Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Francesca Spada
Based on 17 articles published since 2008
||||

Between 2008 and 2019, F. Spada wrote the following 17 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline None 2018

Grimaldi, Franco / Fazio, Nicola / Attanasio, Roberto / Frasoldati, Andrea / Papini, Enrico / Cremonini, Nadia / Davi, Maria V / Funicelli, Luigi / Massironi, Sara / Spada, Francesca / Toscano, Vincenzo / Versari, Annibale / Zini, Michele / Falconi, Massimo / Oberg, Kjell. ·Endocrinology and Metabolic Disease Unit, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumor, European Institute of Oncology, Milan, Italy. · Endocrinology Service, Galeazzi Institute IRCCS, Milan, Italy. · Endocrinology Unit, Azienda Ospedaliera S. Maria Nuova IRCCS, Reggio Emilia, Italy. · Department of Endocrinology and Metabolic Diseases, Regina Apostolorum Hospital, Albano Laziale (Rome), Italy. · Endocrinology Clinics, Clinica Villalba, Bologna, Italy. · Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. · Division of Radiology, European Institute of Oncology, Milan, Italy. · Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. · Endocrinology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Nuclear Medicine Unit, Azienda Ospedaliera S. Maria Nuova IRCCS, Reggio Emilia, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Endocrine Oncology, University Hospital, Uppsala, Sweden. ·Endocr Metab Immune Disord Drug Targets · Pubmed #29237387.

ABSTRACT: Well-established criteria for evaluating the response to treatment and the appropriate followup of individual patients are critical in clinical oncology. The current evidence-based data on these issues in terms of the management of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are unfortunately limited. This document by the Italian Association of Clinical Endocrinologists (AME) on the criteria for the follow-up of GEP-NEN patients is aimed at providing comprehensive recommendations for everyday clinical practice based on both the best available evidence and the combined opinion of an interdisciplinary panel of experts. The initial risk stratification of patients with NENs should be performed according to the grading, staging and functional status of the neoplasm and the presence of an inherited syndrome. The evaluation of response to the initial treatment, and to the subsequent therapies for disease progression or recurrence, should be based on a cost-effective, risk-effective and timely use of the appropriate diagnostic resources. A multidisciplinary evaluation of the response to the treatment is strongly recommended and, at every step in the follow-up, it is mandatory to assess the disease state and the patient performance status, comorbidities, and recent clinical evolution. Local expertise, available technical resources and the patient preferences should always be evaluated while planning the individual clinical management of GEP-NENs.

2 Review Systemic therapies in patients with advanced well-differentiated pancreatic neuroendocrine tumors (PanNETs): When cytoreduction is the aim. A critical review with meta-analysis. 2018

Pozzari, Marta / Maisonneuve, Patrick / Spada, Francesca / Berruti, Alfredo / Amoroso, Vito / Cella, Chiara Alessandra / Laffi, Alice / Pellicori, Stefania / Bertani, Emilio / Fazio, Nicola. ·Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. · Division of Gastrointestinal Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: nicola.fazio@ieo.it. ·Cancer Treat Rev · Pubmed #30352319.

ABSTRACT: INTRODUCTION: Cytoreduction is sometimes an important aim of systemic anti-tumor therapies in well-differentiated pancreatic neuroendocrine tumors (PanNETs). As there is not a gold standard treatment for these tumors in this field, we conducted a literature review in order to identify objective criteria for treatment choice. MATERIALS AND METHODS: We critically reviewed and performed a meta-analysis of all published clinical studies of systemic therapies in patients with well-differentiated unresectable PanNETs, selecting only those articles which reported tumor shrinkage (TS) with a waterfall plot (WP). Tumor downsizing of ≥10% was considered as objective response. RESULTS: We selected 17 out of 2758 studies, comprising 1118 patients with tumor response reported as WP. Proliferation index, tumor burden and anti-tumor therapies were heterogeneous. Chemotherapy alone (mainly, capecitabine/temozolomide) or in combination showed the best results, with ≥10% TS ranging from 65% to 93%. Peptide receptor radionuclide therapy combined with chemotherapy (Chemo-PRRT) and sunitinib appeared promising by inducing objective response in a significant proportion of patients (93% and 60%, respectively). Time to tumor response was reported in only two trials. No clear clinical and/or biological predictive factors emerged. CONCLUSION: Based on response criteria used in our retrospective analysis, systemic chemotherapy alone or in combination appeared to have the main cytoreductive impact. However no conclusions regarding either a specific regimen or combination can be drawn. Furthermore, tumor population selection and/or choice of regimen may have a significant influence. Further analysis should be also conducted to identify potential predictive biomarkers of responses, in order to design future prospective interventional clinical trials enrolling more homogenous populations of advanced well-differentiated PanNETs.

3 Review Predictive Markers of Response to Everolimus and Sunitinib in Neuroendocrine Tumors. 2017

Martins, Diana / Spada, Francesca / Lambrescu, Ioana / Rubino, Manila / Cella, Chiara / Gibelli, Bianca / Grana, Chiara / Ribero, Dario / Bertani, Emilio / Ravizza, Davide / Bonomo, Guido / Funicelli, Luigi / Pisa, Eleonora / Zerini, Dario / Fazio, Nicola / Anonymous5180910. ·Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, 20141 via Ripamonti, 435, Milan, Italy. · Division of Otolaryngology-Head and Neck Surgery, European Institute of Oncology, IEO, Milan, Italy. · Division of Nuclear Medicine, European Institute of Oncology, IEO, Milan, Italy. · Division of Hepatobiliopancreatic Surgery, European Institute of Oncology, IEO, Milan, Italy. · Division of Endoscopy, European Institute of Oncology, IEO, Milan, Italy. · Division of Interventional Radiology, European Institute of Oncology, IEO, Milan, Italy. · Division of Radiology, European Institute of Oncology, IEO, Milan, Italy. · Division of Pathology, European Institute of Oncology, IEO, Milan, Italy. · Division of Radiotherapy, European Institute of Oncology, IEO, Milan, Italy. · Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, 20141 via Ripamonti, 435, Milan, Italy. nicola.fazio@ieo.it. ·Target Oncol · Pubmed #28634872.

ABSTRACT: Neuroendocrine tumors (NETs) represent a large and heterogeneous group of malignancies with various biological and clinical characteristics, depending on the site of origin and the grade of tumor proliferation. In NETs, as in other cancer types, molecularly targeted therapies have radically changed the therapeutic landscape. Recently two targeted agents, the mammalian target of rapamycin inhibitor everolimus and the tyrosine kinase inhibitor sunitinib, have both demonstrated significantly prolonged progression free survival in patients with advanced pancreatic NETs. Despite these important therapeutic developments, there are still significant limitations to the use of these agents due to the lack of accurate biomarkers for predicting tumor response and efficacy of therapy. In this review, we provide an overview of the current clinical data for the evaluation of predictive factors of response to/efficacy of everolimus and sunitinib in advanced pancreatic NETs. Surrogate indicators discussed include circulating and tissue markers, as well as non-invasive imaging techniques.

4 Review Critical focus on mechanisms of resistance and toxicity of m-TOR inhibitors in pancreatic neuroendocrine tumors. 2017

Antonuzzo, L / Del Re, M / Barucca, V / Spada, F / Meoni, G / Restante, G / Danesi, R / Di Costanzo, F / Fazio, N. ·S.C. Oncologia Medica 1, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Medical Genetics, University of Siena, Siena, Italy. Electronic address: lorenzo.antonuzzo@gmail.com. · Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. · Division of Medical Oncology, Misericordia General Hospital, Grosseto, Italy. · Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy. · S.C. Oncologia Medica 1, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. ·Cancer Treat Rev · Pubmed #28535439.

ABSTRACT: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms representing less than 2% of all pancreatic malignancies. The PI3K-AKT-mTOR pathway is often deregulated in pNETs and seems to play a key role in tumorigenesis. Everolimus, an inhibitor of the mTOR pathway, has demonstrated efficacy in the treatment of pNETs. Nevertheless de novo or acquired drug resistance is responsible for disease progression and represents a major obstacle to overcome by clinicians. Blocking the PI3K/AKT/mTOR pathway may cover the supposed main mechanisms of resistance to everolimus. Therefore, BEZ-235, a potent oral dual PI3K/mTOR inhibitor was investigated in clinical trials. Globally more than 250 patients with different types of solid tumors were treated. Two studies were conducted in pNETs with BEZ-235 as single agent. The former was a phase 2 trial conducted in pNETs resistant to everolimus while the latter a randomized trial comparing everolimus and BEZ-235. Unfortunately, both the studies disappointed the expectations and were prematurely halted mainly due to severe toxicity. On this basis we reviewed m-TOR inhibitors in pNETs, focusing on their mechanisms of resistance and toxicity.

5 Review Chemotherapy in gastroenteropancreatic (GEP) neuroendocrine carcinomas (NEC): a critical view. 2013

Fazio, Nicola / Spada, Francesca / Giovannini, Monica. ·Unit of Upper Gastrointestinal and Neuroendocrine Tumors, Department of Medicine, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. nicola.fazio@ieo.it ·Cancer Treat Rev · Pubmed #22819619.

ABSTRACT: Neuroendocrine tumors (NET) are classified according to the Ki67 in low-intermediate grade (Ki67<20%) and high grade (Ki67>20%). The NET of the latter group are also known as neuroendocrine carcinoma (NEC), and their prognosis is dismail. While in the former group biotherapy and radionuclide therapy can be proposed, chemotherapy represents the only treatment usually proposed for NEC. Cisplatin/etoposide combination is usually chosen based on the rationale that NEC are clinically similar to small cell lung cancer. However, evidence for cisplatin/etoposide in NEC is poor and controversial, and different schedules and response rate have been published so far. These aspects, combined with the heterogeneous characteristics of NEC, prompt us to have some doubt in considering cisplatin/etoposide as the gold standard. Some evidence exists that carboplatin can be used instead of cisplatin and irinotecan instead of etoposide without reducing efficacy. Furthermore other drugs, as gemcitabine, oxaliplatin or temozolomide can be evaluated in NEC with non-neuroendocrine component or in mixed adenoneuroendocrine carcinomas. NEC are a category of NET that should be deeply studied to verify if the response to cisplatin/etoposide is homogeneous related to the different Ki67, different morphology and/or different primary site.

6 Review Biological targeted therapies in patients with advanced enteropancreatic neuroendocrine carcinomas. 2010

Fazio, Nicola / Cinieri, Saverio / Lorizzo, Katia / Squadroni, Michela / Orlando, Laura / Spada, Francesca / Maiello, Evaristo / Bodei, Lisa / Paganelli, Giovanni / Delle Fave, Gianfranco / de Braud, Filippo. ·European Institute of Oncology, IEO NET Study Group, Via Ripamonti 435, Milan, Italy. nicola.fazio@ieo.it ·Cancer Treat Rev · Pubmed #21129617.

ABSTRACT: Enteropancreatic (EP) neuroendocrine carcinomas (NECs) represent relatively rare and heterogeneous malignancies. They are the most common group among neuroendocrine tumors (NETs). In most cases they are advanced at diagnosis and slow-growing, therefore conditioning a better prognosis compared with non neuroendocrine carcinomas from the same sites. No standard medical therapy exists, except for somatostatin analogs in functioning tumors, and octreotide LAR in functioning or non functioning well differentiated NECs from small bowel. Several systemic therapeutic options exist, including chemotherapy, somatostatin analog, interferon, peptide receptor radionuclide therapy (PRRT), and molecular targeted drugs. Among them some therapies have specific biological tumor targets and can be defined as "biological targeted therapies". This review focuses on the status of EP NECs targeted therapies in the light of recent advances. Somatostatin receptors (SSTRs) are the first therapeutic target detected in EP NECs. Through them SS analogs and PRRT act, producing symptomatic, biochemical, and, to a lesser extent, antiproliferative effects. New SS analogs, covering a higher number of SSTR subtypes, were developed, including pasireotide (SOM230), which controls 25% of carcinoid syndromes resistant to full dose octreotide LAR. Chimeric analogs, which bind SSTR2/SSTR5 and dopamine-2 receptor subtype (D2), are in preclinical phase of development. Among the numerous molecular targeted agents investigated in NETs, mTOR inhibitors and VEGF/VEGFR/PDGFR inhibitors are in most advanced clinical phase of investigation. In particular, everolimus, sunitinib, and bevacizumab are all studied in phase III trials. Both everolimus and sunitinib produced significant survival benefit versus placebo in advanced progressing well-differentiated pancreatic NECs. Sunitinib data have been presented at the last ASCO in June 2010, and everolimus data will be presented at next ESMO in September 2010.

7 Clinical Trial Real-world study of everolimus in advanced progressive neuroendocrine tumors. 2014

Panzuto, Francesco / Rinzivillo, Maria / Fazio, Nicola / de Braud, Filippo / Luppi, Gabriele / Zatelli, Maria Chiara / Lugli, Francesca / Tomassetti, Paola / Riccardi, Ferdinando / Nuzzo, Carmen / Brizzi, Maria Pia / Faggiano, Antongiulio / Zaniboni, Alberto / Nobili, Elisabetta / Pastorelli, Davide / Cascinu, Stefano / Merlano, Marco / Chiara, Silvana / Antonuzzo, Lorenzo / Funaioli, Chiara / Spada, Francesca / Pusceddu, Sara / Fontana, Annalisa / Ambrosio, Maria Rosaria / Cassano, Alessandra / Campana, Davide / Cartenì, Giacomo / Appetecchia, Marialuisa / Berruti, Alfredo / Colao, Annamaria / Falconi, Massimo / Delle Fave, Gianfranco. ·Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy; Unit of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Oncology and Hematology, Policlinico di Modena, Italy; Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; Departments of Endocrinology and Oncologia Medica, Università Cattolica del S. Cuore, Rome, Italy; Departments of Medical and Surgical Sciences and Medical Oncology, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Oncology, Antonio Cardarelli Hospital, Naples, Italy; Division of Medical Oncology and Endocrinology Unit, Regina Elena National Cancer Institute Rome, IRCCS, Rome, Italy; Oncology, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy; Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy; Oncology, Fondazione Poliambulanza, Brescia, Italy; Oncology, Istituto Oncologico Veneto, Padova, Italy; Departments of Medical Oncology and Pancreatic Surgery, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy; Oncology, S. Croce e Carle Hospital, Cuneo, Italy; Department of Medical Oncology A, IRCCS AOU San Martino-IST, Genova, Italy; Oncologia Medica 1, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy; Oncologia, Spedali Civili di Brescia, University of Brescia, Brescia, Italy. · Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy; Unit of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Oncology and Hematology, Policlinico di Modena, Italy; Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; Departments of Endocrinology and Oncologia Medica, Università Cattolica del S. Cuore, Rome, Italy; Departments of Medical and Surgical Sciences and Medical Oncology, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Oncology, Antonio Cardarelli Hospital, Naples, Italy; Division of Medical Oncology and Endocrinology Unit, Regina Elena National Cancer Institute Rome, IRCCS, Rome, Italy; Oncology, San Luigi Gonzaga Hospital, Orbassano, Torino, Italy; Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy; Oncology, Fondazione Poliambulanza, Brescia, Italy; Oncology, Istituto Oncologico Veneto, Padova, Italy; Departments of Medical Oncology and Pancreatic Surgery, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy; Oncology, S. Croce e Carle Hospital, Cuneo, Italy; Department of Medical Oncology A, IRCCS AOU San Martino-IST, Genova, Italy; Oncologia Medica 1, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy; Oncologia, Spedali Civili di Brescia, University of Brescia, Brescia, Italy gianfranco.dellefave@uniroma1.it. ·Oncologist · Pubmed #25117065.

ABSTRACT: Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

8 Clinical Trial Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study. 2014

Bajetta, Emilio / Catena, Laura / Fazio, Nicola / Pusceddu, Sara / Biondani, Pamela / Blanco, Giusi / Ricci, Sergio / Aieta, Michele / Pucci, Francesca / Valente, Monica / Bianco, Nadia / Mauri, Chiara Maria / Spada, Francesca. ·Institute of Oncology, Polyclinic Hospital, Monza, Italy. ·Cancer · Pubmed #24752410.

ABSTRACT: BACKGROUND: Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long-acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin. METHODS: This was a phase 2, multicenter trial using a Simon's 2-stage minimax design. Treatment-naive patients with advanced well-differentiated NETs of gastroenteropancreatic tract and lung origin received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every 28 days. The primary endpoint was objective response rate (ORR). RESULTS: A total of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had carcinoid syndrome. Treatment-related adverse events (AEs) were mostly grade 1 or 2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs as well as 92% of SDs had a duration ≥ 6 months. The clinical benefit (CR+PR+SD) was 92%. At a median follow-up of 277 days, median time to progression and overall survival were not reached. CONCLUSIONS: The everolimus-octreotide LAR combination was active and well tolerated in these previously treated patients with advanced NETs, suggesting a possible role as first-line treatment in patients with NET.

9 Article Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. 2018

Pusceddu, Sara / Vernieri, Claudio / Di Maio, Massimo / Marconcini, Riccardo / Spada, Francesca / Massironi, Sara / Ibrahim, Toni / Brizzi, Maria Pia / Campana, Davide / Faggiano, Antongiulio / Giuffrida, Dario / Rinzivillo, Maria / Cingarlini, Sara / Aroldi, Francesca / Antonuzzo, Lorenzo / Berardi, Rossana / Catena, Laura / De Divitiis, Chiara / Ermacora, Paola / Perfetti, Vittorio / Fontana, Annalisa / Razzore, Paola / Carnaghi, Carlo / Davì, Maria Vittoria / Cauchi, Carolina / Duro, Marilina / Ricci, Sergio / Fazio, Nicola / Cavalcoli, Federica / Bongiovanni, Alberto / La Salvia, Anna / Brighi, Nicole / Colao, Annamaria / Puliafito, Ivana / Panzuto, Francesco / Ortolani, Silvia / Zaniboni, Alberto / Di Costanzo, Francesco / Torniai, Mariangela / Bajetta, Emilio / Tafuto, Salvatore / Garattini, Silvio Ken / Femia, Daniela / Prinzi, Natalie / Concas, Laura / Lo Russo, Giuseppe / Milione, Massimo / Giacomelli, Luca / Buzzoni, Roberto / Delle Fave, Gianfranco / Mazzaferro, Vincenzo / de Braud, Filippo. ·Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. Electronic address: sara.pusceddu@istitutotumori.mi.it. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy. · Dipartimento di Oncologia, Università degli Studi di Torino, A. O. Ordine Mauriziano, Turin, Italy. · Dipartimento di Oncologia, Santa Chiara Hospital, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. · IEO - Istituto Europeo di Oncologia, ENETS Center of Excellence, Milan, Italy. · Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. · Centro di Osteoncologia e Tumori Rari, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy. · Policlinico Sant'Orsola Malpighi, Bologna, Italy. · Unità di chirurgia tiroidea e paratiroidea, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy. · IOM- Istituto Oncologico del Mediterraneo, Catania, Italy. · Azienda Ospedaliera Universitaria Sant'Andrea, ENETS Center of Excellence, Rome, Italy. · Azienda Ospedaliera Universitaria, Verona, Italy. · Fondazione Poliambulanza, Brescia, Italy. · A. O. U. Careggi, Firenze, Italy. · Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. · Policlinico di Monza, Monza, Italy. · IRCCS Fondazione Pascale, ENETS Center of Excellence, Naples, Italy. · Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine, Italy. · Fondazione IRCCS Policlinico San Matteo, SC oncologia, Pavia, Italy. · Policlinico di Modena, Italy. · Unit of Endocrinology, Ospedale Mauriziano, Torino, Italy. · Istituto Clinico Humanitas, Rozzano, ENETS Center of Excellence, Italy. · Ospedale Policlinico Borgo Roma, Verona, Italy. · Ospedale S Croce e Carle, Cuneo, Italy. · Ospedale Valduce Como, Italy. · Endocrinology Section, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Medical-Surgical Science and Traslational Medicine Departement, Sapienza University, Rome, Italy. · Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy. · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy; Universita' degli Studi di Milano, Milan, Italy. ·Gastroenterology · Pubmed #29655834.

ABSTRACT: BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.

10 Article Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study. 2018

Rinzivillo, Maria / Fazio, Nicola / Pusceddu, Sara / Spallanzani, Andrea / Ibrahim, Toni / Campana, Davide / Marconcini, Riccardo / Partelli, Stefano / Badalamenti, Giuseppe / Brizzi, Maria Pia / Catena, Laura / Schinzari, Giovanni / Carnaghi, Carlo / Berardi, Rossana / Faggiano, Antongiulio / Antonuzzo, Lorenzo / Spada, Francesca / Gritti, Sara / Femia, Daniela / Gelsomino, Fabio / Bongiovanni, Alberto / Ricci, Sergio / Brighi, Nicole / Falconi, Massimo / Delle Fave, Gianfranco / Panzuto, Francesco. ·Digestive and Liver Disease, ENETS Center of Excellence Sant'Andrea Hospital - Sapienza University of Rome, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, ENETS Center of Excellence IEO, Milan, Italy. · Department of Medical Oncology, Fondazione IRCCS Istituto Tumori Milano, ENETS Center of Excellence, Milan, Italy. · Division of Oncology, Department of Oncology and Haematology, University Hospital of Modena, Modena, Italy. · Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, Italy. · Department of Oncology, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Istituto Toscano Tumori, Santa Chiara Hospital, Pisa, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy. · Medical Oncology, AOU S. Luigi Gonzaga Regione Gonzole 10, Orbassano, Italy. · Struttura di Oncologia Policlinico di Monza, Monza, MB, Italy. · Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. · Oncology Unit, Humanitas Clinical and Research Centre, Rozzano, Italy. · Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy. · Divisione di Endocrinologia, Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, ENETS Center of Excellence Naples, Italy. · S.C di Oncologia Medica, AOU Careggi Florence, Italy. · Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, Italy. · Digestive and Liver Disease, ENETS Center of Excellence Sant'Andrea Hospital - Sapienza University of Rome, Italy. Electronic address: fpanzuto@ospedalesantandrea.it. ·Pancreatology · Pubmed #29361429.

ABSTRACT: INTRODUCTION: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. AIM: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. PATIENTS AND METHODS: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th-75th IQR). RESULTS: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received ≥ 3 vs ≤ 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1-2 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. CONCLUSIONS: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases.

11 Article Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors. 2017

Berardi, Rossana / Torniai, Mariangela / Pusceddu, Sara / Spada, Francesca / Ibrahim, Toni / Brizzi, Maria Pia / Antonuzzo, Lorenzo / Ferolla, Piero / Panzuto, Francesco / Silvestris, Nicola / Partelli, Stefano / Ferretti, Benedetta / Freddari, Federica / Gucciardino, Calogero / Testa, Enrica / Concas, Laura / Murgioni, Sabina / Bongiovanni, Alberto / Zichi, Clizia / Riva, Nada / Rinzivillo, Maria / Brunetti, Oronzo / Giustini, Lucio / Di Costanzo, Francesco / Delle Fave, Gianfranco / Fazio, Nicola / De Braud, Filippo / Falconi, Massimo / Cascinu, Stefano. ·Clinica di Oncologia Medica, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy. · Medicina Oncologica 1, ENETS Center of excellence, Fondazione IRCCS Istituto Tumori, Milano, Italy. · Unità di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini (Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors), IEO Istituto Europeo di Oncologia, Milano, Italy. · Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Oncologia Medica, A.O.U. San Luigi, Orbassano (TO), Italy. · SC di Oncologia Medica, Azienda Opedaliero-Universitaria Careggi, Firenze, Italy. · Doctorate Course in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy. · Multidisciplinary NET Group, Umbria Regional Cancer Network, Perugia, Italy. · Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy. · Medical Oncology Unit, National Cancer Institute Giovanni Paolo II, Bari, Italy. · Chirurgia del Pancreas, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy. · Chirurgia del Pancreas, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milano, Italy. · Oncologia Medica, Ospedale di San Severino, San Severino Marche (MC), Italy. · Oncologia Medica, Ospedale di Senigallia, Senigallia, Italy. · Oncologia Medica, Ospedale di Fermo, Fermo, Italy. · Oncologia Medica, Ospedale di Urbino, Urbino, Italy. · Oncologia Medica, Università di Modena e Reggio Emilia, Modena, Italy. ·Cancer Med · Pubmed #28547856.

ABSTRACT: The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A while in Group B it was not reached (HR: 26.9; 95% CI: 11.0-76.7; P < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.

12 Article Everolimus in Pancreatic Neuroendocrine Carcinomas G3. 2017

Panzuto, Francesco / Rinzivillo, Maria / Spada, Francesca / Antonuzzo, Lorenzo / Ibrahim, Toni / Campana, Davide / Fazio, Nicola / Delle Fave, Gianfranco. ·From the *Digestive and Liver Diseases, Sant'Andrea Hospital-Sapienza University of Roma, Rome; †Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan; ‡Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, and Department of Medical Biotechnologies, University of Siena, Siena; §Osteoncology and Rare Tumors Center, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola (FC); and ∥Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. ·Pancreas · Pubmed #28099254.

ABSTRACT: OBJECTIVE: The aim of this study was to investigate everolimus efficacy in well-moderately differentiated pancreatic NEC (pNEC) G3. METHODS: This was a retrospective analysis of patients with pNEC G3 and Ki67 20% to 55% treated with everolimus. RESULTS: Fifteen patients with median Ki67 30% and Eastern Cooperative Oncology Group performance status 0 to 1 were evaluated. Of these, 4 patients received everolimus as first-line treatment, whereas 11 had been pretreated with chemotherapy or peptide receptor radionuclide therapy. Median progression-free survival was 6 months, and median overall survival was 28 months. Eleven patients achieved disease stabilization (DS) at 3 month follow-up. Six patients (40%) maintained DS for at least 12 months. Three of 4 patients who received everolimus as first-line therapy had sustained DS (progression-free survival, 12, 17, and 22 months). The safety profile was consistent with that previously reported, with adverse events occurring in 9 patients (66.7%). CONCLUSIONS: This study suggests that everolimus is active in pNEC G3 with well-moderately differentiated morphology and Ki67 less than 55%, in which more toxic systemic chemotherapy is, to date, the only available treatment.

13 Article The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories. 2017

Milione, Massimo / Maisonneuve, Patrick / Spada, Francesca / Pellegrinelli, Alessio / Spaggiari, Paola / Albarello, Luca / Pisa, Eleonora / Barberis, Massimo / Vanoli, Alessandro / Buzzoni, Roberto / Pusceddu, Sara / Concas, Laura / Sessa, Fausto / Solcia, Enrico / Capella, Carlo / Fazio, Nicola / La Rosa, Stefano. ·Anatomic Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy. ·Neuroendocrinology · Pubmed #26943788.

ABSTRACT: BACKGROUND/AIMS: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with a Ki-67 index >20% according to the 2010 WHO classification. Some reports suggest that this category is heterogeneous. We retrospectively studied a series of 136 patients affected by grade 3 GEP-NECs with the aim to clarify the prognostic role of tumor morphological differentiation, proliferation, defect in mismatch repair proteins (MMRd), CD117 expression, and site of origin. The primary endpoint was the correlation between these parameters and the overall survival (OS). METHODS: Univariate and multivariable Cox proportional hazards regression analyses were used to assess the prognostic significance of various clinical and histopathologic features. RESULTS: With a median follow-up of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (<55% vs. ≥55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p < 0.0001) in poorly differentiated neoplasms with a Ki-67 index ≥55% (type C). CONCLUSIONS: The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.

14 Article Resection of the Primary Tumor Followed by Peptide Receptor Radionuclide Therapy as Upfront Strategy for the Treatment of G1-G2 Pancreatic Neuroendocrine Tumors with Unresectable Liver Metastases. 2016

Bertani, Emilio / Fazio, Nicola / Radice, Davide / Zardini, Claudio / Grana, Chiara / Bodei, Lisa / Funicelli, Luigi / Ferrari, Carlo / Spada, Francesca / Partelli, Stefano / Falconi, Massimo. ·Division of Hepatobilio-pancreatic Surgery, European Institute of Oncology, Milan, Italy. emilio.bertani@ieo.it. · GI and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Surgical Department, Sacro Cuore Hospital, Negrar, Italy. · Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy. · Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA. · Division of Radiology, European Institute of Oncology, Milan, Italy. · Division of Digestive Surgery, European Institute of Oncology, Milan, Italy. · Division of Pancreatic Surgery, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milan, Italy. ·Ann Surg Oncol · Pubmed #27613553.

ABSTRACT: BACKGROUND: A low burden of disease represents an independent favorable prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it is not clear whether this is due to a lower diffusion of the disease or thanks to debulking surgery. METHODS: From 1996 to 2013 those patients diagnosed with G1-G2 pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were not deemed eligible for liver radical surgery but were eligible to receive upfront PRRT were prospectively included in the study. Two groups of comparison were identified: those submitted for primary tumor resection before PRRT and those who were not. The outcome was evaluated as: objective response to PRRT (OR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 94 subjects, 31 were previously submitted for primary tumor resection. After propensity score adjustments, patients who underwent surgery before PRRT showed higher stabilization or objective responses after PRRT (p = .006), and this translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs. 65 months; p = .011), for operated versus nonoperated patients, respectively. At multivariate analysis, operated patients showed a statistically significantly improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048. CONCLUSIONS: Primary tumor resection prior to PRRT can be safely proposed in G1-G2 PNETs with diffuse liver metastases because it seems to enhance response to PRRT and to improve significantly PFS.

15 Article Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors. 2016

Spada, Francesca / Antonuzzo, Lorenzo / Marconcini, Riccardo / Radice, Davide / Antonuzzo, Andrea / Ricci, Sergio / Di Costanzo, Francesco / Fontana, Annalisa / Gelsomino, Fabio / Luppi, Gabriele / Nobili, Elisabetta / Galdy, Salvatore / Cella, Chiara Alessandra / Sonzogni, Angelica / Pisa, Eleonora / Barberis, Massimo / Fazio, Nicola. ·Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy. ·Neuroendocrinology · Pubmed #26789262.

ABSTRACT: PURPOSE: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. METHODS: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples. RESULTS: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. CONCLUSION: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

16 Article Resection of the primary pancreatic neuroendocrine tumor in patients with unresectable liver metastases: possible indications for a multimodal approach. 2014

Bertani, Emilio / Fazio, Nicola / Botteri, Edoardo / Chiappa, Antonio / Falconi, Massimo / Grana, Chiara / Bodei, Lisa / Papis, Davide / Spada, Francesca / Bazolli, Barbara / Andreoni, Bruno. ·Division of General and Laparoscopic Surgery, European Institute of Oncology, University of Milano, Italy. Electronic address: emilio.bertani@ieo.it. · GI and Neuroendocrine Tumors Unit, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology-Milano, Milan, Italy. · Division of General and Laparoscopic Surgery, European Institute of Oncology, University of Milano, Italy. · Pancreas Surgical Unit, Università Politecnica delle Marche, Ancona, Italy. · Division of Nuclear Medicine, European Institute of Oncology-Milano, Milan, Italy. ·Surgery · Pubmed #24582492.

ABSTRACT: BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) present in more than 50% of cases with liver metastases as the only systemic localization. Liver metastases are unresectable in 80% of cases at diagnosis. In the context of a metastatic disease, the benefit of primary tumor removal in terms of survival is controversial. METHODS: A single-center series of patients with PNETs presenting with synchronous unresectable hepatic metastases and treated within a framework of a multidisciplinary team was analyzed retrospectively to assess the prognostic factors and the potential benefit of primary tumor resection on long-term survival. RESULTS: At the time of diagnosis, 12 of 43 patients (28%) underwent primary tumor resection. After a median follow-up of 5 years (range, 0.6-14 years), 22 disease-related deaths were observed. The corresponding 5-year survival and median disease-specific duration of survival were 58% and 77 months, respectively. In the operated and nonoperated patients the 5-year disease-specific survival was 82% and 50%, respectively (P = .027). At multivariate analysis, patients with primary tumor removed had an improved survival compared with patients who did not (hazard ratio 0.18; 95% CI 0.05-0.66; P = .010). Other important factors associated with improved survival at multivariate analysis were lesser age, lesser Ki-67 index, and 25% less liver tumor burden. CONCLUSION: In the present series of patients with PNETs and unresectable liver metastases, resection of the primary tumor was associated with an improved survival. This observation suggests that resection of the primary tumor should be part of a global therapeutic strategy and its indication and timing should be discussed within a multidisciplinary team.

17 Minor When Should Everolimus Be Administered in the Natural History of Pancreatic Neuroendocrine Tumors? 2017

Amoroso, Vito / Fazio, Nicola / Mosca, Alessandra / Roca, Elisa / Spada, Francesca / Foroni, Chiara / Agazzi, Giorgio Maria / Berruti, Alfredo. ·Vito Amoroso, University of Brescia at ASST Spedali Civili, Brescia, Italy · Nicola Fazio, European Institute of Oncology, Milan, Italy · Alessandra Mosca, Maggiore della Carità University Hospital, University of Eastern Piedmont, Novara, Italy · Elisa Roca, University of Brescia at ASST Spedali Civili, Brescia, Italy · Francesca Spada, European Institute of Oncology, Milan, Italy · and Chiara Foroni, Giorgio Maria Agazzi, and Alfredo Berruti, University of Brescia at ASST Spedali Civili, Brescia, Italy. ·J Clin Oncol · Pubmed #28113025.

ABSTRACT: -- No abstract --