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Pancreatic Neoplasms: HELP
Articles by Stefano Cascinu
Based on 26 articles published since 2009
(Why 26 articles?)
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Between 2009 and 2019, S. Cascinu wrote the following 26 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2010

Cascinu, S / Falconi, M / Valentini, V / Jelic, S / Anonymous3340663. ·Department of Medical Oncology, Università Politecnica delle Marche, Ancona, Italy. ·Ann Oncol · Pubmed #20555103.

ABSTRACT: -- No abstract --

2 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.

3 Review Emerging antibodies for the treatment of pancreatic cancer. 2017

Andrikou, Kalliopi / Peterle, Chiara / Pipitone, Stefania / Salati, Massimiliano / Cascinu, Stefano. ·a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy. ·Expert Opin Emerg Drugs · Pubmed #28253833.

ABSTRACT: INTRODUCTION: Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.

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 Review Addressing the challenges of pancreatic cancer: future directions for improving outcomes. 2015

Hidalgo, Manuel / Cascinu, Stefano / Kleeff, Jörg / Labianca, Roberto / Löhr, J-Matthias / Neoptolemos, John / Real, Francisco X / Van Laethem, Jean-Luc / Heinemann, Volker. ·Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. Electronic address: mhidalgo@cnio.es. · Department of Medical Oncology, University of Ancona, Ancona, Italy. · Department of General Surgery, Technische Universität München, Munich, Germany. · Ospedale Papa Giovanni XXIII, Bergamo, Italy. · Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. · National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Cancer Research UK Liverpool Clinical Trials Unit Director, University of Liverpool and Royal Liverpool University Hospital, Liverpool, UK. · Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid and Universitat Pompeu Fabra, Barcelona, Spain. · Department of Gastroenterology-GI Cancer Unit, Erasme University Hospital, Brussels, Belgium. · Comprehensive Cancer Centre Munich, Klinikum der Universität München, Munich, Germany. ·Pancreatology · Pubmed #25547205.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy with an extremely poor prognosis, as shown by a 1-year survival rate of around 18% for all stages of the disease. The low survival rates associated with PDAC primarily reflect the fact that tumours progress rapidly with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. As a result, there is an urgent need to develop accurate markers of pre-invasive pancreatic neoplasms in order to facilitate prediction of cancer risk and to help diagnose the disease at an earlier stage. However, screening for early diagnosis of prostate cancer remains challenging and identifying a highly accurate, low-cost screening test for early PDAC for use in clinical practice remains an important unmet need. More effective therapies are also crucial in PDAC, since progress in identifying novel therapies has been hampered by the genetic complexity of the disease and treatment remains a major challenge. Presently, the greatest step towards improved treatment efficacy has been made in the field of palliative chemotherapy by introducing FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab-paclitaxel. Strategies designed to raise the profile of PDAC in research and clinical practice are a further requirement in order to ensure the best treatment for patients. This article proposes a number of approaches that may help to accelerate progress in treating patients with PDAC, which, in turn, may be expected to improve the quality of life and survival for those suffering from this devastating disease.

8 Review Cetuximab: still an option in the treatment of pancreatic cancer? 2013

Faloppi, Luca / Andrikou, Kalliopi / Cascinu, Stefano. ·University Hospital, Università Politecnica delle Marche, Department of Medical Oncology, via Conca 71, 60126 Ancona, Italy. ·Expert Opin Biol Ther · Pubmed #23560505.

ABSTRACT: INTRODUCTION: In this review, we analyzed the current literature about cetuximab to clarify its role in the treatment of pancreatic cancer. Using single-agent gemcitabine has been the standard treatment for more than 15 years for advanced pancreatic cancer. The attempts at improving the results by combining it with several other drugs, such as fluorouracil, cisplatin, irinotecan, oxaliplatin, or pemetrexed produced no clear survival benefit. Recently, however, new combination chemotherapy regimens (e.g., FOLFIRINOX, nab-paclitaxel plus gemcitabine) achieved a significant survival benefit compared to gemcitabine alone. AREAS COVERED: Epidermal growth factor receptor (EGFR) transmembrane glycoprotein has been demonstrated to be overexpressed in pancreatic cancer, and it correlates with more advanced disease, poor survival, and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway could be an attractive therapeutic target in this tumor. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis, and regression in xenograft models, these benefits remain to be confirmed. EXPERT OPINION: The encouraging results from preclinical and early clinical studies with cetuximab in pancreatic cancer were not confirmed in a Phase III trial. Cetuximab failed to demonstrate improved patient outcome when paired with various chemotherapeutic regimens and/or other biological agents.

9 Review Pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. 2009

Cascinu, S / Jelic, S / Anonymous2870629. ·Department of Medical Oncology, Università Politecnica delle Marche, Ancona, Italy. ·Ann Oncol · Pubmed #19454458.

ABSTRACT: -- No abstract --

10 Clinical Trial A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients. 2017

Laquente, Berta / Lopez-Martin, Jose / Richards, Donald / Illerhaus, Gerald / Chang, David Z / Kim, George / Stella, Philip / Richel, Dirk / Szcylik, Cezary / Cascinu, Stefano / Frassineti, G L / Ciuleanu, Tudor / Hurt, Karla / Hynes, Scott / Lin, Ji / Lin, Aimee Bence / Von Hoff, Daniel / Calvo, Emiliano. ·Institut Català d'Oncologia-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), Barcelona, Spain. · University Hospital and Research Institute, Madrid, Spain. · US Oncology Research, Tyler, USA. · Hematology, Onkology, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany. · Virginia Oncology Associates, Eastern Virginia Medical School, US Oncology Research, Hampton, VA, USA. · 21st Century Oncology, University of Florida Health Oncology, Jacksonville, USA. · St. Joseph Mercy Hospital, Ypsilanti, MI, USA. · Academic Medical Center, Amsterdam, Netherlands. · Department of Oncology, Military Institute of Medicine, Warsaw, Poland. · Department of Oncology and Hematology, Universitá di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy. · Department of Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Institute of Oncology Ion Chiricuta, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca, Romania. · Eli Lilly and Company, Indianapolis, IN, USA. · Translational Genomics Research Institute (TGen) and HonorHealth Research Institute, Phoenix, AZ, USA. · START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Medical Oncology Division, Hospital Universitario Madrid Norte Sanchinarro, Calle Oña, 10, 28050, Madrid, Spain. emiliano.calvo@start.stoh.com. ·BMC Cancer · Pubmed #28202004.

ABSTRACT: BACKGROUND: The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. METHODS: Patients with Stage II-IV locally advanced or metastatic pancreatic cancer were randomized (2:1) to either 230 mg of LY2603618/1000 mg/m RESULTS: Ninety-nine patients (n = 65, LY2603618/gemcitabine; n = 34, gemcitabine) were randomized (intent-to-treat population). The median OS (months) was 7.8 (range, 0.3-18.9) with LY2603618/gemcitabine and 8.3 (range, 0.8-19.1+) with gemcitabine. Similarly, in a Bayesian analysis, the study was not positive since the posterior probability that LY2603618/gemcitabine was superior to gemcitabine in improving OS was 0.3, which did not exceed the prespecified threshold of 0.8. No significant improvements in PFS, ORR, or duration of response were observed. Drug-related treatment-emergent AEs in both arms included nausea, thrombocytopenia, fatigue, and neutropenia. The severity of AEs with LY2603618/gemcitabine was comparable to gemcitabine. The LY2603618 exposure targets (AUC CONCLUSIONS: LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. TRIAL REGISTRATION: NCT00839332 . Clinicaltrials.gov. Date of registration: 6 February 2009.

11 Clinical Trial Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. 2017

Van Laethem, Jean-Luc / Riess, Hanno / Jassem, Jacek / Haas, Michael / Martens, Uwe M / Weekes, Colin / Peeters, Marc / Ross, Paul / Bridgewater, John / Melichar, Bohuslav / Cascinu, Stefano / Saramak, Piotr / Michl, Patrick / Van Brummelen, David / Zaniboni, Alberto / Schmiegel, Wollf / Dueland, Svein / Giurescu, Marius / Garosi, Vittorio L / Roth, Katrin / Schulz, Anke / Seidel, Henrik / Rajagopalan, Prabhu / Teufel, Michael / Childs, Barrett H. ·Department of Gastroenterology, Erasme University Hospital, CP 572/10, route de Lennik 808, 1070, Brussels, Belgium. JL.VanLaethem@erasme.ulb.ac.be. · Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charity Hospital, Virchow-Klinikum Campus, Augustenburger Platz 1, 13353, Berlin, Germany. · Department of Oncology and Radiotherapy, Medical University of Gdansk, M. Skłodowskiej-Curie 3a Street, Gdansk, 80-210, Poland. · Department of Hematology and Oncology, University of Munich Medical Center, Marchioninistraße 15, 81366, Munich, Germany. · Department of Hematology and Oncology, Cancer Center Heilbronn-Franken, Am Gesundbrunnen 20-26, 74078, Heilbronn, Germany. · Division of Medical Oncology, University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, 80045, USA. · Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium. · Department of Medical Oncology, Guy's & St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK. · Department of Oncology, UCL Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK. · Department of Oncology, Palacky University Medical School and University Hospital Olomouc, Křížkovského 8, 771 47, Olomouc, Czech Republic. · Department of Medical Oncology, A.O.U. United Hospitals, Polytechnic University of Marche, Piazza Roma, 22, Ancona, Italy. · Department of Oncological Gastroenterology, Maria Skłodowska-Curie Memorial Cancer Center, ul. W.K. Roentgena 5, 02-781, Warsaw, Poland. · Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital of Giessen and Marburg, Baldingerstraße, 35043, Marburg, Germany. · Universitätsklinikum Halle - University Hospital Halle (Saale), Ernst-Grube-Straße 40, 06120, Halle (Saale), Germany. · Department of Radiotherapy, UZ Brussels, Avenue du Laerbeek 101, 1090, Brussels, Belgium. · Department of Medical Oncology, Poliambulanza Foundation Hospital Institute, Via Bissolati, 57, Brescia, Italy. · Department of Gastroenterology and Hepatology, Medical University Hospital Bochum, Alexandrinenstraße 1, Bochum, 44791, Germany. · Department of Oncology, Oslo University Radium Hospital, Trondheimsveien 235, Bjerke, 0514, Oslo, Norway. · Bayer Pharma AG, Müllerstraße 178, 13353, Berlin, Germany. · Bayer S.p.A., Viale Certosa 126-130, 20156, Milan, Italy. · Bayer HealthCare Pharmaceuticals, Inc., 100 Bayer Blvd, Whippany, NJ, 07981, USA. ·Target Oncol · Pubmed #27975152.

ABSTRACT: BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA. RESULTS: Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m CONCLUSION: Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation.

12 Clinical Trial The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib. 2015

Faloppi, Luca / Bianconi, Maristella / Giampieri, Riccardo / Sobrero, Alberto / Labianca, Roberto / Ferrari, Daris / Barni, Sandro / Aitini, Enrico / Zaniboni, Alberto / Boni, Corrado / Caprioni, Francesco / Mosconi, Stefania / Fanello, Silvia / Berardi, Rossana / Bittoni, Alessandro / Andrikou, Kalliopi / Cinquini, Michela / Torri, Valter / Scartozzi, Mario / Cascinu, Stefano / Anonymous3600843. ·Medical Oncology Unit, Università Politecnica delle Marche, AOU "Ospedali Riuniti", Ancona, Italy. · Medical Oncology Unit, Ospedale S. Martino, Genova, Italy. · Medical Oncology Unit, Ospedali Riuniti, Bergamo, Italy. · Medical Oncology Unit, Ospedale S. Paolo, Milano, Italy. · Medical Oncology Unit, Treviglio Hospital, Treviglio, Italy. · Medical Oncology Unit, C. Poma Hospital, Mantova, Italy. · Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy. · Medical Oncology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy. · New Drug Development Strategies Laboratory, Mario Negri Institute, Milano, Italy. · Medical Oncology Unit, Università degli Studi di Cagliari, Azienda Ospedaliero Universitaria, Cagliari, Italy. ·Oncotarget · Pubmed #26397228.

ABSTRACT: Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.

13 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.

14 Clinical Trial Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study. 2014

Cascinu, Stefano / Berardi, Rossana / Sobrero, Alberto / Bidoli, Paolo / Labianca, Roberto / Siena, Salvatore / Ferrari, Daris / Barni, Sandro / Aitini, Enrico / Zagonel, Vittorina / Caprioni, Francesco / Villa, Federica / Mosconi, Stefania / Faloppi, Luca / Tonini, Giuseppe / Boni, Corrado / Conte, Pierfranco / Di Costanzo, Francesco / Cinquini, Michela / Anonymous2180774. ·Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy. Electronic address: cascinu@yahoo.com. · Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy. · Medical Oncology Unit, Ospedale S. Martino, Genova, Italy. · Medical Oncology Unit, Ospedale S. Gerardo, Monza, Italy. · Medical Oncology Unit, Ospedali Riuniti, Bergamo, Italy. · Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy. · Medical Oncology Unit, Ospedale S. Paolo, Milano, Italy. · Medical Oncology Unit, Treviglio Hospital, Treviglio, Italy. · Medical Oncology Unit, C. Poma Hospital, Mantova, Italy. · Medical Oncology Unit, Istituto Oncologico Veneto, Padova, Italy. · Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy. · Medical Oncology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy. · Medical Oncology Unit, Policlinico Universitario, Modena, Italy. · Medical Oncology Unit Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. · New Drug Development Strategies Laboratory, Mario Negri Institute, Milano, Italy. ·Dig Liver Dis · Pubmed #24189171.

ABSTRACT: BACKGROUND: The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. METHODS: Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B). RESULTS: One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR=0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR=0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B. CONCLUSIONS: Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.

15 Clinical Trial FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. 2012

Zaniboni, Alberto / Aitini, Enrico / Barni, Sandro / Ferrari, Daris / Cascinu, Stefano / Catalano, Vincenzo / Valmadre, Giuseppe / Ferrara, Domenica / Veltri, Enzo / Codignola, Claudio / Labianca, Roberto. ·Medical Oncology Unit, Fondazione Poliambulanza, Via Bissolati 57, 25124, Brescia, Italy. zanib@numerica.it ·Cancer Chemother Pharmacol · Pubmed #22576338.

ABSTRACT: PURPOSE: The purpose of the present study was to evaluate the activity and the tolerability of the FOLFIRI regimen, administered as second-line chemotherapy in patients with locally advanced or metastatic pancreatic cancer after the failure of a gemcitabine-based regimen. METHODS: Patients with locally advanced/metastatic disease who received a first-line chemotherapy (one line only) with gemcitabine ± platinoid (cisplatin, oxaliplatin) and who had measurable disease conform with the RECIST criteria were eligible for the study. FOLFIRI consists of irinotecan 180 mg/m(2) i.v. on day 1, leucovorin (l-form) 200 mg/m(2) i.v. on day 1 and 2, 5-FU 400 mg/m(2) i.v. bolus on days 1 and 2, and 5-FU 600 mg/m(2) i.v. by ci for 22 h on days 1 and 2, repeated every 2 weeks. The primary end point was the response rate. RESULTS: Among the 50 enrolled patients, 4 partial responses (PR) (8%) and 14 stable diseases were observed, for a disease control rate of 18/50 (36%). Forty-one patients (82%) have been pretreated with cisplatin/oxaliplatin+gemcitabine as first-line chemotherapy. The median progression-free and overall survivals were 3.2 and 5 months, respectively. The 6-month survival rate was 32%. Grade 3-4 neutropenia and diarrhea occurred in 10 (20%) and 6 (12%) patients, respectively. CONCLUSION: The FOLFIRI regimen showed a modest clinical activity in this quite heavily pretreated patients' population with locally advanced or metastatic pancreatic cancer with a manageable toxicity profile.

16 Article The Italian Rare Pancreatic Exocrine Cancer Initiative. 2019

Brunetti, Oronzo / Luchini, Claudio / Argentiero, Antonella / Tommasi, Stefania / Mangia, Anita / 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 / Santini, Daniele / Doglioni, Claudio / Maiello, Evaristo / Lawlor, Rita T / Mazzaferro, Vincenzo / Lonardi, Sara / Giuliante, Felice / Brandi, Giovanni / Scarpa, Aldo / Cascinu, Stefano / Silvestris, Nicola. ·1 Medical Oncology Unit, IRCCS Cancer Institute "Giovanni Paolo II" of Bari, Bari, Italy. · 2 Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. · 3 Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. · 4 Functional Biomorphology Laboratory, IRCCS-Istituto Tumori, Bari, Italy. · 5 Medical Oncology Unit, Hospital of Vicenza, Vicenza, Italy. · 6 Medical Oncology Unit, Sant'Andrea Hospital, University of Rome La Sapienza, Rome, Italy. · 7 Medical Oncology Unit, University Hospital of Pisa, Pisa, Italy. · 8 Medical Oncology Unit, Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), Meldola, Italy. · 9 Medical Oncology Unit, University of Cagliari, Cagliari, Italy. · 10 Medical Oncology Unit, ASST Bergamo Ovest, Treviglio, Italy. · 11 Medical Oncology Unit, IRCCS Foundation Polyclinic San Matteo, Pavia, Italy. · 12 Medical Oncology Unit, II University of Naples, Naples, Italy. · 13 Medical Oncology Unit, Careggi University Hospital, Florence, Italy. · 14 Medical Oncology Unit, "Regina Elena" National Cancer Institute, Rome, Italy. · 15 Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), Milan, Italy. · 16 Medical Oncology Unit, Polytechnic University of the Marche, "Ospedali Riuniti Ancona," Ancona, Italy. · 17 Department of Pathology and Diagnostics, University of Verona Hospital Trust, Policlinico GB Rossi, Verona, Italy. · 18 Medical Oncology Unit, University Campus Biomedico, Rome, Italy. · 19 Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · 20 Medical Oncology Unit, IRCCS "Casa Sollievo della Sofferenza" Foundation, San Giovanni Rotondo, Italy. · 21 Arc-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · 22 Hepato-Biliary-Pancreatic Surgery, University of Milan, Istituto Nazionale Tumori, Fondazione IRCCS, Milan, Italy. · 23 Medical Oncology Unit, IRCCS Veneto Institute of Oncology (IOV), Padua, Italy. · 24 Hepatobiliary Surgery Unit, IRCCS A. Gemelli Polyclinic Foundation, Catholic University of the Sacred Heart, Rome, Italy. · 25 Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. · 26 Medical Oncology Unit, Modena Cancer Center, University Hospital of Modena, Modena, Italy. · 27 Scientific Direction, IRCCS Cancer Institute "Giovanni Paolo II" of Bari, Bari, Italy. ·Tumori · Pubmed #30967031.

ABSTRACT: INTRODUCTION: Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available. METHODS: A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway-oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays. CONCLUSIONS: We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.

17 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.

18 Article An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) + gemcitabine vs gemcitabine alone for metastatic pancreatic cancer patients: the APICE study. 2018

Lazzaro, Carlo / Barone, Carlo / Caprioni, Francesco / Cascinu, Stefano / Falcone, Alfredo / Maiello, Evaristo / Milella, Michele / Pinto, Carmine / Reni, Michele / Tortora, Giampaolo. ·a Studio di Economia Sanitaria , Milan , Italy. · b Policlinico Gemelli , Rome , Italy. · c Ospedale S. Martino , Genoa , Italy. · d Policlinico di Modena , Modena , Italy. · e Azienda Ospedaliera Universitaria Pisana , Pisa , Italy. · f Casa Sollievo della Sofferenza , S. Giovanni Rotondo , Italy. · g Istituto Nazionale Tumori Regina Elena , Rome , Italy. · h Ospedale S. Maria Nuova , Reggio Emilia , Italy. · i Ospedale S. Raffaele , Milan , Italy. · j Azienda Ospedaliera Universitaria Integrata Borgo Roma , Verona , Italy. ·Expert Rev Pharmacoecon Outcomes Res · Pubmed #29641931.

ABSTRACT: BACKGROUND: the APICE study evaluates the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel - Nab-P) + gemcitabine (G) vs G alone in metastatic pancreatic cancer (MPC) from the Italian National Health Service (INHS) standpoint. RESEARCH DESIGN AND METHODS: A 4-year, 4 health states (progression-free; progressed; end of life; death) Markov model based on the MPACT trial was developed to estimate costs (Euro [€], 2017 values), and quality-adjusted life years (QALYs). Patients were assumed to receive intravenously Nab-P 125 mg/m RESULTS: Nab-P + G totals 0.154 incremental QALYs and €7082.68 incremental costs vs G alone. ICUR (€46,021.58) is lower than the informal threshold value of €87,330 adopted by the Italian Medicines Agency during 2010-2013 for reimbursing oncological drugs. Sensitivity analyses confirmed the robustness of the baseline findings. CONCLUSIONS: Nab-P + G in MPC patients can be considered cost-effective for the INHS.

19 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.

20 Article Borderline resectable pancreatic cancer: More than an anatomical concept. 2017

Petrelli, Fausto / Inno, Alessandro / Barni, Sandro / Ghidini, Antonio / Labianca, Roberto / Falconi, Massimo / Reni, Michele / Cascinu, Stefano / Anonymous11560889. ·Medical Oncology Unit, ASST Bergamo Ovest, Bergamo, Italy. Electronic address: faupe@libero.it. · Medical Oncology Unit, Sacro Cuore Don Calabria Hospital, Verona, Italy. · Medical Oncology Unit, ASST Bergamo Ovest, Bergamo, Italy. · Medical Oncology Unit, Casa di Cura Igea, Milano, Italy. · Medical Oncology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. · Surgical Department of Pancreas, San Raffaele Hospital, IRCCS, Milano, Italy. · Medical Oncology Unit, San Raffaele Hospital, IRCCS, Milano, Italy. · Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy. ·Dig Liver Dis · Pubmed #27931968.

ABSTRACT: Borderline resectable pancreatic cancer (BRPC) accounts for about 10-15% of newly diagnosed pancreatic cancer, and its management requires a skilled multidisciplinary team. The main definition of BRPC refers to resectability, but also a high risk of positive surgical margins and recurrence. This raises questions about the value of surgery and suggests an opportunity to utilize preoperative treatment in this subset of patients. Besides technical borderline resectable disease which is defined on anatomical and radiological criteria, there is also a biological borderline resectable disease which is defined on clinical and biological prognostic factors. Technical borderline resectable disease requires tumor shrinkage with aggressive therapy including modern drug combinations +/- radiotherapy to achieve radical surgery. Biological BRPC needs always an early systemic treatment in order to select the best candidates for subsequent radical surgery. It is important to distinguish between these different clinical scenarios, both in clinical practice and for clinical trials design.

21 Article Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy? 2016

Crippa, S / Bittoni, A / Sebastiani, E / Partelli, S / Zanon, S / Lanese, A / Andrikou, K / Muffatti, F / Balzano, G / Reni, M / Cascinu, S / Falconi, M. ·Department of Surgery, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Department of Oncology, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Department of Surgery, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Department of Oncology, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Department of Surgery, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #27423449.

ABSTRACT: BACKGROUND: New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. METHODS: Retrospective analysis. EXCLUSION CRITERIA: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. RESULTS: 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). CONCLUSIONS: Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.

22 Article KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma. 2015

Bittoni, Alessandro / Piva, Francesco / Santoni, Matteo / Andrikou, Kalliopi / Conti, Alessandro / Loretelli, Cristian / Mandolesi, Alessandra / Lanese, Andrea / Pellei, Chiara / Scarpelli, Marina / Principato, Giovanni / Cascinu, Stefano. ·Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy. · Department of Specialistic Clinical & Odontostomatological Sciences, Polytechnic University of Marche, Ancona 60131, Italy. · Department of Pathology, AOU Ospedali Riuniti, Università Politecnica delle Marche, via Conca 71, 60126 Ancona, Italy. ·Future Oncol · Pubmed #26161927.

ABSTRACT: AIMS: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations. MATERIALS & METHODS: Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival. RESULTS: MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors. CONCLUSION: KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets.

23 Article HER family receptor expression and prognosis in pancreatic cancer. 2015

Bittoni, Alessandro / Mandolesi, Alessandra / Andrikou, Kalliopi / Santoni, Matteo / Alfonsi, Simona / Lanese, Andrea / Loretelli, Cristian / Pellei, Chiara / Piva, Francesco / Scarpelli, Marina / Cascinu, Stefano. ·Department of Medical Oncology, AOU United Hospitals, Polytechnic University of Marche, Ancona - Italy. ·Int J Biol Markers · Pubmed #26109364.

ABSTRACT: BACKGROUND: HER family receptors play a key role in tumor progression in several malignancies, such as colorectal, lung or breast cancer. The aims of this study were to investigate expression of HER-1, HER-2 and HER-3 in pancreatic cancer (PC) samples and evaluate the association between HER-family receptor expression and patients' clinical outcomes. METHODS: Tissue samples from 91 PC patients were subjected to immunohistochemical staining to assess the expression of HER-1, HER-2 and HER-3. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+ or 3+ were assigned to each sample based on the intensity of staining for HER receptors. Scores of 2+ or 3+ were defined as positive staining. RESULTS: HER-1 overexpression was observed in 41 out of 91 samples (45.1%), while HER-2 was not overexpressed in any of the analyzed samples. HER-3 was overexpressed in 37 samples (40.7%) and was found to be associated with advanced TNM stage. In particular, HER-3 was overexpressed in 12 out of 16 stage IV patients (75%) compared with only 33.3% of stage I-III patients (p = 0.02). Among 79 patients with available survival data, the 6 patients with strong HER-3 expression (score 3+) had a shorter survival compared with remaining patients (median overall survival 6.9 months vs. 12.3 months, respectively). CONCLUSIONS: HER-1 and HER-3 were found to be expressed in a significant proportion of PC patients. Strong HER-3 expression represents an indicator of poor prognosis in PC patients, being associated with advanced stage and shorter survival.

24 Article [Treatment of pancreatic cancer. Actuality and perspective]. 2015

Bittoni, Alessandro / Andrikou, Kalliopi / Lanese, Andrea / Santoni, Matteo / Pellei, Chiara / Faloppi, Luca / Del Prete, Michela / Giampieri, Riccardo / Cascinu, Stefano. · ·Recenti Prog Med · Pubmed #25994537.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest solid malignancies, with an extremely poor prognosis, with a 1-year survival rate of approximately 20%. Low survival rates of PDAC mainly derive from late diagnosis, with only a minority of patients amenable to surgery, as well as high rates of relapse and lack of effective treatments for advanced disease stages. As a result, there is an urgent need for the development of new effective therapies. At present, the greatest step towards an improvement of treatment has been made with the introduction of two combination chemotherapy regimens, namely FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab-paclitaxel. However, current research is also taking a multidirectional approach aiming at developing new treatment options, such as the use of agents targeting the oncogenic network signaling of KRAS or the extracellular matrix, as well as immune therapies.

25 Article Lgr5 expression, cancer stem cells and pancreatic cancer: results from biological and computational analyses. 2015

Andrikou, Kalliopi / Santoni, Matteo / Piva, Francesco / Bittoni, Alessandro / Lanese, Andrea / Pellei, Chiara / Conti, Alessandro / Loretelli, Cristian / Mandolesi, Alessandra / Giulietti, Matteo / Scarpelli, Marina / Principato, Giovanni / Falconi, Massimo / Cascinu, Stefano. ·Medical Oncology, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, 60126 Ancona, Italy. ·Future Oncol · Pubmed #25804119.

ABSTRACT: AIMS: To determine the relationship between Lgr5 and other stemness markers and pathologic features in pancreatic ductal adenocarcinoma (PDAC) samples. MATERIALS & METHODS: In 69 samples, Lgr5 was analyzed by qRT-PCR together with a panel of 29 genes. Bioinformatic analysis was carried out to identify a possible pathway regulating Lgr5 expression in PDAC. RESULTS: Lgr5 expression was not associated with the expression of tested cancer stem cell markers. Moreover, it was not an independent predictor of survival neither at univariate analysis (p = 0.21) nor at multivariate analysis (p = 0.225). CONCLUSION: Based on the lack of correlation between Lgr5 and tested cancer stem cell markers, Lgr5 does not seem to be a potential stemness marker or prognostic factor in PDAC.

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