A case of enterochromaffin-like cell neuroendocrine tumor associated with parietal cell dysfunction which was successfully treated with somatostatin analogue

Several important landmark trials have reshaped the landscape of non-surgical management of small bowel neuroendocrine tumors over the last few years, with the confirmation of the antitumor effect of somatostatin analogue therapy in PROMID and CLARINET trials as well as the advent of therapies with significant potential such as mammalian target of rapamycin inhibitor (mTor) everolimus (RADIANT trials) and peptide receptor radionuclide therapy (PRRT) with 177-Lutetium (NETTER-1 trial). This narrative summarizes the recommended management strategies of small bowel neuroendocrine tumors. We review the main evidence behind each recommendation as well as compare and contrast four major guidelines, namely the 2016 Canadian Consensus guidelines, the 2017 North American Neuroendocrine Tumor Society guidelines, the 2018 National Comprehensive Cancer Network guidelines, and the 2016 European Neuroendocrine Tumor Society guidelines. Different clinical situations will be addressed, from loco-regional therapy to metastatic unresectable disease. Carcinoid syndrome, which is mostly managed by somatostatin analogue therapy and the serotonin antagonist telotristat etiprate for refractory diarrhea, as well as neuroendocrine carcinoma will be reviewed. However, several questions remain unanswered, such as the optimal management of neuroendocrine carcinomas or the effect of combining and sequencing of the aforementioned modalities where more randomized controlled trials are needed.

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Ectopic ACTH-secreting neuroendocrine tumor

Orvosi Hetilap ◽

10.1556/oh.2011.29053 ◽

2011 ◽

Vol 152 (10) ◽

pp. 403-406

Author(s):

Attila Szabó ◽

Péter Igaz ◽

Róbert Kiss ◽

Gergely Lakatos ◽

Ibolya Varga ◽

...

Keyword(s):

Neuroendocrine Tumor ◽

Plasma Cortisol ◽

Clinical Symptoms ◽

Residual Tumor ◽

Histological Evaluation ◽

Ectopic Acth Syndrome ◽

Somatostatin Analogue ◽

Repeat Surgery ◽

Ectopic Acth ◽

Acth Secreting

The authors report a case of an ectopic ACTH-syndrome that resulted in severe hypercortisolism, hypokalemia, diabetes mellitus and osteoporosis. The ACTH-secreting tumor tissue was localized in the lung. The tumor was removed by segmentectomy and histological evaluation revealed an ACTH-secreting neuroendocrine tumor. After surgery, however, plasma cortisol and ACTH levels failed to decrease significantly due to subtotal tumor removal. Long-acting somatostatin analogue therapy resulted in a normalization of both plasma cortisol and ACTH levels and the clinical symptoms improved significantly. Residual tumor was removed by repeat surgery and the patient was permanently cured. Orv. Hetil., 2011, 152, 403–406.

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Contemporary nuclear medicine diagnostics of neuroendocrine tumors

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1502108t ◽

2015 ◽

Vol 143 (1-2) ◽

pp. 108-115 ◽

Cited By ~ 2

Author(s):

Mila Todorovic-Tirnanic ◽

Vera Artiko ◽

Smiljana Pavlovic ◽

Dragana Sobic-Saranovic ◽

Vladimir Obradovic

Keyword(s):

Neuroendocrine Tumor ◽

Intravenous Injection ◽

Neuroendocrine Tumors ◽

Tumor Imaging ◽

Somatostatin Receptor ◽

Somatostatin Analogue ◽

Scintillation Camera ◽

Contemporary Method ◽

Pet Ct ◽

Conventional Methods

The new positron emission tomography (PET/CT) methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In-pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline analogue labeled with iodine-131 or -123 (131I/123I-MIBG); or 3) 99mTc(V)-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F), galium-68 (68Ga), or carbon-11 (11C)]: 1) glucose analogue (18FDG); 2) somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC); 3) aminoacid precursors of bioamines: [a) dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine), b) serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan)]; or 4) dopamine analogue 18F-DA (6-18F-fluorodopamine). Conventional and contemporary (PET/ CT) somatostatin receptor detection showed identical high specificity (92%), but conventional had very low sensitivity (52%) compared to PET/CT (97%). It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic) method. In metastatic pheochromocytoma detection contemporary (PET/ CT) methods (18F-DOPA and 18F-DA) have higher sensitivity than conventional (131I/123I-MIBG). In medullary thyroid carcinoma diagnostics contemporary method (18F-DOPA) is more sensitive than conventional 99mTc(V)-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA) shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET/CT) methods for somatostatin receptor detection (68Ga-DOTATOC/-NOC/-TATE) in neuroendocrine tumors are much more sensitive (almost twice) and more accurate than conventional. Therefore the classical methods should be urgently replaced by contemporary methods.

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Etctn 10388: A phase I trial of triapine and lutetium Lu 177 dotatate in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4660 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS4660-TPS4660

Author(s):

Aman Chauhan ◽

Charles Kunos ◽

Riham El Khouli ◽

Jill Kolesar ◽

Heidi Weiss ◽

...

Keyword(s):

Antitumor Activity ◽

Neuroendocrine Tumor ◽

Neuroendocrine Tumors ◽

Somatostatin Receptor ◽

Phase Iii ◽

Somatostatin Analogue ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Potent Inducer ◽

Radiation Sensitizer ◽

Well Differentiated

TPS4660 Background: Radiolabeled somatostatin analogues provide a means of delivering targeted radiation with a high therapeutic index to NETs that express somatostatin receptors (SSTRs). Radiolabeled somatostatin analogue Lutetium Lu 177 Dotatate (Lutathera) is a beta-emitting radionuclide, recently FDA approved for use in SSTR positive gastroenteropancreatic neuroendocrine tumors (GEPNETS) in the US based on the NETTER-1 Phase III trial. Despite favorable PFS and safety profile, the drug has limited cytoreductive capability with a 17% ORR. We hypothesize that addition of an effective radiation sensitizer could help improve antitumor activity of Lutathera. Ribonucleotide reductase (RNR) is the only enzyme responsible for conversion of ribonucleoside diphosphate to deoxyribonucleotide diphosphate (dNDP), the key building blocks for DNA synthesis. Radiation is a potent inducer of DNA double-strand breaks (DSBs), and RNR is the rate-limiting enzyme in the repair of DNA in this setting. Triapine is an inhibitor of RNR. This study will test the hypothesis that radiation sensitizer triapine can be safely combined with peptide receptor radionuclide therapy and ultimately may improve antitumor activity of Lutetium Lu 177 Dotatate. Methods: This study is an investigator initiated, NCI sponsored, multicenter phase 1 trial of triapine and Lutetium Lu 177 Dotatate in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumor (GEP-NETs) after the failure of at least one line of prior systemic cancer treatment. A total of 29 patients will be enrolled in the dose escalation with help of Bayesian optimal interval design (BOIN) and dose expansion cohorts. The study will be open through the NCI ETCTN (National Cancer Institute Experimental Therapeutics Clinical Trials Network) program. Patients will be treated with 177 lutetium dotatate in combination with triapine. Triapine will be administered orally (100 mg once a day starting dose) from D1-14 with each dose of PRRT [200 mCi]. Primary endpoint is to evaluate recommended phase II dose (RP2D). Secondary endpoints are to evaluate safety, pharmacokinetics, and clinical activity (ORR and PFS). We are also evaluating NETEST, a novel blood based test that evaluates levels of 51 neuroendocrine tumor gene transcripts. In addition, the study will correlate clinical outcome with baseline somatostatin receptor density, somatic tumor mutations and germline mutations. Clinical trial information: 04234568 .

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