Outcomes of peptide receptor radionuclide therapy (PRRT) in metastatic grade 3 neuroendocrine tumors (NETs).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15694-e15694
Author(s):  
Mei Sim Lung ◽  
Michael Hofman ◽  
Grace Kong ◽  
Sue-Ping Thang ◽  
Michael Michael ◽  
...  
Keyword(s):  
Treatment Option ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Receptor Expression ◽  
Unknown Primary ◽  
Receptor Imaging ◽  
Ki 67 ◽  
Prior Chemotherapy ◽  
Platinum Based Chemotherapy

e15694 Background:Grade 3 (G3) NETs have a poor prognosis and limited treatment options (usually chemotherapy). PRRT is a potential treatment option if all sites of disease demonstrate high uptake on somatostatin-receptor imaging (SSRI). We retrospectively evaluated the efficacy of PRRT in G3 NETs. Methods: We reviewed records of patients with metastatic G3 NETs (Ki-67 > 20%) who received PRRT at our institution. Patients were treated with up to 5 cycles of PRRT, predominantly 177Lu-DOTA-octreotate. Further maintenance PRRT was administered upon progression if deemed suitable on SSRI. Radio-sensitizing chemotherapy was administered unless contra-indicated. Kaplan-Meier estimate was used to determine median overall survival (OS) and median time to new treatment/death (TNTD) defined from start of PRRT. Subgroup-analysis was performed for patients with Ki67 < 55% and ≥55%. Results: 26 patients with metastatic G3 NET received PRRT; 22 combined with chemotherapy (capecitabine/temozolomide (n = 12), 5-fluorouracil or capecitabine (n = 8), other (n = 2)). 58% were male. The median age was 62 (range 16-78 years). 61% had pancreatic NET, 19% small bowel, 8% lung, 8% unknown primary, 4% rectal. 77% had received at least one line of prior chemotherapy. 54% received prior platinum-based chemotherapy. Median follow-up was 33 months (range 8-83 months). Patients received a median of 4 cycles of PRRT (range 1-15). The estimated median OS from start of PRRT was 18 months: for Ki-67 < 55% (n = 21), 20 months; and Ki-67≥ 55% (n = 5), 9 months. The estimated median TNTD was 12 months: for Ki-67 < 55%, 16 months; and Ki-67≥55%, 4 months. 31% of patients were alive without a change in treatment modality following PRRT. Conclusions: In thispoor prognosis G3 NET cohort of whom 77% had received prior chemotherapy, a median OS of 18 months from start of PRRT is encouraging and warrants further study. PRRT is a promising treatment option for patients with G3 NET with high somatostatin-receptor expression selected by SSRI.

scholarly journals Neuroendocrine Carcinomas of the Digestive Tract: What Is New?

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3766
Author(s):  
Anna Pellat ◽  
Anne Ségolène Cottereau ◽  
Benoit Terris ◽  
Romain Coriat
Keyword(s):  
Peptide Receptor Radionuclide Therapy ◽  
Large Cell ◽  
Current Data ◽  
World Health ◽  
High Grade ◽  
Ki 67 ◽  
Lung Cancers ◽  
Platinum Based Chemotherapy ◽  
Line Setting ◽  
Neuroendocrine Carcinomas

Neuroendocrine carcinomas (NEC) are rare tumors with a rising incidence. They show poorly differentiated morphology with a high proliferation rate (Ki-67 index). They frequently arise in the lung (small and large-cell lung cancer) but rarely from the gastrointestinal tract. Due to their rarity, very little is known about digestive NEC and few studies have been conducted. Therefore, most of therapeutic recommendations are issued from work on small-cell lung cancers (SCLC). Recent improvement in pathology and imaging has allowed for better detection and classification of high-grade NEN. The 2019 World Health Organization (WHO) classification has described a new entity of well-differentiated grade 3 neuroendocrine tumors (NET G-3), with better prognosis, that should be managed separately from NEC. NEC are aggressive neoplasms often diagnosed at a metastatic state. In the localized setting, surgery can be performed in selected patients followed by adjuvant platinum-based chemotherapy. Concurrent chemoradiotherapy is also an option for NEC of the lung, rectum, and esophagus. In metastatic NEC, chemotherapy is administered with a classic combination of platinum salts and etoposide in the first-line setting. Peptide receptor radionuclide therapy (PRRT) has shown positive results in high-grade NEN populations and immunotherapy trials are still ongoing. Available therapies have improved the overall survival of NEC but there is still an urgent need for improvement. This narrative review sums up the current data on digestive NEC while exploring future directions for their management.

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 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.

scholarly journals Somatostatin receptor expression in parathyroid neoplasms

2019 ◽  
Vol 8 (8) ◽  
pp. 1213-1223 ◽  
Author(s):  
Sara Storvall ◽  
Helena Leijon ◽  
Eeva Ryhänen ◽  
Johanna Louhimo ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Carcinoma ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Expression ◽  
Benign Tumors ◽  
Receptor Subtypes ◽  
Receptor Imaging ◽  
Somatostatin Receptor Subtypes ◽  
Parathyroid Adenomas

Introduction Parathyroid carcinoma represents a rare cause of primary hyperparathyroidism. Distinguishing carcinoma from the benign tumors underlying primary hyperparathyroidism remains challenging. The diagnostic criteria for parathyroid carcinoma are local and/or metastatic spreading. Atypical parathyroid adenomas share other histological features with carcinomas but lack invasive growth. Somatostatin receptors are commonly expressed in different neuroendocrine tumors, but whether this also holds for parathyroid tumors remains unknown. Aim Our aim is to examine the immunohistochemical expression of somatostatin receptor 1–5 in parathyroid typical adenomas, atypical adenomas and carcinomas. Methods We used a tissue microarray construct from a nationwide cohort of parathyroid carcinomas (n = 32), age- and gender-matched typical parathyroid adenomas (n = 72) and atypical parathyroid adenomas (n = 27) for immunohistochemistry of somatostatin receptor subtypes 1–5. We separately assessed cytoplasmic, membrane and nuclear expression and also investigated the associations with histological, biochemical and clinical characteristics. Results All parathyroid tumor subgroups expressed somatostatin receptors, although membrane expression appeared negligible. Except for somatostatin receptor 1, expression patterns differed between the three tumor types. Adenomas exhibited the weakest and carcinomas the strongest expression of somatostatin receptor 2, 3, 4 and 5. We observed the largest difference for cytoplasmic somatostatin receptor 5 expression. Conclusions Parathyroid adenomas, atypical adenomas and carcinomas all express somatostatin receptor subtypes 1–5. Somatostatin receptor 5 may serve as a potential tumor marker for malignancy. Studies exploring the role of somatostatin receptor imaging and receptor-specific therapies in patients with parathyroid carcinomas are needed.

scholarly journals Analysis of miR-29 Serum Levels in Patients with Neuroendocrine Tumors—Results from an Exploratory Study

2020 ◽  
Vol 9 (9) ◽  
pp. 2881
Author(s):  
Burcin Özdirik ◽  
Anna K. Stueven ◽  
Raphael Mohr ◽  
Lukas Geisler ◽  
Alexander Wree ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Malignant Tumors ◽  
Somatostatin Receptor ◽  
Tumor Biology ◽  
Serum Levels ◽  
Tumor Stage ◽  
Receptor Expression ◽  
Related Factors ◽  
Ki 67 ◽  
Clinical Records

Background and aims: Due to its involvement in tumor biology as well as tumor-associated stroma cell responses, recent data suggested a potential role of miR-29 as a biomarker for different malignancies. However, its role in neuroendocrine tumors (NETs) is only poorly understood. Methods: We measured circulating levels of miR-29b in 45 patients with NET and compared them to 19 healthy controls. Results were correlated with clinical records. Results: In our cohort of NET patients treated between 2010 and 2019 at our department, miR-29b serum levels were significantly downregulated when compared to healthy control samples. Further, a significant correlation between chromogranin A (CgA) and relative miR-29b levels was noted. However, serum levels of miR-29b were independent of tumor-related factors such as proliferation activity according to Ki-67 index, tumor grading, the TMN stage of malignant tumors, somatostatin receptor expression or clinical features such as functional or non-functional disease and presence of tumor relapse. Finally, in contrast to previous results from other malignancies, miR-29b serum levels were not a significant predictor of overall survival in NET patients. Conclusion: Our data suggest a role for miR-29b serum levels as a previously unrecognized biomarker for diagnosis of NET. However, miR-29 does not allow for predicting tumor stage or patients’ outcome.

scholarly journals Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Tae Nakano-Tateno ◽  
Kheng Joe Lau ◽  
Justin Wang ◽  
Cailin McMahon ◽  
Yasuhiko Kawakami ◽  
...  
Keyword(s):  
Treatment Options ◽  
Somatostatin Receptor ◽  
Pituitary Tumors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Current Treatment ◽  
Chemotherapeutic Drugs ◽  
Clinical Level ◽  
Medical Therapies ◽  
Surgical Treatments

Up to 35% of aggressive pituitary tumors recur and significantly affect mortality and quality of life. Management can be challenging and often requires multimodal treatment. Current treatment options, including surgery, conventional medical therapies such as dopamine agonists, somatostatin receptor agonists and radiotherapy, often fail to inhibit pituitary tumor growth. Recently, anti-tumor effects of chemotherapeutic drugs such as Temozolomide, Capecitabine, and Everolimus, as well as peptide receptor radionuclide therapy on aggressive pituitary tumors have been increasingly investigated and yield mixed, although sometimes promising, outcomes. The purpose of this review is to provide thorough information on non-surgical medical therapies and their efficacies and used protocols for aggressive pituitary adenomas from pre-clinical level to clinical use.

Somatostatin receptor (SSTR) expression and proliferative index (Ki 67) in 100 patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs): Clinical-pathological correlation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14598-e14598
Author(s):  
Juan Manuel O'Connor ◽  
Veronica Pesce ◽  
Guillermo Ariel Mendez ◽  
Claudia Bestani ◽  
Fabiana Marmissolle ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Univariate Analysis ◽  
Receptor Expression ◽  
Nuclear Antigen ◽  
Rank Test ◽  
Proliferative Index ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Kaplan Meier ◽  
Well Differentiated

e14598 Background: Somatostatin receptor expression (SSTR), mainly subtypes 2 and 5, is a feature of well differentiated GEP-NETs. Such expression has a prognostic and predictive value for the use of somatostatin analogs.Ki 67, present during the cycle phases (G1, S, G2 y M) is a nuclear antigen associated with cell proliferation. The correlation between both clinical and pathological factors is under active investigation in patients with GEP-NETs. Methods: An analysis including 100 patients in the database of the Argentum Group was performed. Consecutive patients were included during the 2006-2007 period. In all cases, a centralized revision of the sample was conducted for diagnosis confirmation.The study of SSTR receptors in tissue and Ki67 was conducted using IHQ.The Kaplan-Meier method was used to analyse survival. Log-rank test was used for the comparative analysis of the variables of interest. Results: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. The univariate analysis showed significant differences in the expression of SSTR2 (a) but not in the expression of SSTR 5.The expression of the proliferative index (Ki 67) was associated with significant differences in relation to OS at 5 years, 84% (Ki 67 under or equal to 2%), 66% (Ki 67 between 3 and 15%) and 13% (Ki 67 over 15%). The OS at 5 years in patients with SSTR 2/5 positive and Ki 67 under 2% was 86%, 64% in pts. with SSTR 2/5 positive and Ki 67 over 2% and 20 % in pts. with SSTR 2/5 negative, independent Ki 67 (p .0023). Conclusions: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. In the population with GEP-NETs under study, a subgroup of patients with a better prognosis was identified in association with the expression of SSTR 2/5 and Ki67 below 2%. The assessment of SSTR 2(a) and 5 in tissues, together with the study of the proliferative index are a useful tool for prognosis assessment in these patients.

Somatostatin receptor imaging of olfactory neuroblastoma

1996 ◽  
Vol 110 (12) ◽  
pp. 1161-1163 ◽  
Author(s):  
Hans A. Ramsay ◽  
Kalevi J. A. Kairemo ◽  
Antti P. Jekunen
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Olfactory Neuroblastoma ◽  
Receptor Expression ◽  
Treatment Modalities ◽  
Somatostatin Analogue ◽  
Receptor Imaging ◽  
Rare Tumour ◽  
Recurrent Tumour ◽  
Base Of The Skull

AbstractNeural-crest tumours, including neuroblastomas, express somatostatin receptors. This can be shown by radionuclide labelling of octreotide, a somatostatin analogue. Studies on imaging with this substance have dealt with childhood neuroblastomas. Olfactory neuroblastoma (aesthesioneuroblastoma) is a rare tumour in which somatostatin receptor content has not been analysed, nor have radionuclide methods for diagnostic purposes been described. We report a case of olfactory neuroblastoma, in which scanning with m In-labelled octreotide was performed. A strong uptake was seen at the base of the skull. This was confirmed as a recurrent tumour by magnetic resonance (MR) imaging. Uptake was also observed in the neck and chest, indicating extensive spread of the disease.Somatostatin receptor expression has been shown to correlate with prognosis in childhood neuroblastoma. The accuracy of labelled octreotide in the diagnosis of olfactory neuroblastoma indicates that it might be useful in radionuclide therapy of patients with advanced disease, when no other treatment modalities are available.

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