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.

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

2020 ◽  
Author(s):  
Virginia Liberini ◽  
Martin W. Hüllner ◽  
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 owing 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.

Peptide Receptor Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors

2019 ◽  
Vol 03 (01) ◽  
pp. 071-080
Author(s):  
Ghassan El-Haddad
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Large Scale ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Peptide Receptor

AbstractPeptide receptor radionuclide therapy (PRRT), a targeted form of systemic radiotherapy allowing the delivery of radionuclides directly to tumor cells, has been used for more than three decades in the treatment of advanced neuroendocrine tumors (NETs) exhibiting high levels of somatostatin receptors. Recently, 177Lu-DOTATATE, a radiolabeled somatostatin analog, was approved by the US Food and Drug administration for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults. Early phase I and II studies have shown the benefits of PRRT, but it was the NETTER-1 trial (a large-scale randomized multicenter trial for progressive well-differentiated advanced or metastatic somatostatin receptor-positive midgut carcinoid tumors) that provided high-level evidence of improved overall response rate, and progression-free survival compared with long-acting octreotide. In this article, we will discuss the evolution, clinical applications, and implementation of PRRT, as well as potential future strategies to enhance its clinical efficacy in the treatment of GEP-NETs.

scholarly journals 90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1463
Author(s):  
Licia Uccelli ◽  
Alessandra Boschi ◽  
Corrado Cittanti ◽  
Petra Martini ◽  
Stefano Panareo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Preclinical Studies ◽  
Peptide Fragment ◽  
Free Survival ◽  
Peptide Receptor ◽  
Yttrium 90

The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177. In this review, covering twenty five years of literature, we describe the characteristics and performances of the two most used therapeutic radiopharmaceuticals for the NETs radio-treatment: [90Y]Y-DOTATOC and [177Lu]Lu-DOTATOC taking this opportunity to retrace the most significant results that have determined their success, promoting them from preclinical studies to application in humans.

scholarly journals Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1813
Author(s):  
Emmanouil Alevroudis ◽  
Maria-Eleni Spei ◽  
Sofia N. Chatziioannou ◽  
Marina Tsoli ◽  
Göran Wallin ◽  
...  
Keyword(s):  
Random Effects ◽  
Neuroendocrine Tumors ◽  
Fdg Pet ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Peptide Receptor ◽  
18F Fdg ◽  
The Impact

The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 623-623
Author(s):  
Heying Duan ◽  
Gaia Ninatti ◽  
Bradley Girod ◽  
Valentina Ferri ◽  
Pamela L. Kunz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
Single Institution ◽  
Free Survival ◽  
Peptide Receptor ◽  
Low Toxicity

623 Background: Neuroendocrine tumors (NETs) are rare but increasing in incidence. The only curative treatment is surgery, which in many cases is not an option due to metastatic disease at diagnosis. The NETTER-1 study showed high efficacy and low toxicity of peptide receptor radionuclide therapy (PRRT) for midgut NETs. Here, we present our initial experience with PRRT in the treatment of patients with NET. Methods: Fifty-two patients (27 males and 25 females; 37 - 81 yo, mean ± SD: 61.8 ± 10.6 years) with documented progressive NET (25 pancreas, 17 small intestine, 1 coecum, 4 unknown primary, 3 paragangliomas, and 2 pheochromocytomas) were referred to undergo PRRT at our institution from July 2018 to September 2019. Laboratory tests were obtained at baseline, 1 week before each cycle and every 3 months following treatment. Progression-free survival (PFS), objective response rate (ORR) and toxicity were assessed. An interim overall survival (OS) analysis was performed. Results, when possible, were compared with the NETTER-1 trial. Lines of therapy were documented. Results: 22/52 (42%) patients completed all 4 cycles of PRRT. 18/52 (34%) patients are currently being treated. 12/52 (23%) patients had to discontinue treatment. Hematotoxicity was the only side effect which can be related to PRRT. The 6-month and 9-month PFS rate was 82.4% and 66.8% respectively vs. 89% and 84% in the NETTER-1 trial. The ORR was 36% vs. 18% in the NETTER-1 trial. In the interim OS analysis, 6 deaths occurred. In contrast to the NETTER-1 study, PRRT in our patient cohort was performed later in the course of treatment (median lines of therapy before PRRT = 4 ±1.3 (range 1-6)). Conclusions: Our preliminary data show overall good results of PRRT in patients with NETs. However, compared to the NETTER-1 trial, PFS is shorter which is most likely due to the extensive pretreatment, but ORR was higher. [Table: see text]

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