Liver-Directed Therapy for Gastroenteropancreatic NETs in the Era of Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 04 (03) ◽  
pp. 282-290
Author(s):  
Adrian Gonzalez-Aguirre ◽  
Etay Ziv
Keyword(s):  
Radionuclide Therapy ◽  
Liver Toxicity ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Case Series ◽  
Peptide Receptor Radionuclide Therapy ◽  
The United States ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Peptide Receptor ◽  
Clinical Scenarios

AbstractGastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of tumors. Current treatment algorithms for these tumors are complex and often require a multidisciplinary approach. Recently, peptide receptor radionuclide therapy (PRRT) was granted Food and Drug Administration approval, making this treatment widely available in the United States. PRRT is now another therapeutic option for patients with GEP-NETs. To date there are no consensus guidelines about how to sequence multiple treatment options. Moreover, there is concern of potential liver toxicity when PRRT is used before or after liver-directed therapies (LDTs). In this review, we describe the characteristics of the most commonly used LDT and their potential interactions with PRRT, as well as specific clinical scenarios that are relevant when deciding on the use of LDT. We also review the limited case series that have been published involving patients treated with different combinations of LDT and PRRT. Finally, we discuss some of the future directions for GEP-NET treatments.

scholarly journals Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 9 (11) ◽  
pp. 3507
Author(s):  
Erika Grossrubatscher ◽  
Giuseppe Fanciulli ◽  
Luca Pes ◽  
Franz Sesti ◽  
Carlotta Dolci ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Radionuclide Therapy ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Medullary Thyroid ◽  
Peptide Receptor

Effective treatment options in advanced/progressive/metastatic medullary thyroid carcinoma (MTC) are currently limited. As in other neuroendocrine neoplasms (NENs), peptide receptor radionuclide therapy (PRRT) has been used as a therapeutic option in MTC. To date, however, there are no published reviews dealing with PRRT approaches. We performed an in-depth narrative review on the studies published in this field and collected information on registered clinical trials related to this topic. We identified 19 published studies, collectively involving more than 200 patients with MTC, and four registered clinical trials. Most cases of MTC were treated with PRRT with somatostatin analogues (SSAs) radiolabelled with 90 yttrium (90Y) and 177 lutetium (177Lu). These radiopharmaceuticals show efficacy in the treatment of patients with MTC, with a favourable radiological response (stable disease, partial response or complete response) in more than 60% of cases, coupled with low toxicity. As MTC specifically also expresses cholecystokinin receptors (CCK2Rs), PRRT with this target has also been tried, and some randomised trials are ongoing. Overall, PRRT seems to have an effective role and might be considered in the therapeutic strategy of advanced/progressive/metastatic MTC.

scholarly journals Peptide Receptor Radionuclide Therapy as a Novel Treatment for Metastatic and Invasive Phaeochromocytoma and Paraganglioma

2019 ◽  
Vol 109 (4) ◽  
pp. 287-298 ◽  
Author(s):  
Ingrid Y.F. Mak ◽  
Aimee R. Hayes ◽  
Bernard Khoo ◽  
Ashley Grossman
Keyword(s):  
Radionuclide Therapy ◽  
Treatment Options ◽  
Hepatic Metastases ◽  
Peptide Receptor Radionuclide Therapy ◽  
Chemotherapeutic Agents ◽  
Symptomatic Disease ◽  
Peptide Receptor ◽  
Radiological Changes ◽  
Randomised Controlled ◽  
National Databases

At present there is no clinical guideline or standardised protocol for the treatment of metastatic or invasive phaeochromocytoma and paraganglioma (collectively known as PPGL) due to the rarity of the disease and the lack of prospective studies or extended national databases. Prognosis is mainly determined by genetic predisposition, tumour burden, rate of disease progression, and location of metastases. For patients with progressive or symptomatic disease that is not amenable to surgery, there are various palliative treatment options available. These include localised therapies including radiotherapy, radiofrequency, or cryoablation, as well as liver-directed therapies for those patients with hepatic metastases (e.g., transarterial chemoembolisation) and systemic therapies including chemotherapy or molecular targeted therapies. There is currently intense research interest in the value of radionuclide therapy for neuroendocrine tumours, including phaeochromocytoma and paraganglioma, with either iodine-131 (131I)-radiolabelled metaiodobenzylguanidine or very recently peptide receptor radionuclide therapy (PRRT), and the most important contemporary clinical studies will be highlighted in this review. The studies to date suggest that PRRT may induce major clinical, biochemical, and radiological changes, with 177Lu-DOTATATE being most efficacious and presenting less toxicity than 90Y-DOTATATE. Newer combination therapies with combined radioisotopes, or combinations with chemotherapeutic agents, also look promising. Given the favourable efficacy, logistic, and safety profiles, we believe that PRRT will probably become the standard treatment for inoperable metastatic PPGL in the near future, but we await data from definitive randomised controlled trials to understand its role.

scholarly journals The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1083
Author(s):  
Virginia Liberini ◽  
Martin W. Huellner ◽  
Serena Grimaldi ◽  
Monica Finessi ◽  
Philippe Thuillier ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Morphological Response ◽  
Peptide Receptor ◽  
Clinical Biomarkers ◽  
Standardized Parameters

The NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owed to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.

Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma

2018 ◽  
Vol 15 (6) ◽  
pp. 100-109 ◽  
Author(s):  
Julia R Schneider ◽  
Deborah R Shatzkes ◽  
Stephen C Scharf ◽  
Tristan M Tham ◽  
Kay O Kulason ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Option ◽  
Somatostatin Receptor ◽  
Malignant Neoplasm ◽  
Peptide Receptor Radionuclide Therapy ◽  
Olfactory Neuroblastoma ◽  
Somatostatin Analogues ◽  
Symptomatic Improvement ◽  
Peptide Receptor ◽  
Molecular Alterations

Abstract BACKGROUND AND IMPORTANCE Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB. CLINICAL PRESENTATION A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease. CONCLUSION We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.

scholarly journals Case Series of Metastatic VIPoma With Partial Response to Somatostatin Receptor Ligand and Review of Therapeutic Options

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A993-A993
Author(s):  
Lim Sue Wen ◽  
Goh Kian Guan ◽  
Jin Hui Ho ◽  
Serena Sert Kim Khoo ◽  
Zanariah Hussein
Keyword(s):  
Targeted Therapy ◽  
Disease Control ◽  
Radionuclide Therapy ◽  
Symptom Relief ◽  
Somatostatin Receptor ◽  
Case Series ◽  
Peptide Receptor Radionuclide Therapy ◽  
Cytotoxic Chemotherapy ◽  
Peptide Receptor ◽  
Secretory Diarrhoea

Abstract Background: Vasoactive intestinal polypeptide secreting islet cell tumors (VIPoma) are rare neuroendocrine tumors of pancreatic origin, characterized by secretory diarrhoea and electrolyte imbalances. Metastasis, commonly hepatic, frequently occur at diagnosis in up to 80% patients. Surgery of the primary tumour remains the gold standard management and in metastatic tumors, somatostatin receptor ligands (SRL) are the drugs of choice for symptom relief and disease control. Some patients will require other approaches to control symptoms, such as liver-targeted therapy, peptide receptor radionuclide therapy (PRRT) or chemotherapy. We describe a case series of metastatic VIPoma which partially-responded to SRL and review of other treatment modalities to achieve disease and symptom control. Case: We report 3 cases, ages 37 to 58 years, with metastatic VIPoma whom presented with secretory diarrhoea, hypokalaemia, achlorhydria and elevated serum VIP levels. CT and 68Gallium PET-CT imaging identified metastases in liver, bone, lungs, spleen and lymph nodes. One case underwent distal pancreatectomy and splenectomy at diagnosis and two cases were advanced and non-resectable. All received long-acting SRL initially and achieved partial control of the gastrointestinal symptoms. Two cases underwent Peptide Receptor Radionuclide Therapy (PRRT) and one case received cytotoxic chemotherapy. Two patients have progressive disease and one succumbed to advanced disease. For inoperable disease, PRRT is useful adjuvant therapy for symptom relief and may improve progression free survival (PFS). Cytotoxic chemotherapy is an option for patients with progressive or symptomatic unresectable tumor. Chemoembolization or liver-targeted therapy are used in liver metastasis for loco-regional control. Alfa-interferon and targeted therapies such as everolimus and sunitinib are other treatment options that can be considered. Conclusion: Metastatic VIPoma remains a challenging disease to manage, requiring multimodal treatment approaches. With timely diagnosis and advancing therapeutic options, more patients can achieve improved symptom and disease control as well as increased survival.

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