Presence Of Somatostatin Receptors Research Articles

LANTana trial protocol: An open label, single arm, phase Ib study to evaluate the effect of pre-treatment with ASTX727 (a demethylating agent) followed by lutetium Lu 177 dotatate in patients with progressive, metastatic neuroendocrine neoplasias (NENs).

TPS4192 Background: Neuroendocrine neoplasias (NENs) are characterised by the presence of somatostatin receptors (SSTR) on cell surface, in particular SSTR2. Somatostatin and its stable analogue (SSA) bind with high affinity to SSTR2. SSA can be radiolabelled, to both stage NENs using positron emission tomography (PET), and to deliver selective radiotherapy; peptide receptor radionuclide therapy (PRRT). PRRT consists of SSA linked to the long acting radionuclide. Radiolabelled SSA binds to SSTR2 and the complex is internalised delivering high dose radiation directly to the cancer. PRRT has been significantly improve survival outcomes and maintain quality of life in metastatic disease. Suitability for PRRT depends on presence of SSTR2 as determined by PET imaging, commonly with [68Ga]-dotatate-PET. 20% of patients will have low or no uptake on [68Ga]-dotatate-PET precluding PRRT. The upstream promoter region of SSRT2 is methylated, with percentage of methylation correlating with SSTR2 expression. We have shown that the use of the demethylating agent, guadecitabine, increases uptake on PET imaging in such that tumours previously negative on PET imaging, become positive, correlating with a dose dependent increase in tumoural SSTR2 expression. Combination guadecitabine and PRRT was well tolerated in vivo models of NETs. Overall aim was to utilise [68Ga]-dotatate-PET as a biomarker of SSTR2 re-expression following treatment with the demethylating agent, ASTX727, such that patients previously unsuitable for PRRT can receive therapy, improving clinical outcome. 1) Utilise [68Ga]-dotatate-PET to image epigenetic regulation of SSTR2 in response to ASTX727. 2) Evaluate clinical efficacy and safety of ASTX727 pre-treatment in combination with PRRT. 3) Explore impact on quality of life of combination therapy. Methods: 27 patients with no or equivocal uptake on [68Ga]-dotatate-PET will be enrolled. [68Ga]-dotatate-PET will be performed at baseline and after 8days of ASTX727 (oral, fixed dose 100mg cedazuridine + 35mg decitabine). If there is a significant increase in PET uptake, patients will receive combination ASTX727 and PRRT (Lutathera). Treatment will be repeated every 2months for 4 cycles. Response assessment (RECIST 1.1), tolerability and QoL will be assessed at start of each cycle. Tumour biopsies will be taken at baseline, and after cycle1 of ASTX727 (n=5), for SSTR2 methylation. Methylation will be correlated with PET uptake and outcome. LINE-1 methylation in peripheral blood monocytes will be assessed throughout. Current enrolment: 4. Clinical trial information: NCT05178693 .

Successful Treatment with <sup>177</sup>Lutetium-Dotatate and Maintenance Octreotide in a Patient with Esthesioneuroblastoma with Central Nervous System Invasion: Case Report and Review of the Literature

This article presents a case of a patient with relapsed esthesioneuroblastoma (ENB), an aggressive rare tumor that arises from the specialized sensory epithelial olfactory cells in the skull base area, which was initially treated with endoscopic surgery, followed by adjuvant radiotherapy. After local relapse, new surgical approaches and subsequent lines of platin-based chemotherapy were performed. A PET-CT with 68GALIUM DOTATATOC (PET-DOTATOC) showed intense uptake of disease, compatible with the presence of somatostatin receptors, in the face, nodes, liver, bones, and meningeal area. Treatment with 4 cycles of 177Lutetium-Dotatate was performed, followed by maintenance octreotide, with a major radiological and clinical response that is lasting more than 1 year after treatment. This article describes a rare case of a skull-base tumor, with multiple recurrences, in which disease control was achieved with a targeted Peptide Receptor Radionuclide Therapy (PRRT) with 177Lutetium-Dotatate, and discusses factors that could influence the incorporation of this form of therapy. Previous case reports proved the potential efficacy of this therapy usually given for low-grade neuroendocrine tumors and will be carefully reviewed.

Neuroendocrine tumor of the small bowel and carcinoid syndrome: diff culties in diagnosis: a case report

Background. Neuroendocrine tumors (NETs) of the small bowel are rare and slow-growing tumors arising from intraepithelial endocrine cells that synthesize serotonin. Diagnosis of these tumors poses a signifcant challenge because they are often not diagnosed until an advanced stage, since the tumor may be asymptomatic or accompanied by non-specifc gastrointestinal complaints. Approximately 40 % of patients develop carcinoid syndrome due to hormonal activity of NETs. Surgery is the mainstay treatment of locoregional small bowel NETs. The fve-year survival rate of patients is about 85 %, with a median rate of 9.3 years. Case description. The female patient complained of facial redness and, to a lesser extent, redness of the skin of the trunk, accompanied by a feeling of heat, severe headache, lacrimation, and general feeling of weakness. The patient unsuccessfully received symptomatic treatment prescribed by various specialists (gynecologist, therapist, psychiatrist, endocrinologist, etc.) for 14 years. Based on the comprehensive examination, NET of the small bowel was diagnosed. The patient underwent radical surgery (pT2N1M0, stage IIIB, G2), but taking into account the unfavorable prognostic factors (metastases in the mesenteric lymph node, presence of carcinoid syndrome, elevated biochemical markers, Ki67 level = 6 %, presence of somatostatin receptors of 2 and 5 types in 60 % of tumor cells), the patient was further treated with somatostatin analogues. Conclusion. When small bowel NETs are suspected, especially with the evidence of carcinoid syndrome, every effort should be made to confrm the diagnosis using a combination of anatomical and functional tumor imaging with biochemical markers.

Molecular and Clinical Implications of Somatostatin Receptor Profile and Somatostatin Analogues Treatment in Oral Cavity Squamous Cell Carcinoma.

Simple SummaryThe treatment of oral squamous cell carcinoma (OSCC) represents a significant problem worldwide. Among cancers with the highest incidence, OSCC renders one of the worst prognoses. Therefore, novel prognostic biomarkers and therapeutic tools to tackle OSCC are urgently needed. Somatostatin-analogues (SSA) are an invaluable therapeutic option in the treatment of several cancers. We aimed to determine the expression levels of all somatostatin-receptors (SSTs) in OSCC, compared to adjacent healthy control tissues, to analyze the relationship of SSTs expression with key clinical and histopathological data, and to explore the direct in vitro effect of different SSAs on OSCC cancer cells. Our findings highlight a potential role of SST2 as a good prognostic biomarker for recurrence and metastasis in OSCC and unveil that SSA exerts antitumoral effects on OSCC cells, providing a relevant clinical conclusion, which should be soon tested for their use in humans.Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.

Somatostatin analogues in the therapy of neuroendocrine tumors: Indications, contraindications, side-effects

The presence of somatostatin receptors (SSTRs) is crucial in planning the therapy of patients with neuroendocrine tumors. This applies especially to patients in whom surgery has proven unsuccessful or there are contraindications for it. Increased SSTR expression has been observed in many cancers originating in the neuroendocrine system. Among them we distinguish anterior pituitary adenomas producing GH in excess and leading to the development of acromegaly, adenocorticotropic adenomas that autonomously synthesize ACTH, which leads to the development of ACTH-dependent Cushing’s syndrome (Cushing’s disease), as well as adenomas of the anterior pituitary from thyrotropic cells. Rich expression of these receptors has been confirmed in epithelial tumors of neuroendocrine origin in the gastrointestinal tract, pancreas and lungs. Somatostatin analogues, also called somatostatin receptor ligands, are effective in symptomatic therapy; they enable disease control, exhibit anti-proliferative effects and allow hormonal balance, which reduces mortality among patients and improves their quality of life. The antitumor effect of somatostatin analogues has been proven in in vitro and in vivo studies. In therapy they are usually well tolerated and safe. For many years, somatostatin analogues have maintained an important place in the treatment of neuroendocrine tumors and are still the subject of many studies. The aim of the study is to analyze, based on available literature, therapeutic indications for the use of somatostatin analogues, taking into account contraindications for therapy and its possible side effects.

Evaluation of the expression of somatostatin receptors by immunohistochemistry in neuroendocrine tumors of the small intestine.

Most neuroendocrine neoplasms (NEN) are characterized by thepresence ofsomatostatin receptors (SSTR) which we use in location diagnostics and treatment. Theaim ofthis study was to evaluate theexpression ofsomatostatin receptors by immunohistochemistry in tissue obtained after surgery oftheprimary focus in thesmall intestine. The group ofpatients consisted of41 people, in 18 cases theprimary tumor was in thejejunum and in 23 in theileum. Theimmunohistochemical method was used to visualize thereceptors, using polyclonal antibodies in atwo-stage peroxidase method. In patients with NEN ofthesmall intestine, theSSTR2a and SSTR5 receptors are most commonly expressed, followed by SSTR2b and 3. In statistical analysis, it was shown that theexpression ofsomatostatin receptors was not dependent on theprimary site ofthetumor (p>0.05). Thedependence ofSSTR expression on histological maturity is evident. SSTR1, SSTR2b, SSTR3 and SSTR5 are more common in tumors with grading G1 (p<0.05). In thestudy group, theexception was SSTR2a, whose incidence was comparable in both groups (p=0.35). In NEN ofthesmall intestine, theexpression SSTR2a and SSTR5 is themost common.

2609 Use of Dotatate Scan to Establish Diagnosis of a Neuroendocrine Tumor

INTRODUCTION: Neuroendocrine tumors (NETs) are rare malignancies, defined at a cellular level by the presence of somatostatin receptors, which has recently been exploited in the development of positron-emitting somatostatin analogs for use in the 68-Gallium DOTATATE PET scan (hereafter “Dotatate scan”). Compared to previously-used technology, the Dotatate scan has shown dramatic improvements in sensitivity for lesion detection. The Dotatate scan exposes patients to lower doses of radiation, and is completed much more quickly. We present a case of a new diagnosis of a neuroendocrine tumor that illustrates multiple benefits of Dotatate scan including improved lesion detection and characterization which quickly led to changes in the treatment plan for a patient who previously was given a presumptive diagnosis of advanced pancreatic adenocarcinoma. CASE DESCRIPTION/METHODS: A 52-year-old man with history of two episodes of pancreatitis presented with one day of acute-onset epigastric pain, diarrhea, and nausea. Initial ultrasound and computed tomography (CT) scan demonstrated numerous hypervascular lesions in the liver, a mesenteric mass with associated lymphadenopathy, and a possible pancreatic tail lesion, leading to clinical concern for pancreatic adenocarcinoma. Upon further questioning, the patient reported 12–18 months of intermittent flushing and rash. A Dotatate scan revealed increased avidity in the hepatic and mesenteric lesions suggestive of carcinoid malignancy. The improved lesion characterizations provided by the Dotatate scan were useful for identifying the larger small bowel lesion as the likely primary tumor, as well as for surgical planning for debulking. Subsequent serum and urine tests were consistent with carcinoid malignancy, and a biopsy of a liver lesion confirmed the diagnosis of metastatic carcinoid tumor. The pancreatic lesion also demonstrated uptake on the scan, most consistent with a metastasis to the pancreas, with a confirmatory biopsy via endoscopic ultrasound pending. DISCUSSION: We demonstrate the utility of the Dotatate scan to support the rapid diagnosis of a neuroendocrine tumor, to assist in identification of the likely primary lesion, and to better characterize the extent of disease. Dotatate scans have been infrequently used due to novelty and cost, but cases such as this demonstrate that the cost can be well-justified in the right clinical setting.

1401P - An Australian multi-centre experience of the use of peptide receptor radionuclide therapy for bronchial carcinoid tumours

BackgroundPeptide receptor radionuclide therapy (PRRT) is an established treatment modality for advanced midgut neuroendocrine tumours (NET) (1), based on the presence of somatostatin receptors (SSTR). This therapy should be effective for SSTR expressing NETs from all sites of origin. SSTR expression correlates with grade, with higher expression seen in lower grade disease (2). No trials of PRRT have been undertaken in patients with typical carcinoid (TC) or atypical carcinoid (AC) of bronchial origin. Most guidelines for bronchopulmonary NET either do not comment on PRRT or acknowledge lack of data. However, small retrospective case series, reporting 11 to 34 patients, suggest potential benefit from lutetium (177Lu)-based PRRT (3-10). MethodsWe undertook a retrospective chart review of patients with TC and AC who had received at least one dose of lutetium-based PRRT in six major NET centres across Australia. Demographics, histopathology and information on clinical course were collected. ResultsData was collected from 53 patients treated across six centres between January 2002 and 2019. Patient details from four centres are presented in the table. Each of these four centres had 1, 8, 9 and 15 eligible patients respectively. Of these 33 patients, 22 are still alive, with the duration of follow up post the first cycle of PRRT ranging from 3 to 67 months. Analysis of the whole cohort for treatment, dose, response, patient and disease outcomes will be presented.Table1401P Clinical characteristics (Four centres in South Australia, Victoria, New South Wales)TableGenderNumber (n=33)Male22 (67%)Female11 (33%)Age (years)<7021 (64%)≥7012 (36%)HistopathologyTC12 (36%)AC21 (64%)Current statusAlive22 (67%)Dead11 (33%) ConclusionsThis is the largest series of patients with bronchial carcinoid treated with PRRT to be reported to date. Evaluation of lutetium-based PRRT in a prospective clinical trial is of interest to validate its efficacy as a therapeutic option. Legal entity responsible for the studyMonash Health. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Prognostic Significance of Somatostatin Receptor Heterogeneity in Progressive Neuroendocrine Tumor Treated with Lu-177 DOTATOC or Lu-177 DOTATATE.

One of the primary prerequisites for peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine tumors (NET) is the presence of somatostatin receptors (SSTR) on NET cells. NET are highly heterogeneous and an individual patient as well as separate metastases can harbor cells with different clones, which influence the SSTR expression on NET cells. With this background we looked into our institutional database to assess the prognostic significance of quality of SSTR expression on SSTR PET/CT imaging in patients treated with at least two cycles of Lu-177 DOTATOC or Lu-177 DOTATATE. Clinical reports and images from 65 (25 females, 40 males; 65 ± 11 years old) patients with progressive grade 1 or grade 2 NET with 2-5 therapy cycles of PRRT with an average administered dose of 6.6 ± 0.97GBq Lu-177 DOTATOC or Lu-177 DOTATATE were analyzed. All patients were examined with baseline Ga-68 DOTATATE or Ga-68 DOTATOC PET/CT (PET). Quality of SSTR expression as a measure of heterogeneity on indexed lesions was assessed visually. Patients were followed for a median duration of 25months after the first PRRT (range 5-77months). A total of 70% of the patients received three or more therapy cycles. Twenty-six patients (40%) were treated with PRRT as first or second line while 39 (60%) as third line or more. SSTR expression was heterogeneous in 28 (44.4%) and homogeneous in 35 (55.6%) patients. Disease stabilization could be achieved in 23 patients (35.4%), whereas 17 (26.1%) showed partial remission and 25 patients (38.5%) had disease progression. Median OS was not reached. The 24-month survival rate of the whole study cohort was 83%. In univariate analyses, factors influencing OS were carcinoid heart disease, carcinoid syndrome and quality of SSTR expression (p < 0.05). Patients with heterogeneous SSTR expression on target lesions had a significantly lower OS (p = 0.01). Median time to progression in total patient population was found to be 40months. Patients with heterogeneous SSTR expression on target lesions had significantly lower TTP (26months vs 54months log Rank p = 0.013). By multivariate analyses, quality of SSTR was found to be the only prognostic factor for OS (p = 0.04; HR = 3.68) and also for TTP (p = 0.03; HR = 3.09). Visual assessment of SSTR heterogeneity has both predictive and prognostic value in progressive grade 1 or grade 2 NET patients undergoing PRRT.

Somatostatin Receptor Positron Emission Tomography: Beyond Gastroenteropancreatic Neuroendocrine Tumors

Similar to various gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), somatostatin receptors (SSTRs) are overexpressed in a wide array of malignant and benign conditions. Using somatostatin positron emission tomography (PET) analogs ([68Ga]DOTA-peptides) this overexpression of SSTRs can be exploited for clinical management in terms of diagnosis, therapy, and for peptide receptor radionuclide therapy (PRRT). Recent reports suggest that [68Ga]DOTA-peptide PET tracers have an emerging role in the management of wide array of non-GEP-NETs due to overexpression of SSTRs. The potential role of SSTR-PET imaging in the management of medullary thyroid cancer, paraganglioma, Merkel cell carcinoma, phosphaturic mesenchymal tumors, and inflammation will be discussed. The emerging role of theranostic and personalized medicine with PRRT using peptides labeled with yttrium-90 (90Y) or lutetium-177 (177Lu) beta emitters will also be discussed. SSTR-PET imaging with [68Ga]DOTA-peptides has utility in malignant and benign conditions other than GEP-NETs. Combining SSTR-PET with other anatomic and functional imaging modalities has demonstrated superior diagnostic accuracy. The presence of SSTRs in these conditions opens up new possibilities in the management of these conditions in terms of imaging and therapeutics.

68Ga-DOTATATE PET/CT to predict response to peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumours (NETs).

4093 Background: PRRT represents a step change in NET management, significantly improving survival. However, objective response to PRRT, approximately 20%, is poor. There are no predictive biomarkers of response. Uptake on 68Ga-DOTATATE PET/CT imaging is used to assess patient suitability for PRRT, highlighting the presence of somatostatin receptors (SSTR) to which PRRT selectively binds. We hypothesise that the density of SSTRs, as defined by a minimum SUV uptake, predicts for response to PRRT. Methods: 54 patients underwent PRRT. Modified PERCIST assessment was performed: up to 2 target lesions per organ were identified and volume of interest drawn. Maximum 5 targets were counted. Average SUV (SUVave) was calculated by dividing sum of SUVmax of target lesions by number of lesions. Response was determined by RECIST 1.1. Ki67 and SSTR2 expression were assessed on tumour samples and compared with SUVave. Results: Response to PRRT: partial response (PR) 26%, stable disease (SD) 40% progressive disease (PD) 12%. Response to PRRT predicted progression free survival (PFS) with patients experiencing PR having a PFS 2.5x that of those with SD, and almost 20x as long as PD. Using ROC curve analysis, SUVave of 21.6 predicted for tumour response with high sensitivity (0.74) and specificity (1.0), p = 0.15, 95% CI 0.71-3.96. No association between baseline SUVave and SSTR2 or Ki-67 was observed. SUVave &gt; 21.6 was an independent predictor of clinical outcome. Conclusions: Objective response to PRRT defines a subset of patients with markedly improved PFS. SUVave 21.6 defines a threshold below which patients have a poor response to PRRT. This threshold should be taken forward into prospective study.

Diagnostic Computed Tomography Coregistration With In-111-DTPA-Octreotide Single Photon Emission Tomography/Low-Dose Computed Tomography.

In-111-DTPA-octreotide (OctreoScan) is still pivotal for neuroendocrine tumor imaging, despite the introduction of Ga-68-octreotide tracers. Low-dose computed tomography (LDCT) assists in the localization of SPECT findings but often results in uncertain interpretation. This retrospective study evaluates the impact of coregistration of In-111-DTPA-octreotide SPECT/LDCT with diagnostic CT on interpretation. Thirty-five consecutive studies, in which coregistration was performed because of uncertain interpretation, were evaluated. Presence of somatostatin receptors was categorized retrospectively as definitely positive, probably positive, probably negative, or definitely negative with and without rigid registration with diagnostic CT, and possible added value of coregistration was evaluated. Coregistration was performed in 35 studies. However, on subsequent reading, 4 SPECT/CTs yielded definite results and were omitted. Coregistration was helpful in 30 of the remaining 31 cases, changing reading to definitely positive (7) or to definitely negative (23). In 13 of the 23 cases, diagnosis changed from probably positive to definitely negative. Coregistration contributed in 42 of 48 sites, with greatest benefit in the liver (13/14), pancreas (10/10), and lymph nodes (6/6). Coregistration is becoming increasingly easier and may be utilized when SPECT/LDCT is inconclusive.

Lutetium 177-DOTA-TATE therapy for esthesioneuroblastoma: A case report.

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant tumor that accounts for 3% of all tumors of the nasal cavity. The incidence of ENB is 0.4 cases per million in the general population, and the most common symptoms are nasal obstruction and epistaxis. Previous studies have indicated the presence of somatostatin receptors in this tumor type. Common treatment strategies for ENB include resection and adjuvant radiotherapy and/or chemotherapy (combined treatment); however, the rate of recurrence is high. Treatment of neuroendocrine tumors using radionuclides bound to somatostatin analogues is well established in clinical practice. However, a standard and effective therapeutic approach has not been reported for ENB. The current study described the case of a 74-year-old female with numerous recurrences of ENB following multiple treatments and without possibility of resection. The patient was treated with the radiolabeled-somatostatin analogue, 177Lutetium-DOTA-octreotate (177Lu-DOTA-TATE), which successfully controlled the disease. This suggests that 177Lu-DOTA-TATE is a potential treatment for ENB and may represent an effective alternative and novel therapeutic strategy for this disease.

Evaluation of Survival in Gastric Nen Patients According to Tumor Characteristic -Polish Experience

ABSTRACT Aim: Aim of study was to analyze tumor biology and survival according to tumor subtype and WHO 2010 classification in Polish patients with gastric NEN. Methods: A data of 87 patients, 55 women and 32 men (mean mean age 54.7 years), with gastric NEN were analyzed. 48 pts (55,2%) had type I gastric NEN, 4 pts (4,6%)- type II and type III-28 pts (32,2%), 7 pts (8%) had MANEC. All had histopathology confirmed diagnosis, also clinical, biochemical and imaging follow-up including hormonal status, and genetic testing in case of MEN-1. All had gastroscopy as initial technique and tumor sampling. Imaging technique performed CT or MRI and SRS-Somatostatin Receptor Scintigraphy, using 99Tc HYNICTOC (Polatom, PL). Management recommendations were issued: endoscopic or surgical treatment of type I and II (including antrectomy to abolish hypergastrinemia) and radical resection with lymph node dissection for type III and IV, or sampling in case of non-resectable tumor. In widespread NEC, patients were treated with chemotherapy platinum based regiments. In case of presence of somatostatin receptor (SST) in SRS, somatostatin analogs therapy and also peptide receptor radionuclide therapy–PRRT 90Y DOTATATE were used for NET. Results: In type I 42 had pT1/1m disease treated with endoscopy, 2 pts pT2 and one pT3. In type II - 2 of 4 pts had MEN-1 (1 with regional lymph node involvement). In type III pT2-3pts, pT3-8 and pT4-10 pts were reported, 7 pts had pTx due to non-resectable tumour. N1 noted in 75% and 71% had also distant metastases at initial diagnosis. In group with MANEC pT3 = 4 pts, pT4 = 10 pts, 2 had pT2 cancers. Consider WHO 2010 classification: NETG1 53 pts (61%), NETG2-11 pts (13%), NECG3-23 pts (26%) including those with MANEC. Mean Ki-67 in NETG2 tumors was 8.1% and NECG3 56%. There were 50 pts with gastric NETG1 out of those 45 pts with type I, 11 with NETG2, 19 with NECG3, 6 MANETS (all NECG3). In type I there were 2 deaths, not related to tumor. In type II single death in pt with MEN-1. There were 21 deaths in type III gastric NEN (75%) during follow-up. Median OS in type I was N.R, (type II 4 cases), type III 14.5M and in MANEC 20M (P Conclusions: Base of our results there is significant difference in OS according to tumors groups. Type III and NECG3 base on Ki-67 had similar median OS. Disclosure: All authors have declared no conflicts of interest.

P06.08 * SYSTEMIC TREATMENT OF MENINGIOMAS: IS THERE A ROLE FOR LONG-ACTING SOMATOSTATIN?

BACKGROUND: Meningiomas are the most common primary brain tumors. Resection and/or radiation therapy are the treatments of choice. Medical therapies have been investigated for inoperable, recurrent and aggressive meningiomas (grade III), but the optimal medical treatment is yet to be defined. Among biologic agents somatostatin has been found to inhibit meningioma growth due to the presence of somatostatin receptors on the surface of the tumors. AIM: We retrospectively reviewed our experience with sandostatin to assess the efficacy and toxicity in the treatment of recurrent meningiomas failing standard treatments. PATIENTS AND METHOD: A total of 17 patients (7 women and 10 men, median age 65 years) with recurrent grade I or II or III meningiomas have been studied. All patients had already been treated with multiple surgeries or radiation treatments, and all had an overexpression of somatostatin receptors by octreotide scintigraphy. Before treatment KPS ranged from 60 to 90. The patients received long-acting somatostatin on a monthly administration schedule. Radiographic response on MRI has been assessed by MacDonald Criteria. RESULTS: Patients received 3 to 18 cycles (median 9) of somatostatin. Response was as follows: PR in 1 patient, MR in 1 patient, SD in 2 patients and PD in 13 patients. Progression-free survival at 6 months was 56%, while PFS ranged from 3 to 25 months with a median of 6 months. Toxicity was uncommon (2 patients) and manageable. CONCLUSION: Long acting somatostatin displays only minor activity as salvage treatment for recurrent meningiomas after surgery and radiation therapy.

Use of 111In-Pentetreotide Scan in a Subject With Treatment Refractory Atypical Meningioma

A 57-year-old man with a history of multiple recurrent atypical meningiomas (World Health Organization grade II) had several surgical resections including γ knife resection of the parafalcine meningioma, followed with a stereotactic radiosurgical ablation. Despite these treatments, an MRI scan performed 7 months later showed progression of the disease. The patient remained symptomatic with intermittent severe headaches associated with nausea, vomiting, and visual disturbance. He had a positive In-pentetreotide indicating the presence of somatostatin receptors. Therefore, he was placed on systemic Sandostatin (octreotide acetate) treatment, and at follow-up, he was clinically responsive to treatment.

Somatostain receptor (SSTR)-targeted therapy in pulmonary large-cell neuroendocrine carcinoma (LCNEC) patients with intermediate proliferation rate (PR).

e17509 Background: LCNEC is classified as a high-grade (HG) foregut-derived neuroendocrine tumor (NET), exceeded only by small-cell lung carcinoma (SCLC) in terms of aggressiveness. It is a recent disease entity, only two decades old, and uncommon: 2%-3% of all lung cancer cases. Therefore, therapy guidelines are still evolving. Methods: A single institution observational study, consecutive series. Histopathology diagnosis conformed to WHO criteria for thoracic tumors (Travis et al, IARC Press, 2004). Immunohistochemistry included proliferation Ki67 index evaluation. SSTRs' affinity was assessed either by 111 In octreotate SPECT, or by Ga68 DOTA-NOC octreotate PET CT total body scans. Results: We have treated nine metastatic LCNEC patients over the last four years. Seven were scanned for presence of somatostatin receptors; 4 were positive. Three of the four had Ki67 staining ranging 10-20% (intermediate PR, IPR), one had 80% (high PR). All four have received octreotide LAR as a therapy component. In two cases octreotide was given upfront and conferred PFS of 18 and 8 months and, in the former- regression of hepatic lesions. The other patient also received 177 Lutetium radionuclide therapy (PRRT) upon progression, resulting in uptake normalization at an hepatic mass and stabilization of other lesions. The 3rd patient had started with induction chemotherapy and then maintained imaging-confirmed stable disease and normal function, during octreotide treatment, for three years. The fourth, HG patient, survived only 8 months. Three of the 9 patients are alive with disease on treatment, surviving 25+, 57+ and one, with 50% proliferation index and a negative DOTANOC scan, has survived 16+ months, with no targeted therapy. Conclusions: This small series illustrates the diagnostic value and therapeutic implication of SSTR scans, combined with Ki67 assessment, aiming at therapy selection for IPR subgroup, receptor positive, pulmonary LCNEC patients who can benefit from octreotide targeted therapy.

Somatostatin receptors are strongly expresssed in palmoplantar sweat glands and ducts: studies of normal and palmoplantar pustulosis skin

The acrosyringium is the target for inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat-gland apparatus seems to be an immunocompetent structure that probably contributes to skin defence. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ. To obtain further information about the neuroendocrine properties of the sweat-gland apparatus by examining expression of the somatostatin receptors (SSTRs) 1-5 in healthy palmar skin and in PPP skin. Biopsy specimens were taken from 25 patients with PPP and 25 healthy controls. Immunohistochemical analysis was used to investigate expression of SSTRs 1-5. SSTRs 1-5 were expressed in both epidermal and endothelial structures. The staining intensity of the sweat-gland apparatus was more pronounced than that of the epidermis. Expression differed significantly between lesional PPP and normal plantar skin, with increased expression of SSTRs 3 and 4 in ducts in epidermis, and decreased expression of SSTR 1 in ducts in both papillary and reticular dermis. In specimens with pronounced inflammation, numerous dendritic cells with strong expression of SSTRs 1, 2 and 4 were seen, especially in the papillary dermis. The presence of SSTRs in palmoplantar skin, and specifically at high density in the sweat glands and ducts, might be of particular importance in skin neuroimmunoendocrinology. Although the relevance of the changes in SSTR expression in PPP skin compared with normal skin is unclear, our hypothesis is that these differences might influence the function of both the neuroendocrine and neuroimmunological properties of palmoplantar skin, especially in the sweat-gland apparatus.

586 IMAGING OF NEUROENDOCRINE TUMORS AND LIVER METASTASIS BY F18-DOPA PET SCANNING

Introdction: In patients with neuroendocrine tumors it is important to accurately diagnose tumor localization and metastases, biochemical activity, and progression. The initial workup for NET patients consists of morphological imaging methods by CT/MRI, combined with functional whole-body imaging with somatostatin-receptor scintigraphy (SRS). However, there may be difficulties for CT and MRI to separate tumors and mesenterial metastases from intestinal structures. Furthermore, SRS can produce false-negative findings, because of the variable affinity and expression of somatostatin receptors and the restricted resolution of gamma cameras and single-photon-emission tomography (SPECT) methods. Methods: A new imaging method for neuroendocrine tumors using PET and the catecholamine precursor 6-[fluoride-18]fluorolevodopa (18F-DOPA) has been developed. 18F-DOPA PETscanning is a metabolic scanning while SRS scanning depends on the presence of somatostatin receptors on NET cancer cells. We used 18F-DOPA PET scan and SRS in 15 patienst with known or suspected NET. Results: F18-DOPA PET scan was able to detect primary tumors not demonstrated by SRS scintigraphy. Further, 18F-DOPA PET was able to detect more metatatasis in the liver and extrahepatic tissues comparedf to conventional SRS imaging. Conclusion: F18-DOPA PET scanning demonstrated more tumors in more regions compared to the conventional imaging modalities in NET patients. The combination of this specific PET tracer with the high resolution provided by PET was clinically relevant with improvement in the detection and staging of neuroendocrine tumors. In several patients this has clinical impact on patient handling with a change in treatment modality.

P.133 DIAGNOSTIC VALUE OF LENS CULINARIS AGGLUTININ ISOFORM 3 FRACTION (AFP-L3%) AND DES-GAMMA-CARBOXY PROTHROMBIN (DCP) FOR THE DIAGNOSIS OF HCC IN CIRRHOTIC PATIENTS

Introdction: In patients with neuroendocrine tumors it is important to accurately diagnose tumor localization and metastases, biochemical activity, and progression. The initial workup for NET patients consists of morphological imaging methods by CT/MRI, combined with functional whole-body imaging with somatostatin-receptor scintigraphy (SRS). However, there may be difficulties for CT and MRI to separate tumors and mesenterial metastases from intestinal structures. Furthermore, SRS can produce false-negative findings, because of the variable affinity and expression of somatostatin receptors and the restricted resolution of gamma cameras and single-photon-emission tomography (SPECT) methods. Methods: A new imaging method for neuroendocrine tumors using PET and the catecholamine precursor 6-[fluoride-18]fluorolevodopa (18F-DOPA) has been developed. 18F-DOPA PETscanning is a metabolic scanning while SRS scanning depends on the presence of somatostatin receptors on NET cancer cells. We used 18F-DOPA PET scan and SRS in 15 patienst with known or suspected NET. Results: F18-DOPA PET scan was able to detect primary tumors not demonstrated by SRS scintigraphy. Further, 18F-DOPA PET was able to detect more metatatasis in the liver and extrahepatic tissues comparedf to conventional SRS imaging. Conclusion: F18-DOPA PET scanning demonstrated more tumors in more regions compared to the conventional imaging modalities in NET patients. The combination of this specific PET tracer with the high resolution provided by PET was clinically relevant with improvement in the detection and staging of neuroendocrine tumors. In several patients this has clinical impact on patient handling with a change in treatment modality.