scholarly journals Asphericity of Somatostatin Receptor Expression in Neuroendocrine Tumors: An Innovative Predictor of Outcome in Everolimus Treatment?

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 732
Author(s):  
Christoph Wetz ◽  
Julian Rogasch ◽  
Philipp Genseke ◽  
Imke Schatka ◽  
Christian Furth ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Receptor Expression ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Primary Tumor Site ◽  
Risk Benefit Assessment ◽  
Octreotide Scintigraphy

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48–81) years) with pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®). ASP of functional volumes of up to three leading lesions per patient (n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained. Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1–11.4 months) versus 14.4 (12.5–16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028). Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment.

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 Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Sowon Oh ◽  
Vikas Prasad ◽  
Dong Soo Lee ◽  
R. P. Baum
Keyword(s):  
Glucose Metabolism ◽  
Neuroendocrine Tumors ◽  
Fdg Pet ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Receptor Expression ◽  
Peptide Receptor ◽  
Pet Ct ◽  
Fdg Pet Ct

The heterogeneous nature of the neuroendocrine tumors (NET) makes it challenging to find one uniformly applicable management protocol which is especially true for diagnosis. The discovery of the overexpression of somatostatin receptors (SMS-R) on neuroendocrine tumor cells lead to the generalized and rapid acceptance of radiolabeled somatostatin receptor analogs for staging and restaging of NET as well as for Peptide Receptor Radionuclide Therapy (PRRNT) using Y-90 and Lu-177 DOTATATE/DOTATOC. In this present work we tried to look in to the effect of PRRNT on the glucose metabolism assessed by F-18 FDG PET/CT and SMS-R density assessed by Ga-68 DOTANOC PET/CT. We observed a complex relationship between the somatostatin receptor expression and glucose metabolism with only 56% (77/138) of the lesions showing match, while the others show mismatch between the receptor status and metabolism. The match between receptor expression and glucose metabolism increases with the grade of NET. In grade 3 NET, there is a concurrence between the changes in glucose metabolism and somatostatin receptor expression. PRRNT was found to be more effective in lesions with higher receptor expression.

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 Gastroenteropancreatic Neuroendocrine Tumors (GEPNET) Registry 2009-2018: A Large Multi-country Registry with Over 1000 GEPNET Patients

2021 ◽  
Author(s):  
Suayib Yalcin ◽  
Hande Turna ◽  
Ilan Shimon ◽  
Yi-Ming Shyr ◽  
Yan-Shen Shan ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Primary Tumor ◽  
Initial Treatment ◽  
Progression Free Survival ◽  
Asia Pacific ◽  
Treatment Modalities ◽  
Tumor Site ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Primary Tumor Site ◽  
Free Survival

Abstract Background: This 8-year observational, multicenter, registry study was undertaken to assess the incidence and regional trends in diagnosis, clinical management, and outcome assessments of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) in the Asia-Pacific region, the Middle East, Turkey, and South Africa.Materials and Methods: Patient data including demographics, primary tumor site, tumor differentiation, diagnosis, treatment modalities, outcomes were collected via a web-based data entry portal.Results: Overall, 974 patients were enrolled, and 951 of which were evaluated (median age: 54 years). Pancreas was the most commonly reported primary tumor site. Non‑functioning and functioning (most common: carcinoid) tumors were reported in 61.9% and 27.9% of patients, respectively. Abdominal pain was the most commonly reported symptom. Surgery was the most-commonly employed initial treatment, followed by treatment with somatostatin analogs; >80% of patients had open surgery and R0 resection. Satisfactory response to the initial treatment modality was reported for 56.4% of patients. Overall survival rate was 96.3% at 6 months since diagnosis and 72.9% at 60 months. Median progression-free survival was 60.9 months since first diagnosis and 60.5 months after first treatment, with a 6-month progression-free survival of 95.0%. Conclusion: The GEP-NET registry provides important information relating to the diagnosis and treatment of patients in the participating countries. This analysis highlighted the need for improvements in the clinical practice to ensure better evaluation and treatment management.

scholarly journals Clinical Challenges in the Management of Neuroendocrine Tumors

2021 ◽  
Vol 10 (2) ◽  
pp. 257
Author(s):  
Francesco Panzuto
Keyword(s):  
Neuroendocrine Tumors ◽  
Primary Tumor ◽  
Somatostatin Receptor ◽  
Receptor Expression ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Disease Staging

Neuroendocrine tumors (NET) are rare and heterogeneous diseases, whose prognosis is affected by several factors including the primary tumor site, grading, somatostatin receptor expression, and disease staging [...]

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.

scholarly journals Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA0-Tyr3-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors

2021 ◽  
Author(s):  
Noritoshi Kobayashi ◽  
Shoko Takano ◽  
Kenichi Ito ◽  
Madoka Sugiura ◽  
Matsuyoshi Ogawa ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Solution ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Japanese Patients ◽  
Receptor Expression ◽  
Amino Acid Solution ◽  
Peptide Receptor

Abstract Purpose Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. Methods Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. Results Six Japanese patients (three men and three women; mean age 61.5 years; range 50–70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%–69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0–21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2–21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. Conclusion PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

scholarly journals Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 504
Author(s):  
Fiona Ohlendorf ◽  
Rudolf Werner ◽  
Christoph Henkenberens ◽  
Tobias Ross ◽  
Hans Christiansen ◽  
...  
Keyword(s):  
Treatment Response ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tumor Burden ◽  
Inflammatory Biomarkers ◽  
Whole Body ◽  
Prognostic Impact ◽  
Peptide Receptor

Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., Creactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [68Ga]GaDOTATATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP (P < 0.001), ANC (P = 0.002), and PCM (P < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP (P = 0.0157) and NLR (P = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, P = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; P = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEPNETs receiving PRRT.

scholarly journals The state of PRRT and its sequencing amongst current therapeutic options for gastroenteropancreatic neuroendocrine tumors

2021 ◽  
Author(s):  
Lauren M Raymond ◽  
Tetiana Korzun ◽  
Adel Kardosh ◽  
Kenneth J. Kolbeck ◽  
Rodney Pommier ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Standard Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Tumor Burden ◽  
Treatment Modalities ◽  
Its Sequencing ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Reduce Tumor Burden ◽  
Spectrum Of Patients

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common form of neuroendocrine neoplasia, but there is no current consensus for the sequencing of approved therapies, particularly with respect to peptide receptor radionuclide therapy (PRRT). This comprehensive review evaluates the data supporting approved therapies for GEP-NETs and recommendations for therapeutic sequencing with a focus on how PRRT currently fits within sequencing algorithms. The current recommendations for PRRT sequencing restrict its use to metastatic, inoperable, progressive midgut NETs, however, this may change with emerging data to suggest PRRT might be beneficial as neoadjuvant therapy for inoperable tumors, is more tolerable than other treatment modalities following first-line standard dose somatostatin analogues, and can be used as salvage therapy after disease relapse following prior successful cycles of PRRT. PRRT has also been shown to reduce tumor burden, improve quality of life, and prolong the time to disease progression in a broad spectrum of patients with GEP-NETs. As the various potential benefits of PRRT in GEP-NET therapy continues to expand, it is necessary to review and critically evaluate our treatment algorithms for GEP-NETs.

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