scholarly journals Chemotherapy in NEN: still has a role?

2021 ◽  
Author(s):  
Paula Espinosa-Olarte ◽  
Anna La Salvia ◽  
Maria C. Riesco-Martinez ◽  
Beatriz Anton-Pascual ◽  
Rocio Garcia-Carbonero
Keyword(s):  
Therapeutic Strategy ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Treatment Algorithm ◽  
Somatostatin Analogues ◽  
Neuroendocrine Neoplasms ◽  
Primary Tumor Site ◽  
Novel Drugs ◽  
Well Differentiated ◽  
Extent Of Disease

AbstractNeuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and 177Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.

scholarly journals Self-Administration of Long-Acting Somatostatin Analogues in NET Patients—Does It Affect the Clinical Outcome?

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1287
Author(s):  
Anna Sowa-Staszczak ◽  
Marta Opalińska ◽  
Anna Kurzyńska ◽  
Karolina Morawiec-Sławek ◽  
Aleksandra Gilis-Januszewska ◽  
...  
Keyword(s):  
Medical Staff ◽  
Somatostatin Receptor ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Self Administration ◽  
Good Expression ◽  
Well Differentiated ◽  
Long Acting

Background and Objectives: Long-acting somatostatin analogues (SSA) (octreotide LAR and lanreotide Autogel) are recommended as first line treatment of locally advanced or metastatic well-differentiated neuroendocrine tumors (NETs) with a good expression of somatostatin receptor (SSTR). Both of these SSAs are usually administered via injections repeated every 4 weeks. The purpose of the study was to compare the route of SSA administration (injection performed by professional medical staff and self-administration of the drug) with progression-free survival. Materials and methods: 88 patients in 2019 and 96 patients in 2020 with locally advanced or metastatic well-differentiated NETs were included in the study. All patients had a good expression of SSTR type 2 and had been treated for at least 3 months with a stable dose of long-acting somatostatin analogue every 4 weeks. All of them had received training on drug self-injections from professional NET nurses at the beginning of the COVID-19 epidemic. Results: The rate of NET progression in the study group in 2020 was higher than in 2019 29.1% vs. 18.1% (28 vs. 16 cases), p = 0.081. Conclusions: The method of administration of long-acting SSA injection performed by professional medical staff vs. self-injection of the drug may significantly affect the risk of NET progression. The unequivocal confirmation of such a relationship requires further observation.

scholarly journals Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors

2020 ◽  
Vol 9 (11) ◽  
pp. 3655
Author(s):  
Mauro Cives ◽  
Eleonora Pelle’ ◽  
Jonathan Strosberg
Keyword(s):  
Clinical Trials ◽  
Growth Factor ◽  
Neuroendocrine Tumors ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Growth Factor Receptor ◽  
Small Samples ◽  
Neuroendocrine Neoplasms ◽  
Two Phase ◽  
Gastroenteropancreatic Neuroendocrine Tumors

Treatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides incorporating somatostatin receptor antagonists (rather than agonists) have been developed. Several tyrosine kinase inhibitors (TKIs) with antiangiogenic potential have been evaluated in patients with NETs, including lenvatinib, axitinib, cabozantinib and pazopanib. Recently, two phase 3 clinical trials have demonstrated the efficacy and safety of surufatinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, fibroblast growth factor receptor (FGFR)-1 and colony stimulating factor-1 receptor (CSF-1R), in patients with pancreatic and extra-pancreatic NETs. Multiple clinical trials of combination immunotherapy have been recently completed, but interpretation of the results is hampered by small samples sizes and discordant outcomes. This review summarizes recent data on emerging treatments for neuroendocrine neoplasms.

scholarly journals Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)

2018 ◽  
Vol 108 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Halfdan Sorbye ◽  
Eric Baudin ◽  
Ivan Borbath ◽  
Martyn Caplin ◽  
Jie Chen ◽  
...  
Keyword(s):  
Patient Group ◽  
Unmet Needs ◽  
Proliferation Rate ◽  
Pancreatic Tumors ◽  
Neuroendocrine Neoplasms ◽  
Low Grade ◽  
High Grade ◽  
Primary Tumor Site ◽  
Net G3 ◽  
Well Differentiated

Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.

Severe metabolic acidosis and hyperkalemia after peptide receptor radionuclide therapy. A case report, review of the literature and proposed treatment algorithm

2021 ◽  
pp. 239936932110197
Author(s):  
Nikolaos A Trikalinos ◽  
Hyun Kim ◽  
Amir Iravani ◽  
Lauren Henke ◽  
Anitha Vijayan
Keyword(s):  
Radionuclide Therapy ◽  
Treatment Algorithm ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Review Of The Literature ◽  
Peptide Receptor ◽  
Life Threatening ◽  
Well Differentiated ◽  
Intravenous Sodium ◽  
Electrolyte Abnormalities

Peptide receptor radionuclide therapy (PRRT) has been increasingly used in the treatment of patients with well-differentiated neuroendocrine neoplasms (WD-NENs), but electrolyte abnormalities during prophylactic aminoacid (AA) infusion can complicate its administration. We describe a case of AA-induced acidosis and hyperkalemia associated with PRRT. We tailored an oral and intravenous sodium bicarbonate regimen for pre-emptive treatment prior to subsequent PRRT session, thereby preventing hospitalization. We provide a relevant review of the literature and our treatment algorithm, that can serve as a point of reference in treatment of this life-threatening complication of PRRT.

scholarly journals Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

2020 ◽  
Vol 9 (6) ◽  
pp. 1860
Author(s):  
Lola-Jade Palmieri ◽  
Solène Dermine ◽  
Amélie Barré ◽  
Marion Dhooge ◽  
Catherine Brezault ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Treatment Options ◽  
Somatostatin Analogs ◽  
Treatment Algorithm ◽  
Proliferation Index ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Histologic Differentiation ◽  
Surgical Treatments

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.

scholarly journals Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
K. Lithgow ◽  
H. Venkataraman ◽  
S. Hughes ◽  
H. Shah ◽  
J. Kemp-Blake ◽  
...  
Keyword(s):  
Primary Tumour ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Treatment Strategies ◽  
Biological Behavior ◽  
Queen Elizabeth Hospital ◽  
Neuroendocrine Neoplasms ◽  
Single Centre ◽  
Net G3 ◽  
Well Differentiated

AbstractNeuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

scholarly journals Targeted Cancer Therapy: What’s New in the Field of Neuroendocrine Neoplasms?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1701
Author(s):  
Anna La Salvia ◽  
Paula Espinosa-Olarte ◽  
Maria Del Carmen Riesco-Martinez ◽  
Beatriz Anton-Pascual ◽  
Rocío Garcia-Carbonero
Keyword(s):  
Treatment Options ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Neuroendocrine Neoplasms ◽  
Antiangiogenic Agents ◽  
Drug Conjugates ◽  
Therapeutic Drugs ◽  
Anatomic Distribution ◽  
Pancreatic Origin

Neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms of increasing incidence and high prevalence due to their relatively indolent nature. Their wide anatomic distribution and their characteristic ability to secrete hormonally active substances pose unique challenges for clinical management. They are also characterized by the common expression of somatostatin receptors, a target that has been extremely useful for diagnosis and treatment (i.e., somatostatin analogues (SSAs) and peptide-receptor radionuclide therapy (PRRT)). Chemotherapy is of limited use for NETs of non-pancreatic origin, and the only approved targeted agents for advanced progressive NETs are sunitinib for those of pancreatic origin, and everolimus for lung, gastrointestinal and pancreatic primaries. Despite recent therapeutic achievements, thus, systemic treatment options remain limited. In this review we will discuss the state-of-the-art targeted therapies in the field of NETs, and also future perspectives of novel therapeutic drugs or strategies in clinical development, including recently presented results from randomized trials of yet unapproved antiangiogenic agents (i.e., pazopanib, surufatinib and axitinib), PRRT including both approved radiopharmaceuticals (177Lu-Oxodotreotide) and others in development (177Lu-Edotreotide, 177Lu-Satoreotide Tetraxetan), immunotherapy and other innovative targeted strategies (antibody-drug conjugates, bites,…) that shall soon improve the landscape of personalized treatment options in NET patients.

Molecular profiling of pancreatic neuroendocrine neoplasms (panNENs): A single-institution experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16207-e16207
Author(s):  
Ibrahim Azar ◽  
Omid Yazdanpanah ◽  
Shiva Swaroop Bongu ◽  
Mohammed Najeeb Al Hallak ◽  
W. Michael Korn ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Predictive Biomarkers ◽  
Molecular Profiling ◽  
Response To Therapy ◽  
New Drugs ◽  
Neuroendocrine Neoplasms ◽  
Molecular Alteration ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Tumor Biopsies

e16207 Background: PanNENs are rare with a heterogeneous pathophysiology and widely differing clinical course. Despite a recent update of the grading system, prognostication and prediction of response to therapy remain challenging. Somatostatin receptor aside, there are currently no predictive biomarkers or targeted agents for panNENs. Molecular profiling offers an opportunity to develop new drugs and personalize treatments. Methods: We compiled data from patients diagnosed with panNENs from Karmanos Cancer Institute between 2014 and 2020. Of the 35 patients with panNENs, 33 underwent Next Generation Sequencing (Caris Molecular Intelligence). Two tumor biopsies were insufficient for molecular analysis. Results: Of the 35 tumors analyzed, 11 were grade 1, 18 were G2, 2 were well-differentiated G3 and 4 were poorly differentiated pancreatic neuroendocrine carcinomas (panNEC). Median age at diagnosis was 61. 21 patients identified as White, 6 as Black and 8 as other. 21 were men. 28 patients were metastatic at diagnosis. The most frequently detected molecular alteration was MEN1 mutations (11 G1, 1 G1 and 1 G3). 3 G2 and 2 G3 tumors expressed PTEN mutations. All 3 p53 mutations were G3, 2 of them panNEC. An FGFR3 amplification was detected in a single G1 panNEN. Her2/Neu amplification was detected in a G2 tumor. Other frequent alterations were MGMT (4), TOP2A (4), ARID1A (3), TUBB3 (3) and TSC2 (3). 3 tumors were PD-L1 positive. All tumors were TMB non-high and MMR-proficient. Conclusions: Molecular profiling of panNEN can detect targetable alterations with currently validated commercial agents. panNENs are immunologically cold. Further genomic and epigenomic profiling studies can help understand the molecular underpinnings of pathophysiology and aid in the development of biology-driven targeted therapies.

Sign in / Sign up

Export Citation Format

Share Document