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Pancreatic Neoplasms: HELP
Articles by Alfredo Carrato
Based on 32 articles published since 2010
(Why 32 articles?)
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Between 2010 and 2020, A. Carrato wrote the following 32 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Management and supportive treatment of frail patients with metastatic pancreatic cancer. 2019

Macarulla, T / Carrato, A / Díaz, R / García, A / Laquente, B / Sastre, J / Álvarez, R / Muñoz, A / Hidalgo, M. ·Dpt. Medical Oncology, Hospital Vall d'Hebrón, Barcelona, Spain. Electronic address: tmacarulla@vhio.net. · Dpt. Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. · Dpt. Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. · Dpt. Medical Oncology, Instituto Catalán de Oncología, de Girona, Spain. · Dpt. Medical Oncology, Instituto Catalán de Oncología, L'Hospitalet de Llobregat, Barcelona, Spain. · Dpt. Medical Oncology, Hospital Clínico Universitario San Carlos, Spain. · Dpt. Medical Oncology, Centro Integral Oncológico Clara Campal, Hospital Universitario Sanchinarro, Madrid, Spain. · Dpt. Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. · Dpt. Medical Oncology, Beth Israel Deaconess Medical Center, Boston, USA. ·J Geriatr Oncol · Pubmed #30005980.

ABSTRACT: Data regarding management of frail patients with pancreatic ductal adenocarcinoma practice is currently very scarce. Randomized clinical trials usually exclude these subgroup of patients and the majority of the publications only consider chronological age and ECOG performance status for their classification. Therefore, the current available data do not reflect daily clinical practice. Only data from a phase two study (FRAGANCE study), designed to select a tolerable dose-schedule of nab-placitaxel + gemcitabine (Phase one) and to evaluate the efficacy of the selected regimen (Phase two) in patients with ECOG-2 and previously untreated advanced PDAC, are currently available. Management of these particular patients is exceedingly complex and requires collaboration of multidisciplinary teams and intensive support treatment. This article reviews the literature available regarding the management of the so-called frail patients and provide guidance for chemotherapy as well as supportive care treatments.

2 Review From First Line to Sequential Treatment in the Management of Metastatic Pancreatic Cancer. 2018

Martín, Andrés Muñoz / Hidalgo, Manuel / Alvarez, Rafael / Arrazubi, Virginia / Martínez-Galán, Joaquina / Salgado, Mercedes / Macarulla, Teresa / Carrato, Alfredo. ·Dpt. Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid, Spain. · Div. Medical Oncology, Beth Israel Deaconess Medical Center, Boston, USA. · Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, Madrid, Spain. · Dpt. Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, Spain. · Dpt. Medical Oncology, H.U. Virgen de las Nieves, Complejo Hospitalario de Granada, Granada, Spain. · Dpt. Medical Oncology, Complejo Hospitalario Universitario de Orense, Orense, Spain. · Dpt. Medical Oncology, Hospital Vall d´Hebrón, Barcelona, Spain. · Dpt. Medical Oncology, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERONC, Madrid, Spain. ·J Cancer · Pubmed #29896283.

ABSTRACT: The current management of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is based on systemic chemotherapy. The results of the MPACT and PRODIGE clinical trials have demonstrated that the combination of nab-paclitaxel and gemcitabine (GEM) as well as FOLFIRINOX regimen result in improvement in overall survival when compared to GEM alone. Treatment guidelines now recommend either one of these two regimens as first line treatment for fit patients with mPDAC. Because no head-to-head comparison between the two regimens exists, the selection of one versus the other is based on clinical criteria. The design and eligibility criteria of these two clinical trials are dissimilar, making the results of the MPACT trial more applicable to the general population of patients with mPDAC. In addition, the combination of nab-paclitaxel and GEM is better tolerated and easier to administer in clinical practice than FOLFIRINOX. Furthermore, when the regimens are studied in comparable patient populations the efficacy results are very similar. Nanoliposomal irinotecan plus 5FU has recently demonstrated a significant increase in efficacy rates after a GEM-based treatment. Importantly, treatment of mPDAC should now be considered as a continuum care for patients who are fit, with second and even third line treatments. Different sequential treatment algorithms are proposed based on available data. In retrospective studies, patients who were managed with GEM-based regimens followed by fluoropyrimidine-based regimens appear to have the most favorable outcome.

3 Review Management of hyperbilirubinaemia in pancreatic cancer patients. 2018

Álvarez, R / Carrato, A / Adeva, J / Alés, I / Prados, S / Valladares, M / Macarulla, T / Muñoz, A / Hidalgo, M. ·Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, Madrid, Spain. Electronic address: ralvarezgallego@hmhospitales.com. · Department Medical Oncology, Ramón y Cajal University Hospital, Alcalá University, IRYCIS, CIBERONC, Madrid, Spain. · Department Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. · Department Medical Oncology, Hospital Regional Universitario de Málaga, Málaga, Spain. · Department of Gastroenterology, Hospital Universitario HM Sanchinarro, Madrid, Spain. · Department Medical Oncology, Hospital Universitario Virgen Del Rocío, Sevilla, Spain. · Department Medical Oncology, Hospital Vall D'Hebrón, Barcelona, Spain. · Department Medical Oncology, Hospital Gregorio Marañón, Madrid, Spain. · Department Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. ·Eur J Cancer · Pubmed #29505968.

ABSTRACT: Development of hyperbilirubinaemia is common in patients with advanced pancreatic adenocarcinoma, both at diagnosis as well throughout disease evolution. For this reason, hyperbilirubinaemia determines chemotherapy treatment selection, and therefore it should be considered one of the most relevant conditions. There is very little evidence for the use of chemotherapy in this setting. This article summarises the main causes of hyperbilirubinaemia, how to treat them as well as their differential diagnosis. The current clinical evidence of the available drugs as well as the recommendations of use different combinations in the context of hyperbilirubinaemia are also reviewed.

4 Review Surgery for pancreatic ductal adenocarcinoma. 2017

Vera, R / Díez, L / Martín Pérez, E / Plaza, J C / Sanjuanbenito, A / Carrato, A. ·Department of Medical Oncology, Complejo Hospitalario de Navarra, C/de Irunlarrea 3, Planta Baja, 31008, Pamplona, Spain. ruth.vera.garcia@cfnavarra.es. · Department of Surgery, Hospital Clínico San Carlos, Madrid, Spain. · Department of Surgery, Hospital Universitario La Princesa, Madrid, Spain. · Department of Pathology, Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro, Madrid, Spain. · Department of Surgery, Hospital Universitario Ramón y Cajal, Madrid, Spain. · Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. ·Clin Transl Oncol · Pubmed #28646282.

ABSTRACT: Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient's conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail.

5 Review Biomarkers in pancreatic ductal adenocarcinoma. 2017

Gallego, J / López, C / Pazo-Cid, R / López-Ríos, F / Carrato, A. ·Department of Medical Oncology, University Hospital of Elche, Camí de l'Almazara, 11, Elche, 03203, Alicante, Spain. j.gallegoplazas@gmail.com. · Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. · Department of Medical Oncology, Hospital Universitario Miguel Servet, Saragossa, Spain. · Department of Pathology, Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro, Madrid, Spain. · Department of Medical Oncology, Madrid, Spain. ·Clin Transl Oncol · Pubmed #28616721.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice.

6 Review Supportive care in pancreatic ductal adenocarcinoma. 2017

Laquente, B / Calsina-Berna, A / Carmona-Bayonas, A / Jiménez-Fonseca, P / Peiró, I / Carrato, A. ·Department Medical Oncology, Instituto Catalán de Oncología, L'Hospitalet de Llobregat, Av. Gran Vía 199-203, 0898, Barcelona, Spain. blaquente@iconcologia.net. · Department Palliative Care, Hospital Germans Trias I Pujol, Instituto Catalán de Oncología, Badalona, Spain. · Department Medical Oncology and Hematology, Hospital Universitario Morales Meseguer, Murcia, Spain. · Department Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain. · Clinical Nutrition Unit, Instituto Catalán de Oncología, L'Hospitalet de Llobregat, Barcelona, Spain. · Department Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. ·Clin Transl Oncol · Pubmed #28612201.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with poorest prognosis and represents the third leading cause of cancer-related deaths in Western countries. Despite advances in diagnostic procedures and treatment, diagnosis is made in most cases when the disease is locally advanced or metastatic. Supportive care aims to improve symptoms, reduce hospital admission rates, and preserve quality of life. Proper symptomatic management is critical to allow administration of chemotherapy and radiotherapy. Symptomatic management should be accomplished in a multidisciplinary fashion. Its primary aims include relief of biliary or duodenal obstruction, prevention and/or treatment of thromboembolic disease, and control cancer-related pain. Nutritional support and optimal replacement therapy in patients with endocrine and/or exocrine insufficiency, is mandatory. This manuscript highlights the most significant problems faced when caring for patients with advanced PDAC and provides an evidence-based approach to symptomatic management.

7 Review Diagnosis and staging of pancreatic ductal adenocarcinoma. 2017

Guillén-Ponce, C / Blázquez, J / González, I / de-Madaria, E / Montáns, J / Carrato, A. ·Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo, km 9,100, Madrid, Spain. carmenguillenponce@gmail.com. · Department of Radiology, Hospital Universitario Ramón y Cajal, Madrid and Hospital MD Anderson, Madrid, Spain. · Department of Medical Oncology, Complejo Hospitalario de Granada, Granada, Spain. · Pancreatic Unit, Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, Spain. · Department of Pathology, Centro Anatomopatológico, Madrid, Spain. · Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo, km 9,100, Madrid, Spain. ·Clin Transl Oncol · Pubmed #28612200.

ABSTRACT: The management of pancreatic ductal adenocarcinoma (PDAC) is a major public health concern worldwide. Currently, most PDAC patients are diagnosed in advanced stages. The signs and symptoms of the disease, except for jaundice, are non-specific. Thus, the current challenge is to identify earlier those individuals for whom specific screening tools and specific treatments would be beneficial. On the basis of the recommendations of the group of experts of multiple medical specialties of the GALLgo Project, the patients with PDAC should be managed by a multidisciplinary team to assess the personal and family history, the best diagnostic and staging procedures and consider all important aspects for treatment decisions. In this article, the group of experts proposes strategies to shorten the diagnosis times in PDAC patients.

8 Review Reduced risk of pancreatic cancer associated with asthma and nasal allergies. 2017

Gomez-Rubio, Paulina / Zock, Jan-Paul / Rava, Marta / Marquez, Mirari / Sharp, Linda / Hidalgo, Manuel / Carrato, Alfredo / Ilzarbe, Lucas / Michalski, Christoph / Molero, Xavier / Farré, Antoni / Perea, José / Greenhalf, William / O'Rorke, Michael / Tardón, Adonina / Gress, Thomas / Barberà, Victor / Crnogorac-Jurcevic, Tatjana / Domínguez-Muñoz, Enrique / Muñoz-Bellvís, Luís / Alvarez-Urturi, Cristina / Balcells, Joaquim / Barneo, Luis / Costello, Eithne / Guillén-Ponce, Carmen / Kleeff, Jörg / Kong, Bo / Lawlor, Rita / Löhr, Matthias / Mora, Josefina / Murray, Lim / O'Driscoll, Damian / Peláez, Pablo / Poves, Ignasi / Scarpa, Aldo / Real, Francisco X / Malats, Núria / Anonymous5500850. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. · Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. · National Cancer Registry Ireland, Cork, Ireland, and Institute of Health & Society, Newcastle University, UK. · Hospital Madrid-Norte-Sanchinarro, Madrid, Spain. · Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. · Technical University of Munich, Munich, Germany. · Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain. · Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. · The Royal Liverpool University Hospital, Liverpool, UK. · Centre for Public Health, Queen's University Belfast, Belfast, UK. · Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital Giessen and Marburg, Marburg, Germany. · Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain. · Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. · Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Cirugía General y del Aparato Digestivo, Hospital Universitario de Salamanca, Salamanca, Spain. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Gastrocentrum, Karolinska Institutet, Stockholm, Sweden. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ·Gut · Pubmed #26628509.

ABSTRACT: OBJECTIVE: Studies indicate an inverse association between ductal adenocarcinoma of the pancreas (PDAC) and nasal allergies. However, controversial findings are reported for the association with asthma. Understanding PDAC risk factors will help us to implement appropriate strategies to prevent, treat and diagnose this cancer. This study assessed and characterised the association between PDAC and asthma and corroborated existing reports regarding the association between allergies and PDAC risk. DESIGN: Information about asthma and allergies was collated from 1297 PDAC cases and 1024 controls included in the PanGenEU case-control study. Associations between PDAC and atopic diseases were studied using multilevel logistic regression analysis. Meta-analyses of association studies on these diseases and PDAC risk were performed applying random-effects model. RESULTS: Asthma was associated with lower risk of PDAC (OR 0.64, 95% CI 0.47 to 0.88), particularly long-standing asthma (>=17 years, OR 0.39, 95% CI 0.24 to 0.65). Meta-analysis of 10 case-control studies sustained our results (metaOR 0.73, 95% CI 0.59 to 0.89). Nasal allergies and related symptoms were associated with lower risk of PDAC (OR 0.66, 95% CI 0.52 to 0.83 and OR 0.59, 95% CI 0.46 to 0.77, respectively). These results were supported by a meta-analysis of nasal allergy studies (metaOR 0.6, 95% CI 0.5 to 0.72). Skin allergies were not associated with PDAC risk. CONCLUSIONS: This study shows a consistent inverse association between PDAC and asthma and nasal allergies, supporting the notion that atopic diseases are associated with reduced cancer risk. These results point to the involvement of immune and/or inflammatory factors that may either foster or restrain pancreas carcinogenesis warranting further research to understand the molecular mechanisms driving this association.

9 Review Post-gemcitabine therapy for patients with advanced pancreatic cancer - A comparative review of randomized trials evaluating oxaliplatin- and/or irinotecan-containing regimens. 2016

Vogel, Arndt / Ciardiello, Fortunato / Hubner, Richard A / Blanc, Jean-Frédéric / Carrato, Alfredo / Yang, Yoojung / Patel, Dipen A / Ektare, Varun / de Jong, Floris A / Gill, Sharlene. ·Medical School Hannover, Department of Gastroenterology, Hematology and Endocrinology, Carl-Neubergstr. 1, 30659 Hannover, Germany. Electronic address: vogel.arndt@mh-hannover.de. · Dipartimento di Medicina Clinica e Sperimentale "F. Magrassi", Seconda Università degli Studi di Napoli, Via S. Pansini 5, 80131 Napoli, Italy. Electronic address: Fortunato.CIARDIELLO@unina2.it. · Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. Electronic address: Richard.Hubner@christie.nhs.uk. · Department of Hepato-Gastroenterology and Digestive Oncology, CHU Bordeaux, Hôpital Haut-Lévêque, avenue de Magellan, 33600 Pessac, France. Electronic address: jean-frederic.blanc@chu-bordeaux.fr. · Medical Oncology Department, Ramon y Cajal University Hospital, IRYCIS, Alcala University, Carretera Colmenar Viejo km 9.1, 28034 Madrid, Spain. Electronic address: acarrato@telefonica.net. · Shire, 650 East Kendall Street, Cambridge, MA 02145, United States. Electronic address: Yoojung.yang@baxalta.com. · Pharmerit International, 4350 East West Highway, Suite 430, Bethesda, MD 20814, United States. Electronic address: dpatel@pharmerit.com. · Pharmerit International, 4350 East West Highway, Suite 430, Bethesda, MD 20814, United States. Electronic address: vektare@pharmerit.com. · Shire, Thurgauerstrasse 130, 8152 Glattpark (Opfikon), Zürich, Switzerland. Electronic address: Floris.de.Jong@shire.com. · University of British Columbia, BC Cancer Agency, 600 W. 10th Avenue, Vancouver, BC V5Z 4E6, Canada. Electronic address: sgill@bccancer.bc.ca. ·Cancer Treat Rev · Pubmed #27676174.

ABSTRACT: A systematic review and critical evaluation of randomized trial evidence for oxaliplatin- or irinotecan-containing regimens in patients with advanced pancreatic cancer previously treated with gemcitabine has not yet been published. We conducted a comparative systematic review of randomized trials evaluating oxaliplatin- or irinotecan-based therapies in patients with advanced pancreatic cancer previously treated with gemcitabine to assess trial similarity and the feasibility of performing an indirect treatment comparison (ITC). Studies were identified through PubMed and key oncology conference abstracts. The following trials met our criteria: NAPOLI-1 (nanoliposomal irinotecan [nal-IRI] or nal-IRI+5-fluorouracil [5-FU]/leucovorin [LV] vs 5-FU/LV), CONKO-003 (oxaliplatin+5-FU/LV [OFF] vs 5-FU/LV), PANCREOX (oxaliplatin+5-FU/LV [mFOLFOX6] vs 5-FU/LV), and Yoo et al. (2009) (irinotecan+5-FU/LV [mFOLFIRI3] vs mFOLFOX). Fundamental differences were identified in study design (i.e., number of study sites, number of countries), patient (i.e., locally advanced vs metastatic disease, stratification variables, prior and subsequent treatments) and treatment (i.e., regimens, dose intensity) characteristics, and primary and secondary outcomes (i.e., primary vs secondary outcomes, overall survival [OS], progression-free survival [PFS]) among the 4 included trials. Our comparative review demonstrated significant dissimilarity across trials, which precluded conducting an ITC. In the absence of head-to-head nal-IRI- and/or oxaliplatin-based therapy trials, clinicians are advised to interpret these studies separately within the context of their individual patient population.

10 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.

11 Review TTD consensus document on the diagnosis and management of exocrine pancreatic cancer. 2014

Benavides, M / Abad, A / Ales, I / Carrato, A / Díaz Rubio, E / Gallego, J / García-Foncillas, J / Grávalos, C / Laquente, B / Pericay, C / Rivera, F / Tabernero, J / Aranda, E. ·Hospital Regional Universitario Carlos Haya, Málaga, Spain, manuel.benavides.sspa@juntadeandalucia.es. ·Clin Transl Oncol · Pubmed #24728654.

ABSTRACT: Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0-1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management.

12 Review Advances in the therapy of gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). 2010

Grande, Enrique / Díez, Juan José / Pachón, Vanessa / Carrato, Alfredo. ·Medical Oncology Service, Ramon y Cajal University Hospital, Madrid, Spain. egrande@oncologiahrc.com ·Clin Transl Oncol · Pubmed #20615825.

ABSTRACT: Neuroendocrine tumours (NET) of the digestive tract comprise a broad range of malignancies. The therapeutic approach to these tumours has not evolved as it did in other tumour types in the last two decades. The deeper knowledge of the underlying molecular biology behind the growth of neuroendocrine cells has brought much information to light. We now know that somatostatin analogues may not only be considered as symptomatic treatment but also as antitumour agents. Sunitinib, a tyrosine kinase (TK) inhibitor with antiangiogenic and antitumoural properties, has been shown to induce significant improvement in progression-free survival in a randomised trial conducted in well-differentiated pancreatic islet-cell NETs. The relevance of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway seems to be crucial in gastroenteropancreatic (GEP)-NETs. In fact, mTOR inhibitors have shown activity in uncontrolled trials, and large, randomised trial results will be available shortly. In this article, we summarise the most recent available data on medical therapy for GEPNETs.

13 Clinical Trial Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE). 2015

Grande, E / Capdevila, J / Castellano, D / Teulé, A / Durán, I / Fuster, J / Sevilla, I / Escudero, P / Sastre, J / García-Donas, J / Casanovas, O / Earl, J / Ortega, L / Apellaniz-Ruiz, M / Rodriguez-Antona, C / Alonso-Gordoa, T / Díez, J J / Carrato, A / García-Carbonero, R. ·Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid egrande@oncologiahrc.com. · Department of Medical Oncology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona. · Department of Medical Oncology, I + 12 Research Institute, 12 de Octubre University Hospital, Madrid. · Department of Medical Oncology, IDIBELL, Catalan Institute of Oncology L'Hospitalet, Barcelona. · Department of Medical Oncology, Instituto de Biomedicina de Sevilla (IBIS) [HUVR, CSIC, University of Seville], Virgen del Rocío University Hospital, Seville. · Department of Medical Oncology, Son Espases Hospital, Palma de Mallorca. · Department of Medical Oncology, Virgen de la Victoria University Hospital, Malaga. · Department of Medical Oncology, Clínico Lozano Blesa University Hospital, Zaragoza. · Department of Medical Oncology, Clínico San Carlos Hospital, Madrid. · Department of Medical Oncology, Centro Integral Oncológico Clara Campal, Madrid. · Tumor Angiogenesis Group, IDIBELL, Catalan Institute of Oncology L'Hospitalet, Barcelona. · Department of Medical Oncology Research Laboratory, Ramón y Cajal University Hospital, Madrid. · Department of Pathology, Clínico San Carlos Hospital, Madrid. · Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center, ISCIII Center for Biomedical Research on Rare Disease (CIBERER) Madrid, Madrid. · Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid. · Department of Endocrinology, Ramón y Cajal University Hospital, Madrid, Spain. ·Ann Oncol · Pubmed #26063633.

ABSTRACT: BACKGROUND: The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs. METHODS: This was a multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated. RESULTS: A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months [95% confidence interval (CI) 4.8-14.1]. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms [hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively]. CONCLUSIONS: Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201). CLINICAL TRIAL NUMBER: NCT01280201.

14 Clinical Trial A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. 2015

Fuchs, C S / Azevedo, S / Okusaka, T / Van Laethem, J-L / Lipton, L R / Riess, H / Szczylik, C / Moore, M J / Peeters, M / Bodoky, G / Ikeda, M / Melichar, B / Nemecek, R / Ohkawa, S / Świeboda-Sadlej, A / Tjulandin, S A / Van Cutsem, E / Loberg, R / Haddad, V / Gansert, J L / Bach, B A / Carrato, A. ·Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA charles_fuchs@dfci.harvard.edu. · Oncology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. · Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia. · Department of Hematology, Oncology, and Tumor Immunology, Charité University, Berlin, Germany. · Department of Oncology, Military Institute of Health Services, Warsaw, Poland. · Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. · Department of Oncology, Antwerp University Hospital, Edegum, Belgium. · Department of Oncology, St László Hospital, Budapest, Hungary. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc. · Department of Oncology, Masaryk University Medical School and Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. · Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russia. · Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium. · Medical Sciences, Amgen Inc., Thousand Oaks, USA. · Global Biostatistical Science, Amgen Ltd, Cambridge, UK. · Global Development, Thousand Oaks. · Development Oncology Therapeutics, Amgen Inc., Thousand Oaks, USA. · Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain. ·Ann Oncol · Pubmed #25609246.

ABSTRACT: BACKGROUND: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. RESULTS: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. CONCLUSION: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01231347.

15 Article Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. 2020

Goggins, Michael / Overbeek, Kasper Alexander / Brand, Randall / Syngal, Sapna / Del Chiaro, Marco / Bartsch, Detlef K / Bassi, Claudio / Carrato, Alfredo / Farrell, James / Fishman, Elliot K / Fockens, Paul / Gress, Thomas M / van Hooft, Jeanin E / Hruban, R H / Kastrinos, Fay / Klein, Allison / Lennon, Anne Marie / Lucas, Aimee / Park, Walter / Rustgi, Anil / Simeone, Diane / Stoffel, Elena / Vasen, Hans F A / Cahen, Djuna L / Canto, Marcia Irene / Bruno, Marco / Anonymous1461018. ·Pathology, Medicine Oncology, Johns Hopkins University, Baltimore, Maryland, USA mgoggins@jhmi.edu. · Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. · GI Cancer Genetics and Prevention Program, Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA. · Department of Surgery, Division of Surgical Oncology, Denver, Colorado, USA. · Division of Visceral, Thoracic and Vascular Surgery, University of Marburg, Marburg, Germany. · Department of Surgey, University of Verona, Verona, Italy. · Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. · The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, Maryland, USA. · Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands. · Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, Marburg, Germany. · Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands. · Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA. · Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City, New York, USA. · Division of Digestive and Liver Diseases, Columbia University, New York City, New York, USA. · Oncology, Johns Hopkins University, Baltimore, Maryland, USA. · Medicine, Johns Hopkins University, Baltimore, Maryland, USA. · Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. · New York University Medical Center, New York City, New York, USA. · University of Michigan, Ann Arbor, Michigan, USA. · Gastroenterology and Hepatology, Leiden University, Leiden, The Netherlands. ·Gut · Pubmed #31672839.

ABSTRACT: BACKGROUND AND AIM: The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals). METHODS: A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed. RESULTS: Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline CONCLUSIONS: Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

16 Article Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches. 2019

Gomez-Rubio, Paulina / Piñero, Janet / Molina-Montes, Esther / Gutiérrez-Sacristán, Alba / Marquez, Mirari / Rava, Marta / Michalski, Christoph W / Farré, Antoni / Molero, Xavier / Löhr, Matthias / Perea, José / Greenhalf, William / O'Rorke, Michael / Tardón, Adonina / Gress, Thomas / Barberá, Victor M / Crnogorac-Jurcevic, Tatjana / Muñoz-Bellvís, Luís / Domínguez-Muñoz, Enrique / Balsells, Joaquim / Costello, Eithne / Yu, Jingru / Iglesias, Mar / Ilzarbe, Lucas / Kleeff, Jörg / Kong, Bo / Mora, Josefina / Murray, Liam / O'Driscoll, Damian / Poves, Ignasi / Lawlor, Rita T / Ye, Weimin / Hidalgo, Manuel / Scarpa, Aldo / Sharp, Linda / Carrato, Alfredo / Real, Francisco X / Furlong, Laura I / Malats, Núria / Anonymous2240962. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain. · Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. · Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain. · Department of Surgery, Technical University of Munich, Munich, Germany. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain. · Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain. · Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden. · Department of Surgery, University Hospital 12 de Octubre, Madrid, Spain. · Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom. · Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. · Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany. · Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain. · Centre for Molecular Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. · General and Digestive Surgery Department, Hospital Universitario de Salamanca, Salamanca, Spain. · Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, (Saale), Germany. · Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland. · ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University Hospital, Sweden. · Hospital Madrid-Norte-Sanchinarro and Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. · Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom. · Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. · PanGenEU Study Investigators (Additional file 1: Annex S1). ·Int J Cancer · Pubmed #30229903.

ABSTRACT: Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case-control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00, respectively). Several inflammatory-related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

17 Article Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. 2019

Huang, Lei / Jansen, Lina / Balavarca, Yesilda / Molina-Montes, Esther / Babaei, Masoud / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Fristrup, Claus W / Mortensen, Michael B / Primic-Žakelj, Maja / Zadnik, Vesna / Becker, Nikolaus / Hackert, Thilo / Mägi, Margit / Cassetti, Tiziana / Sassatelli, Romano / Grützmann, Robert / Merkel, Susanne / Gonçalves, Ana F / Bento, Maria J / Hegyi, Péter / Lakatos, Gábor / Szentesi, Andrea / Moreau, Michel / van de Velde, Tony / Broeks, Annegien / Sant, Milena / Minicozzi, Pamela / Mazzaferro, Vincenzo / Real, Francisco X / Carrato, Alfredo / Molero, Xavier / Besselink, Marc G / Malats, Núria / Büchler, Markus W / Schrotz-King, Petra / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · Geneticand Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, ISCIII, Madrid, Spain. · Netherlands Cancer Registry (NCR), Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Registry Department, The Cancer Registry of Norway (CRN), Oslo, Norway. · Danish Pancreatic Cancer Database (DPCD), Odense, Denmark. · Danish Pancreatic Cancer Group, HPB Section, Department of Surgery, Odense University Hospital, Odense, Denmark. · Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia. · Clinical Cancer Registry, DKFZ and NCT, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Estonian Cancer Registry, National Institute for Health Development, Tallinn, Estonia. · Pancreatic Cancer Registry of Reggio Emilia Province, Unit of Gastroenterology and Digestive Endoscopy AUSL-RE, Local Health Authority-IRCCS, Reggio Emilia, Italy. · Department of Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. · Departments of Epidemiology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · Department of Oncology, St. Istvan and St. Laszlo Hospital and Out-Patient Department, Budapest, Hungary. · Department of Surgical Oncology, Jules Bordet Institute (IJB), Brussels, Belgium. · Biometrics Department, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands. · Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy. · Hepato-Biliary Surgery Unit, Istituto Nazionale dei Tumori (INT), and University of Milan, Milan, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, Madrid, Spain. · Department de Ciencies Experimentals i de la, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Oncology, Ramon y Cajal University Hospital, IRYCIS, Alcala University, CIBERONC, Madrid, Spain. · Hospital Universitari Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Campus de la UAB, Barcelona, Spain. · CIBEREHD and CIBERESP, Madrid, Spain. · Dutch Pancreatic Cancer Group, Academic Medical Centre Amsterdam, Amsterdam, Netherlands. ·Gut · Pubmed #29158237.

ABSTRACT: OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

18 Article Increased plasma levels of galectin-1 in pancreatic cancer: potential use as biomarker. 2018

Martinez-Bosch, Neus / Barranco, Luis E / Orozco, Carlos A / Moreno, Mireia / Visa, Laura / Iglesias, Mar / Oldfield, Lucy / Neoptolemos, John P / Greenhalf, William / Earl, Julie / Carrato, Alfredo / Costello, Eithne / Navarro, Pilar. ·Cancer Research Program, IMIM, Hospital del Mar Medical Research Institute, Unidad Asociade CSIC, Barcelona, Spain. · Department of Gastroenterology, Universidad Autonoma de Barcelona, Hospital del Mar, Barcelona, Spain. · Department of Medical Oncology, Hospital del Mar, Barcelona, Spain. · Department of Pathology, Universidad Autonoma de Barcelona, Hospital del Mar, CIBERONC, Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Department of General Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Medical Oncology, Ramon y Cajal University Hospital, CIBERONC, IRYCIS, Alcala University, Madrid, Spain. · Institute of Biomedical Research of Barcelona (IIBB-CSIC), Barcelona, Spain. ·Oncotarget · Pubmed #30250644.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is the most frequent type of pancreatic cancer and one of the deadliest diseases overall. New biomarkers are urgently needed to allow early diagnosis, one of the only factors that currently improves prognosis. Here we analyzed whether the detection of circulating galectin-1 (Gal-1), a soluble carbohydrate-binding protein overexpressed in PDA tissue samples, can be used as a biomarker for PDA. Gal-1 levels were determined by ELISA in plasma from healthy controls and patients diagnosed with PDA, using three independent cohorts. Patients with chronic pancreatitis (CP) were also included in the study to analyze the potential of Gal-1 to discriminate between cancer and inflammatory process. Plasma Gal-1 levels were significantly increased in patients with PDA as compared to controls in all three cohorts. Gal-1 sensitivity and specificity values were similar to that of the CA19-9 biomarker (the only FDA-approved blood test biomarker for PDA), and the combination of Gal-1 and CA19-9 significantly improved their individual discriminatory powers. Moreover, high levels of Gal-1 were associated with lower survival in patients with non-resected tumors. Collectively, our data indicate a strong potential of using circulating Gal-1 levels as a biomarker for detection and prognostics of patients with PDA.

19 Article Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives. 2018

Molina-Montes, E / Gomez-Rubio, P / Márquez, M / Rava, M / Löhr, M / Michalski, C W / Molero, X / Farré, A / Perea, J / Greenhalf, W / Ilzarbe, L / O'Rorke, M / Tardón, A / Gress, T / Barberà, V M / Crnogorac-Jurcevic, T / Domínguez-Muñoz, E / Muñoz-Bellvís, L / Balsells, J / Costello, E / Huang, J / Iglesias, M / Kleeff, J / Kong, Bo / Mora, J / Murray, L / O'Driscoll, D / Poves, I / Scarpa, A / Ye, W / Hidalgo, M / Sharp, L / Carrato, A / Real, F X / Malats, N / Anonymous1210933. ·Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group, Madrid, and CIBERONC, Spain. · Karolinska Institutet and University Hospital, Gastrocentrum, Stockholm, Sweden. · Technical University of Munich, Department of Surgery, Munich, Germany. · University of Heidelberg, Department of Surgery, Heidelberg, Germany. · Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD, Spain. · Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology, Barcelona, Spain. · University Hospital 12 de Octubre, Department of Surgery, Madrid, Spain. · Royal Liverpool University Hospital, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK. · Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. · Queen's University Belfast, Centre for Public Health, Belfast, UK. · Instituto Universitario de Oncología del Principado de Asturias, Department of Medicine, Oviedo, and CIBERESP, Spain. · University Hospital of Giessen and Marburg, Department of Gastroenterology, Marburg, Germany. · General University Hospital of Elche, Molecular Genetics Laboratory, Elche, Spain. · Barts Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, London, UK. · University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology, Santiago de Compostela, Spain. · Salamanca University Hospital, General and Digestive Surgery Department, Salamanca, Spain. · Martin-Luther-University Halle-Wittenberg, Department of Visceral, Vascular and Endocrine Surgery, Halle (Saale), Germany. · National Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland. · ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy. · Madrid-Norte-Sanchinarro Hospital, Madrid, Spain. · Newcastle University, Institute of Health and Society, Newcastle upon Tyne, UK. · Ramón y Cajal University Hospital, Department of Oncology, IRYCIS, Alcala University, Madrid, and CIBERONC, Spain. · Spanish National Cancer Research Centre (CNIO), Epithelial Carcinogenesis Group, Madrid, Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, and CIBERONC, Spain. ·Int J Epidemiol · Pubmed #29329392.

ABSTRACT: Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

20 Article A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk. 2017

Gomez-Rubio, P / Rosato, V / Márquez, M / Bosetti, C / Molina-Montes, E / Rava, M / Piñero, J / Michalski, C W / Farré, A / Molero, X / Löhr, M / Ilzarbe, L / Perea, J / Greenhalf, W / O'Rorke, M / Tardón, A / Gress, T / Barberá, V M / Crnogorac-Jurcevic, T / Muñoz-Bellvís, L / Domínguez-Muñoz, E / Gutiérrez-Sacristán, A / Balsells, J / Costello, E / Guillén-Ponce, C / Huang, J / Iglesias, M / Kleeff, J / Kong, B / Mora, J / Murray, L / O'Driscoll, D / Peláez, P / Poves, I / Lawlor, R T / Carrato, A / Hidalgo, M / Scarpa, A / Sharp, L / Furlong, L I / Real, F X / La Vecchia, C / Malats, N / Anonymous3520902. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, Spain. · Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro," Department of Clinical Sciences and Community Health, University of Milan, Milan. · Unit of Medical Statistics, Biometry and Bioinformatics, National Cancer Institute, IRCCS Foundation, Milan. · Department of Epidemiology, Mario Negri Institute for Pharmacological Research-IRCCS, Milan, Italy. · Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Pompeu Fabra Univeristy (UPF), Barcelona, Spain. · Department of Surgery, Technical University of Munich, Munich. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology, Santa Creu i Sant Pau Hospital, Barcelona. · Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Barcelona. · Department of Medicine, Universitat Autònoma de Barcelona, Barcelona. · Network of Biomedical Research Centres (CIBER), Hepatic and Digestive Diseases and Epidemiology and Public Health, Madrid, Spain. · Gastrocentrum, Karolinska Institutet and University Hospital, Stockholm, Sweden. · Department of Gastroenterology, Parc de Salut Mar University Hospital, Barcelona. · Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. · Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool. · Centre for Public Health, Queen's University Belfast, Belfast, UK. · Department of Medicine, University Institute of Oncology of Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany. · Molecular Genetics Laboratory, General University Hospital of Elche, Elche, Spain. · Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UK. · General and Digestive Surgery Department, Salamanca University Hospital, Salamanca. · Department of Gastroenterology, Clinical University Hospital of Santiago de Compostela, Santiago de Compostela. · Department of Oncology, Ramón y Cajal Hospital, Madrid, and CIBERONC, Spain. · Research Programme, National Cancer Registry Ireland. · ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital trust of Verona, Verona, Italy. · Clara Campal Integrated Oncological Centre, Sanchinarro Hospital, Madrid, Spain. · Institute of Health & Society, Newcastle University, UK. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, and CIBERONC. · Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain. ·Ann Oncol · Pubmed #28383714.

ABSTRACT: Background: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. Methods: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. Results: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. Conclusions: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

21 Article Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic cancer in Spain. 2017

Hidalgo, M / Álvarez, R / Gallego, J / Guillén-Ponce, C / Laquente, B / Macarulla, T / Muñoz, A / Salgado, M / Vera, R / Adeva, J / Alés, I / Arévalo, S / Blázquez, J / Calsina, A / Carmona, A / de Madaria, E / Díaz, R / Díez, L / Fernández, T / de Paredes, B G / Gallardo, M E / González, I / Hernando, O / Jiménez, P / López, A / López, C / López-Ríos, F / Martín, E / Martínez, J / Martínez, A / Montans, J / Pazo, R / Plaza, J C / Peiró, I / Reina, J J / Sanjuanbenito, A / Yaya, R / Carrato, Alfredo. ·Spanish National Cancer Centre, C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain. mhidalgo@cnio.es. · Beth Israel Deaconess Medical Center, Boston, USA. mhidalgo@cnio.es. · Department of Medical Oncology, Centro Integral Oncológico Clara Campal, Madrid, Spain. · University Hospital of Elche, Elche, Spain. · Hospital Universitario Ramón y Cajal, Ctra. de Colmenar Viejo km. 9,100, 28034, Madrid, Spain. · Institut Català d´Oncologia, Duran y Reynals Hospital, Hospitalet Llobregat, Barcelona, Spain. · Vall d'Hebrón University Hospital, Barcelona, Spain. · University Hospital Gregorio Marañón, Madrid, Spain. · University Hospital of Ourense, Ourense, Spain. · Complejo Hospitalario de Navarra, Pamplona, Spain. · University Hospital 12 de Octubre, Madrid, Spain. · Hospital Carlos Haya, Málaga, Spain. · University Hospital Donostia, San Sebastián, Spain. · Department of Radiology, University Hospital Ramón y Cajal, Madrid, Spain. · MD Anderson Hospital, Madrid, Spain. · Department of Palliative Care, Hospital Germans Trias I Pujol, Institut Catalá d´Oncologia, Badalona, Spain. · Department of Medical Oncology and Hematology, University Hospital Morales Messeguer, Murcia, Spain. · Department of Gastroenterology, Hospital General Universitario de Alicante, Alicante, Spain. · Department of Medical Oncology, Hospital Universitari I Politècnic La Fe, Valencia, Spain. · Department of Surgery, Hospital Clínico San Carlos, Madrid, Spain. · Department of Medical Oncology, Hospital Son Llàtzer, Palma de Mallorca, Spain. · Hospital Clínico San Carlos, Madrid, Spain. · Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain. · Complejo Hospitalario de Granada, Granada, Spain. · Department of Radiotherapy, University Hospital HM Sanchinarro, Madrid, Spain. · University Hospital HM Puerta del Sur, Madrid, Spain. · Department of Medical Oncology, Hospital Universitario Central de Asturias, Asturias, Spain. · Hospital Universitario de Burgos, Burgos, Spain. · Hospital Universitario Marqués de Valdecilla, Santander, Spain. · Department of Pathology, University Hospital HM Sanchinarro, Madrid, Spain. · Department of Surgery, Hospital Universitario de la Princesa, Madrid, Spain. · Department of Medical Oncology, University Hospital Virgen de las Nieves, Granada, Spain. · Hospital del Mar, Barcelona, Spain. · Department of Pathology, Centro Anatomopatológico, Madrid, Spain. · Department of Medical Oncology, University Hospital Miguel Servet, Saragossa, Spain. · Department of Endocrinology, Instituto Catalán de Oncología, Hospital Duran I Reynals, Hospitalet de Llobregat, Barcelona, Spain. · Department of Medical Oncology, University Hospital Virgen de la Macarena, Seville, Spain. · Department of Surgery, University Hospital Ramón y Cajal, Madrid, Spain. · Department of Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. · Hospital Universitario Ramón y Cajal, Ctra. de Colmenar Viejo km. 9,100, 28034, Madrid, Spain. acarrato@telefonica.net. ·Clin Transl Oncol · Pubmed #27995549.

ABSTRACT: The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.

22 Article Refinement of screening for familial pancreatic cancer. 2016

Bartsch, D K / Slater, E P / Carrato, A / Ibrahim, I S / Guillen-Ponce, C / Vasen, H F A / Matthäi, E / Earl, J / Jendryschek, F S / Figiel, J / Steinkamp, M / Ramaswamy, A / Vázquez-Sequeiros, E / Muñoz-Beltran, M / Montans, J / Mocci, E / Bonsing, B A / Wasser, M / Klöppel, G / Langer, P / Fendrich, V / Gress, T M. ·Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany. · Department of Medical Oncology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Radiology, Philipps University Marburg, Marburg, Germany. · Department of Gastroenterology and Endocrinology, Philipps University Marburg, Marburg, Germany. · Department of Pathology, Philipps University Marburg, Marburg, Germany. · Department of Gastroenterology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Department of Radiology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Department of Pathology, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. · Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Pathology, Consultation Centre for Pancreatic Tumors, Technical University Munich, Munich, Germany. · Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany Department of General Surgery, Klinikum Hanau GmbH, Hanau, Germany. ·Gut · Pubmed #27222532.

ABSTRACT: OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened at ≥24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

23 Article Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers. 2016

Vasen, Hans / Ibrahim, Isaura / Ponce, Carmen Guillen / Slater, Emily P / Matthäi, Elvira / Carrato, Alfredo / Earl, Julie / Robbers, Kristin / van Mil, Anneke M / Potjer, Thomas / Bonsing, Bert A / de Vos Tot Nederveen Cappel, Wouter H / Bergman, Wilma / Wasser, Martin / Morreau, Hans / Klöppel, Günter / Schicker, Christoph / Steinkamp, Martin / Figiel, Jens / Esposito, Irene / Mocci, Evelina / Vazquez-Sequeiros, Enrique / Sanjuanbenito, Alfonso / Muñoz-Beltran, Maria / Montans, José / Langer, Peter / Fendrich, Volker / Bartsch, Detlef K. ·Hans Vasen, Isaura Ibrahim, Kristin Robbers, Anneke M. van Mil, Thomas Potjer, Bert A. Bonsing, Wilma Bergman, Martin Wasser, and Hans Morreau, Leiden University Medical Center, Leiden · Wouter H. de Vos tot Nederveen Cappel, Isala Clinics, Zwolle, the Netherlands · Carmen Guillen Ponce, Alfredo Carrato, Julie Earl, Evelina Mocci, Enrique Vazquez-Sequeiros, Alfonso Sanjuanbenito, Maria Muñoz-Beltran, and José Montans, Ramón y Cajal University Hospital, Ramón y Cajal Health Research Institute, Madrid, Spain · Emily P. Slater, Elvira Matthäi, Volker Fendrich, and Detlef K. Bartsch, University Hospital Marburg · Christoph Schicker, Martin Steinkamp, and Jens Figiel, Philipps University Marburg, Marburg · Günter Klöppel, Consultation Centre for Pancreatic and Endocrine Tumors, Technical University Munich · Peter Langer, Klinikum Hanau, Hanau, Germany · and Irene Esposito, Innsbruck University Hospital, Innsbruck, Austria. ·J Clin Oncol · Pubmed #27114589.

ABSTRACT: PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis. PATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound. RESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program. CONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.

24 Article Circulating tumor cells (Ctc) and kras mutant circulating free Dna (cfdna) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer. 2015

Earl, Julie / Garcia-Nieto, Sandra / Martinez-Avila, Jose Carlos / Montans, José / Sanjuanbenito, Alfonso / Rodríguez-Garrote, Mercedes / Lisa, Eduardo / Mendía, Elena / Lobo, Eduardo / Malats, Núria / Carrato, Alfredo / Guillen-Ponce, Carmen. ·Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. julie.earl@live.co.uk. · Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. sandragarcianieto@hotmail.com. · Genetic and Molecular Epidemiology Group, Spanish Cancer Research Cancer Center, Madrid, Spain. jcmartinezavila@gmail.com. · Pathology Department, Ramón y Cajal University Hospital, Madrid, Spain. jmontans@anatomia.e.telefonica.net. · Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. asanjuanbenito@gmail.com. · Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. mercedes3110@yahoo.es. · Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. edulisa@hotmail.com. · Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. mendiaelena@hotmail.com. · Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain. eduardo.lobo@salud.madrid.org. · Genetic and Molecular Epidemiology Group, Spanish Cancer Research Cancer Center, Madrid, Spain. nmalats@cnio.es. · Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. acarrato@telefonica.net. · Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain. carmenguillenponce@gmail.com. ·BMC Cancer · Pubmed #26498594.

ABSTRACT: BACKGROUND: Pancreatic cancer remains one of the most difficult cancers to treat with the poorest prognosis. The key to improving survival rates in this disease is early detection and monitoring of disseminated and residual disease. However, this is hindered due to lack reliable diagnostic and predictive markers which mean that the majority of patients succumb to their condition within a few months. METHODS: We present a pilot study of the detection circulating free DNA (cfDNA) combined with tumor specific mutation detection by digital PCR as a novel minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC). This was compared to the detection of CTC by the CellSearch® system and a novel CTC enrichment strategy based on CD45 positive cell depletion. The aim of the study was to assess tumor specific DNA detection in plasma and CTC detection as prognostic markers in PDAC. RESULTS: We detected KRAS mutant cfDNA in 26% of patients of all stages and this correlated strongly with Overall Survival (OS), 60 days (95% CI: 19-317) for KRAS mutation positive vs 772 days for KRAS mutation negative (95% CI: 416-1127). Although, the presence of CTC detected by the CellSearch® system did correlate significantly with OS, 88 days (95% CI: 27-206) CTC positive vs 393 days CTC negative (95% CI: 284-501), CTC were detected in only 20% of patients, the majority of which had metastatic disease, whereas KRAS mutant cfDNA was detected in patients with both resectable and advanced disease. CONCLUSIONS: Tumor specific cfDNA detection and CTC detection are promising markers for the management of patients with PDAC, although there is a need to validate these results in a larger patient cohort and optimize the detection of CTC in PDAC by applying the appropriate markers for their detection.

25 Article PanGen-Fam: Spanish registry of hereditary pancreatic cancer. 2015

Mocci, E / Guillen-Ponce, C / Earl, J / Marquez, M / Solera, J / Salazar-López, M-T / Calcedo-Arnáiz, C / Vázquez-Sequeiros, E / Montans, J / Muñoz-Beltrán, M / Vicente-Bártulos, A / González-Gordaliza, C / Sanjuanbenito, A / Guerrero, C / Mendía, E / Lisa, E / Lobo, E / Martínez, J C / Real, F X / Malats, N / Carrato, A. ·Medical Oncology Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Molecular Oncogenetics Unit, Institute of Medical and Molecular Genetics, La Paz Hospital, Madrid, Spain. · Digestive Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Pathology Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Radiology Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Surgery Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Department de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. ·Eur J Cancer · Pubmed #26212471.

ABSTRACT: PURPOSE: To describe the organisation of the registry and the preliminary results in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC) families recruited to date and findings of the screening programme. To compare early onset sporadic cases (⩽50 years), sporadic cases (>50 years) and cases with family history of cancer, for PDAC possible risk factors. METHODS/PATIENTS: Families with hereditary cancer syndromes predisposing to PDAC were recruited from two main sources: Spanish hospitals participating in PanGenEU, a pan-European multicentre case-control study, and their genetic counseling unit. Individuals at high-risk of PDAC were enrolled into a screening programme, consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance imaging. Genetic testing of candidate genes was offered according to each patient's risk. RESULTS: Among 577 consecutive PDAC cases, recruited via PanGenEU, 36 (6%) had ⩾2 first-degree relative with PDAC: Familial pancreatic cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25 (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for BRCA1 germline mutations. In the second year of prospective PDAC screening, one neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic-pancreatitis-like parenchymal changes in 15 patients. CONCLUDING STATEMENT: The identification and recruitment of PDAC high-risk families into the PanGen-Fam registry provides an opportunity to detect early onset cancer and precursor pancreatic cancer lesions at a potentially curative stage and to increase the knowledge of the natural history of the disease.

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