Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Alfredo Falcone
Based on 16 articles published since 2010
(Why 16 articles?)

Between 2010 and 2020, A. Falcone wrote the following 16 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review The emerging role of liquid biopsy in diagnosis, prognosis and treatment monitoring of pancreatic cancer. 2019

Rofi, Eleonora / Vivaldi, Caterina / Del Re, Marzia / Arrigoni, Elena / Crucitta, Stefania / Funel, Niccola / Fogli, Stefano / Vasile, Enrico / Musettini, Gianna / Fornaro, Lorenzo / Falcone, Alfredo / Danesi, Romano. ·Unit of Clinical Pharmacology & Pharmacogenetics, Department of Clinical & Experimental Medicine, University of Pisa, Italy. · Unit of Medical Oncology, Department of Translational Research & New Technologies in Medicine, University of Pisa, Italy. · Department of Translational Research & The New Technologies in Medicine & Surgery, University of Pisa, Pisa, Italy. ·Pharmacogenomics · Pubmed #30520336.

ABSTRACT: Circulating tumor DNA, circulating tumor cells and tumor-related exosomes may offer new opportunities to provide insights into the biological and clinical characteristics of a neoplastic disease. They represent alternative routes for diagnostic and prognostic purposes, and for predicting and longitudinally monitoring response to treatment and disease progression. Hence, circulating biomarkers represent promising noninvasive tools in the scenario of pancreatic cancer, where neither molecular nor clinical predictors of treatment benefit have been identified yet. This review aims to provide an overview of the current status of circulating biomarker research in pancreatic cancer, and discusses their potential clinical utility to facilitate clinical decision-making.

2 Review FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer. 2016

Caparello, Chiara / Meijer, Laura L / Garajova, Ingrid / Falcone, Alfredo / Le Large, Tessa Y / Funel, Niccola / Kazemier, Geert / Peters, Godefridus J / Vasile, Enrico / Giovannetti, Elisa. ·Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy. ·World J Gastroenterol · Pubmed #27610011.

ABSTRACT: Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase III trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARC levels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microRNAs as predictive biomarkers.

3 Review Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. 2016

Caparello, Chiara / Vivaldi, Caterina / Fornaro, Lorenzo / Musettini, Gianna / Pasquini, Giulia / Catanese, Silvia / Masi, Gianluca / Lencioni, Monica / Falcone, Alfredo / Vasile, Enrico. ·Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. ·Future Oncol · Pubmed #26883177.

ABSTRACT: BACKGROUND: FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC) and no accepted second-line regimen exists. MATERIAL & METHODS: We enrolled 71 aPC patients progressed to modified FOLFIRINOX (mFOLFIRINOX) treated with second-line chemotherapy. RESULTS: Five partial responses (7.1%) and 19 (27.1%) disease stabilizations were reported. After a median follow-up of 20.1 months, median progression-free survival was 2.5 months (95% CI: 2.1-2.9 months) and median overall survival was 6.2 months (95% CI: 5.3-7.1 months). At multivariate analysis, CA19.9 level ≥ 59 upper normal limit resulted associated with worse survival (hazard ratio: 2.32; 95% CI: 1.12-4.78; p = 0.023). CONCLUSION: Salvage chemotherapy could be useful for a subgroup of aPC patients. Prognostic factors might be helpful to identify patients with greater benefit.

4 Review A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs. 2015

Carrato, A / Falcone, A / Ducreux, M / Valle, J W / Parnaby, A / Djazouli, K / Alnwick-Allu, K / Hutchings, A / Palaska, C / Parthenaki, I. ·Medical Oncology Department, Ramon y Cajal University Hospital, Ctra. Colmenar Viejo Km. 9,100, Madrid, Spain. ·J Gastrointest Cancer · Pubmed #25972062.

ABSTRACT: PURPOSE: The purpose of this study was to assess the overall burden of pancreatic cancer in Europe, with a focus on survival time in a real-world setting, and the overall healthy life lost to the disease. METHODS: Real-world data were retrieved from peer-reviewed, observational studies identified by an electronic search. We performed two de novo analyses: a proportional shortfall analysis to quantify the proportion of healthy life lost to pancreatic cancer and an estimation of the aggregate life-years lost annually in Europe. RESULTS: Ninety-one studies were included. The median, age-standardised incidence of pancreatic cancer per 100,000 was 7.6 in men and 4.9 in women. Overall median survival from diagnosis was 4.6 months; median survival was 2.8-5.7 months in patients with metastatic disease. The proportional shortfall analysis showed that pancreatic cancer results in a 98 % loss of healthy life, with a life expectancy at diagnosis of 4.6 months compared to 15.1 years for an age-matched healthy population. Annually, 610,000-915,000 quality-adjusted life-years (QALYs) are lost to pancreatic cancer in Europe. Patients had significantly lower scores on validated health-related quality of life instruments versus population norms. CONCLUSIONS: To the best of our knowledge, this is the first study to systematically review real-world overall survival and patient outcomes of pancreatic cancer patients in Europe outside the context of clinical trials. Our findings confirm the poor prognosis and short survival reported by national studies. Pancreatic cancer is a substantial burden in Europe, with nearly a million aggregate life-years lost annually and almost complete loss of healthy life in affected individuals.

5 Clinical Trial Adjuvant chemoradiotherapy (gemcitabine-based) in pancreatic adenocarcinoma: the Pisa University experience. 2017

Sainato, Aldo / Montrone, Sabrina / Pasqualetti, Francesco / Coppola, Marianna / Cernusco, Nunzia L V / Panichi, Marco / Gonnelli, Alessandra / Vasile, Enrico / Morganti, Riccardo / Falcone, Alfredo / Boggi, Ugo / Paiar, Fabiola. ·Department of Radiotherapy, Pisa University, Pisa - Italy. · Department of Medical Oncology, Pisa University, Pisa - Italy. · Biostatistical Consulting Department of Oncology, Pisa University, Pisa - Italy. · Department of Surgery and Transplants, Pisa University, Pisa - Italy. ·Tumori · Pubmed #28708229.

ABSTRACT: INTRODUCTION: The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. METHODS: 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly). RESULTS: Median follow-up was 22.7 months (range 4-109). Gastrointestinal toxicity (G3), neutropenia (G3-G4) and cardiac toxicity (G2-G3) were observed in 2.4%, 10.6% and 1.6% of patients, respectively. OS at 12, 24 and 60 months was 79%, 55% and 31%, respectively (median 25 months). Two-year OS in patients with postoperative Karnofsky performance status (KPS) ≤70 and ≥80 was 37.1% and 62.3%, respectively (p<0.0001). OS was better in the group of patients with a postoperative CA 19-9 level ≤100 U/mL (p = 0.014). Median DFS was 17 months. CONCLUSIONS: The combination of concomitant gemcitabine and radiotherapy in patients with radically resected PA was well tolerated and associated with a low incidence of local recurrences. Five-year OS was significantly influenced by postoperative KPS and CA 19-9 values.

6 Article Tumor Regression Grading Assessment in Locally Advanced Pancreatic Cancer After Neoadjuvant FOLFIRINOX: Interobserver Agreement and Prognostic Implications. 2020

Cacciato Insilla, Andrea / Vivaldi, Caterina / Giordano, Mirella / Vasile, Enrico / Cappelli, Carla / Kauffmann, Emanuele / Napoli, Niccolò / Falcone, Alfredo / Boggi, Ugo / Campani, Daniela. ·Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy. · Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy. · Division of Medical Oncology, Pisa University Hospital, Pisa, Italy. · Diagnostic and Interventional Radiology, Pisa University Hospital, Pisa, Italy. · Department of Transplant and General Surgery, University of Pisa, Pisa, Italy. ·Front Oncol · Pubmed #32117724.

ABSTRACT: Neoadjuvant therapy represents an increasingly used strategy in pancreatic cancer, and this means that more pancreatic resections need to be evaluated for therapy effect. Several grading systems have been proposed for the histological assessment of tumor regression in pre-treated patients with pancreatic cancer, but issues like practical application, level of agreement and prognostic significance are still debated. To date, a standardized and widely accepted score has not been established yet. In this study, two pathologists with expertise in pancreatic cancer used 4 of the most frequently reported systems (College of American Pathologists, Evans, MD Anderson, and Hartman) to evaluate tumor regression in 29 locally advanced pancreatic cancers previously treated with modified FOLFIRINOX regimen, to establish the level of agreement between pathologists and to determine their potential prognostic value. Cases were additionally evaluated with a fifth grading system inspired to the Dworak score, normally used for colo-rectal cancer, to identify an alternative, relevant option. Results obtained for current grading systems showed different levels of agreement, and they often proved to be very subjective and inaccurate. In addition, no significant correlation was observed with survival. Interestingly, Dworak score showed a higher degree of concordance and a significant correlation with overall survival in individual assessments. These data reflect the need to re-evaluate grading systems for pancreatic cancer to establish a more reproducible and clinically relevant score.

7 Article Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study. 2019

Vivaldi, Caterina / Fornaro, Lorenzo / Cappelli, Carla / Pecora, Irene / Catanese, Silvia / Salani, Francesca / Cacciato Insilla, Andrea / Kauffmann, Emanuele / Donati, Francescamaria / Pasquini, Giulia / Massa, Valentina / Napoli, Niccolò / Lencioni, Monica / Boraschi, Piero / Campani, Daniela / Boggi, Ugo / Caramella, Davide / Falcone, Alfredo / Vasile, Enrico. ·Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy. caterinavivaldi@gmail.com. · Division of Medical Oncology, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy. caterinavivaldi@gmail.com. · Division of Medical Oncology, Pisa University Hospital, Via Roma 67, 56126 Pisa, Italy. · Department of Diagnostic Imaging, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Surgical Pathology, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Department of Transplant and General Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy. · Diagnostic and Interventional Radiology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. · Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Savi 6, 56126 Pisa, Italy. ·Cancers (Basel) · Pubmed #31277449.

ABSTRACT: Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions' longest diameters (SLD) after 6-8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group;

8 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.

9 Article Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer. 2017

Del Re, Marzia / Vivaldi, Caterina / Rofi, Eleonora / Vasile, Enrico / Miccoli, Mario / Caparello, Chiara / d'Arienzo, Paolo Davide / Fornaro, Lorenzo / Falcone, Alfredo / Danesi, Romano. ·Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. marzia.delre@ao-pisa.toscana.it. · Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy. · Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Sant'Anna School of Advanced Studies, Department of Medical Sciences, Pisa, Italy. ·Sci Rep · Pubmed #28801547.

ABSTRACT: Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled. Three ml of plasma were collected: 1) before starting chemotherapy (baseline); 2) at day 15 of treatment; and 3) at each clinical follow-up. cftDNA was extracted and analysed for KRAS mutations (

10 Article First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors. 2016

Vivaldi, Caterina / Caparello, Chiara / Musettini, Gianna / Pasquini, Giulia / Catanese, Silvia / Fornaro, Lorenzo / Lencioni, Monica / Falcone, Alfredo / Vasile, Enrico. ·Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. ·Int J Cancer · Pubmed #27038273.

ABSTRACT: FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated efficacy in metastatic colorectal cancer. We aimed to evaluate activity and tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative prognostic factors. One hundred thirty-seven consecutive aPC patients were treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical, laboratory and pathological data were collected and their association with activity, progression free survival (PFS) and overall survival (OS) was investigated. After a median follow up of 30 months, median PFS and OS were 8.0 months (95% CI 6.19-9.81) and 12 months (95% CI 9.75-14.25), respectively. Response rate was 38.6%, while disease-control rate 72.2%. At multivariate analysis liver metastases (p = 0.019; Hazard Ratio, HR, 0.59, 95% Confidence Interval, CI, 0.380.96), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 (p = 0.001; HR 2.26, 95%CI 1.42-3.59) and neutrophil-lymphocyte ratio (NLR)> 4 (p= 0.002; HR: 2.42; 95% CI 1.38-4.25) were associated with poorer OS. We categorized 119 pts with complete available data as good-risk (0 factors, 38 pts), intermediate-risk (1 factor, 49 pts) and poor-risk (≥2 factors, 32 pts). Median OS for these three groups were 17.6, 11.1 and 7.4 months, respectively (p < 0.001). FOLFOXIRI is active and feasible in aPC. Prognosis of aPC pts treated with FOLFOXIRI is influenced by easily available factors: our analysis revealed ECOG PS, liver metastases and NLR as the most important predictors of survival. These factors could be helpful for treatment decision and clinical trial design.

11 Article Adjuvant chemotherapy seems beneficial for invasive intraductal papillary mucinous neoplasms. 2013

Caponi, S / Vasile, E / Funel, N / De Lio, N / Campani, D / Ginocchi, L / Lucchesi, M / Caparello, C / Lencioni, M / Cappelli, C / Costa, F / Pollina, L / Ricci, S / Mosca, F / Falcone, A / Boggi, U. ·Department of Oncology, Transplants, and New Technologies, U.O. Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Polo Oncologico Area Vasta Nord-Ovest, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy. ·Eur J Surg Oncol · Pubmed #23290583.

ABSTRACT: AIMS: The incidence of intraductal papillary mucinous neoplasm (IPMN) is rising and these neoplasms now represent up to 25% of resected pancreatic neoplasms. The optimal postoperative management of resected invasive IPMN is still debated in the absence of large prospective clinical trials and of validated prognostic factors in this setting. The objective of our study was to identify potential prognostic factors and to investigate the role of adjuvant therapies for patients radically resected for invasive IPMN. METHODS: We retrospectively reviewed clinical and pathological data regarding a large series of patients with invasive IPMN who underwent surgical resection in the last six years at University Hospital of Pisa. RESULTS: Sixty-four patients were considered for the analysis, thirty-three of whom received adjuvant chemotherapy with gemcitabine. In our series node involvement and high tumoral grade emerged as the major pathologic prognostic factors. Patients treated with adjuvant chemotherapy with gemcitabine experienced a longer disease-free survival than those who received surgery alone. CONCLUSIONS: Gemcitabine-based chemotherapy seems beneficial as adjuvant treatment for patients with resected invasive IPMN.

12 Article The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms. 2013

Caponi, S / Funel, N / Frampton, A E / Mosca, F / Santarpia, L / Van der Velde, A G / Jiao, L R / De Lio, N / Falcone, A / Kazemier, G / Meijer, G A / Verheul, H M / Vasile, E / Peters, G J / Boggi, U / Giovannetti, E. ·Unit Medical Oncology-2, Azienda Ospedaliero-Universitaria Pisana, Pisa. ·Ann Oncol · Pubmed #23139258.

ABSTRACT: BACKGROUND: This multicenter study evaluated three candidate microRNAs (miRNAs) (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. PATIENTS AND METHODS: miRNA expression was quantified by quantitative RT-PCR in 86 laser-microdissected specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs and clinical parameters with overall (OS) and disease-free survival (DFS). RESULTS: miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non-invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues. Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and normal tissues compared with invasive IPMNs. High levels of miR-21 were associated with worse OS [hazard ratio (HR) = 2.47, 95% confidence interval (CI) = 1.37-5.65, P = 0.0047]. Patients with high-miR-21 expression also had a shorter median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed miR-21 as independently prognostic for mortality and disease progression (death risk: HR = 3.3, 95% CI = 1.5-7.0, P = 0.02; progression risk: HR = 2.3, 95% CI = 1.2-4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6, 95% CI = 1.1-6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0-4.8, P = 0.04). CONCLUSIONS: miR-21, miR-155 and miR-101 showed significant differences in invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic biomarker in invasive IPMNs and should be validated in prospective studies.

13 Article High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer. 2012

Giovannetti, Elisa / van der Velde, Arjan / Funel, Niccola / Vasile, Enrico / Perrone, Vittorio / Leon, Leticia G / De Lio, Nelide / Avan, Amir / Caponi, Sara / Pollina, Luca E / Gallá, Valentina / Sudo, Hiroko / Falcone, Alfredo / Campani, Daniela / Boggi, Ugo / Peters, Godefridus J. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. elisa.giovannetti@gmail.com ·PLoS One · Pubmed #23155457.

ABSTRACT: BACKGROUND: Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities to evaluate whether they can predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients. METHODOLOGY/PRINCIPAL FINDINGS: High-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28 days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed that PDACs clustered according to their short/long-OS classification, while the feature selection algorithm RELIEF identified the top 4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts, including 169 targeted by two or more. MiR-211 emerged as the best discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according to median value had a significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI = 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR-211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome. CONCLUSIONS/SIGNIFICANCE: Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.

14 Article MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. 2010

Giovannetti, Elisa / Funel, Niccola / Peters, Godefridus J / Del Chiaro, Marco / Erozenci, Leyla A / Vasile, Enrico / Leon, Leticia G / Pollina, Luca E / Groen, Annemieke / Falcone, Alfredo / Danesi, Romano / Campani, Daniela / Verheul, Henk M / Boggi, Ugo. ·VU University Medical Center, Amsterdam, the Netherlands. ·Cancer Res · Pubmed #20460539.

ABSTRACT: MicroRNA-21 (miR-21) was reported to be overexpressed and contributes to invasion and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether miR-21 expression was associated with the overall survival (OS) of PDAC patients treated with gemcitabine and to provide mechanistic insights for new therapeutic targets. miR-21 expression was evaluated in cells (including 7 PDAC cell lines, 7 primary cultures, fibroblasts, and a normal pancreatic ductal cell line) and tissues (neoplastic specimens from 81 PDAC patients and normal ductal samples) isolated by laser microdissection. The role of miR-21 on the pharmacologic effects of gemcitabine was studied with a specific miR-21 precursor (pre-miR-21). Patients with high miR-21 expression had a significantly shorter OS both in the metastatic and in the adjuvant setting. Multivariate analysis confirmed the prognostic significance of miR-21. miR-21 expression in primary cultures correlated with expression in their respective tissues and with gemcitabine resistance. Pre-miR-21 transfection significantly decreased antiproliferative effects and apoptosis induction by gemcitabine, whereas matrix metalloproteinase (MMP)-2/MMP-9 and vascular endothelial growth factor expression were upregulated. Addition of inhibitors of phosphoinositide 3-kinase and mammalian target of rapamycin resulted in decrease of phospho-Akt and prevented pre-miR-21-induced resistance to the proapoptotic effects of gemcitabine. miR-21 expression correlated with outcome in PDAC patients treated with gemcitabine. Modulation of apoptosis, Akt phosphorylation, and expression of genes involved in invasive behavior may contribute to the role of miR-21 in gemcitabine chemoresistance and to the rational development of new targeted combinations.

15 Minor Comment on: 'Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort'. 2016

Vivaldi, Caterina / Fornaro, Lorenzo / Caparello, Chiara / Falcone, Alfredo / Vasile, Enrico. ·Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy. ·Br J Cancer · Pubmed #27124336.

ABSTRACT: -- No abstract --

16 Minor Correlation of basal EGFR expression with pancreatic cancer grading but not with clinical outcome after gemcitabine-based treatment. 2011

Funel, N / Vasile, E / Del Chiaro, M / Boggi, U / Falcone, A / Campani, D / Scarpa, A / Giovannetti, E. · ·Ann Oncol · Pubmed #21196439.

ABSTRACT: -- No abstract --