Publications by authors named "Roberta Modica"

25 Publications

  • Page 1 of 1

Cardio-Metabolic Indices and Metabolic Syndrome as Predictors of Clinical Severity of Gastroenteropancreatic Neuroendocrine Tumors.

Front Endocrinol (Lausanne) 2021 18;12:649496. Epub 2021 Mar 18.

Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Endocrinology Unit, Department of Clinical Medicine and Surgery, University Medical School of Naples, Naples, Italy.

Background: Obesity, mainly visceral obesity, and metabolic syndrome (MetS) are major risk factors for the development of type 2 diabetes, cardiovascular diseases, and cancer. Data analyzing the association of obesity and MetS with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are lacking. Fatty liver index (FLI) is a non-invasive tool for identifying individuals with non-alcoholic fatty liver disease (NAFLD). Visceral adiposity index (VAI) has been suggested as a gender-specific indicator of adipose dysfunction. Both indexes have been proposed as early predictors of MetS. This study aimed to investigate the association of FLI VAI as early predictors of MetS with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: A cross-sectional, case-control, observational study was carried out at the ENETS Centers of Excellence Multidisciplinary Group for Neuroendocrine Tumors, University "Federico II". VAI and FLI were calculated.

Results: We enrolled 109 patients with histologically confirmed G1/G2 GEP-NET (53 M; 57.06 ± 15.96 years), as well as 109 healthy subjects, age, sex- and body mass index-matched. Forty-four GEP-NET patients were G2, of which 21 were with progressive disease, and 27 patients had metastases. GEP-NET patients had a higher value of VAI ( < 0.001) and FLI ( = 0.049) and higher MetS presence ( < 0.001) compared with controls. VAI and FLI values and MetS presence were higher in G2 than in G1 patients ( < 0.001), in patients with progressive disease, and in metastatic non-metastatic patients ( < 0.001). In addition, higher values of VAI and FLI and higher MetS presence were significantly correlated with the worst clinical severity of NENs. The cut-off values for the FLI and MetS to predict high grading of GEP-NETs and the presence of metastasis were also provided.

Conclusions: This is the first study investigating an association between VAI and FLI as early predictors of MetS and GEP-NET. Our findings report that the worsening of clinicopathological characteristics in GEP-NET is associated with higher presence of MetS, NAFLD, evaluated by FLI, and visceral adiposity dysfunction, evaluated by VAI. Addressing the clinical evaluation of MetS presence, NAFLD, and visceral adiposity dysfunction might be of crucial relevance to establish targeted preventive and treatment interventions of NEN-related metabolic comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.649496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018238PMC
March 2021

Clinical Epigenetics of Neuroendocrine Tumors: The Road Ahead.

Front Endocrinol (Lausanne) 2020 15;11:604341. Epub 2020 Dec 15.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Neuroendocrine tumors, or NETs, are cancer originating in neuroendocrine cells. They are mostly found in the gastrointestinal tract or lungs. Functional NETs are characterized by signs and symptoms caused by the oversecretion of hormones and other substances, but most NETs are non-functioning and diagnosis in advanced stages is common. Thus, novel diagnostic and therapeutic strategies are warranted. Epigenetics may contribute to refining the diagnosis, as well as to identify targeted therapy interfering with epigenetic-sensitive pathways. The goal of this review was to discuss the recent advancement in the epigenetic characterization of NETs highlighting their role in clinical findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.604341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770585PMC
December 2020

Quality of Life in Patients with Neuroendocrine Neoplasms: The Role of Severity, Clinical Heterogeneity, and Resilience.

J Clin Endocrinol Metab 2021 Jan;106(1):e316-e327

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Context: Although health-related quality of life (HRQoL) is a fundamental outcome in oncological clinical trials, its evaluation in the neuroendocrine neoplasm (NEN) research field is still limited.

Objectives: This study assessed the role of clinical severity (ie, presence or absence of metastasis and lines of therapies) and heterogeneity (ie, primary site, types of therapy, biology, and surgery) of NEN in relation to HRQoL, as well as resilience as a moderator between clinical severity and HRQoL.

Design: Cross-sectional multicentric study.

Setting: Italian university hospitals.

Patients: A total of 99 Italian patients (53 men and 46 women) with NEN and ranged in age from 22-79 years old.

Main Outcome Measure: Severity and heterogeneity of NENs, HRQoL, and resilience.

Results: The presence of metastasis and a greater number of therapies affected the global health and some physical symptoms. Resilience was associated with global health, functional status, and some physical symptoms, and it moderated the impact of metastases on constipation and of the multiple therapies on diarrhea and financial problems. Patients with NEN in districts other than the gastroenteropancreatic system and those in follow-up perceived fewer physical symptoms than their counterparts. Patients with a sporadic NEN perceived their functional status, global health, and disease-related worries as better than those with a hereditary NEN. Patients who underwent surgery were lower in constipation than their counterparts.

Conclusion: These findings highlight the need to assess the relationships between the clinical severity and heterogeneity of NEN with HRQoL and the role of resilience in improving patients' HRQoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa760DOI Listing
January 2021

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Rev Endocr Metab Disord 2020 Sep 15. Epub 2020 Sep 15.

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host's metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host's immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11154-020-09589-yDOI Listing
September 2020

Lanreotide Induces Cytokine Modulation in Intestinal Neuroendocrine Tumors and Overcomes Resistance to Everolimus.

Front Oncol 2020 7;10:1047. Epub 2020 Jul 7.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Somatostatin analogs mantain their major role in the treatment of patients with advanced neuroendocrine tumors (NETs) and have multiple modulatory effects on the immune system. Here, we evaluated the effects of lanreotide treatment on expression of Th1, Th2 cytokine patterns in serum of patients with NETs and in bronchial and pancreatic NET cell lines. Our results showed that lanreotide treatment promoted a Th1 cytotoxic immune-phenotype in patients with NETs originated by intestinal sites. Similar results were obtained also where lanreotide induced expression of Th1 cytokines only in pancreatic and not in bronchial-derived NET cell lines. It seems, therefore, that cytokinomics can represent a useful tool for the identification of tumor biomarkers for the early diagnosis and evaluation of the response to therapy in NET patients. To avoid the drug-resistance induced by everolimus (mTOR inhibitor), we made the pancreatic NET cell line resistant to this drug. After treatment with lanreotide we found that the drug reduced its viability compared to that of sensitive cells. These data may have direct implications in design of future translation combination trial on NET patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379869PMC
July 2020

Laryngeal Neuroendocrine Tumor With Elevated Serum Calcitonin: A Diagnostic and Therapeutic Challenge. Case Report and Review of Literature.

Front Endocrinol (Lausanne) 2020 16;11:397. Epub 2020 Jul 16.

Department of Experimental Medicine Sapienza University of Rome, Rome, Italy.

Laryngeal neuroendocrine neoplasms (NENs) are a rare group of NENs of the neck, which commonly show immunostaining for calcitonin. Laryngeal NENs with calcitonin hypersecretion and lymph node metastases represent a diagnostic and therapeutic challenge, which should be included in the differential diagnosis of medullary thyroid carcinoma (MTC). We report a complex case of laryngeal NEN with calcitonin hypersecretion and a review of the literature. A 59-year-old man presented with dysphagia, dyspnea, and lateral cervical mass; he was a smoker. At first imaging, a laryngeal lesion with lateral cervical lymphadenopathies was found, and it resulted as a moderately differentiated neuroendocrine tumor (G2), Ki67 = 5%, positive for calcitonin. Increased levels of serum calcitonin (50 pg/ml) were found. The patient started somatostatin analogs for lesions positivity to somatostatin receptor-based imaging. After 5 months, the disease progressed at 18F-fluorodeoxyglucose (F-FDG) PET-CT, and also new painful cutaneous lesions occurred. Considering high serum levels of calcitonin, differential diagnosis with MTC was required. Patient performed a thyroid color Doppler ultrasound, nodule fine needle aspiration, calcitonin dosage in fine needle washout fluid, and a calcium gluconate stimulation test. After multidisciplinary evaluation, we decided to perform a total thyroidectomy associated with lateral cervical lymphadenectomy and resection of skin metastases. No MTC was found. Two of the five resected lymph nodes, left upper parathyroid, and skin lesions were metastases of NEN G2, positive for calcitonin. After 2 months, new painful skin lesions occurred, and a target therapy with everolimus 10 mg/day was started. After 6 months of therapy, partial metabolic response with a reduction of 53.7% of radiotracer uptake at primary tumor was detected together with an improvement of patient's quality of life. The present case is the seventh described in the literature of laryngeal NEN associated with elevated serum calcitonin levels and the first case with parathyroid metastasis, suggesting the importance of a correct differential diagnosis between MTC and calcitonin-secreting laryngeal NEN, using an integrated approach of biochemistry and advanced imaging. This is also the first time that somatostatin analogs and then everolimus were used in this setting, resulting in clinical and partial metabolic response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378381PMC
May 2021

Pancreatic Neuroendocrine Tumors in patients with Multiple Endocrine Neoplasia Type 1: Diagnostic Value of Different MRI Sequences.

Neuroendocrinology 2020 Jun 24. Epub 2020 Jun 24.

Background: Magnetic Resonance Imaging (MRI) is a useful imaging modality to assess the presence of Pancreatic Neuroendocrine Tumors (PNETs), allowing repeat monitoring examinations in MEN-1 patients.

Objectives: We aimed to compare the diagnostic accuracy of conventional MRI sequences identifying which better depict the presence of PNETs in MEN-1 patients.

Method: We performed a retrospective analysis of consecutive MEN-1 patients who underwent a conventional MRI protocol to monitor previously proven PNETs. MRI sequences T1-w Chemical-Shift (CS), T2-w HASTE, fat-suppressed (FS) T2-w HASTE, Diffusion Weighted Imaging (DWI), pre- and post-contrast FS T1-w sequences were independently analyzed by two experienced radiologists using a three-grade score (no lesion, uncertain lesion, certain lesion); lesion size and signal intensity were recorded. ANOVA Friedman and a Wilcoxon pairwise tests for the post-hoc analysis were used. The sensitivity of each sequence was measured; the results were analyzed with the Chi-squared test.

Results: We included 21 patients with a total of 45 PNETs proven by histology, EUS guided fine needle aspiration, CT and nuclear medicine studies. A statistically significant (p<0.01) difference was observed in the detection performance of each MRI sequence, particularly between both DWI (91%) and T2-w FS (85%) sequences in comparison to the others (T1-w CS, T2-w, pre- and post-contrast FS T1-w, ≤56% for all); no significant (p=0.5) difference was found between the detection performance of DWI and T2-w FS sequences. No correlation was observed between the qualitative score of each sequence and lesion tumor size.

Conclusions: DWI and T2-w FS sequences proved to be the most accurate in the detection of PNETs, thus suggesting a role for an abbreviated MRI protocol without contrast medium administration for monitoring MEN-1 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509647DOI Listing
June 2020

Epidemiology of pancreatic neuroendocrine neoplasms: a gender perspective.

Endocrine 2020 08 28;69(2):441-450. Epub 2020 May 28.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Purpose: Pancreatic neuroendocrine neoplasms (PNENs) are a group of clinically rare and heterogeneous tumors of the pancreas. Currently there are no studies investigating the gender difference in PNEN susceptibility. Thus, the purpose of this study was aimed at examining how gender shapes risk factors, clinicopathological features, and comorbidities in PNENs.

Methods: The study design consisted of an Italian multicenter, retrospective study. The study included all consecutive patients with PNENs followed at the participating centers. Two hundred and twenty-nine patients (105 males,124 females, age 54 ± 0.98 years) with PNENs were enrolled at the participating centers. The clinicopathological features (age, gender, BMI, histology, tumor size, tumor grade, distant metastasis, hormonal function, and diagnostic circumstances), comorbidities (cardiovascular diseases (CVD), pancreatitis, type 2 diabetes (T2DM), and potential risk factors (smoking and drinking) were included in the analysis.

Results: Females were slightly prevalent (54.15%). PNENs were diagnosed at younger age in females compared to males (p = 0.04). The prevalence of CVD was significantly higher in males than in females (p = 0.006). In the female group, the presence of T2DM was significantly associated with higher tumor grade (p = 0.04) and metastatic disease (p = 0.02). The proportion of smokers and alcohol drinkers was significantly higher in the male group (p < 0.001). No significant gender differences were detected regarding the other parameters included in the analysis.

Conclusions: This study has identified gender differences of PNENs in terms of age at diagnosis, associated comorbidities, and potential risk factors. A gender-tailored approach could become a potential strategy to better understand the natural history of PNENs and improve the effectiveness of PNENs clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-020-02331-3DOI Listing
August 2020

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors.

Nutrients 2020 Apr 8;12(4). Epub 2020 Apr 8.

Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.

Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12041021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230756PMC
April 2020

Diagnosis of Flier's syndrome in a patient with nondiabetic hypoglycemia: a case report and critical appraisal of the literature.

Endocrine 2020 07 9;69(1):73-78. Epub 2020 Apr 9.

Department of Translational Medicine, Federico II University of Naples and URT "Genomic of Diabetes" of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy.

Purpose: Autoimmune hypoglycemia includes rare syndromes characterized by the presence of either anti-insulin antibodies (IAA) (Hirata's disease) or anti-insulin receptor (anti-ISR) antibodies (Flier's syndrome). Diagnosis is usually based on identification of the specific antibodies, in presence of the Whipple triad. However, most of these cases are classified as idiopathic diseases due to the difficulty to define the pathogenic culprit.

Methods: Basic research methodologies, including Western Blot and ELISA tests, have been used in this study.

Results: We describe a 21-year-old young woman (PT), non-obese and non-diabetic, with a positive history of autoimmune diseases, admitted to the hospital for recurrent episodes of severe symptomatic hypoglycemia. Counterregulatory response to hypoglycemia was normal as well as the fasting test, so excluding both hormone deficiencies and insulinoma. Since an autoimmune hypoglycemic syndrome was suspected, the hyperactivation of the insulin pathway was experimentally evaluated. At this purpose, human hepatocarcinoma (HepG2) cells were incubated with serum obtained from the patient (PT) and from control individuals. Interestingly, a significant increase of phosphorylation of insulin receptor, Akt, and ERK1/2 was observed in the HepG2 cells incubated with PT serum compared with the controls. ELISA tests revealed significantly increased levels of anti-ISR antibodies in PT serum, while IAA were similar both in PT and in control sera, supporting diagnosis of Flier's syndrome.

Conclusions: This study emphasizes the importance to identify new strategies for the differential diagnosis of hypoglycemia, not always possible with the routinely used diagnostic tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-020-02287-4DOI Listing
July 2020

Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study.

Oncologist 2020 03 6;25(3):259-265. Epub 2019 Nov 6.

NET Team Bologna ENETS Center of Excellence, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Background: Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs.

Materials And Methods: A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start.

Results: A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease.

Conclusion: We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned.

Implications For Practice: The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066710PMC
March 2020

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family.

J Clin Med 2020 Feb 21;9(2). Epub 2020 Feb 21.

Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9020588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074269PMC
February 2020

An incidental rectal neuroendocrine microcarcinoma ('micro-NEC') coexistent with a high grade adenoma.

Pathol Int 2020 05 20;70(5):300-302. Epub 2020 Feb 20.

Department of Advanced Biomedical Sciences, Pathology Section, Division of Endocrinology, University of Naples Federico II - Italy, Naples, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.12916DOI Listing
May 2020

Lanreotide Therapy vs Active Surveillance in MEN1-Related Pancreatic Neuroendocrine Tumors < 2 Centimeters.

J Clin Endocrinol Metab 2020 01;105(1)

Department of Clinical Medicine and Surgery, Division of Endocrinology, University Federico II of Naples, Naples, Italy.

Purpose: Pancreatic neuroendocrine tumors (pNETs) are frequent in multiple endocrine neoplasia type 1 (MEN1) syndrome. They are usually not surgically treated unless larger than 1 to 2 cm or a growth rate > 0.5 cm per year. Somatostatin analogues represent one of the main therapeutic options in pNETs, but they have never been prospectively investigated in MEN1-related pNETs. The aim of this study was to prospectively evaluate the effectiveness of lanreotide in patients with MEN1-related pNETs < 2 cm.

Methods: MEN1 patients with 1 or more pNETs < 2 cm of maximal diameter were considered. Study design was prospective observational, comparing patients treated with lanreotide autogel 120 mg every 28 days (LAN group) and patients in active surveillance, not receiving any therapy (AS group).

Results: Forty-two patients were enrolled: 23 in LAN and 19 in AS group. Median follow-up was 73 months. Initial imaging identified a total of 91 pNETs. The median progression-free survival was significantly longer in the LAN than in the AS group (median not reached vs 40 months, P < 0.001). In the LAN group, 4 patients had an objective tumor response, 15 patients had stable disease, while 4 had tumor progression. In the AS group, 13 patients had pNET progression, while 6 were stable.

Conclusions: This is the first prospective study evaluating the efficacy of somatostatin analogues in MEN1-related pNETs. These findings highlight that lanreotide autogel is effective as antiproliferative therapy in MEN1-related pNETs < 2cm, suggesting the utility of somatostatin analogues to arrest the development of tumor lesions as well as to delay or avoid pancreatic surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgz007DOI Listing
January 2020

Nonconventional Doses of Somatostatin Analogs in Patients With Progressing Well-Differentiated Neuroendocrine Tumor.

J Clin Endocrinol Metab 2020 01;105(1)

NET Team Bologna ENETS Center of Excellence, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Purpose: To evaluate the antiproliferative activity and safety of nonconventional high doses of somatostatin analogs (HD-SSA) in patients with well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NET) with radiological disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on a previous treatment.

Methods: A retrospective analysis of prospectively maintained databases from 13 Italian NET-dedicated centers was performed. Main inclusion criteria were: well-differentiated G1 or G2 GEP-NET, progressive disease on a previous treatment, and subsequent treatment with HD-SSA (either by increased administered dose [dose intensity] or shortened interval between administrations [dose density]). Main endpoints were progression-free survival (PFS) and safety.

Results: Of 198 patients, 140 matched inclusion criteria and were included in the analysis. Overall, median PFS was 31 months. Use of HD-SSA as second-line treatment was associated with reduced risk for progression or death compared with third- or further-line treatment (HR: 2.12; P = 0.004). There was no difference in PFS between HD-SSA by increased dose density (N = 133; 95%) or intensity (N = 7; 5%). Partial response according to RECIST criteria was observed in 12 patients (8.6%), and stable disease was achieved in 106 (75.7%) patients. Adverse events occurred in 21 patients (15.0%), 2 of whom had grade 3 biliary stone disease. No patients discontinued HD-SSA treatment due to adverse events.

Conclusions: HD-SSA is an active and safe treatment option in patients with progressive well-differentiated GEP-NET. The high rate of objective responses observed deserves prospective validation in ad hoc clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgz035DOI Listing
January 2020

Safety and Activity of Metronomic Temozolomide in Second-Line Treatment of Advanced Neuroendocrine Neoplasms.

J Clin Med 2019 Aug 15;8(8). Epub 2019 Aug 15.

Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS-Fondazione "G. Pascale", 80131 Naples, Italy.

Background: Platinum-based chemotherapy is the mainstay of front-line treatment of patients affected by pluri-metastatic intermediate/high grade NeuroEndocrine Neoplasms (NENs). However, there are no standard second-line treatments at disease progression. Previous clinical experiences have evidenced that temozolomide (TMZ), an oral analog of dacarbazine, is active against NENs at standard doses of 150 to 200 mg/mq per day on days 1 to 5 of a 28-day cycle, even if a significant treatment-related toxicity is reported.

Methods: Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with a second-line alternative metronomic schedule of TMZ, 75 mg/m "one week on/one week off". Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG.

Results: Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. More than half of patients had a PS 2 (15 vs. 11 with PS 1). The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4-19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from TMZ start was 28.3 months. PS improved in 73% of patients.

Conclusions: Metronomic TMZ is a suitable treatment for G2 and G3 NENs particularly in PS 2 patients. Prospective and larger trials are needed to confirm these results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8081224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723560PMC
August 2019

Therapeutic sequences in patients with grade 1-2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group.

Endocrine 2019 11 14;66(2):417-424. Epub 2019 Mar 14.

Division of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.

Purpose: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET.

Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation.

Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1-G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03).

Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1-G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-019-01894-0DOI Listing
November 2019

Nutrition and neuroendocrine tumors: An update of the literature.

Rev Endocr Metab Disord 2018 06;19(2):159-167

Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy.

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with worldwide increasing incidence, high prevalence and survival. Both the tumor itself and the systemic therapy may have an impact on patients' nutrition. Malnutrition negatively impacts on outcome in NETs patients. Moreover, it has been demonstrated that body mass index was a risk factor for NET development and that metabolic syndrome was associated with worse prognosis in these patients. Of note, food could also interact with the metabolism of oral target therapy and antineoplastic agents used for the treatment of progressive NETs. Therefore, the nutritional assessment, based on body composition, and lifestyle modifications should be an integral component of management of the NET patients. The nutrition care plans are an integral part of the multidisciplinary management team for patients with NETs. Nutritionists with expertise in NETs can provide dietary approaches to improve the quality of life and nutritional status during various therapeutic modalities used in patients with NETs. The aim of this review is to critically discuss the importance of nutrition and body composition in patients with NETs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11154-018-9466-zDOI Listing
June 2018

The antiproliferative effect of pasireotide LAR alone and in combination with everolimus in patients with medullary thyroid cancer: a single-center, open-label, phase II, proof-of-concept study.

Endocrine 2018 10 23;62(1):46-56. Epub 2018 Mar 23.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Purpose: Medullary thyroid cancer (MTC) is a neuroendocrine tumour of the thyroid C cells. Pasireotide, a multi-receptor targeted somatostatin analogue, and everolimus, an inhibitor of mTOR, showed antitumour properties in neuroendocrine tumours. Aim of this study was to evaluate pasireotide alone and in combination with everolimus in patients with MTC.

Methods: Patients with progressive metastatic or persistent postoperative MTC received pasireotide LAR 60 mg/m for at least 6 months. Patients exhibiting progressive disease received everolimus 10 mg/d as combination therapy. Primary endpoint was progression free survival (PFS). Secondary endpoints included, overall survival, objective response rates, change in circulating markers, safety. Study registration no. NCT01625520.

Results: Nineteen consecutive patients were enrolled. Median follow-up was 31 months. Median PFS with pasireotide was 36 months (95% CI: 19.5-52.5). Nine patients (47%) had tumour progression: seven of them started everolimus in combination with pasireotide, achieving a median PFS of 9.0 months (95% CI: 0-21.83). Five of them (71%) had further tumour progression, one objective response (14.3%), one stopped treatment because of pulmonary embolism. Pasireotide alone and with everolimus was safe and required withdrawal only in one case. Diarrhoea and hyperglycaemia were the most frequent adverse events with pasireotide (grade 3 in 5.3% each). Hyperglycaemia was the most frequent grade 3 toxicity with the combination therapy (28.6%).

Conclusions: Pasireotide therapy shows antiproliferative effects in persistent postoperative MTC suggesting further investigation on larger series of patients. In progressive MTC lesions, the combination pasireotide plus everolimus may be of benefit. Both schemes were safe and well tolerated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-018-1583-7DOI Listing
October 2018

Efficacy and Safety of Everolimus in Extrapancreatic Neuroendocrine Tumor: A Comprehensive Review of Literature.

Oncologist 2016 07 6;21(7):875-86. Epub 2016 Apr 6.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Background: Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs.

Patients And Methods: A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary.

Results: The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation.

Conclusion: Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic.

Implications For Practice: The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2015-0420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943387PMC
July 2016

Pituitary function and morphology in Fabry disease.

Endocrine 2015 Nov 21;50(2):483-8. Epub 2015 Apr 21.

Section of Endocrinology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p < 0.001). Pituitary volume was significantly smaller in FD than in controls (p < 0.001). Determinants of pituitary volume were age and alpha-galactosidase enzyme activity. Both parameters resulted independently correlated at multivariate analysis. Pituitary function was substantially preserved in FD patients. Empty sella is a common finding in patients with FD. The major prevalence in the elderly supports the hypothesis of a progressive pituitary shrinkage overtime. Pituitary function seems not to be impaired in FD. An endocrine workup with pituitary hormone assessment should be periodically performed in FD patients, who are already at risk of cardiovascular complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-015-0604-zDOI Listing
November 2015

Hepatic arterial embolization in patients with neuroendocrine tumors.

J Exp Clin Cancer Res 2014 May 19;33:43. Epub 2014 May 19.

Divisione di Endocrinologia, Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Naples, Italy.

Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient's quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy, but in most of NEN patients with liver metastases, when surgery can not be applied, minimally invasive therapeutic approaches are adopted. They include trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency thermal ablation and new emerging techniques.TAE is based on selective infusion of particles in the branch of the hepatic artery supplying the tumor lesions. The goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis. Many reports have shown that TAE can reduce tumor size and hormone output, resulting in palliation of symptoms without the use of cytotoxic drugs, resulting in better tolerability. This review will focus on TAE performance and safety in NEN patients with liver metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1756-9966-33-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038067PMC
May 2014

Carcinoma showing thymus-like differentiation (CASTLE): a case report.

Ann Ital Chir 2013 Jan-Feb;84(1):77-80

Introdution: Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant thyroid cancer. We report a case of CASTLE treated with surgery and adjuvant external neck radiation therapy.

Materials And Methods: We experienced a case of CASTLE in a 63-year-old man, who presented with a neck mass due to enlarged and hard thyroid gland, most notably in the right lobe, without palpable cervical nodes.

Results: Total thyroidectomy was performed for both diagnostic and therapeutic purposes. Histologic examination of the specimen showed a "thymus like" thyroid cancer; the tumor, partially circumscribed, lobulated, involved both lobes, and in more points reached the capsule of the organ and infiltrated perithyroid muscle tissue. After immunohistochemical assay (CK19 +, CK20 -, thyroglobulin -, calcitonin -, CD5 +, CD117 +), a diagnosis of CASTLE was made.

Discussion: CASTLE is a rare, malignant tumour of the thyroid gland, with histopathological features similar to squamous cell carcinoma, but with a more favourable prognosis. Preoperative diagnosis is difficult. CASTLE is usually cured surgically with total thyroidectomy and selective neck dissection, followed by radiotherapy.

Conclusions: Surgery and radiotherapy are effective to manage thyroid CASTLE tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2015