Endocrine Abstracts

Background: Neuroendocrine tumors (NETs), also known as carcinoid, comprise a heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, most commonly originating from the gastrointestinal tract and lungs. Lung NETs originate from pulmonary neuroendocrine cells (PNECs) that occur as individual cells or small clusters, accounting for approximately 25% of primary lung neoplasms. Lungs NETs can be classified into four subtypes: well-differentiat...

Background: A small portion (11%) of radioactive decay of 177Lu involves the emission of gamma photons, allowing for post-treatment imaging. Despite this capability, most centers do not routinely conduct post-treatment imaging. It is not well recognized that qualitative findings from post-PRRT imaging can influence clinical management. The aim of this study was to evaluate the rate of change in management from post treatment imaging.Methods: 100 patients...

Background: To determine the safety and efficacy of Yttrium 90 (Y90) transarterial radioembolizations (TARE) for neuroendocrine liver metastasis (NLM) and elucidate factors that affect outcomes.Methods: Retrospective analysis of 39 patients with NLM in a single center who underwent 65 Y90 TAREs with glass or resin microspheres between April 2012 and December 2022. There were 17 male and 22 female with a mean age at time of treatment of 65.5 years (SD &pm...

Background: Pheochromocytoma/Paraganglioma (PPGL) are rare neuroendocrine tumors that expresses somatostatin receptors (SSTR) and can be treated with radiolabeled somatostatin analogues such as Lu-177-DOTATATE. Ga-68-DOTATATE PET scans show the distribution and density of SSTR+ tumors, and F-18-FDG PET scans show hypermetabolism in lesions. Total uptake volumes (TUV) for each respective scan can be obtained consistently and semi-automatically using standardized workflow in ima...

Background: Pheochromocytoma/Paraganglioma (PPGL) are rare neuroendocrine tumors that expresses somatostatin receptors (SSTR) and can be treated with radiolabeled somatostatin analogues such as Lu-177-DOTATATE. This study is the first prospective study to examine the safety and efficacy of Lu-177-DOTATATE in the treatment of metastatic or inoperable PPGL in a phase 2 clinical trial setting, and results from a planned interim analysis are presented.Method...

Background: GI neuroendocrine tumors express somatostatin (SSTR) receptors, and the radioloabeled SSTR analog Lu-177-DOTATATE is an FDA-approved systemic treatment for those with metastatic disease. Olaparib is a poly (ADP-ribose) polymerase inhibitor (PARPi) which inhibits cells from repairing damaged DNA, especially single-stranded DNA breaks caused by beta particle emissions from the radioactive decay of Lu-177. We report the first results of a phase 1/2 study evaluating th...

Background: The clinical heterogeneity of G2 and G3 well-differentiated GEP-NENs make it difficult to choose an effective treatment plan, highlighting the need of molecular imaging in the treatment of NETs patients. It has been suggested that a dual-tracer 68Ga-DOTATATE/18F-FDG grading scoring system could be a useful imaging biomarker. This pilot study aims to validate the prior observation from Chan et al. (BJC 2022) of variability in NETPET scores in G2-G3 WD GEP NENs and a...

Background: Expected progression free survival (PFS) for patients with grade 3 well-differentiated neuroendocrine tumors (WD NET) treated with peptide receptor radionuclide therapy (PRRT) is approximately 9 months, and objective response rate (ORR) is 35%. Response rate to single agent immune checkpoint inhibitors (ICI) for patients with G1-3 NET is <15%. Delivery of targeted radiation using PRRT may potentiate the anti-tumor immune response. The purpose of this study is t...

Background: Well-differentiated neuroendocrine tumors (WD-NET) have a relatively low tumor mutation burden and do not commonly express the programmed death ligand 1 (PD-L1), characteristics which may limit the anti-tumor activity of PD-L1 inhibitors in this disease. Response rate to single agent immune checkpoint inhibitors (ICI) for patients with G1-3 NET is <15%. The intensity of anti-tumor immune response may be enhanced by addition of liver-directed therapy (LDT), such...

Background: Radiation is a potent inducer of DNA double-strand breaks, and ribonucleotide reductase (RNR) is the rate-limiting enzyme in the synthesis and repair of DNA, making RNR-targeted therapy a rationale therapeutic strategy for radiosensitization. ETCTN 10388 (NCT04234568) evaluated safety and efficacy of the combination of lutetium 177 DOTATATE, a beta-emitting radionuclide in combination with triapine, a ribonucleotide reductase (RNR) inhibitor. <p class="abstext"...

Background: Radiolabeled somatostatin analogs provide a means of delivering targeted radiation with a high therapeutic index to NETs that express somatostatin receptors (SSTRs). We hypothesize that the addition of an effective radiation sensitizer could help improve the antitumor activity of Lutathera. Radiation is a potent inducer of DNA damage. The primary repair mechanism of radiation-induced double-stranded breaks (DSBs) is the nonhomologous end-joining (NHEJ) pathway, in ...

Background: 177Lutetium (Lu)-Dotatate is a safe and well tolerated treatment for metastatic gastroenteropancreatic (GEP) NETs. However, radiation can cause transient inflammation/swelling of tumors which can result in toxicity. Treatment-related small bowel obstruction associated with mesenteric or peritoneal disease has been described. We investigated the potential for intestinal ischemia in 177Lu-Dotatate treated patients.Methods:...

Background: Evaluating treatment (Tx) Response in NETs using CT/MRI scans can be difficult. Previous studies, including the E2211, have shown improved progression-free survival (PFS) but no significant difference in Rp as measured by RECIST 1.1 (R1.1) criteria. Therefore, it is difficult to determine Tx effectiveness with short-term imaging, further complicated by differences in imaging protocols and inter-reader variability. Incorporating tumor density, using smaller threshol...

Background: Metastatic pheochromocytomas and paragangliomas are rare neuroendocrine tumors with limited treatment options. We studied the efficacy and safety of off-label High-Specific-Activity I-131-meta-iodobenzylguanidine (HSA-I-131-MIBG) in routine clinical practice. Methods: This is a retrospective cohort study. The primary endpoint is objective response rate (ORR) as per RECIST v1.1. Secondary endpoints are blood pressure control, safety, overall a...

Background: Peptide receptor radionuclide therapy (PRRT) was introduced in 2018 as one of the major advances in treatment of patients with neuroendocrine neoplasms (NENs). Initial results from the NETTER-1 trial suggested a very low percentage of secondary hematological malignancies, including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We sought to confirm that data in a large institutional database. Methods: Under an institutio...

Background: Hormonally-refractory, lethal forms of PCa may express neuroendocrine features, including PCa with neuroendocrine differentiation (NEDPCa) and treatment emergent small cell neuroendocrine PCa (tSCNC). We hypothesize that some lethal metastatic PCa may show higher expression of SSTR than of PSMA and that a dual imaging approach with PET radiopharmaceuticals targeting these moieties will enable informed selection of patients for the future corresponding therapeutic r...

Background: Accurate imaging is essential for NETs. 111In-octreotide scintigraphy, 68Ga-DOTATOC PET/CT and 18F-FDG PET/CT are the most commonly used modalities. This study compared the three modalities to ascertain the added value of newer functional imaging approaches.Methods: A retrospective review was performed on patients who underwent 68Ga-DOTATOC PET/CT and 18F-FDG PET/CT between 07/2018 and 03/2023 as part of a clinical trial at BC Cancer. Patient...

Background: Metastatic paragangliomas (PGL) and pheochromocytomas (PCC) are rare neuroendocrine diseases with an incidence of 2 to 8 people per million, a prevalence between 1:2500 and 1:6500 and a strong hereditary disposition. However, due to the rarity of the disease, there is relatively limited data on treatment options, including radionuclide therapy using radioisotope analogs of MIBG and dotatate. There are a few published small series on clinical benefits of treating PG...

Background: 0.55T MRI is a new MRI technology offering increased patient accessibility with a wider bore (80cm) and reduced acoustic noise. We compared the sensitivity of liver metastases detection on gadoxetate-enhanced 0.55T MRI to 68Ga-DOTATATE PET/CT while evaluating patient experience.Methods: Nine patients with neuroendocrine liver metastases were imaged using gadoxetate-enhanced 0.55T MRI (MAGNETOM Free.Max, Siemens Healthineers, Erlang...

Background: Peptide receptor radionuclide therapy (PRRT) with Lutetium-177 DOTATATE (LUTATHERA) is an effective treatment option for somatostatin receptor (SSTR) positive metastatic gastroenteropancreatic neuroendocrine tumors (NETs) and has also demonstrated antitumor activity in SSTR positive NETs from other primary sites. While the median progression free survival (mPFS) is around 29 months, there is a subset of patients who are refractory to PRRT and demonstrate progressio...

Background: Lu177 DOTATATE Peptide Receptor Radionucleotide Therapy (PRRT) was FDA approved in the United States in 2018, however, the data for the safety and efficacy of repeat PRRT are almost exclusively from European centers. We present an updated experience with repeat PRRT in a cohort of US patients.Methods: We used our single-center longitudinal IRB approved neuroendocrine tumor (NET) registry to identify patients who had been previously treated wi...

Background: Clinicians are concerned about increased hepatotoxicity in patients who received hepatic artery bland embolizations (TAE) and subsequent Peptide Receptor Radionuclide Therapy (PRRT). The body of literature describing the safety of PRRT following prior TAE is very limited. The purpose of this study is to evaluate the degree of long-term liver toxicity in patients who received PRRT in addition to previous hepatic embolizations for liver dominant disease.<p class=...

Background: Peptide receptor radionuclide therapy (PRRT) is a form of targeted systemic radiopharmaceutical therapy that has been approved for treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Persistent hematologic dysfunction is a recognized potential long-term toxicity after PRRT, including the development of hematologic malignancies and persistent cytopenias. Therapy-related myeloid neoplasms (t-MN) are a well-recognized entity that ...

Background: Lutetitum-177 (Lu-DOTATE) is an approved treatment regimen for patients with advanced neuroendocrine tumors (NETs). Improving patient experience is one of main goals of a cancer treatment plan. "Time-toxicity" describes the period that patients spend in doing administrative or medical procedures, including medical visits, scans, lab analyses, emergency room admissions, drug applications and hospitalizations. Modern therapies are usually approved after an im...