-
ESMO Open Aug 2020Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the... (Review)
Review
Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the latter allowing the use of targeted therapeutic concepts. Currently accepted treatment strategies for advanced well-differentiated NET include somatostatin analogues octreotide and lanreotide, peptide receptor radionuclide therapy using radiolabelled somatostatin analogues, mammalian target of Rapamycin inhibitor everolimus, tyrosine kinase inhibitor sunitinib, interferon alpha and classical cytostatic, such as streptozotocin-based and temozolomide-based treatment. Indication, use and approval of these treatments differ based on primary tumour origin, grading and symptomatic burden and require an optimised multidisciplinary cooperation of medical oncologists, endocrinologists and nuclear medicine specialists. Interestingly, hot topics in oncology including immunotherapy and use of next-generation-sequencing techniques currently play a minor role for the treatment of NETs. The recent revision of the WHO classification including the recognition of the novel NET G3 category allows for potentially more tailored treatment strategies in the near future. However, this new entity also poses a therapeutic challenge as only limited data are currently available. The present article aims to provide an overview on our personal treatment concepts for advanced NETs with a focus on tumours of gastroenteropancreatic origin.
Topics: Everolimus; Humans; Neuroendocrine Tumors; Octreotide; Receptors, Somatostatin; Sunitinib
PubMed: 32817134
DOI: 10.1136/esmoopen-2020-000811 -
The Journal of Clinical Endocrinology... Nov 2022The concept of using a targeting molecule labeled with a diagnostic radionuclide for using positron emission tomography or single photon emission computed tomography...
The concept of using a targeting molecule labeled with a diagnostic radionuclide for using positron emission tomography or single photon emission computed tomography imaging with the potential to demonstrate that tumoricidal radiation can be delivered to tumoral sites by administration of the same or a similar targeting molecule labeled with a therapeutic radionuclide termed "theranostics." Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs (SSAs) is a well-established second/third-line theranostic treatment for somatostatin receptor-positive well-differentiated (neuro-)endocrine neoplasms (NENs). PRRT with 177Lu-DOTATATE was approved by the regulatory authorities in 2017 and 2018 for selected patients with low-grade well-differentiated gastroenteropancreatic (GEP) NENs. It improves progression-free survival as well as quality of life of GEP NEN patients. Favorable symptomatic and biochemical responses using PRRT with 177Lu-DOTATATE have also been reported in patients with functioning metastatic GEP NENs like metastatic insulinomas, Verner Morrison syndromes (VIPomas), glucagonomas, and gastrinomas and patients with carcinoid syndrome. This therapy might also become a valuable therapeutic option for inoperable low-grade bronchopulmonary NENs, inoperable or progressive pheochromocytomas and paragangliomas, and medullary thyroid carcinomas. First-line PRRT with 177Lu-DOTATATE and combinations of this therapy with cytotoxic drugs are currently under investigation. New radiolabeled somatostatin receptor ligands include SSAs coupled with alpha radiation emitting radionuclides and somatostatin receptor antagonists coupled with radionuclides.
Topics: Humans; Neuroendocrine Tumors; Receptors, Somatostatin; Quality of Life; Octreotide; Organometallic Compounds; Somatostatin; Radioisotopes; Radiopharmaceuticals
PubMed: 36198028
DOI: 10.1210/clinem/dgac574 -
Neuropeptides Dec 2019Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the... (Review)
Review
Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the threat. Itch-inducing (pruritogenic) substances activate primary afferent neurons in the skin through interactions with specific receptors that converts the stimulus into an electrical signal. These signals are conveyed to the dorsal horn of the spinal cord through the release of neurotransmitters such as natriuretic polypeptide b and somatostatin, leading to an integrated response within a complex spinal interneuronal network. A large sub-population of somatostatin-expressing spinal interneurons also carry the Neuropeptide Y (NPY) Y1 receptor, indicating that NPY and somatostatin partly regulate the same neuronal pathway. This review focuses on recent findings regarding the role of the NPY/Y1 and somatostatin/SST receptor in itch, and also presents data integrating the two neurotransmitter systems.
Topics: Animals; Humans; Neural Pathways; Neurons; Neuropeptide Y; Pruritus; Receptors, Neuropeptide Y; Receptors, Somatostatin; Somatostatin; Spinal Cord
PubMed: 31668651
DOI: 10.1016/j.npep.2019.101976 -
Seminars in Nuclear Medicine Jul 2023Neuroendocrine neoplasms (NEN) are rare and heterogeneous tumors, originating mostly from the gastro-entero-pancreatic (GEP) tract followed by the lungs.... (Review)
Review
Neuroendocrine neoplasms (NEN) are rare and heterogeneous tumors, originating mostly from the gastro-entero-pancreatic (GEP) tract followed by the lungs. Multidisciplinary discussion is mandatory for optimal diagnostic and therapeutic management. Well-differentiated NEN (NET) present a high expression of somatostatin receptors (SSTR) and can be studied with [68Ga]-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE) PET/CT to assess disease extension and the eligibility for peptide receptor radionuclide therapy (PRRT). SSTR-analogues labelled with 90Y or 177Lu have been used since mid-90s for NET therapy. PRRT is now considered an effective and safe treatment option for SSTR-expressing NET: following the approval of 177Lu-DOTATATE by FDA and EMA, PRRT is now part of the therapeutic algorithms of the main scientific societies. New strategies to improve PRRT efficacy and to reduce its toxicity are under evaluation (eg, personalization of treatment schemes, the selection of the most suitable patients, improvement of response assessment criteria, optimization of treatment sequencing, feasibility of PRRT-retreatment, combination of PRRT with other treatments options). Recently, several emerging radiopharmaceuticals showed encouraging results for both imaging and therapy (eg, SSTR-analogues labelled with 18F, SSTR-antagonists for both diagnosis and therapy, alpha-labelling for therapy, radiopharmaceuticals binding to new cellular targets). Aim of this review is to focus on current knowledge and to outline emerging perspectives for NEN's diagnosis and therapy.
Topics: Humans; Positron Emission Tomography Computed Tomography; Yttrium Radioisotopes; Radiopharmaceuticals; Neuroendocrine Tumors; Precision Medicine; Molecular Imaging; Receptors, Somatostatin
PubMed: 36623974
DOI: 10.1053/j.semnuclmed.2022.12.007 -
Current Oncology (Toronto, Ont.) Aug 2022Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after...
Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas ( = 29); 57.1% for WHO grade II ( = 21); and 0 % for WHO grade III ( = 12). For all grades ( = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines.
Topics: Humans; Meningeal Neoplasms; Meningioma; Positron-Emission Tomography; Precision Medicine; Radionuclide Imaging; Receptors, Somatostatin; Retrospective Studies; Treatment Outcome; Yttrium Radioisotopes
PubMed: 36005176
DOI: 10.3390/curroncol29080438 -
Endocrine-related Cancer Mar 2021Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic NETs. An understanding of benefits and risks is important for the appropriate implementation of this therapy. This review summarizes study data supporting the use of radiolabeled somatostatin analogs for the treatment of advanced NETs and highlights risks, including potential toxicities in specific populations. Key ongoing clinical trials, including randomized studies, are designed to better define the position of PRRT within the broader therapeutic landscape. Preclinical and early-phase human studies are focused on the development of novel somatostatin-receptor agonists and antagonists, new radionuclides, and radiosensitizing combination therapies.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Radioisotopes; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin
PubMed: 33608483
DOI: 10.1530/ERC-20-0360 -
The Journal of Clinical Endocrinology... Nov 2022Somatostatin receptor ligands (SRLs) are the cornerstone medical treatments for acromegaly; however, many patients remain unresponsive to SRLs. Well-established... (Observational Study)
Observational Study
CONTEXT
Somatostatin receptor ligands (SRLs) are the cornerstone medical treatments for acromegaly; however, many patients remain unresponsive to SRLs. Well-established predictive markers of response are needed.
OBJECTIVE
We aimed to explore the relationship between responsiveness to SRLs relative to somatostatin (SST)2A and 5 receptor expression, adenoma granularity, and T2-weighted magnetic resonance imaging (MRI) signal intensity (T2WSI).
METHODS
We conducted a multicentric, prospective, observational cohort study, in France. Forty-nine naïve patients (ie, patients without preoperative SRL treatment) with active acromegaly following surgery were treated with octreotide (group 1; n = 47), or pasireotide if uncontrolled under first-generation SRLs (group 2; n = 9). Data were collected at baseline and months 3 and 6. Biochemical measurements, immunohistochemistry studies, and MRI readings were centralized.
RESULTS
In group 1, IGF-I decrease from baseline to month 6 positively correlated with SST2A immunoreactive score (IRS), P = 0.01. Densely granulated/intermediate adenomas had a greater IGF-I and GH decrease under octreotide compared with sparsely granulated adenomas (P = 0.02 and P = 0.006, respectively), and expressed greater levels of SST2A (P < 0.001), coupled with lower levels of SST5 (P = 0.004). T2WSI changed between preoperative MRI and month 6 MRI in one-half of the patients. Finally, SST5 IRS was higher in preoperative hyperintense compared with preoperative hypointense adenomas (P = 0.04), and most sparsely granulated and most hyperintense adenomas expressed high SST5 levels.
CONCLUSION
We prospectively confirm that SST2A and adenoma granularity are good predictors of response to octreotide. We propose the IRS for scoring system harmonization. MRI sequences must be optimized to be able to use the T2WSI as a predictor of treatment response.
Topics: Humans; Acromegaly; Prospective Studies; Growth Hormone-Secreting Pituitary Adenoma; Receptors, Somatostatin; Octreotide; Insulin-Like Growth Factor I; Ligands; Adenoma
PubMed: 36136828
DOI: 10.1210/clinem/dgac512 -
Surgical Oncology Clinics of North... Oct 2022Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we... (Review)
Review
Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we review the role of SSTR PET scan in the management of NETs, including the indications for the scan, pitfalls in interpretation, and imaging selection criteria for peptide receptor radionuclide therapy. We also discuss the complementary role of fluorodeoxyglucose PET particularly for patients with high-grade disease.
Topics: Humans; Ligands; Neuroendocrine Tumors; Positron-Emission Tomography; Radioisotopes; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 36243499
DOI: 10.1016/j.soc.2022.06.009 -
Endocrine Practice : Official Journal... Mar 2022Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone... (Review)
Review
Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone normalization as well as tumor shrinkage, the treatment goals include relieving symptoms, managing complications, and improving patients' quality of life. Surgical resection is a first-line treatment option for most patients, with few being pretreated preoperatively with medications. Somatostatin receptor ligands (SRLs), injectable and, more recently, oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent or low somatostatin receptor status, T2-hyperintensity imaging, young age, and aryl hydrocarbon receptor-interacting protein mutations, can predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the growth hormone receptor antagonist pegvisomant, or in cases of large tumors, the second-generation SRL pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have a high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is becoming increasingly important to tailor treatment to patients' unique characteristics and preferences, with a goal of personalizing management to achieve high-quality outcomes.
Topics: Acromegaly; Adenoma; Combined Modality Therapy; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Quality of Life; Receptors, Somatostatin
PubMed: 35032649
DOI: 10.1016/j.eprac.2021.12.017 -
Current Oncology Reports Nov 2021Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs). The search for the optimal imaging technique has triggered... (Review)
Review
PURPOSE OF REVIEW
Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs). The search for the optimal imaging technique has triggered rapid development in the field. This review aims at giving an overview on contemporary imaging methods and providing an outlook on current progresses.
RECENT FINDINGS
The discovery of molecular targets due to the overexpression of specific peptide hormone receptors on the NEN's surface has triggered the development of multiple radionuclide imaging modalities. In addition to the established imaging technique of targeting somatostatin receptors, several alternative radioligands have been developed. Targeting the glucagon-like peptide-1 receptor by exendin-4 has a high sensitivity in localizing insulinomas. For dedifferentiated NENs, new molecular targets such as the C-X-C motif chemokine-receptor-4 have been evaluated. Other new targets involve the fibroblast activation protein and the cholecystokinin-2 receptors, where the ligand minigastrin opens new possibilities for the management of medullary thyroid carcinoma. Molecular imaging is an emerging field that improves the management of NENs.
Topics: Humans; Neuroendocrine Tumors; Peptides; Radionuclide Imaging; Receptors, Cholecystokinin; Receptors, Somatostatin
PubMed: 34735669
DOI: 10.1007/s11912-021-01139-2