Search Results (38)

Somatostatin is a potent endocrine regulator and neurotransmitter, exerting predominantly inhibitory effects in different tissues of the body, via G-protein coupled receptors. Five such specific receptors have been identified, with different effects and tissue distribution. The multifaceted actions and effects of somatostatin make it useful as a potential therapeutical means in various pathologies; however, in clinical practice, somatostatin analogues, namely octreotide, lanreotide and pasireotide, are commonly used instead, due to their increased half-life and increased receptor selectivity, with pasireotide showing a more extensive receptor binding profile and high affinity for somatotastin receptor (SSTR) 5, which may prove effective in cases of resistance to first-generation analogues. Apart from their many uses in neoplastic pathologies, somatostatin analogues represent viable treatment choices in some ocular pathologies, congenital hyperinsulinism, gastrointestinal bleedings and portal hypertension, acute pancreatitis, and dumping syndrome. They have also been used in some cases, with varying degrees of success, in patients with post-surgical gastrointestinal and lymphatic fistulas, refractory chronic diarrhoea and polycystic kidney disease; many applications in paediatric patients have also been documented. The aim of this review is to present the applications of somatostatin and its analogues as alternative or second-line therapies, along with insights into their effectiveness and future potential. Full article

Background/Objectives: Metabolic alterations, including dyslipidemia, may influence tumor biology and treatment outcomes in neuroendocrine tumors. However, the clinical relevance of dyslipidemia and lipid-lowering therapy in bronchopulmonary neuroendocrine tumors (BP-NETs) treated with somatostatin analogues (SSAs) remains poorly defined. This translational proof-of-concept study evaluated progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs according to dyslipidemia and statin therapy and explored the effects of statin-SSA combination treatment in vitro. Methods: We retrospectively analyzed 24 patients with advanced well-differentiated BP-NETs treated with SSAs as first-line therapy. Fourteen patients (58.3%) had dyslipidemia, and 11 of them were receiving statins. In parallel, NCI-H727 cells were treated with atorvastatin (10 µM), lanreotide (5 or 10 µM), or their combination for 48–72 h. Cell viability, proliferation, cell death, apoptosis, DNA damage, and ATP production were assessed. Results: Median PFS was 22.5 months overall. A trend toward longer PFS was observed in non-dyslipidemic vs. dyslipidemic patients (70 vs. 36 months, p = 0.08). Among dyslipidemic patients, statin therapy was associated with a non-significant trend toward longer PFS compared with no statin therapy (36 vs. 18 months, p = 0.30). In vitro, combined atorvastatin–lanreotide treatment reduced cell viability and proliferation, increased cell death, enhanced cleaved caspase-3 and p-γH2AX expression, and reduced ATP production. Conclusions: These findings support the potential relevance of lipid metabolism modulation as an adjunct strategy in advanced BP-NETs while highlighting the need for larger prospective studies and dedicated biochemical investigation of the underlying lipid-related pathways. Full article

Grade 1–2 pancreatic neuroendocrine tumors exhibit considerable biological and clinical diversity, which translates into a broad range of available therapeutic approaches. Given the absence of a universally accepted treatment sequence, treatment selection requires a practical framework based on tumor biology and clinical presentation. Clinical management should be individualized by integrating the histologic grade, disease extent, symptom burden, and somatostatin receptor (SSTR) expression. For patients with low-volume, SSTR-positive, and clinically indolent disease (Ki-67 < 10%), long-acting somatostatin analogues, including octreotide and lanreotide, are commonly used as initial therapies to control hormonal symptoms and delay tumor progression. In patients with radiologic progression requiring systemic disease control, targeted agents such as everolimus and sunitinib represent established subsequent options, particularly when disease stabilization is the primary therapeutic goal. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE has demonstrated meaningful antitumor activity and is generally considered in patients with SSTR-positive tumors with progressive disease (Ki-67 ≥ 10%) or increasing tumor burdens, especially when tumor reduction is desirable. Combination cytotoxic chemotherapy, most notably the capecitabine–temozolomide (CAPTEM) regimen, remains an important consideration for patients with higher tumor burdens or more aggressive tumor biology. This review summarizes current evidence and provides a practical overview of treatment selection and sequencing for the systemic management of Grade 1–2 pancreatic neuroendocrine tumors, while also highlighting emerging therapeutic strategies, including targeted alpha therapy and SSTR2 antagonist-based approaches. Full article

Background: Pancreatic neuroendocrine tumor (pNET) is a rare and complex disease that requires careful management and treatment. Currently, a range of treatments, including surgery, somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy, exist for pNETs. However, determining the optimal treatment strategies remains challenging. Aim: To evaluate the efficacy and safety of non-surgical therapies, such as somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy in treating pNETs. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science databases for relevant studies published from inception until August 2025. Randomized clinical trials (RCTs), non-randomized clinical trials, and prospective studies were included in this meta-analysis if they evaluated the efficacy and safety of any treatment of interest in patients with pNETs. Results: Thirty-three studies involving 2374 pNET patients were analyzed. Targeted therapies showed modest objective response rates (ORRs) but high disease control rates (DCRs): everolimus (ORR 7%, 95% CI: 3–10%; DCR 81%, 95% CI: 75–87%), sunitinib (ORR 12%, 95% CI: 5–19%; DCR 79%, 95% CI: 70–88%), surufatinib (ORR 19%, 95% CI: 12–27%; DCR 81%, 95% CI: 73–89%). Cytotoxic chemotherapy demonstrated higher ORRs: dacarbazine-based (32%, 95% CI: 21–43%), streptozocin-based (40%, 95% CI: 25–54%), temozolomide-based (42%, 95% CI: 29–55%). PRRT showed varying efficacy: ¹⁷⁷Lu-DOTATATE (ORR 36%, 95% CI: 27–44%; DCR 84%, 95% CI: 76–92%), ⁹⁰Y-DOTATOC (ORR 27%, 95% CI: 18–36%; DCR 73%, 95% CI: 63–83%). SSAs had low ORRs but high DCRs: lanreotide (ORR 0%, DCR 67%, 95% CI: 57–77%), octreotide (ORR 23%, 95% CI: 15–31%; DCR 75%, 95% CI: 66–84%). Immunotherapy with pembrolizumab showed limited efficacy (ORR 7%, 95% CI: 0–14%). Treatment-related adverse events were common across therapies, with specific toxicity profiles for each modality. Conclusions: Cytotoxic chemotherapy offers better response rates than other treatment modalities. However, toxicity management is crucial. PRRT also shows robust antitumor activity and disease control, while SSAs and targeted therapies are effective treatment options for disease stabilization. Immunotherapy demonstrated limited antitumor activity, and further research is needed to establish its role in pNET treatment. Full article

Acromegaly is associated with a higher risk of certain malignancies, but not hematological neoplasia, although multiple myeloma (MM) was found in very limited cases. We aim to present such a case, adding a particular presentation with co-occurrence of a plasmocytoma. A 52-year-old male with acromegaly confirmed at 46 (MRI: pituitary macroadenoma of 12 × 11 × 10 mm) underwent hypophysectomy followed by 3 years of octreotide LAR then lanreotide depot. After another 6 months, he experienced a rapidly growing, painful lump in the right lateral thoracic area confirmed by CT as a 9-cm osteolytic lesion at the third rib. Core biopsy revealed plasmocytoma of the bone and medullary biopsy confirmed MM. Plasmacytoma was managed with 10 radiotherapy sessions, with favorable outcome and mass resorption; MM was managed with a VRD regimen, followed by autologous hematopoietic stem-cell transplantation. Six months after sFLC normalization and plasmacytoma resorption, complete remission was reported. In the meantime, lanreotide was continued, with complete acromegaly control. To conclude, what started as a rather typical scenario for an otherwise rare condition, as is acromegaly in the general population (but not so rare for endocrinologists), turned into an unexpected and more severe outcome. Noting this exceptional association, we pinpoint that further research is needed for understanding the dual acromegaly–MM relationship. Full article

Background: Parathyromatosis, an exceptional clinical and pathological entity, involves multiple small nodules of hyper-functional parathyroid tissue scattered throughout the neck and/or mediastinum, in relationship with a prior parathyroidectomy (mostly) or embryologic remnant. Since its first identification in 1975, many aspects of this condition have remained a matter of debate. Objective: We introduce an updated perspective on parathyromatosis covering the main clinical points for everyday practice, from diagnosis to management, as well as the current level of pathogenic understanding. Methods: A narrative review. Results: A total of 22 patients were identified, with the following characteristics: an age range of 33–68 (mean 46.18) years; 4/22 subjects <40 years; female-to-male ratio = 14:8. Of the 22 subjects, 21 had undergone previous parathyroidectomy for primary (n = 14) or secondary (n = 7) hyperparathyroidism. One case was a surgically naïve patient. Analysis of the surgical procedures (seeding circumstances) revealed the following: parathyroid cyst removal, left/right parathyroidectomy; removal of 3.5 parathyroids ± self-transplantation, VATS for mediastinal parathyroid tumours. Parathyroidectomy was accompanied by thyroid surgery (n = 3 patients), specifically hemi-thyroidectomy, partial left-thyroid lobectomy, and partial thyroidectomy. The shortest timeframe from parathyroidectomy to parathyromatosis-related hyperparathyroidism recognition was 1 year, and the longest was 17 years. The highest number of previous surgeries was four. The recognition of parathyromatosis was due to the clinical picture of associated hyperparathyroidism, except for in 2/21 cases with incidental detection. The implant sites coincided with the prior surgical area, but also with unusual locations (clavicle, pleura, mediastinum, sternocleidomastoid muscle and forearm, thyroid). The imaging evaluation included ultrasound plus CT plus 99m-Tc sestamibi scintigraphy, as well as (variable rates) neck MRI, SPECT/CT, 11-Choline PET-CT, Gallium-68 DOTATATE, and 4D CT. Surgery implied serial procedures in some cases (e.g., up to seven). The surgery spectrum largely varied, including not only cervicotomy, but also thoracoscopy, VATS, pericardial adipose tissue excision and thymectomy, etc. Conclusions: Awareness remains a key factor when approaching such an unusual ailment underlying little-understood pathogenic loops, which, if left unrecognized and untreated, might impair patients’ quality of life and the overall parathyroid disease burden. Full article

Background and Clinical Significance: Carcinoid tumors are rare, slow-growing neuroendocrine cell neoplasms that typically affect the gastrointestinal tract. While metastasis may occur, it most commonly occurs in the liver, and orbital metastasis is extremely rare, especially while on systemic somatostatin suppression. Case Presentation: A 57-year-old man with a history of gastrointestinal carcinoid tumor treated with lanreotide for 5 years presented with a left proptotic, red eye and double vision for several months. Clinical examination revealed left proptosis, supraduction deficit, lower lid retraction, and dilated episcleral vessels inferiorly. Magnetic resonance imaging demonstrated a 1.8 cm enhancing lesion centered within the left inferior rectus muscle. Left orbitotomy and biopsy were performed, which confirmed metastatic carcinoid tumor. He will undergo localized orbital radiation and substitution of lanreotide with systemic chemotherapy. Conclusions: Orbital metastasis of carcinoid tumor is extremely uncommon. Given its rarity, diagnosis may be challenging. In patients presenting with ocular complaints including chronic red eye, double vision, proptosis, and mass effect with a prior history of neuroendocrine cancer, a high index of suspicion for orbital metastasis is necessary with timely workup and treatment even if the disease has been otherwise well-controlled with somatostatin analogs. Full article

Introduction: Bronchopulmonary Neuroendocrine Neoplasms (NEN) occur in 2–7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions have been identified for MEN1-related pancreatic, duodenal, and gastric NEN. The aim of the current study using a MEN1 mouse model was to define the precursor lesions of bronchopulmonary NEN and evaluate the potential prophylactic antitumor effects of somatostatin analogues in a transgenic MEN1 mouse model. Methods: Fifteen mice, germline heterozygous for Men1(+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel^®, IPSEN Pharma), while 15 mice were treated with subcutaneous injections of physiologic sodium chloride as the control group. Five mice from each group were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and evaluated after hematoxylin and eosin staining and immunohistochemistry for synaptophysin and chromogranin A. Results: In the lungs of the 30 evaluated mice, whether treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia was detected through histopathology. However, pulmonary adenocarcinoma developed in 2 (13%) of the 15 untreated mice and in 1 (7%) of the 15 lanreotide-treated mice. Conclusions: Heterozygous Men1(+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail. Full article

Objectives: The aim of this study was to investigate the treatment patterns and outcomes in two propensity score-matched cohorts of patients with neuroendocrine tumours (NETs) treated with first-line somatostatin analogue (SSA). Methods: Metastatic NET patients treated with first-line SSA (2009–2022) were retrospectively examined. First-line lanreotide vs. octreotide cohorts were matched 1:1 by propensity scores for demographics, tumour characteristics, and diagnosis year. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier analysis and the Cox proportional hazards model. Results: Among 441 patients, 310 were matched (155 in both the octreotide and lanreotide groups). First-line SSA was monotherapy (63.5%) or combination with other medications (36.5%). A total of 77% of second-line patients (188/244) maintained their initial SSA medication in combination with other therapies. Radioligand therapy with lanreotide (N = 72; 29.5%) or octreotide (N = 70; 28.7%) was the most common second-line treatment. First-line lanreotide and octreotide cohorts had similar median PFS (15.5; 95% CI: 13.6–19.1 vs. 14.0; 95% CI: 12.0–15.8 months), despite octreotide having a 36% higher likelihood of moving to the second line than lanreotide (95% CI: 1.05–1.76, p = 0.018). Multiple metastases (HR = 1.45; p = 0.004, 95% CI: 1.13–1.87) and Ki-67 > 20% (HR = 2.34; p < 0.001, 95% CI: 1.43–3.83) were significantly associated with the worst PFS. First-line lanreotide patients had a median OS of 10.4 years (95% CI: 7.5-NA) and octreotide 9.2 years (95% CI: 7.3-NA) (p = 0.537). Bone metastases increased death risk by 91% (p = 0.014; 95% CI: 1.14–3.20). Conclusions: SSA monotherapy is the main first-line treatment and most subsequent treatments include SSA with additional medications. Cohorts had similar PFS/OS, but octreotide demonstrated a 36% significantly higher likelihood of moving to the second-line treatment. Full article

Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, due, in the vast majority of cases, to the presence of a GH-secreting pituitary tumour. The chronic elevation of GH and the resulting high circulating levels of insulin-like growth factor-1 (IGF-1) cause the characteristic tissue overgrowth and a number of associated comorbidities, including several metabolic changes, such as glucose intolerance and overt diabetes mellitus (DM). Elevated GH concentrations directly attenuate insulin signalling and stimulate lipolysis, decreasing glucose uptake in peripheral tissues, thus leading to the development of impaired glucose tolerance and DM. Acromegaly treatment aims to normalize plasma GH and IGF-1 levels using surgery, medical treatment, or radiotherapy. The effect of the different medical therapies on glucose homeostasis varies. This literature review explores the impact of the currently available pharmacological therapies for acromegaly (first- and second-generation somatostatin receptor ligands, a GH receptor antagonist, and dopamine agonists) on glucose homeostasis. We also discuss the underlying biological mechanisms through which they impact glucose metabolism. Full article

Regulatory authorities typically require bioequivalence to be demonstrated by comparing pharmacokinetic parameters like area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C_max). Because in certain cases, AUC and C_max alone may not be adequate to identify formulation differences in early and/or late segments of the dosing interval, partial AUCs (pAUCs) have been proposed as additional metrics to evaluate bioequivalence. Even though cut-off points for pAUCs are usually decided based on clinical relevance, the identification of the correct cut-off range remains elusive in many other cases and tends to contribute to increased pAUC estimate variabilities. The choice of meaningful cut-off points in pAUC estimates can be especially difficult in the case of long-acting injectable (LAI) products, where long dosing intervals and complex pharmacokinetic (PK) and pharmacodynamic (PD) profiles apply, but most importantly, because there is not always a clear PK/PD relationship established. In this communication, authors discuss the usefulness and challenges associated with the estimation of pAUCs in the development of generic LAI products through the review of six case studies under the lens of regulatory requirements from the two major authorities, namely the FDA and EMA. Full article

Background/Objectives: Pasireotide (PAS) is a somatostatin receptor ligand (SRL) used to treat acromegaly, a chronic condition caused by excess growth hormone. While it offers significant benefits as a second-line treatment for uncontrolled acromegaly, its use raises major concerns due to hyperglycemic side effects and gastrointestinal issues, the latter being similar to those seen with first-generation SRLs. The aim of this study is to evaluate the real-world evidence on adverse drug reactions (ADRs) reported for PAS in the EudraVigilance database, in comparison to other established drug-based therapies for acromegaly. Methods: A descriptive analysis and a disproportionality analysis were conducted. Results: The fewest individual case safety reports (ICSRs) and adverse drug reactions (ADRs) were reported for PAS, with 698 (4%) ICSRs and 1,647 (4%) ADRs, which is even lower than for pegvisomant (PEG), which had 1765 (11%) ICSRs and 4842 (10%) ADRs. Both PAS and lanreotide (LAN) exhibited the lowest proportion of cases classified as serious. Among the total reported ADRs, those categorized as “Metabolic and nutrition disorders” were most frequent and severe for PAS (PAS—17.5% vs. OCT—4.6%, LAN—4.5%, and PEG—2.7%). Additionally, PAS demonstrated a higher likelihood of reporting endocrine disorders, which were frequently classified as serious, as well as stones affecting the hepatobiliary system compared to other drugs. Conclusions: Although PAS had the fewest ICSRs and ADRs, and less frequent serious ADRs, it had more reports frequently classified as serious in the “Metabolism and Nutrition Disorders” category (including events such as elevated blood glucose levels or diabetes) and “Endocrine Disorders” category compared to other SRLs and PEG. Furthermore, there was a higher likelihood of reporting hepatobiliary stones with PAS compared to OCT and PEG. This highlights the importance of adequately monitoring glycemic control and the biliary tract through ultrasound at the initiation and during follow-up of PAS therapy. Improved monitoring and reporting of these ADRs could enhance care for patients with acromegaly. Full article

The CLARINET trial led to the approval of lanreotide for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (NETs). It is hypothesized that lanreotide regulates proliferation, hormone synthesis, and other cellular functions via binding to somatostatin receptors (SSTR1–5) present in NETs. However, our knowledge of how lanreotide affects the immune system is limited. In vitro studies have investigated functional immune response parameters with lanreotide treatment in healthy donor T cell subsets, encompassing the breadth of SSTR expression, apoptosis induction, cytokine production, and activity of transcription factor signaling pathways. In our study, we characterized in vitro immune mechanisms in healthy donor T cells in response to lanreotide. We also studied the in vivo effects by looking at differential gene expression pre- and post-lanreotide therapy in patients with NET. Immune-focused gene and protein expression profiling was performed on peripheral blood samples from 17 NET patients and correlated with clinical response. In vivo, lanreotide therapy showed reduced effects on wnt, T cell receptor (TCR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling in CD8+ T cells in responders compared to non-responders. Compared to non-responders, responders showed reduced effects on cytokine and chemokine signaling but greater effects on ubiquitination and proteasome degradation genes. Our results suggest significant lanreotide pharmacodynamic effects on immune function in vivo, which correlate with responses in NET patients. This is not evident from experimental in vitro settings. Full article

Somatostatin is a peptide that plays a variety of roles such as neurotransmitter and endocrine regulator; its actions as a cell regulator in various tissues of the human body are represented mainly by inhibitory effects, and it shows potent activity despite its physiological low concentrations. Somatostatin binds to specific receptors, called somatostatin receptors (SSTRs), which have different tissue distributions and associated signaling pathways. The expression of SSTRs can be altered in various conditions, including tumors; therefore, they can be used as biomarkers for cancer cell susceptibility to certain pharmacological agents and can provide prognostic information regarding disease evolution. Moreover, based on the affinity of somatostatin analogs for the different types of SSTRs, the therapeutic range includes conditions such as tumors, acromegaly, post-prandial hypotension, hyperinsulinism, and many more. On the other hand, a number of somatostatin antagonists may prove useful in certain medical settings, based on their differential affinity for SSTRs. The aim of this review is to present in detail the principal characteristics of all five SSTRs and to provide an overview of the associated therapeutic potential in neoplasias. Full article

The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [⁶⁸Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [¹⁷⁷Lu]LuDOTA-LM3 and [²²⁵Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest–abdomen–pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity. Full article