Neuroendocrine Tumor Grade Research Articles

Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study.

Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1-2 (G1-G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21-54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3-4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.

Real-world treatment patterns, resource use and costs of treating uncontrolled carcinoid syndrome and carcinoid heart disease: a retrospective Swedish study

Objectives: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns.Materials and methods: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group.Results: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500€/patient during controlled CS (8 months), rising to 21,700€/patient during uncontrolled CS (8 months), representing an increase of ∼40% (6200€/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100€/patient without CHD, compared to 4600€/patient with CHD, a difference of 3500€/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography.Conclusions: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.

Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms

IntroductionPatients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known. MethodsWe identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group. ResultsOf 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months. ConclusionsPatients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.

Can You See the Carcinoid Tumor? A Case of Autoimmune Metaplastic Atrophic Gastritis (AMAG) and Carcinoid Tumor

Atrophic gastritis is a known risk factor for the development of carcinoid tumor and gastric adenocarcinoma. In AMAG, there is destruction of parietal cells which leads to G-cell hyperplasia and elevated gastrin levels resulting in the proliferation of enterochrommaffin-like cells. These cells serve as precursors to carcinoid tumors, thus can be neoplastic in nature. A majority of carcinoid tumors appear on upper endoscopy (EGD) as polypoid lesions in the gastric body or fundus. We would like to present a unique case of carcinoid tumor in the context of AMAG, with grossly normal EGD. Our patient is a 25 year old female without significant past medical history with sole complaint of chronic dyspepsia and upper abdominal pain. She presented to clinic for a second opinion after a recent diagnosis of a neuroendocrine malignancy on EGD one month prior. The patient underwent repeat EGD with biopsies taken from the antrum, body, and fundus. An area of hypopigmented mucosa was identified in the antrum, prompting biopsies. The remainder of the stomach, duodenum, and esophagus were grossly normal. Pathology from the antrum and fundus all revealed chronic gastritis with mild enterochromaffin-like cell hyperplasia and severe reactive changes. The fundic biopsy showed chronic atrophic gastritis with antralized mucosa, suggestive of AMAG. The biopsies from the body of the stomach demonstrated well-differentiated neuroendocrine tumor (NET) grade 1, arising in the background of chronic atrophic gastritis. KI67 demonstrates proliferation index less than 2%. No lymphovascular invasion was seen. Her prior EGD showed well differentiated NET on antral biopsy. Patient underwent EGD/EUS with biopsies at a tertiary center, which was unremarkable, and biopsy showed atrophic gastritis. She was advised to repeat EGD every 6-12 months. This case raises concern for therapy modalities as minimal literature exists in regards to treatment of NET in the setting of AMAG with normal EGD. Given the lack of gross focality to the carcinoid lesion, does one resect or surveil? Although gastric carcinoid in the setting of atrophic gastritis is rarely malignant, one must ponder the malignancy potential given that we were unable to pinpoint the lesion despite multiple EGD's. Further cases must be studied to adequately manage such patients and better understand disease progression.3087_A Figure 1. EGD with normal appearing mucosa3087_B Figure 2. EGD with normal appearing mucosa and narrow band imaging

Simple Vascular Architecture Classification in Predicting Pancreatic Neuroendocrine Tumor Grade and Prognosis.

Vascularity is a critical feature in the evaluation of pancreatic neuroendocrine tumor (PNET). When done by EUS, contrast agents are recommended. However, vascular architecture (VA) can also be evaluated by routine Doppler flow in EUS without contrast agents. Our aim was to provide a simple VA classification in EUS for PNET grade and prognosis. All pathologically proven PNET cases with EUS between 2012 and 2018 were retrospectively analyzed. The Doppler imaging was retrieved for VA classification. Predictive model construction was performed by machine learning algorithms. A total of 112 PNET cases were evaluated, among which 93 cases were subjected to VA classification. The VA was classified into type A (peritumoral with or without intratumoral vessels [A1 or A2]); type B (only intratumoral vessels); and type C (flow was absent). The VA classification was significantly correlated with tumor grades: 74% type A1 was G1, 73% type B was G2, and 58% type C was G3. Multivariate analysis indicated that elevated serum CA19-9 and type C classification were the independent predictors of G3 tumor. Five machine learning models were constructed, among which random forest was the best one with an AUC of 0.9972. Low-risk patients classified by this model exhibited better prognosis than high-risk patients (p = 0.0087). In the novel simple VA classification, peritumoral, intratumoral, and absent vessels are prone to be G1, G2, and G3, respectively. Combined with serum CA19-9 and lesion size, the VA classification could predict tumor grade and prognosis in PNET.

Leucine-rich repeat-containing G-protein-coupled receptor 5 expression and clinicopathological features of colorectal neuroendocrine neoplasms.

LGR5 is expressed in various tumors and has been identified as a putative intestinal stem cell marker. Here we investigated LGR5 expression in colorectal neuroendocrine neoplasms and analyzed the correlation with pathological characteristics. We evaluated the clinicopathological features of 8 neuroendocrine tumor (NET) grade 1 (NET G1), 4 NET Grade 2 (NET G2), and 8 NET Grade 3 (NET G3; also termed neuroendocrine carcinoma, or NEC) cases. We examined LGR5 expression using an RNAscope, a newly developed RNA in situ hybridization technique, with a tissue microarray of the neuroendocrine neoplasm samples. LGR5 staining in individual tumor cells was semi-quantitatively scored using an H-score scale. We also performed a combination of LGR5 RNA in situ hybridization and synaptophysin immunohistochemistry. All cases contained tumor cells with some LGR5-positive dots. For all cases, H-scores showed a positive correlation with nuclear beta-catenin expression. In the NEC group, there was a strong positive correlation between H-score and beta-catenin expression. Our findings suggest that LGR5 may serve as a stem cell marker in NEC, as is the case in colon adenocarcinoma. The positive correlation between H-score and beta-catenin expression suggests that LGR5 expression might be affected by beta-catenin expression in neuroendocrine neoplasms and especially in NEC.

Abstract 3134: Pilot study of immune status of GEP-NETs in tumor microenvironment

Abstract Introduction: Neuroendocrine tumor (NET) is a rare cancer, however, morbidity rate is increasing every year. Recently, effective molecular targeting drugs for NET were developed and leading acceptable results, however, it is still not enough. Immune checkpoint inhibitor is becoming a very effective drug in malignant melanoma, lung cancer, and some kind of cancer showing microsatellite instability (MSI). Aim: Aim of this study is to investigate NET about MSI status and immune status of microenvironment using NET patients' operative or biopsy samples. Method: Patients were 20 NETs, male: 11, female: 9, G1: 6, G2: 8, G3: 6, pancreas: 11, duodenum: 4, colon: 2, liver: 1, unknown: 2. Using patients' samples by operative resection or biopsy, examinations by immunohistochemistry were performed to confirm MSI status using MSH2, MSH6, PMS2 and MLH1 antibody and count the cell number expressing PD-L1, PD-1, CD8 or Foxp3. Expression of MSH2, MSH6, PMS2, MLH1 and PD-L1 was evaluated on tumor cells. Specimens were categorized as IHC negative or positive if &amp;lt; 1% or &amp;gt; 1% of cells were stained by each monoclonal antibody. Expression of PD-1, CD8, Foxp3 was evaluated on the infiltrating lymphocyte of intratumor and peritumor respectively. Positive cells absolute number of each staining were counted in the 3 hot spot field (X400) and then the average of the 3 field of each specimen was utilized. Results: MSI: Expression of the 4 mismatch repair protein could be detected in the all 20 NETs tumor, then there was no case showing MSI. PD-L1 was detected in the 15 cases (75%). PD-L1 was expressed in the surface of tumors. PD-1 was also detected 15 cases (75%). PD-1 was expressed in the surface of infiltrative intratumoral and peritumoral lymphocyte. Both of PD-L1 in the tumor and PD-1 in the lymphocyte were detected in the 12 cases (60%). PD-L1 was detected in 72.7% of pancreatic NET, 72% of gastroenteral NET. PD-L1 was detected in 100% of NET-G1, 75% of G2 and 50% of G3. The absolute number of intratumoral PD-1+ lymphocyte, CD8+ lymphocyte or Foxp3+ lymphocyte was higher in the PD-L1+ tumor than in the PD-L1- tumor. In peritumor, there was not a similar tendency. In the PD-L1 positive NET, the absolute number of intratumoral PD-1+ lymphocyte or CD8+ lymphocyte increased according to NET grade. Conclusion: Seventy-five% of GEP-NET expressed PD-L1. It might be higher rate of PD-L1 expression compared with other cancers. The absolute number of Intratumoral infiltrating lymphocyte expressing PD-1 or CD8 was also high. There might be a fraction of a good target for immune check point therapy in NETs. Citation Format: Yasushi Ichikawa, Noritoshi Kobayashi, Ayumu Goto, Motohiko Tokuhisa, Yukihiko Hiroshima, Takashi Ishikawa, Shoko Takano, Tomio Inoue, Itaru Endo. Pilot study of immune status of GEP-NETs in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3134.

Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours

With the widespread use of endoscopy, small and low-grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological behaviour and appropriate treatment strategy for these NETs remain unclear. Patients with biopsy-proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long-term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade. Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty-two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow-up of 59 (range 6-102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases. Low-grade type 3 gastric NET has non-aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.

Pembrolizumab (P) monotherapy in patients with previously treated metastatic high grade neuroendocrine neoplasms (HG-NENs).

4104Background: There is currently no standard therapy for metastatic HG-NENs after progression on platinum based therapy and available chemotherapy is of limited benefit. Given the promising activ...

Open issues on G3 neuroendocrine neoplasms: back to the future.

The recent recognition that grade 3 (G3) neuroendocrine neoplasms (NENs) can be divided into two different categories according to the histopathological differentiation, that is G3 neuroendocrine tumors (NETs) and G3 neuroendocrine carcinomas (NECs) has generated a lot of interest concerning not only the diagnosis, but also the differential management of such new group of NENs. However, several issues need to be fully clarified in order to put G3 NETs and G3 NECs in the right place. The aim of this review is to focus on those issues that are still undetermined starting from the current knowledge, evaluating the available evidence and the possible clinical implications.

Ki67 Scoring in Pancreatic Neuroendocrine Tumors By a New Method.

Ki67 scoring is required for the grading of pancreatic neuroendocrine tumors. Ongoing debate exists about the best scoring method in terms of accuracy and practicality. Manual counting of cells in camera-captured/printed images is a widely used and accepted method and considered the most reliable one among the manual methods. It requires counting 500 to 2000 cells to determine the Ki67 score accurately and it is time and energy consuming. We investigated the possibility of achieving the same results by counting only a particular fraction of tumor cells in a printed image in a series of 45 (24 grade 1 and 21 grade 2) pancreatic neuroendocrine tumors. After counting Ki67-positive tumor cells in the whole image, the tumor cells were counted within one-tenth of the same image with the aid of a previously prepared grid on an acetate sheet. The cell number obtained was multiplied by 10 to estimate the total cell count and the Ki67 score was calculated. The agreement between the results of the acetate grid and conventional whole-image counting method was assessed. Near-perfect agreement was achieved regarding the total cell count and Ki67 score. The agreement on tumor grade between the two methods was perfect. The time spent on the process was significantly less than that spent on the conventional method. Although it needs to be validated in a larger series, the acetate grid method might be considered an alternative method for Ki67 scoring in neuroendocrine tumors.

Neuroendocrine tumor of the common bile duct: a case report and review of the literature.

We report a rare case of neuroendocrine tumor (NET) in the common bile duct (CBD). The patient is a 56-year-old female who presented to our department with symptoms of fever but without jaundice. A preoperative examination showed a tumor in the CBD. The tumor volume was almost 5.5 × 4.5 × 4 cm3, which is the biggest NET in the CBD reported on PubMed. The imaging results (computed tomography [CT] and magnetic resonance imaging [MRI]) were not consistent with CBD adenocarcinoma. The tumor appeared to oppress the growth of the CBD rather than originate in the bile duct wall; combined with the low blood bilirubin index and lack of jaundice symptoms, the preoperative diagnosis was not clear. We performed a radical resection of the cholangiocarcinoma. The patient recovered well before going home. The pathology was NET (Grade 2). The patient showed no recurrence to date, without intravenous chemotherapy (8 months).

Neuroendocrine Neoplasms in Rare Locations: Clinicopathological Features and Review of the Literature.

Introduction:Neuroendocrine tumors (NETs) occur more often in lungs, gastrointestinal tract, or pancreas. Data about terminology and grading of NETs in rare locations are scarce and variable, and they have been reported mainly as case reports.Materials and Methods:We here describe our experience with NETs in unusual locations. We have reviewed all NETs diagnosed in our institution and summarized their clinicopathological features. We have also reviewed the literature and discussed the main characteristics of NETs in each site.Results:Two hundred and forty-three primary NETs were diagnosed. About 55.2% of patients were men and the mean age was 62 years. About 90.7% of NETs were located in lungs, gastrointestinal tract, or pancreas, and 50.8% of them were low-grade tumors. We identified 13 NETs in rare locations: breast, ovary, endometrium, vulva, uterine cervix, extrahepatic biliary tract, kidney, sinonasal tract, and thymus. Three additional tumors were diagnosed by the senior author in other institution. Patients were asymptomatic or presented with nonspecific symptoms. All NETs were treated with surgery and 31% of patients received adjuvant therapy. There were 10 Grade 3 (62.5%), 2 Grade 2 (12.5%), and 4 Grade 1 (25%) tumors. Mean follow-up was 72 months. About 60% of G3 tumors recurred or progressed. G2 tumors were located in breast, and both patients are stable. About 50% of G1 tumors recurred or progressed (both renal NETs).Conclusions:NETs in rare locations are heterogeneous, and their behavior does not seem to correlate absolutely with tumor grade. More studies are needed to clarify the role of proliferation rate in these tumors.

Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

The aim of our study was to correlate tumor uptake of 68Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUVmax) and averaged SUV SUVmean of “main tumor lesions” were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3–20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUVmax of tumor and Ki-67 index (r = −0.241) and negatively poor agreement between SUVmean of tumor and Ki-67 index (r = −0.094). SUVmax of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUVmean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUVmax and SUVmean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.

Role of diffusion-weighted MR imaging in predicting the grade of nonfunctional pancreatic neuroendocrine tumors.

The purpose of this study was to describe the magnetic resonance imaging (MRI) findings including diffusion-weighted MRI of nonfunctional pancreatic neuroendocrine tumors (PanNETs) and their hepatic metastases, and investigate the relationships between MRI features and histopathological findings for each grade of PanNETs. A total of 30 patients were included. There were 14 men and 16 women with a mean age of 61.60±11 (SD) years (range: 31-81years). PanNET lesions were analyzed qualitatively (signal intensities, contrast enhancement, lesion margins, presence of metastasis and characteristics of metastases) and quantitatively (signal intensity ratios, contrast enhancement indices and normalized apparent diffusion coefficient [ADC]). The relationships between MRI findings and histopathological findings were evaluated. Among 30 nonfunctional PanNETs, 11 were high-grade tumors, 10 were intermediate and 9 were low-grade tumors. All high grade PanNETs showed low to intermediate signal on T2-weighted images and ill-defined borders. All intermediate grade PanNETs had intermediate and 6 low grade PanNETs have high signal on T2-weighted images. Patients with hepatic metastases from high grade PanNETs had cystic component in 8/10 (80%) and wash-out in 7/10 (70%) whereas intermediate grade PanNETs had none (P<0.05). The normalized ADC values of high grade PanNETs was lower than those of intermediate and low grade PanNETs (P<0.05). The presence of cystic component or contrast wash-out in hepatic metastases correlates with high grade PanNETs. The pre-operative MRI combined with DWI has an important role in grading and surgical planning of PanNETs.

Composite neuroendocrine tumor and adenocarcinoma of the rectum

BackgroundAlthough adenocarcinomas showing neuroendocrine differentiation or those mixed with high-grade neuroendocrine carcinoma (NEC) are sometimes encountered, composite tumors comprising neuroendocrine tumor (NET) Grade 1 and adenocarcinoma are exceedingly rare.Case presentationA 64-year-old male presented after testing positive for fecal occult blood at a medical check-up. A biopsy demonstrated the presence of a NET and endoscopic submucosal dissection was undertaken. Histologic examination revealed that a well differentiated tubular adenocarcinoma was present in addition to the NET. Furthermore, histological transition between the two tumors was evident. Accordingly, this case was considered to be a composite tumor comprising NET and adenocarcinoma.ConclusionComposite tumors consisting of NET Grade 1 and adenocarcinoma are exceedingly rare, and only a few examples have been reported hitherto.

Octreotide long-acting repeatable in the treatment of neuroendocrine tumors: patient selection and perspectives.

Over the past three decades, the incidence and prevalence of neuroendocrine tumors have gradually increased. Due to the slow-growing nature of these tumors, most cases are diagnosed at advanced stages. Prognosis and survival are associated with location of primary lesion, biochemical functional status, differentiation, initial staging, and response to therapy. Octreotide, the first synthetic somatostatin analog, was initially used for the management of gastrointestinal symptoms associated with functional carcinoid tumors. Its commercial development over time led to long-acting repeatable octreotide acetate, a long-acting version that provided greater administration convenience. Recent research demonstrates that octreotide’s efficacy has evolved beyond symptomatic management to targeted therapy with antitumoral effects. This review examines the history and development of octreotide, provides a synopsis on the classification, grading, and staging of neuroendocrine tumors, and reviews the evidence of long-acting repeatable octreotide acetate as monotherapy and in combination with other treatment modalities in the management of non-pituitary neuroendocrine tumors with special attention to recent high-quality Phase III trials.

Prediction of Pancreatic Neuroendocrine Tumor Grade Based on CT Features and Texture Analysis.

The purposes of this study were to assess whether CT texture analysis and CT features are predictive of pancreatic neuroendocrine tumor (PNET) grade based on the World Health Organization (WHO) classification and to identify features related to disease progression after surgery. Preoperative contrast-enhanced CT images of 101 patients with PNETs were assessed. The images were evaluated for tumor location, tumor size, tumor pattern, predominantly solid or cystic composition, presence of calcification, presence of heterogeneous enhancement on contrast-enhanced images, presence of pancreatic duct dilatation, presence of pancreatic atrophy, presence of vascular involvement by the tumor, and presence of lymphadenopathy. Texture features were also extracted from CT images. Surgically verified tumors were graded according to the WHO classification, and patients underwent CT or MRI follow-up after surgical resection. Data were analyzed with chi-square tests, kappa statistics, logistic regression analysis, and Kaplan-Meier curves. The CT features predictive of a more aggressive tumor (grades 2 and 3) were size larger than 2.0 cm (odds ratio [OR], 3.3; p = 0.014), presence of vascular involvement (OR, 25.2; p = 0.003), presence of pancreatic ductal dilatation (OR, 6.0; p = 0.002), and presence of lymphadenopathy (OR, 6.8; p = 0.002). The texture parameter entropy (OR, 3.7; p = 0.008) was also predictive of more aggressive tumors. Differences in progression-free survival distribution were found for grade 1 versus grades 2 and 3 tumors (χ2 [df, 1] = 21.6; p < 0.001); for PNETs with vascular involvement (χ2 [df, 1] = 20.8; p < 0.001); and for tumors with entropy (spatial scale filter 2) values greater than 4.65 (χ2 (df, 1) = 4.4; p = 0.037). CT texture analysis and CT features are predictive of PNET aggressiveness and can be used to identify patients at risk of early disease progression after surgical resection.

PUB034 Automated Quantification of Ki-67 Index Associates with Pathologic Grade and Prognosis of Pulmonary Neuroendocrine Tumors

PUB034 Automated Quantification of Ki-67 Index Associates with Pathologic Grade and Prognosis of Pulmonary Neuroendocrine Tumors

Can the Ki-67 Labeling Index in Biopsy Specimens Predict the World Health Organization Grade of Rectal Neuroendocrine Tumors?

Background: Being grade 2 is a known risk factor for metastasis in rectal neuroendocrine tumors (R-NETs). We aimed to identify the efficacy of the Ki-67 labeling index (LI) in endoscopic biopsy specimens to predict the World Health Organization (WHO) grade of R-NETs. Methods: A total of 59 patients with 60 R-NETs (43 WHO grade 1 and 17 WHO grade 2), treated between October 2002 and December 2014, were retrospectively evaluated. The patients included in the study underwent biopsies followed by endoscopic submucosal resection with a ligation device, trans-anal full-thickness surgical resection, or radical surgery with lymph node dissection. The Ki-67 LI in the biopsy and resected specimens were compared between the 2 tumor grade groups, and the diagnostic sensitivity, specificity, and positive and negative predictive values for the detection of WHO grade 2 tumors were evaluated. Results: The sensitivity, specificity, and positive and negative predictive values of the Ki-67 LI in biopsy specimens for predicting grade 2 tumors were 53% (9 of 17), 95% (41 of 43), 100% (9 of 9), and 87% (41 of 47), respectively. Pearson’s rank correlation coefficient between the Ki-67 LI in the biopsy and resected specimens was 0.92. Conclusions: The Ki-67 LI of the biopsy specimen is useful for determining the appropriate treatment for R-NETs.