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Pancreatic Neoplasms: HELP
Articles by Oronzo Brunetti
Based on 9 articles published since 2009
(Why 9 articles?)
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Between 2009 and 2019, Oronzo Brunetti wrote the following 9 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Mast cells and angiogenesis in pancreatic ductal adenocarcinoma. 2018

Longo, Vito / Tamma, Roberto / Brunetti, Oronzo / Pisconti, Salvatore / Argentiero, Antonella / Silvestris, Nicola / Ribatti, Domenico. ·Department of Medical Oncology, Hospital of Taranto, Taranto, Italy. · Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy. · National Cancer Institute "Giovanni Paolo II", Bari, Italy. · Medical Oncology Unit and Scientific Directorate, Cancer Institute "Giovanni Paolo II", Viale Orazio Flacco, 65, 70124, Bari, Italy. · Medical Oncology Unit and Scientific Directorate, Cancer Institute "Giovanni Paolo II", Viale Orazio Flacco, 65, 70124, Bari, Italy. n.silvestris@oncologico.bari.it. ·Clin Exp Med · Pubmed #29492715.

ABSTRACT: Mast cells are recognized as critical components of the tumor stromal microenvironment in several solid and hematological malignancies, promoting angiogenesis and tumor growth. A correlation between mast cells infiltration, angiogenesis and tumor progression has been reported for pancreatic ductal adenocarcinoma as well. Mast cells contribute to the aggressiveness of the pancreatic ductal carcinoma enhancing the expression of several pro-angiogenic factors such as vascular endothelial growth factor, fibroblast growth factor-2, platelet-derived growth factor and angiopoietin-1 as well as stimulating the pancreatic cancer cells proliferation by IL-13 and tryptase. The disruption of this pro-angiogenic and proliferative stimulation by inhibiting the mast cells migration and degranulation is under investigation as a potential therapeutic approach in pancreatic ductal adenocarcinoma patients. This review will summarize the literature concerning the mast cells infiltration in the pancreatic ductal adenocarcinoma analyzing its role in angiogenesis and tumor progression.

2 Review Second-line chemotherapy for advanced pancreatic cancer: Which is the best option? 2017

Aprile, Giuseppe / Negri, Francesca V / Giuliani, Francesco / De Carlo, Elisa / Melisi, Davide / Simionato, Francesca / Silvestris, Nicola / Brunetti, Oronzo / Leone, Francesco / Marino, Donatella / Santini, Daniele / Dell'Aquila, Emanuela / Zeppola, Tea / Puzzoni, Marco / Scartozzi, Mario. ·Department of Oncology, University and General Hospital, Udine, Italy; Department of Oncology, San Bortolo General Hospital, ULSS8 Berica, East District, Vicenza, Italy. Electronic address: giuseppe.aprile@aulss8.veneto.it. · Medical Oncology, University Hospital, Parma, Italy. · Medical Oncology Unit, National Cancer Institute IRCCS "Giovanni Paolo II", Bari, Italy. · Department of Oncology, University and General Hospital, Udine, Italy. · Medical Oncology, University of Verona, Italy. · Medical Oncology, Candiolo Cancer Institute, FPO, IRCCS, University of Torino (TO), Italy. · Department of Medical Oncology, University Campus Bio-Medico, Roma, Italy. · Department of Oncology, University Hospital, Cagliari, Italy. ·Crit Rev Oncol Hematol · Pubmed #28602164.

ABSTRACT: Despite recent biological insight and therapeutic advances, the prognosis of advanced pancreatic cancer still remains poor. For more than 15 years, gemcitabine monotherapy has been the cornerstone of first-line treatment. Recently, prospective randomized trials have shown that novel upfront combination regimens tested in prospective randomized trials have resulted in improved patients' outcome increasing the proportion of putative candidate to second-line therapy. There is no definite standard of care after disease progression. A novel formulation in which irinotecan is encapsulated into liposomal-based nanoparticles may increase the efficacy of the drug without incrementing its toxicity. NAPOLI-1 was the first randomized trial to compare nanoliposomal irinotecan and fluorouracil-leucovorin (5-FU/LV) to 5-FU/LV alone after a gemcitabine-based chemotherapy. This review focuses on the current data for the management of second-line treatment for metastatic pancreatic adenocarcinoma, presents the most interesting ongoing clinical trials and illustrates the biologically-driven future options beyond disease progression.

3 Review Multimodal treatment of resectable pancreatic ductal adenocarcinoma. 2017

Silvestris, Nicola / Brunetti, Oronzo / Vasile, Enrico / Cellini, Francesco / Cataldo, Ivana / Pusceddu, Valeria / Cattaneo, Monica / Partelli, Stefano / Scartozzi, Mario / Aprile, Giuseppe / Casadei Gardini, Andrea / Morganti, Alessio Giuseppe / Valentini, Vincenzo / Scarpa, Aldo / Falconi, Massimo / Calabrese, Angela / Lorusso, Vito / Reni, Michele / Cascinu, Stefano. ·Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy. Electronic address: n.silvestris@oncologico.bari.it. · Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy. Electronic address: dr.oronzo.brunetti@tiscali.it. · Department of Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. Electronic address: e.vasile@ao.pisa.toscana.it. · Radiation Oncology Department, Gemelli ART, Università Cattolica del Sacro Cuore, Roma, Italy. Electronic address: francesco.cellini@uniroma3.it. · ARC-NET Research Centre, University of Verona, Verona, Italy. Electronic address: cataldo.ivana@gmail.com. · Medical Oncology Unit, University of Cagliari, Cagliari, Italy. Electronic address: oncologiamedica2reparto@gmail.com. · Department of Medical Oncology, University and General Hospital, Udine, Italy. Electronic address: aprile83@gmail.com. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy. Electronic address: partelli.stefano@hsr.it. · Medical Oncology Unit, University of Cagliari, Cagliari, Italy. Electronic address: marioscartozzi@gmail.com. · Department of Medical Oncology, University and General Hospital, Udine, Italy; Department of Medical Oncology, General Hospital of Vicenza, Vicenza, Italy. Electronic address: aprile.giuseppe@aoud.sanita.fvg.it. · Medical Oncology Unit, IRCCS, Meldola, Italy. Electronic address: casadeigardini@gmail.com. · Radiation Oncology Center, Dept. of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Italy. Electronic address: alessio.morganti2@unibo.it. · Radiation Oncology Department, Gemelli ART, Università Cattolica del Sacro Cuore, Roma, Italy. Electronic address: vincenzo.valentini@unicatt.it. · ARC-NET Research Centre, University of Verona, Verona, Italy. Electronic address: aldo.scarpa@univr.it. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. · Radiology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy. Electronic address: acalabrese22@gmail.com. · Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy. Electronic address: vito.lorusso@oncologico.bari.it. · Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: reni.michele@hsr.it. · Modena Cancer Center, Policlinico di Modena Università di Modena e Reggio Emilia, Italy. Electronic address: cascinu@yahoo.com. ·Crit Rev Oncol Hematol · Pubmed #28259290.

ABSTRACT: After a timing preoperative staging, treatment of resectable pancreatic adenocarcinoma (PDAC) includes surgery and adjuvant therapies, the former representing the initial therapeutic option and the latter aiming to reduce the incidence of both distant metastases (chemotherapy) and locoregional failures (chemoradiotherapy). Herein, we provide a critical overview on the role of multimodal treatment in PDAC and on new opportunities related to current more active poli-chemotherapy regimens, targeted therapies, and the more recent immunotherapy approaches. Moreover, an analysis of pathological markers and clinical features able to help clinicians in the selection of the best therapeutic strategy will be discussed. Lastly, the role of neoadjuvant treatment of initially resectable disease will be considered mostly in patients whose malignancy shows morphological but not clinical or biological criteria of resectability. Depending on the results of these investigational studies, today a multidisciplinary approach can offer the best address therapy for these patients.

4 Review Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue. 2016

Longo, Vito / Brunetti, Oronzo / Gnoni, Antonio / Cascinu, Stefano / Gasparini, Giampietro / Lorusso, Vito / Ribatti, Domenico / Silvestris, Nicola. ·Department of Medical Oncology, Hospital of Taranto, Taranto, Italy. · Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy. · Department of Medical Oncology, Hospital "Vito Fazi" of Lecce, Lecce, Italy. · Medical Oncology Unit, University of Modena, Modena, Italy. · Scientific Direction, Cancer Institute "Giovanni Paolo II", Bari, Italy. · Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy. · National Cancer Institute "Giovanni Paolo II", Bari, Italy. ·Oncotarget · Pubmed #27462915.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early loco-regional spread and distant metastases at diagnosis, leading to dismal prognosis with a 5-year overall survival rate moderately over than 5%. This malignancy is largely resistant to chemotherapy and radiation, but the reasons of the refractoriness to the therapies is still unknown. Evidence is accumulating to indicate that the PDAC microenvironment and vascularity strongly contribute to the clinical features of this disease. In particular, PDAC is characterized by excessive dense extracellular matrix deposition associated to vasculature collapse and hypoxia with low drug delivery, explaining at least partly the low efficacy of antiangiogenic drugs in this cancer. Strategies aimed to modulate tumor stroma favoring vasculature perfusion and chemotherapeutics delivery are under investigation.

5 Review Neoadjuvant multimodal treatment of pancreatic ductal adenocarcinoma. 2016

Silvestris, Nicola / Longo, Vito / Cellini, Francesco / Reni, Michele / Bittoni, Alessandro / Cataldo, Ivana / Partelli, Stefano / Falconi, Massimo / Scarpa, Aldo / Brunetti, Oronzo / Lorusso, Vito / Santini, Daniele / Morganti, Alessio / Valentini, Vincenzo / Cascinu, Stefano. ·Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy. Electronic address: n.silvestris@oncologico.bari.it. · Medical Oncology Unit, 'Mons R Dimiccoli' Hospital, Barletta, Italy. · Radiation Oncology Department, Policlinico Universitario Campus Bio-Medico, Rome, Italy. · Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Milano, Italy. · Medical Oncology Clinic, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy. · ARC-NET Research Centre, University of Verona, Italy. · Pancreatic Unit, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy. · Medical Oncology Unit, University Campus Biomedico, Roma, Italy. · Radiation Oncology Center, Dept. of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Italy. ·Crit Rev Oncol Hematol · Pubmed #26653573.

ABSTRACT: Treatment of pancreatic ductal adenocarcinoma (PDAC) is increasingly multidisciplinary, with neoadjuvant strategies (chemotherapy, radiation, and surgery) administered in patients with resectable, borderline resectable, or locally advanced disease. The rational supporting this management is the achievement of both higher margin-negative resections and conversion rates into potentially resectable disease and in vivo assessment of novel therapeutics. International guidelines suggest an initial staging of the disease followed by a multidisciplinary approach, even considering the lack of a treatment approach to be considered as standard in this setting. This review will focus on both literature data supporting these guidelines and on new opportunities related to current more active chemotherapy regimens. An analysis of the pathological assessment of response to therapy and the potential role of target therapies and translational biomarkers and ongoing clinical trials of significance will be discussed.

6 Review MicroRNA in pancreatic adenocarcinoma: predictive/prognostic biomarkers or therapeutic targets? 2015

Brunetti, Oronzo / Russo, Antonio / Scarpa, Aldo / Santini, Daniele / Reni, Michele / Bittoni, Alessandro / Azzariti, Amalia / Aprile, Giuseppe / Delcuratolo, Sabina / Signorile, Michele / Gnoni, Antonio / Palermo, Loredana / Lorusso, Vito / Cascinu, Stefano / Silvestris, Nicola. ·Medical Oncology Unit, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy. · Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy. · Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy. · AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy. · Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy. · Department of Medical Oncology, University Hospital of Udine, Udine, Italy. · Department of Medical Oncology, Hospital of Taranto, Taranto, Italy. ·Oncotarget · Pubmed #26259238.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets. In the current literature, many studies have analyzed the role of miRNAs in PDAC. In fact, the absence of appropriate biomarkers, the difficultly of early detection of this tumor, and the lack of effective chemotherapy in patients with unresectable disease have focused attention on miRNAs as new, interesting advance in this malignancy. In this review we analyzed the role of miRNAs in PDAC in order to understand the mechanisms of action and the difference between the onco-miRNA and the tumor suppressor miRNA. We also reviewed all the data related to the use of these molecules as predictive as well as prognostic biomarkers in the course of the disease. Finally, the possible therapeutic use of miRNAs or anti-miRNAs in PDAC is also discussed. In conclusion, although there is still no clinical application for these molecules in PDAC, it is our opinion that the preclinical evidence of the role of specific miRNAs in carcinogenesis, the possibility of using miRNAs as diagnostic or prognostic biomarkers, and their potential therapeutic role, warrant future studies in PDAC.

7 Article Systemic Chemotherapy for Advanced Rare Pancreatic Histotype Tumors: A Retrospective Multicenter Analysis. 2018

Brunetti, Oronzo / Aprile, Giuseppe / Marchetti, Paolo / Vasile, Enrico / Casadei Gardini, Andrea / Scartozzi, Mario / Barni, Sandro / Delfanti, Sara / De Vita, Fernando / Di Costanzo, Francesco / Milella, Michele / Cella, Chiara Alessandra / Berardi, Rossana / Cataldo, Ivana / Scarpa, Aldo / Basile, Debora / Mazzuca, Federica / Graziano, Giusi / Argentiero, Antonella / Santini, Daniele / Reni, Michele / Cascinu, Stefano / Silvestris, Nicola. ·Medical Oncology Unit, Sant'Andrea Hospital, University of Rome La Sapienza, Rome. · Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa. · Department of MedicalOncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola. · Medical Oncology Unit, University of Cagliari, Cagliari. · Medical Oncology Unit, ASST Bergamo Ovest, Treviglio. · Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia. · Medical Oncology Unit, II University of Naples, Naples. · Medical OncologyUnit, Azienda Ospedaliero-Universitaria Careggi, Florence. · Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome. · Division of Gastrointestinal and Neuroendocrine Tumors, IEO, Milan. · Medical Oncology Unit, Università Politecnica Marche - Ospedali Riuniti Ancona, Ancona. · Department of Pathology and Diagnostics, University of Verona, ARCNET, Verona. · Department of Medical Oncology, University and General Hospital, Udine. · Scientific Direction, Cancer Institute "Giovanni Paolo II," Bari. · Medical Oncology Unit, University Campus Biomedico, Rome. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan. · Modena Cancer Center, University of Modena and Reggio Emilia, Azienda Ospedaliera-Universitaria di Modena, Modena, Italy. ·Pancreas · Pubmed #29771769.

ABSTRACT: OBJECTIVES: Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients? METHODS: We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival. RESULTS: Of approximately 4300 exocrine pancreatic cancer patients, 79 advanced cases affected by rare histological types were identified, with pancreatic acinar cell cancer (n = 23), pancreatic adenosquamous cancer (n = 16), and mucinous cystic neoplasm with an associated invasive mucinous cystadenocarcinoma (n = 15) most represented. Survival analyses for each subgroup in relation with the different chemotherapy regimens showed the lack of statistical significance correlations. CONCLUSIONS: Because of the lack of clinical trials in patients affected by these rare pancreatic histotypes, only their molecular classification would help clinicians in future therapeutic choice.

8 Article Immunological mutational signature in adenosquamous cancer of pancreas: an exploratory study of potentially therapeutic targets. 2018

Silvestris, Nicola / Brunetti, Oronzo / Pinto, Rosamaria / Petriella, Daniela / Argentiero, Antonella / Fucci, Livia / Tommasi, Stefania / Danza, Katia / De Summa, Simona. ·a Medical Oncology Unit and Scientific Directorate , Istituto Tumori "Giovanni Paolo II" , Bari , Italy. · b Medical Oncology Unit , Hospital of Barletta , Barletta , Italy. · c Pharmacogenetics and Molecular Diagnostic Unit , Istituto Tumori "Giovanni Paolo II" , Bari , Italy. · d Medical Oncology Unit , Istituto Tumori "Giovanni Paolo II" , Bari , Italy. · e Histopathological Unit , Istituto Tumori "Giovanni Paolo II" , Bari , Italy. ·Expert Opin Ther Targets · Pubmed #29561217.

ABSTRACT: OBJECTIVES: Adenosquamous cancer of pancreas (ASCP) is a rare variant of pancreatic adenocarcinoma (PDAC). It is characterized by poor prognosis and lacks of literature data supporting the choice of systemic therapies. The role of immunotherapy for this malignancy is still unknown. In this study, we evaluated any differences between immune-related genes of PDAC and its adenosquamous variant with the aim to characterize these histothistotypes and eventually identify potential biomarkers useful for an immune-therapy approach in ASCP. METHODS: We compared the mutational status of a customized gene panel, including 41 genes involved in immunity checkpoint, inflammation and control of leukocytes, B and T cells proliferation of PDAC and ASCP. Moreover, we evaluated the immunohistochemical expression of programmed death ligand 1 (PD-L1). RESULTS: We observed a status of 'hypermutation' of genes included in our panel in ASCP (22/41 mutated genes). Furtheremore, PD-L1 was found to be expressed in about 15% of the squamous component of ASCP tissue. CONCLUSION: Due to genetic characteristics and to PD-L1 expression in ASCP compared to PDAC tissue, we can conclude that ASCP presents a potential sensitivity to immunological therapy.

9 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.