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Pancreatic Neoplasms: HELP
Articles by Michel Ducreux
Based on 30 articles published since 2010
(Why 30 articles?)
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Between 2010 and 2020, M. Ducreux wrote the following 30 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Screening and surveillance in hereditary gastrointestinal cancers: Recommendations from the European Society of Digestive Oncology (ESDO) expert discussion at the 20th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona, June 2018. 2018

Vangala, Deepak B / Cauchin, Estelle / Balmaña, Judith / Wyrwicz, Lucian / van Cutsem, Eric / Güller, Ulrich / Castells, Antoni / Carneiro, Fatima / Hammel, Pascal / Ducreux, Michel / van Laethem, Jean-Luc / Matysiak-Budnik, Tamara / Schmiegel, Wolff. ·Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany. Electronic address: meduni-kkh@rub.de. · Institut des Maladies de L'Appareil Digestif, Hepato-Gastroenterology and Digestive Oncology, Nantes University Hospital, Nantes, France. · Vall D'Hebron University Hospital and Institute of Oncology, Barcelona, Spain. · Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland. · Digestive Oncology, University Hospitals and KU Leuven, Leuven, Belgium. · Division of Medical Oncology and Hematology, Kantonsspital St Gallen, Switzerland. · Gastroenterology Department, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Catalonia, Spain. · Faculty of Medicine of the University of Porto (FMUP), Centro Hospitalar de Sao Joao (CHSJ) and Ipatimup/i3S, Porto, Portugal. · Department of Digestive Oncology, Hôpital Beaujon, Clichy, University Paris VII Denis Diderot, France. · Department of Medical Oncology, Gustave Roussy, Villejuif and Université Paris-Saclay, Saint Aubain, France. · Department of Gastroenterology and Digestive Oncology, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium. · Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany. ·Eur J Cancer · Pubmed #30342310.

ABSTRACT: Patients with hereditary gastrointestinal (GI) cancers represent a substantial fraction of the overall affected population. Although awareness for hereditary GI cancer syndromes is on the rise, identification of patients and measures of surveillance are often unclear in everyday clinical routine. Therefore, the European Society of Digestive Oncology expert discussion 2018 at the World Congress on Gastrointestinal Cancer focussed on screening and surveillance of hereditary colorectal, gastric and pancreatic cancers. An international panel of experts and opinion leaders developed the here presented recommendations based on published evidence and on profound clinical expertise to facilitate clinical routine in identification and caretaking of patients with familial GI cancers.

2 Guideline Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). 2014

Bonnetain, Franck / Bonsing, Bert / Conroy, Thierry / Dousseau, Adelaide / Glimelius, Bengt / Haustermans, Karin / Lacaine, François / Van Laethem, Jean Luc / Aparicio, Thomas / Aust, Daniela / Bassi, Claudio / Berger, Virginie / Chamorey, Emmanuel / Chibaudel, Benoist / Dahan, Laeticia / De Gramont, Aimery / Delpero, Jean Robert / Dervenis, Christos / Ducreux, Michel / Gal, Jocelyn / Gerber, Erich / Ghaneh, Paula / Hammel, Pascal / Hendlisz, Alain / Jooste, Valérie / Labianca, Roberto / Latouche, Aurelien / Lutz, Manfred / Macarulla, Teresa / Malka, David / Mauer, Muriel / Mitry, Emmanuel / Neoptolemos, John / Pessaux, Patrick / Sauvanet, Alain / Tabernero, Josep / Taieb, Julien / van Tienhoven, Geertjan / Gourgou-Bourgade, Sophie / Bellera, Carine / Mathoulin-Pélissier, Simone / Collette, Laurence. ·Methodology and Quality of Life Unit in Cancer, EA 3181, University Hospital of Besançon and CTD-INCa Gercor, UNICNCER GERICO, Besançon, France. Electronic address: franck.bonnetain@univ-fcomte.fr. · Leiden University Medical Center, Leiden, Netherlands. · Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France. · Bordeaux Segalen University & CHRU, Bordeaux, France. · Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden. · Department of Radiation Oncology, Leuven, Belgium. · Digestive Surgical Department, Tenon hospital, Paris, France. · Gastro Intestinal Cancer Unit Erasme Hospital Brussels, Belgium. · Gastroenterology Department, Avicenne Hospital, Paris 13, Bobigny, France. · Institute for Pathology, University Hospital Carl-Gustav-Carus, Dresden, Germany. · Surgical and Gastroenterological Department, Endocrine and Pancreatic Unit, Hospital of 'G.B.Rossi', University of Verona, Italy. · Institut de Cancérologie de l'Ouest - Centre Paul Papin Centre de Lutte Contre le Cancer (CLCC), Angers, France. · Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Oncology Department, Hôpital Saint-Antoine & CTD-INCa GERCOR, Assistance Publique des Hôpitaux de Paris, UPMC Paris VI, Paris, France. · Gastroenterology Department, Hopital la Timone, Assitance publique des Hopitaux de Marseille, Marseille, France. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Gastroenterology, Institut Gustave Roussy, Villejuif, France. · Biostatistician, Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Department of Radiotherapy, Institut fuer Radioonkologie, Vienna, Austria. · Department of Surgical Oncology, Royal Liverpool Hospital, United Kingdom. · Department of Gastroenterology, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Digestive Oncology and Gastro-enterology Department, Jules Bordet Institute, Brussels, Belgium. · Digestive Cancer Registry, INSERM U866, Dijon, France. · Medical Oncology Unit, Ospedali Riuniti di Bergamo, Bergame, Italy. · Inserm, Centre for Research in Epidemiology and Population Health, U1018, Biostatistics Team, Villejuif, France. · Gastroenterology Department, Caritas Hospital, Saarbrücken, Germany. · Department of the Gastrointestinal Tumors and Phase I Unit, Vall d'Hebron University Hospital, Barcelona, Spain. · Statistics Department, EORTC, Brussels, Belgium. · Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. · Division of Surgery and Oncology at the University of Liverpool and Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Digestive Surgery, Universitu Hospital Strasbourg, France. · Department of Hepato-pancreatic and Biliary Surgery, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Department of Hepato-gastroenterology and Digestive Oncology, Georges Pompidou European hospital, Paris, France. · Department of Radiation Oncology, Academisch Medisch Centrum, Amsterdam, The Netherlands. · Institut Du Cancer de Montpellier, Comprehensive Cancer Centre, and Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France. · Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France; Data Center for Cancer Clinical Trials, CTD-INCa, Bordeaux, France; INSERM, Centre d'Investigation Clinique - Épidémiologie Clinique CIC-EC 7, F-33000 Bordeaux, France. ·Eur J Cancer · Pubmed #25256896.

ABSTRACT: BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

3 Guideline New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. 2012

Van Laethem, J-L / Verslype, C / Iovanna, J L / Michl, P / Conroy, T / Louvet, C / Hammel, P / Mitry, E / Ducreux, M / Maraculla, T / Uhl, W / Van Tienhoven, G / Bachet, J B / Maréchal, R / Hendlisz, A / Bali, M / Demetter, P / Ulrich, F / Aust, D / Luttges, J / Peeters, M / Mauer, M / Roth, A / Neoptolemos, J P / Lutz, M / Anonymous1151075. ·Gastrointestinal Cancer Unit, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. jl.vanlaethem@erasme.ulb.ac.be ·Ann Oncol · Pubmed #21810728.

ABSTRACT: Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

4 Review An update on treatment options for pancreatic adenocarcinoma. 2019

Lambert, Aurélien / Schwarz, Lilian / Borbath, Ivan / Henry, Aline / Van Laethem, Jean-Luc / Malka, David / Ducreux, Michel / Conroy, Thierry. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy, France. · Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, France. · Department of Gastroenterology and Digestive Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium. · Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Nancy, France. · Department of Gastroenterology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Belgium. · Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. · Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 50519 Vandoeuvre-lès-Nancy CEDEX, France. ·Ther Adv Med Oncol · Pubmed #31598142.

ABSTRACT: Pancreatic cancer is one of the most lethal solid organ tumors. Due to the rising incidence, late diagnosis, and limited treatment options, it is expected to be the second leading cause of cancer deaths in high income countries in the next decade. The multidisciplinary treatment of this disease depends on the stage of cancer at diagnosis (resectable, borderline, locally advanced, and metastatic disease), and combines surgery, chemotherapy, chemoradiotherapy, and supportive care. The landscape of multidisciplinary pancreatic cancer treatment is changing rapidly, especially in locally advanced disease, and the number of treatment options in metastatic disease, including personalized medicine, innovative targets, immunotherapy, therapeutic vaccines, adoptive T-cell transfer, or stemness inhibitors, will probably expand in the near future. This review summarizes the current literature and provides an overview of how new therapies or new therapeutic strategies (neoadjuvant therapies, conversion surgery) will guide multidisciplinary disease management, future clinical trials, and, hopefully, will increase overall survival.

5 Review Systemic treatment of pancreatic cancer revisited. 2019

Ducreux, Michel / Seufferlein, Thomas / Van Laethem, Jean-Luc / Laurent-Puig, Pierre / Smolenschi, Cristina / Malka, David / Boige, Valérie / Hollebecque, Antoine / Conroy, Thierry. ·Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, Université Paris Saclay, France. Electronic address: michel.ducreux@gustaveroussy.fr. · Department of Internal Medicine I, University of Ulm, Ulm, Germany. · Department of Gastroenterology and Digestive oncology, Erasme University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. · Assistance Publique-Hôpitaux de Paris, Department of Biology, European Georges Pompidou Hospital, Paris, France. · Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, France. · Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, France; Département d'Innovation Thérapeutique, Gustave Roussy Cancer Center Grand Paris, France. · Département d'oncologie médicale, Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France. ·Semin Oncol · Pubmed #30638624.

ABSTRACT: Pancreatic cancer is considered to be one of the most aggressive cancers. For unknown reasons, the incidence of pancreatic cancer is slowly rising and so too are mortality rates. Over 75% of patients are diagnosed with locally advanced disease or with metastases; and more than 95% of patients have metastases at diagnosis or will develop metastases during their follow-up. Despite recent improvements in the therapy of pancreatic cancer, initially with demonstration of the activity of the FOLFIRINOX regimen and subsequently the approval of nab-paclitaxel in combination with gemcitabine, prognosis remains poor and the 5-year survival rate is less than 5%. To date, neither personalized medicine nor immunotherapy, the 2 recent revolutions of cancer treatment, have delivered major positive results in the treatment of pancreatic cancer; and it is especially clear that immune checkpoint inhibitors will not become a major tool in the treatment of pancreatic cancer. There are many ongoing studies, including those exploring combinations of chemotherapy with immunotherapy. Vaccines or T cells modified with a chimeric antigen receptor (CAR-T cells) could also play a role in the treatment of cancer in the future. The aim of this review is to discuss recent improvements in standard of care, major obstacles to overcome, recent results of new treatment combinations, and the most interesting innovative approaches.

6 Review Imaging of neuroendocrine tumors of the pancreas. 2016

Dromain, C / Déandréis, D / Scoazec, J-Y / Goere, D / Ducreux, M / Baudin, E / Tselikas, L. ·Service de radiodiagnostic et radiologie interventionnelle, bureau CIBM 09-084, rue Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Clarisse.Dromain@chuv.ch. · Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Anapathology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Surgery department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Oncology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. ·Diagn Interv Imaging · Pubmed #27876341.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan

7 Review Current standards and new innovative approaches for treatment of pancreatic cancer. 2016

Conroy, Thierry / Bachet, Jean-Baptiste / Ayav, Ahmet / Huguet, Florence / Lambert, Aurélien / Caramella, Caroline / Maréchal, Raphaël / Van Laethem, Jean-Luc / Ducreux, Michel. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. Electronic address: t.conroy@nancy.unicancer.fr. · Department of Hepato-Gastroenterology, Pitié-Salpétrière University Hospital, 47-83 boulevard de l'hôpital, 75651, Paris Cedex 13, France. · Department of Surgery, Nancy University Hospital Lorraine and Lorraine University, rue du Morvan, 54511, Vandoeuvre-lès Nancy, France. · Department of Radiation Therapy, Tenon Hospital, Paris Est University Hospitals, 4 rue de la Chine, 75020, Paris, France. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. · Gustave Roussy Cancer Campus Grand Paris, 114 rue Edouard-Vaillant, 94805, Villejuif Cedex, France. · Department of Gastroenterology, Erasme University Hospital-ULB-Brussels, Lennikstreet 808, 1070, Brussels, Belgium. ·Eur J Cancer · Pubmed #26851397.

ABSTRACT: Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.

8 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.

9 Review GEP-NETS update: Interventional radiology: role in the treatment of liver metastases from GEP-NETs. 2015

de Baere, Thierry / Deschamps, Frederic / Tselikas, Lambros / Ducreux, Michel / Planchard, David / Pearson, Ernesto / Berdelou, Amandine / Leboulleux, Sophie / Elias, Dominique / Baudin, Eric. ·Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France debaere@igr.fr. · Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France. · Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France. ·Eur J Endocrinol · Pubmed #25385817.

ABSTRACT: Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.

10 Review Tumour-stroma interactions in pancreatic ductal adenocarcinoma: rationale and current evidence for new therapeutic strategies. 2014

Heinemann, V / Reni, M / Ychou, M / Richel, D J / Macarulla, T / Ducreux, M. ·Department of Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, Ludwig-Maximilians-Universität München, Germany. ·Cancer Treat Rev · Pubmed #23849556.

ABSTRACT: Most patients with pancreatic cancer present with advanced/metastatic disease and have a dismal prognosis. Despite the proven albeit modest benefits of gemcitabine demonstrated over a decade ago, subsequent advances have been slow, suggesting it may be time to take a different approach. It is thought that some key characteristics of pancreatic cancer, such as the desmoplasia, restricted vasculature and hypoxic environment, may prevent the delivery of chemotherapy to the tumour thereby explaining the limited benefits observed to-date. Moreover, there is evidence to suggest that the stroma is not only a mechanical barrier but also constitutes a dynamic compartment of pancreatic tumours that is critically involved in tumour formation, progression and metastasis. Thus, targeting the stroma and the tumour represents a promising therapeutic strategy. Currently, several stroma-targeting agents are entering clinical development. Among these, nab-paclitaxel appears promising since it combines cytotoxic therapy with targeted delivery via its proposed ability to bind SPARC on tumour and stromal cells. Preclinical data indicate that co-treatment with nab-paclitaxel and gemcitabine results in stromal depletion, increased tumour vascularization and intratumoural gemcitabine concentration, and increased tumour regression compared with either agent alone. Phase I/II study data also suggest that a high level of antitumor activity can be achieved with this combination in pancreatic cancer. This was recently confirmed in a Phase III study which showed that nab-paclitaxel plus gemcitabine significantly improved overall survival (HR 0.72) and progression-free survival (HR 0.69) versus gemcitabine alone for the first-line treatment of patients with metastatic pancreatic cancer.

11 Review The role of the FOLFIRINOX regimen for advanced pancreatic cancer. 2013

Conroy, Thierry / Gavoille, Céline / Samalin, Emmanuelle / Ychou, Marc / Ducreux, Michel. ·EA 4360 and Department of Medical Oncology, Centre Alexis Vautrin, Université de Lorraine, Vandoeuvre-lès-Nancy, France. t.conroy@nancy.unicancer.fr ·Curr Oncol Rep · Pubmed #23341367.

ABSTRACT: In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.

12 Review Intervention in gastro-enteropancreatic neuroendocrine tumours. 2012

Baudin, Eric / Planchard, David / Scoazec, Jean-Yves / Guigay, Joël / Dromain, Clarisse / Hadoux, Julien / Debaere, Thierry / Elias, Dominique / Ducreux, Michel. ·Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. baudin@igr.fr ·Best Pract Res Clin Gastroenterol · Pubmed #23582924.

ABSTRACT: Neuroendocrine tumours require dedicated interventions to control their capacity to secrete hormones but also, antitumour growth strategies. Recommendations for early interventions in NET include the management of hormone-related symptoms and poorly differentiated neuroendocrine carcinomas. In contrast, prognostic heterogeneity is a key feature of well differentiated NET that complexified the antitumour strategy whatever the stage in this subgroup of tumour. In this review, timely therapeutic interventions to control hormone-related symptoms and tumour growth in GEP NET patients are discussed. The necessity of controlling hormone-related symptoms as the first step of any strategy affects also the tumour growth control strategy. In the absence of cure at the metastatic stage, progresses are expected in the recognition of well differentiated NET subgroups that display either excellent or poor prognosis.

13 Review Pancreatic cancer treatment and research: an international expert panel discussion. 2011

Tempero, M A / Berlin, J / Ducreux, M / Haller, D / Harper, P / Khayat, D / Schmoll, H-J / Sobrero, A / Van Cutsem, E. ·Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, USA. mtempero@medicine.ucsf.edu ·Ann Oncol · Pubmed #21199884.

ABSTRACT: BACKGROUND: Pancreatic cancer has proven extremely challenging to treat. A collaborative effort is needed to advance research and improve treatment. An expert conference was conducted to elicit perspectives regarding the current treatment and future research of pancreatic cancer. METHODS: The conference comprised an international panel of experts representing five European countries and the United States. RESULTS: Adjuvant radiotherapy is used more frequently in the United States than in Europe. In locally advanced disease, there is now more emphasis on early chemotherapy in both Europe and the United States. In metastatic disease, combination chemotherapy is commonly used in Europe and the United States. This varies by country. Advancing pancreatic research will require improving biorepositories and developing a roadmap to prioritize therapeutic targets in different models. Small randomized phase II trials of both non-selected and enriched patient populations will help identify activity of new agents. Phase III trials should only be initiated in appropriate patients based on strong clinical and biological signals. Developing drugs in the adjuvant setting may be preferable to eliminate some of the challenges of drug development in the advanced disease setting. CONCLUSION: Progress in research combined with encouraging improvements from the past offer hope for the future of pancreatic cancer patients.

14 Guideline Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2015

Ducreux, M / Cuhna, A Sa / Caramella, C / Hollebecque, A / Burtin, P / Goéré, D / Seufferlein, T / Haustermans, K / Van Laethem, J L / Conroy, T / Arnold, D / Anonymous4311075. ·Département de médecine, Gustave Roussy, Villejuif Faculté de Médecine, Université Paris Sud, le Kremlin Bicêtre. · Faculté de Médecine, Université Paris Sud, le Kremlin Bicêtre Département de Chirugie Hépato-biliaire, Hopital Paul Brousse, Villejuif. · Département d'imagerie. · Département de médecine, Gustave Roussy, Villejuif Département d'Innovation Thérapeutique. · Département de médecine, Gustave Roussy, Villejuif. · Département de Chirurgie Générale, Gustave Roussy, Villejuif, France. · Department of Internal Medicine I, Ulm University Hospital Medical Center, Ulm, Germany. · Department of Radiation Oncology, Leuven Kankerinstitute, Leuven. · Departement of Gastroenterology, Hôpital Erasme, Cliniques Universitaires de Bruxelles, Brussels, Belgium. · Département de médecine, Institut de Cancérologie de Lorraine, Vandoeuvre lés Nancy, France. · Department of Medical Oncology, Tumor Biology Center, Freiburg, Germany. ·Ann Oncol · Pubmed #26314780.

ABSTRACT: -- No abstract --

15 Clinical Trial Evaluating lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours. 2017

Lepage, Côme / Dahan, Laetitia / Bouarioua, Nadia / Toumpanakis, Christos / Legoux, Jean-Louis / Le Malicot, Karine / Guimbaud, Rosine / Smith, Denis / Tougeron, David / Lievre, Astrid / Cadiot, Guillaume / Di Fiore, Frédéric / Bouhier-Leporrier, Karine / Hentic, Olivia / Faroux, Roger / Pavel, Marianne / Borbath, Ivan / Valle, Juan W / Rinke, Anja / Scoazec, Jean-Yves / Ducreux, Michel / Walter, Thomas. ·Department of Digestive Oncology, Burgundy Franche-Conté University, University hospital Dijon, Dijon, France; Burgundy Franche-Conté University, EPICAD, INSERM LNC UMR1231, Dijon, France; French Federation of Digestive Oncology (FFCD), INSERM LNC UMR1231 EPICAD, Dijon, France. Electronic address: come.lepage@u-bourgogne.fr. · Department of Digestive Oncology, Aix-Marseille University - Assistance Publique Hôpitaux de Marseille, Marseille, France. · Department of Gastroenterology and Digestive Oncology, Saint Etienne, France. · Royal Free Hospital, Neuroendocrine Tumour Unit, Londres, Grande-Bretagne, UK. · Regional Hospital of Orleans, Orleans, France. · French Federation of Digestive Oncology (FFCD), INSERM LNC UMR1231 EPICAD, Dijon, France. · Hôpital Rangueil, Toulouse, France. · Hôpital Haut Lévêque, Service d'hépato-gastroentérologie, Pessac, France. · Hôpital de la Milétrie, Poitiers, France. · CHU de Rennes-Hôpital Pontchaillou, Rennes, France. · Hôpital Robert Debré, Reims, France. · CHU Charles Nicolle, Rouen, France. · CHU Côte de Nacre, Caen, France. · Hôpital Beaujon, Clichy, France. · CH Les Oudairies, La Roche sur Yon, France. · Charite Campus Virchow Kinikum, Berlin, Germany. · Cliniques universitaires Saint-Luc, Bruxelles, Belgium. · University of Manchester, Division of Cancer Sciences/The Christie NHS Foundation Trust, Manchester, UK. · University Hospital Marburg, Marburg, Germany. · Pathology Department, Gustave Roussy, Villejuif, France. · Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Faculté de Médecine, Paris Sud University Le Kremlin Bicêtre, France. · Edouard Herriot Hospital, Department of Gastroenterology, Hospices Civils de Lyon, Lyon, France. ·Dig Liver Dis · Pubmed #28292641.

ABSTRACT: INTRODUCTION: Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30-50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained. AIM(S): The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET. MATERIALS AND METHODS: Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization. RESULTS: 222 patients will be randomly assigned in a 1:1 ratio to receive 120mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted. CONCLUSION: The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377).

16 Clinical Trial Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)--a phase II non-randomised trial. 2014

Ducreux, Michel / Dahan, Laetitia / Smith, Denis / O'Toole, Dermot / Lepère, Céline / Dromain, Clarisse / Vilgrain, Valérie / Baudin, Eric / Lombard-Bohas, Catherine / Scoazec, Jean-Yves / Seitz, Jean-François / Bitoun, Laurence / Koné, Sébastien / Mitry, Emmanuel. ·Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Faculté de Médecine, Paris Sud Uiversty Le Kremlin Bicêtre, France. Electronic address: Michel.DUCREUX@igr.fr. · Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: laetitia.dahan@mail.hp-hm.fr. · Medical Oncology Department, Saint-André Hospital, Bordeaux, France. Electronic address: denis.smith@chu-bordeaux.fr. · Clinical Medicine and Gastroenterology Department, St James's Hospital and Trinity College, Dublin, Ireland. Electronic address: OTOOLED1@tcd.ie. · Medical Oncology Department, Georges Pompidou European Hospital, Paris, France. Electronic address: celine.lepere@egp.aphp.fr. · Radio Diagnostic Department, Gustave Roussy Institute, Villejuif, France. Electronic address: dromain@igr.fr. · Radiology Department, Beaujon Hospital, Clichy, France. Electronic address: valerie.vilgrain@bjn.aphp.fr. · Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy Institute, Villejuif, France. Electronic address: Eric.BAUDIN@igr.fr. · Medical Oncology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: catherine.lombard-bohas@chu-lyon.fr. · Pathology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: jy.scoazec@gmail.com. · Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: Jean-francois.SEITZ@ap-hm.fr. · Clinial Operating Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: laurence.bitoun@roche.com. · Oncology Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: sebastien.kone@roche.com. · Medical Oncology Department, Curie Institute, Paris, France. Electronic address: emmanuel.mitry@curie.net. ·Eur J Cancer · Pubmed #25454412.

ABSTRACT: AIM OF THE STUDY: Neuroendocrine tumours are highly vascular neoplasms known to overexpress vascular endothelial growth factor (VEGF) and its receptor. Bevacizumab, an inhibitor of VEGF, was assessed in combination with chemotherapy in pancreatic neuroendocrine tumour (P-NET). PATIENTS AND METHODS: BETTER was a multicentre, open-label, non-randomised, two-group phase II trial. Patients with progressive metastatic, well-differentiated P-NET received a minimum of 6 month treatment of bevacizumab at 7.5 mg/kg IV on d1 q3w with 5-FU at 400 mg/m2/day and streptozocin at 500 mg/m2/day IV from d1 to d5 every 42 days. The primary end-point was progression-free survival (PFS); secondary end-points were overall survival (OS), overall response rate, safety and quality of life. RESULTS: A total of 34 patients were included. Median age was 55 years, 65% of patients were men, 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and 97% had a Ki-67 proliferative index of <15%. After a maximum of 24 month follow-up per patient, the median PFS assessed by investigators was 23.7 months [95% confidence interval (CI): 13.1; not reached], 19 (56%) patients had a partial response and 15 (44%) had stable disease as best response. OS rate at 24 months was 88%. The most frequently reported grade 3-4 adverse events were hypertension (21% patients), abdominal pain (12%) and thromboembolic events (9%). CONCLUSION: Bevacizumab with 5-FU/streptozocin in the treatment of pancreatic NETs seems to be feasible with a PFS of 23.7 months, which deserves further attention. No unexpected toxicity was observed.

17 Clinical Trial Radiation plus docetaxel and cisplatin in locally advanced pancreatic carcinoma: a non-comparative randomized phase II trial. 2014

Ducreux, Michel / Giovannini, Marc / Baey, Charlotte / Llacer, Carmen / Bennouna, Jaafar / Adenis, Antoine / Peiffert, Didier / Mornex, Françoise / Abbas, Moncef / Boige, Valèrie / Pignon, Jean-Pierre / Conroy, Thierry / Cellier, Patrice / Juzyna, Beata / Viret, Frédéric. ·Gustave Roussy, Villejuif, France; Université Paris Sud, Le Kremlin Bicetre, France. Electronic address: michel.ducreux@gustaveroussy.fr. · Institut Paoli Calmettes, Marseille, France. · Gustave Roussy, Villejuif, France. · Institut du Cancer Montpellier - Val d'Aurelle, Montpellier, France. · Institut de Cancérologie de l'Ouest - René Gauducheau, Nantes, France. · Centre Oscar Lambret, Lille, France. · Institut de Cancérologie de Lorraine - Alexis Vautrin, Nancy, France. · Hôpital Lyon Sud, Lyon, France. · Institut de Cancérologie de l'Ouest - Paul Papin, Angers, France. · Unicancer, Paris, France. ·Dig Liver Dis · Pubmed #25027552.

ABSTRACT: BACKGROUND: We performed a randomized, non-comparative phase II study evaluating docetaxel in combination with either daily continuous (protracted IV) 5-fluorouracil or cisplatin administered weekly, concurrent to radiotherapy in the treatment of locally advanced pancreatic carcinoma. Results of the docetaxel plus cisplatin regimen are reported. METHODS: Forty chemotherapy-naive patients with locally advanced pancreatic carcinoma were randomly assigned to receive 5-fluorouracil and docetaxel or docetaxel 20mg/m(2) and cisplatin 20mg/m(2)/week, plus concurrent radiotherapy for 6 weeks. The radiation dose to the primary tumour was 54Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate. RESULTS: 51 patients from 7 centres were included in the docetaxel-cisplatin treatment group. Six-month non-progression rate was 39% (95% confidence interval: 26-53). Median overall survival was 9.6 months (95% confidence interval: 2.4-60.7); 6 complete and 8 partial responses were obtained. Six patients survived more than 2 years after their inclusion in the trial. Grade ≥3 toxicity was reported in 63% of patients; no treatment-related death occurred. Severe toxicities were mainly anorexia (22%), vomiting (20%) and fatigue (24%). CONCLUSIONS: Despite inadequate efficacy according to the main end point, this regimen gave a satisfactory rate of objective response (27%) with tolerable toxicity.

18 Clinical Trial Phase II, randomized, biomarker identification trial (MARK) for erlotinib in patients with advanced pancreatic carcinoma. 2014

Propper, D / Davidenko, I / Bridgewater, J / Kupcinskas, L / Fittipaldo, A / Hillenbach, C / Klughammer, B / Ducreux, M. ·Barts Cancer Institute, Queen Mary University of London, London, UK d.j.propper@qmul.ac.uk. · State Medical Institution Clinical Oncology Dispensary, Krasnodar, Russia. · University College London Cancer Institute, London, UK. · Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Roche Products Ltd, Welwyn Garden City, UK. · F. Hoffmann-La Roche Ltd, Basel, Switzerland. · Institut Gustave Roussy, Villejuif, France. ·Ann Oncol · Pubmed #24827134.

ABSTRACT: BACKGROUND: A prospective, randomized phase II study, with mandatory tumor sampling at current disease stage, aimed to identify biomarkers predictive of improved progression-free survival (PFS) in patients with pancreatic cancer treated with erlotinib. PATIENTS AND METHODS: Patients with histologically/cytologically confirmed, unresectable, locally advanced/metastatic pancreatic cancer, who had failed on or were unsuitable for first-line chemotherapy, underwent a tumor biopsy and were then randomized to receive once-daily erlotinib 150 mg or placebo. The primary end point was identification of biomarkers predicting improved PFS with erlotinib. Secondary end points included PFS, overall survival, response and toxicity. RESULTS: At data cut-off, 207 patients were enrolled and analyzed. Prespecified biomarker analyses of EGFR protein expression, EGFR gene copy number/mutations/polymorphisms and KRAS mutations did not identify any subgroups with a detrimental effect or a strong benefit for PFS with erlotinib. In the primary analysis, the median PFS was 6.1 versus 5.9 weeks in the erlotinib and placebo arms, respectively [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.63-1.10; P = 0.1909]. However, observed baseline imbalances indicated worse prognosis in the erlotinib arm. After adjustment for baseline characteristics, a significant PFS benefit for erlotinib was observed (HR 0.68; 95% CI 0.50-0.91; P = 0.0102). Exploratory biomarker analyses showed patients with high baseline serum amphiregulin levels might benefit from erlotinib. CONCLUSION: This study in patients with inoperable pancreatic cancer did not identify any prespecified biomarkers predictive of PFS benefit with erlotinib. Exploratory analyses suggested high amphiregulin might predict PFS benefit from erlotinib. CLINICALTRIALSGOV NUMBER: NCT00674973.

19 Clinical Trial Docetaxel- and 5-FU-concurrent radiotherapy in patients presenting unresectable locally advanced pancreatic cancer: a FNCLCC-ACCORD/0201 randomized phase II trial's pre-planned analysis and case report of a 5.5-year disease-free survival. 2011

Oberic, Lucie / Viret, Frédéric / Baey, Charlotte / Ychou, Marc / Bennouna, Jaafar / Adenis, Antoine / Peiffert, Didier / Mornex, Françoise / Pignon, Jean-Pierre / Celier, Patrice / Berille, Jocelyne / Ducreux, Michel. ·Institut Gustave Roussy, Villejuif, France. ·Radiat Oncol · Pubmed #21943032.

ABSTRACT: BACKGROUND: To explore possible improvement in the treatment of locally advanced pancreatic carcinoma (LAPC) we performed a randomized, non-comparative phase II study evaluating docetaxel - plus either daily continuous 5 FU or weekly cisplatin concurrent to radiotherapy. We report here the results of the docetaxel plus 5 FU regimen stopped according to the interim analysis. The docetaxel plus cisplatin arm was continued. METHODS: Forty (40) chemotherapy-naive patients with unresectable LAPC were randomly assigned (1:1) to either continuous fluorouracil (5-FU) 200 mg/m(2)/day (protracted IV) and docetaxel (DCT) 20 mg/m(2)/week or DCT 20 mg/m2 and cisplatin (CDDP) 20 mg/m(2), plus concurrent radiotherapy for a period of 6 weeks. The radiation dose to the primary tumor was 54 Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate (NPR). Secondary endpoints were tolerance, objective response rate, and overall survival. Accrual was to be stopped if at 6 months more than 13 disease progressions were observed in 20 patients. RESULTS: Eighteen (18) progressions occurred at 6 months in the 5-FU-DCT arm. Six-month NPR was 10% (95%CI: 0-23). Six and 12-month survivals were 85% (95%CI: 64-95) and 40% (95%CI: 22-61); median overall survival was 10.1 months. Median progression-free survival was 4.3 months. We report the case of one patient who was amenable to surgery and has been in complete response (CR) for 5.5 years. Toxicities grade ≥ 3 were reported in 75% of patients; no treatment-related death occurred. Severe toxicities were mainly vomiting (35%), abdominal pain (10%) and fatigue (10%). CONCLUSIONS: Combination of 5-FU, docetaxel and radiotherapy has inadequate efficacy in the treatment of LAPC despite good tolerance for the 5-FU-DCT regimen. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00112697.

20 Clinical Trial FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. 2011

Conroy, Thierry / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Guimbaud, Rosine / Bécouarn, Yves / Adenis, Antoine / Raoul, Jean-Luc / Gourgou-Bourgade, Sophie / de la Fouchardière, Christelle / Bennouna, Jaafar / Bachet, Jean-Baptiste / Khemissa-Akouz, Faiza / Péré-Vergé, Denis / Delbaldo, Catherine / Assenat, Eric / Chauffert, Bruno / Michel, Pierre / Montoto-Grillot, Christine / Ducreux, Michel / Anonymous1530694 / Anonymous1540694. ·Nancy University and Department of Medical Oncology, Centre Alexis Vautrin, Nancy, France. t.conroy@nancy.fnclcc.fr ·N Engl J Med · Pubmed #21561347.

ABSTRACT: BACKGROUND: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. RESULTS: The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). CONCLUSIONS: As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).

21 Article Opinions and use of neoadjuvant therapy for resectable, borderline resectable, and locally advanced pancreatic cancer: international survey and case-vignette study. 2019

Heinrich, Stefan / Besselink, Marc / Moehler, Markus / van Laethem, Jean-Luc / Ducreux, Michel / Grimminger, Peter / Mittler, Jens / Lang, Hauke / Lutz, Manfred P / Lesurtel, Mickael / Anonymous301018. ·Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany. stefan.heinrich@unimedizin-mainz.de. · Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands. · First Department of Internal Medicine, University Hospital of Mainz, Mainz, Germany. · Department of Gastroenterology and Digestive Oncology, Erasme Hospital, 1070, Brussels, Belgium. · Gastrointestinal Unit, Institute Gustave Roussy, Villejuif, France. · Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany. · Department of Internal Medicine, CaritasKlinikum, Saarbrücken, Germany. · Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, University of Lyon, Lyon, France. ·BMC Cancer · Pubmed #31288786.

ABSTRACT: BACKGROUND: Several new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC), but the support for their use for resectable, borderline resectable and locally advanced PDAC is unclear. METHODS: A survey was distributed to the members of the European-African Hepato-Pancreato Biliary Association (E-AHPBA) and the pancreas group of the European Organization for Research and Treatment of Cancer (EORTC) regarding 1) definitions of local resectability, 2) indications for neoadjuvant therapy and 3) case-vignettes regarding the resectability and treatment of PDAC. RESULTS: In total, 114 participants from 37 countries were registered. About 35% of respondents, each, were of the opinion that borderline resectability is defined by any venous tumor contact and venous involvement < 180° or > 180°, respectively. The majority (75.4%) of participants believed that borderline resectable PDAC has a high risk for R1 resection and that neoadjuvant therapy might increase the R0-resection rate (79.8%) and improve oncological patient selection (84.2%). Chemotherapy was regarded useful to convert locally advanced to resectable PDAC by 55.7% of respondents. In the cases with resectable, borderline resectable, and locally advanced PDAC, 10 (8.8%), 78 (68.4%), 55 (48.2%) of participants would start with chemotherapy, respectively. CONCLUSIONS: Although definitions for borderline resectability differ among European surgeons, there seems to be a rather strong support for preoperative chemotherapy in PDAC aiming at minimizing R1 resections while increasing resection rates.

22 Article Adjuvant treatment of pancreatic cancer. 2019

Conroy, Thierry / Ducreux, Michel. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy. · Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. ·Curr Opin Oncol · Pubmed #30994497.

ABSTRACT: PURPOSE OF REVIEW: Pancreatic cancer will soon become one of the most common causes of cancer death. Early detection of pancreatic cancer remains impossible and only 20% of patients are suitable for surgery once diagnosed. Even in this specific subgroup of patients, and despite improvements in surgery, overall survival remains poor, with an 80% recurrence rate. Consequently, many attempts have been made to prevent recurrence by adding chemotherapy, radiotherapy, or both. RECENT FINDINGS: Here, we will focus on results of randomized trials evaluating the role of different postoperative treatments. Over 15 years ago, a trial demonstrated that chemoradiotherapy has a deleterious effect on survival. The same trial recommended adjuvant chemotherapy with fluorouracil as standard of care. Subsequent trials sought to identify better chemotherapy regimens. Two recently published trials evaluated the role of combination therapies for resected pancreatic cancer and demonstrated better outcomes with a gemcitabine and capecitabine combination and a fluorouracil, oxaliplatin, and irinotecan combination (FOLFIRINOX) versus gemcitabine alone. SUMMARY: Results from recent trials suggest that FOLFIRINOX should be considered standard of care for fit patients.

23 Article Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE). 2018

Roquin, Guillaume / Baudin, Eric / Lombard-Bohas, Catherine / Cadiot, Guillaume / Dominguez, Sophie / Guimbaud, Rosine / Niccoli, Patricia / Legoux, Jean-Louis / Mitry, Emmanuel / Rohmer, Vincent / Ruszniewski, Philippe / Walter, Thomas / Ducreux, Michel / Couvelard, Anne / Scoazec, Jean-Yves / Ramond-Roquin, Aline / Caroli-Bosc, François-Xavier / Hentic, Olivia. ·Department of Hepatogastroenterology and Digestive Oncology, CHU Angers, Angers University, LUNAM University, Angers, France. ·Neuroendocrinology · Pubmed #28152531.

ABSTRACT: BACKGROUND: The best chemotherapy regimen for well- differentiated pancreatic neuroendocrine tumours (pNETs) with a Ki-67 index ≥10% is still debated. We evaluated the antitumour efficacy of various first-line chemotherapy regimens (streptozocin based, platinum based, or dacarbazine/temozolomide based) in this situation. METHODS: In this retrospective multicentre study of the French Group of Endocrine Tumours (GTE), we recruited consecutive patients with advanced well-differentiated pNETs and a Ki-67 index ≥10% receiving chemotherapy between 2000 and 2012. The primary endpoint was progression-free survival (PFS) according to RECIST. RESULTS: Seventy-four patients (42 men, median age 55.5 years) were enrolled from 10 centres. Fifty-one patients (69%) had grade 2 NET and 61 (82%) were stage IV. Median overall survival was 36.3 months. Forty-four patients (59%) received streptozocin-based, 18 (24%) platinum-based, and 12 (16%) dacarbazine/temozolomide-based chemotherapy regimens. These 3 groups were similar regarding age, functioning tumours, grade, the number of metastatic sites, and surgery for primary tumours, but not regarding surgery for metastases and time since diagnosis. Grade 3 NET (HR 2.15, 95% CI: 1.18-3.92, p = 0.012) and age above 55 years (HR 1.84, 95% CI: 1.06-3.18, p = 0.030) were associated with shorter median PFS in the multivariate analyses. Compared to streptozocin-based chemotherapy, no difference was found in terms of PFS for the platinum-based or for the dacarbazine/temozolomide-based chemotherapy regimen: median PFS was 7.2, 7.5, and 7.2 months, respectively (p = 0.51). CONCLUSIONS: Patients with intermediate or highly proliferative well-differentiated pNETs may benefit from 1 of the 3 chemotherapy regimens. Increased age and grade 3 were associated with shorter median PFS. Randomised studies searching for response predictors and the best efficacy-tolerance ratio are required to personalise the strategy.

24 Article 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer. 2017

Lutz, Manfred P / Zalcberg, John R / Ducreux, Michel / Aust, Daniela / Bruno, Marco J / Büchler, Markus W / Delpero, Jean-Robert / Gloor, Beat / Glynne-Jones, Rob / Hartwig, Werner / Huguet, Florence / Laurent-Puig, Pierre / Lordick, Florian / Maisonneuve, Patrick / Mayerle, Julia / Martignoni, Marc / Neoptolemos, John / Rhim, Andrew D / Schmied, Bruno M / Seufferlein, Thomas / Werner, Jens / van Laethem, Jean-Luc / Otto, Florian. ·CaritasKlinikum St. Theresia, Saarbrücken, Germany. Electronic address: m.lutz@caritasklinikum.de. · Department of Epidemiology and Preventive Medicine, School of Public Health, Monash University, The Alfred Centre, Melbourne, Australia. · Institut Gustave Roussy, Villejuif, France. · Department of Pathology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany. · Department of Gastroenterology & Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, The Netherlands. · Chirurgische Universitätsklinik, Heidelberg, Germany. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Klinik für Viszerale und Transplantationschirurgie, Inselspital, Bern, Switzerland. · Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK. · Department of General, Visceral and Transplantation Surgery, Klinikum der Universität München, Munich, Germany. · Radiooncology Service, Hôpital Tenon (Hôpitaux Universitaires Est Parisien), Paris Cedex 20, France. · Université René Descartes, UFR Biomédicale des Saints-Pères, Paris, France. · University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Germany. · Istituto Europeo di Oncologia, Divisione di Epidemiologia e Biostatistica, Milan, Italy. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin, Greifswald, Germany; Medizinische Klinik und Poliklinik II, Klinikum der Universität München, Munich, Germany. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München, Munich, Germany. · Department of Surgery, Liverpool University, Liverpool, UK. · University of Michigan, Ann Arbor, MI, USA. · Klinik für Chirurgie, Kantonsspital St. Gallen, St. Gallen, Switzerland. · Department of Internal Medicine I, Ulm University, Ulm, Germany. · Hopital Erasme, Anderlecht, Belgium. · Tumor- und Brustzentrum ZeTuP, St. Gallen, Switzerland. ·Eur J Cancer · Pubmed #28460245.

ABSTRACT: The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment.

25 Article Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study. 2017

Berdelou, Amandine / Boige, Valérie / Arfi-Rouche, Julia / Malka, David / Ederhy, Stéphane / Izzedine, Hassan / Leboulleux, Sophie / Chougnet, Cécile N / Burtin, Pascal / De Baere, Thierry / Laplanche, Agnès / Elias, Dominique / Schlumberger, Martin / Scoazec, Jean-Yves / Ducreux, Michel / Baudin, Eric. ·Department of Nuclear Medicine and Endocrine Tumours, Gustave Roussy, Université Paris XI, Villejuif, France. ·Neuroendocrinology · Pubmed #27225439.

ABSTRACT: BACKGROUND: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. METHODS: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. RESULTS: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. CONCLUSION: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

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