scholarly journals Multicenter Analysis of Presacral Neuroendocrine Neoplasms—Clinicopathological Characterization and Treatment Outcomes of a Rare Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Sami Matrood ◽  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Sebastian Krug ◽  
Harald Lahner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Outcomes ◽  
Rare Disease ◽  
Median Overall Survival ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Receptor Imaging ◽  
Presacral Space

Background and AimsNeuroendocrine neoplasms (NENs) of the presacral space are an extremely rare disease entity with largely unknown outcome and no established standard of care treatment. Therefore, we wanted to analyze clinical presentation, histopathological findings, treatment outcomes, and prognosis in a multicentric patient cohort.MethodsWe searched local databases of six German NEN centers for patients with presacral NEN. Retrospective descriptive analyses of age, sex, stage at diagnosis, symptoms, grade, immunohistochemical investigations, biomarkers, treatment, and treatment outcome were performed. Kaplan–Meier analysis was used to determine median overall survival.ResultsWe identified 17 patients (11 female, 6 male) with a median age of 50 years (range, 35–66) at diagnosis. Twelve cases presented initially with distant metastases including bone metastases in nine cases. On pathological review the majority of patients had well-differentiated G2 tumors. Immunohistochemical profile resembled rectal NENs. All but one patient had non-functioning tumors. Somatostatin receptor imaging was positive in 14 of 15 investigated cases. Eight patients were treated surgically including palliative resections; 14 patients received somatostatin analogs with limited efficacy. With 14 PRRTs completed, 79% showed clinical benefit, whereas only one patient with neuroendocrine carcinoma (NEC) responded to chemotherapy. Treatment with everolimus in three patients was not successful, whereas cabozantinib resulted in a disease stabilization in a heavily pretreated patient. During a median observation period of 44.5 months, 6 patients died. Median overall survival was not reached.ConclusionPresacral NEN are histopathologically similar to rectal NENs. Presacral NEN should be considered as possible primary in NEN of unknown primary. The majority of tumors is non-functioning and somatostatin receptor positive. PRRT demonstrated promising activity; tyrosine kinase inhibitors warrant further investigations. Further molecular characterization and prospective evaluation of this rare tumor entity are needed.

Inferior outcome of neuroendocrine tumor patients negative on somatostatin receptor imaging

2020 ◽  
Vol 27 (11) ◽  
pp. 615-624
Author(s):  
Julie Refardt ◽  
Wouter T Zandee ◽  
Tessa Brabander ◽  
Richard A Feelders ◽  
Gaston J H Franssen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Tumor Biology ◽  
Survival Rates ◽  
Receptor Imaging ◽  
Cox Regression Analysis

Sufficient expression of somatostatin receptor (SSTR) in well-differentiated neuroendocrine tumors (NETs) is crucial for treatment with somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) using radiolabeled SSAs. Impaired prognosis has been described for SSTR-negative NET patients; however, studies comparing matched SSTR-positive and -negative subjects who have not received PRRT are missing. This retrospective analysis of two prospectively maintained NET databases aimed to compare matched metastatic grade 1 or 2 SSTR-positive and –negative NET patients. SSTR-negativity was defined as having insufficient tumor uptake on diagnostic SSTR imaging. Patients that underwent PRRT were excluded. Seventy-seven SSTR-negative and 248 SSTR-positive grade 1–2 NET patients were included. Median overall survival rates were significantly lower for SSTR-negative compared to SSTR-positive NET patients (53 months vs 131 months; P < 0.001). To adjust for possible confounding by age, gender, grade and site of origin, 69 SSTR-negative NET patients were propensity score matched to 69 SSTR-positive NET patients. Group characteristics were similar, with the exception of SSTR-negative patients receiving more often chemotherapy and targeted treatment. The inferior survival outcome of SSTR-negative compared to SSTR-positive NET patients persisted with a median overall survival of 38 months vs 131 months (P = 0.012). This relationship upheld when correcting for the main influencing factors of having a higher grade tumor or receiving surgery in a multivariate Cox regression analysis. In conclusion, we showed that propensity score-matched SSTR-negative NET patients continue to have a worse prognosis compared to SSTR-positive NET patients despite receiving more aggressive treatment. Differences in tumor biology likely underlie this survival deficit.

scholarly journals Gynecologic large cell neuroendocrine carcinoma: A review

Rare Tumors ◽  
2020 ◽  
Vol 12 ◽  
pp. 203636132096840
Author(s):  
Grant Burkeen ◽  
Aman Chauhan ◽  
Rohitashva Agrawal ◽  
Riva Raiker ◽  
Jill Kolesar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Cell Lineage ◽  
Large Cell ◽  
Driver Mutations ◽  
Neuroendocrine Neoplasms ◽  
Disease Biology ◽  
Oncogenic Pathways ◽  
Pubmed Search ◽  
Disease Stages

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with a median age of 54 years. Median overall survival was 8 months. 13 LCNEC cases of uterine origin were identified; 12 out of 13 were of endometrial origin and the median age was 71 years. The majority of patients presented with Stage III/IV disease (stages I–IV were 31%, 8%, 38%, and 23%, respectively). Gynecologic LCNEC is an aggressive malignancy. Our current understanding of the disease biology is very limited. Efforts are required to better understand the genomic and molecular characterizations of gynecological LCNEC. These efforts will elucidate the underlying oncogenic pathways and driver mutations as potential targets.

scholarly journals Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Libo Zhang ◽  
Douglass C. Vines ◽  
Deborah A. Scollard ◽  
Trevor McKee ◽  
Teesha Komal ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Expression Profiles ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Xenograft Model ◽  
Tumor Growth Inhibition ◽  
Receptor Imaging ◽  
Expression Levels ◽  
Variable Expression ◽  
Xenograft Models

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.

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 Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors

2010 ◽  
Vol 17 (1) ◽  
pp. R53-R73 ◽  
Author(s):  
Dik J Kwekkeboom ◽  
Boen L Kam ◽  
Martijn van Essen ◽  
Jaap J M Teunissen ◽  
Casper H J van Eijck ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pet Imaging ◽  
Tumor Regression ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Receptor Subtype ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Pet Tracer ◽  
First Choice

Somatostatin receptor imaging (SRI) with [111In-DTPA0]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [68Ga-DOTA0,Tyr3]octreotate or [68Ga-DOTA0,Tyr3]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111In-, 90Y-, or 177Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [177Lu-DOTA0,Tyr3]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [177Lu-DOTA0,Tyr3]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.

Neuroendokrine Tumoren im Gastrointestinaltrakt

2019 ◽  
Vol 144 (21) ◽  
pp. 1509-1521
Author(s):  
Lutz Philipp Breitling ◽  
Anja Rinke ◽  
Thomas Mathias Gress
Keyword(s):  
Somatostatin Receptor ◽  
Growth Control ◽  
Interdisciplinary Team ◽  
Neuroendokrine Tumoren ◽  
Complete Resection ◽  
Neuroendocrine Neoplasms ◽  
Receptor Imaging ◽  
Symptomatic Therapy ◽  
Somatostatin Receptor Imaging ◽  
Curative Intention

AbstractNeuroendocrine neoplasms (NEN) are increasingly diagnosed tumors with great clinical and prognostic heterogeneity. One of the peculiarities of NEN is the presence of a clinical hormone syndrome in about 30 % of cases. Somatostatin receptor imaging plays an important role in the diagnosis of spreading and in the planning of therapy. NEN patients should be co-supervised by specialized centers and if possible treated as part of studies. In the case of NEN with no or only circumscribed metastases, complete resection in curative intention is generally the highest therapeutic goal. Small neuroendocrine tumors (NET) G1 of the stomach, duodenum and rectum can be curatively endoscopically resected. In the case of a metastatic, non-curative disease, an antiproliferative therapy with the aim of growth control takes place. In patients with functionally active tumors, an antisecretory or symptomatic therapy is used to control the hormone syndrome. The treatment of metastatic NET is often multimodal and must be established by an experienced interdisciplinary team. The prognosis of NEN is mainly determined by the stage at the time of diagnosis, tumor differentiation, grading and localization of the primary tumor.

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 Immunohistochemical Expression of Somatostatin Receptor Subtypes in a Panel of Neuroendocrine Neoplasias

2019 ◽  
Vol 67 (10) ◽  
pp. 735-743 ◽  
Author(s):  
Satu M. Remes ◽  
Helena L. Leijon ◽  
Tiina J. Vesterinen ◽  
Johanna T. Arola ◽  
Caj H. Haglund
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Membrane Receptors ◽  
Receptor Subtypes ◽  
Receptor Imaging ◽  
Primary Tumors ◽  
Somatostatin Receptor Subtypes ◽  
Negative Controls ◽  
G Protein Coupled

Neuroendocrine neoplasias (NENs) are known to express somatostatin receptors (SSTRs) 1–5, which are G-protein-coupled cell membrane receptors. Somatostatin receptor imaging and therapy utilizes the SSTR expression. Synthetic somatostatin analogs with radioligands are used to detect primary tumors, metastases, and recurrent disease. Receptor analogs are also used for treating NENs. Furthermore, commercially available SSTR antibodies can be used for the immunohistochemical (IHC) detection of SSTRs. We investigated different SSTR antibody clones applying diverse IHC protocol settings to identify reliable clones and feasible protocols for NENs. A tissue microarray including NENs from 12 different primary sites were stained. Only UMB clones were able to localize SSTR on the cell membranes of NENs. SSTR2 (UMB1) emerged as the most common subtype followed by SSTR5 (UMB4) and SSTR1 (UMB7). SSTR3 (UMB5) expression was mainly cytoplasmic. Yet, SSTR4 expression was weak and located primarily in the cytoplasm. Thus, appropriate IHC protocols, including proper positive and negative controls, represent requirements for high-quality NEN diagnostics and for planning personalized therapy.

scholarly journals Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayank Patel ◽  
Isabel Tena ◽  
Abhishek Jha ◽  
David Taieb ◽  
Karel Pacak
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Rare Condition ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Well Differentiated ◽  
Succinate Dehydrogenase Subunit B

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.

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