek Jha ◽  
David Taieb ◽  
Karel Pacak
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Rare Condition ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Well Differentiated ◽  
Succinate Dehydrogenase Subunit B

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.

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