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Pancreatic Neoplasms: HELP
Articles from German Cancer Research Center
Based on 238 articles published since 2008
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These are the 238 published articles about Pancreatic Neoplasms that originated from German Cancer Research Center during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 Editorial [Pancreatic lesions]. 2016

Delorme, S / Helmberger, T. ·Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Deutschland. s.delorme@dkfz-heidelberg.de. · Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin, Städtisches Klinikum München, Klinikum Bogenhausen, Englschalkinger Straße 77, 81925, München, Deutschland. ·Radiologe · Pubmed #27000275.

ABSTRACT: -- No abstract --

3 Editorial Recent advances in proteomically subtyping pancreatic ductal adenocarcinomas and their potential clinical impact. 2015

Roesli, Christoph. ·Junior Research Group Biomarker Discovery, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. ·Expert Rev Proteomics · Pubmed #25407217.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival of 6 months. Late diagnosis due to the absence of specific symptoms during disease development, in addition to extensive metastatic potential and resistance to chemotherapy and radiotherapy, are the most important reasons for short survival. Research efforts have therefore been focused on the development of early disease detection. However, the only US FDA-approved clinical biomarker, CA19-9, is considered inapplicable for screening and/or early detection of PDAC. The following editorial provides the reader with a short introduction to the topic of PDAC and gives focus to the current state of proteomic research in the field of PDAC biomarker discovery. This editorial also highlights the efforts made to subdivide this tumor entity and the potential clinical impact of patient stratification. Finally, the author provides opinions on the impact of proteomics to PDAC subtype stratification over the next 5 years.

4 Review Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature. 2018

Benzel, Julia / Fendrich, Volker. ·Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany. · Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany. · Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Clinic for Endocrine Surgery, Schön Klinik Hamburg Eilbek, Hamburg, Germany. ·Digestion · Pubmed #29587290.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma is one of the most lethal types of cancer with a 5-year survival rate of around 7%. Due to the relatively poor prognosis, the potential need of an effective chemoprevention is highly needed. SUMMARY: Different risk factors like smoking or hereditary tumour syndromes should be known for early detection of pancreatic intraepithelial neoplasia. Chemopreventive dietary agents include curcumin, capsaicin and flavonoid, whereas potential chemopreventive drugs compromise aspirin, metformin or statins. This review aims to give an overview on potential risk factors for the development of pancreatic cancer. Furthermore, we try to summarise known chemopreventive agents to support the fight against this lethal disease. Key Messages: On the one hand, there are natural agents that exhibit preventive properties and can lead to the prohibition of pancreatic cancer. On the other hand, there are drugs and agents that are currently used in other contexts and are thus already approved and studied in terms of their mechanisms of effects and the related secondary effects.

5 Review Oncogenic KRAS and the EGFR loop in pancreatic carcinogenesis-A connection to licensing nodes. 2018

Schneeweis, Christian / Wirth, Matthias / Saur, Dieter / Reichert, Maximilian / Schneider, Günter. ·a II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München , München , Germany. · b German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK) , Heidelberg , Germany. ·Small GTPases · Pubmed #27880072.

ABSTRACT: EGFR signaling has a critical role in oncogenic KRAS-driven tumorigenesis of the pancreas, whereas it is dispensable in other organs. The complex signaling network engaged by oncogenic KRAS and its modulation by EGFR signaling, remains incompletely understood. In order to study early signaling events activated by oncogenic KRAS in the pancreas, we recently developed a novel model system based on murine primary pancreatic epithelial cells enabling the time-specific expression of mutant Kras

6 Review Effective radiotherapeutic treatment intensification in patients with pancreatic cancer: higher doses alone, higher RBE or both? 2017

Dreher, Constantin / Habermehl, Daniel / Jäkel, Oliver / Combs, Stephanie E. ·Department of Radiation Oncology, University Hospital Rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, Munich, Germany. · Department of Radiation Sciences (DRS), Institute of Innovative Radiotherapy (iRT), Helmholtz Zentrum München, Oberschleißheim, Germany. · Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site München, München, Germany. · Department of Medical Physics in Radiation Oncology, German Cancer Research Center, INF, 280, Heidelberg, Germany. · Heidelberg Ion Beam Therapy Center (HIT), INF 450, 69120, Heidelberg, Germany. · Department of Radiation Oncology, University Hospital Rechts der Isar, Technical University Munich (TUM), Ismaninger Str. 22, Munich, Germany. Stephanie.Combs@tum.de. · Department of Radiation Sciences (DRS), Institute of Innovative Radiotherapy (iRT), Helmholtz Zentrum München, Oberschleißheim, Germany. Stephanie.Combs@tum.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site München, München, Germany. Stephanie.Combs@tum.de. ·Radiat Oncol · Pubmed #29282139.

ABSTRACT: Pancreatic cancer, especially in case of locally advanced stage has a poor prognosis. Radiotherapy in general can lead to tumor volume reduction, but further improvements, such as ion beam therapy have to be promoted in order to enable dose escalation, which in turn results in better local control rates and downsizing of the tumor itself. Ion beam therapy with its highly promising physical properties is also accompanied by distinct inter- and intrafractional challenges in case of robustness. First clinical results are promising, but further research in motion mitigation and biological treatment planning is necessary, in order to determine the best clinical rationales and conditions of ion beam therapy of pancreatic cancer. This review summarizes the current knowledge and studies on ion beam therapy of pancreatic cancer.

7 Review Intraoperative radiation therapy (IORT) in pancreatic cancer. 2017

Krempien, Robert / Roeder, Falk. ·Department of Radiation Oncology, Helios Clinic Berlin-Buch, Schwanebecker Chaussee 50, Berlin-Buch, 13125, Berlin, Germany. Robert.krempien@helios-kliniken.de. · Department of Radiation Oncology, University Hospital of Munich (LMU), Munich, Germany. · Clinical Cooperation Unit Molecular Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Radiat Oncol · Pubmed #28069018.

ABSTRACT: Despite the important improvements made in the fields of surgery, chemotherapy and radiation therapy, pancreatic cancer remains one of the most lethal malignancies. Improved outcomes with novel chemotherapy regimes led again to increased attention on the role of localized radiotherapy, since local tumor progression causes significant morbidity and mortality in patients. Even after resection local failure rates are as high as 50-80%. The immediate proximity to critical structures (bone marrow, spinal cord, kidneys, liver, and intestine) limits the dose of radiation that can be administered to the tumor bed with conventional external beam radiation therapy (EBRT). The intraoperative radiotherapy (IORT) appears to be an ideal therapeutic strategy for this disease, having the advantage of enabling the delivery of high doses of radiation to areas that are at risk for microscopic disease, saving critical organs and reducing the possibility of inducing radiotoxicity. This technique allows a theoretical increase in the radiation therapeutic index to tumor compared to the adjacent organs at risk (OAR). The aim of this review is to update and comment on IORT in the multidisciplinary management of pancreatic cancer.

8 Review Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon? 2017

Hessmann, Elisabeth / Johnsen, Steven A / Siveke, Jens T / Ellenrieder, Volker. ·Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany. · Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany. · Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · West German Cancer Center, University Hospital Essen, Essen, Germany. ·Gut · Pubmed #27811314.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of <7%. Due to growing incidence, late diagnosis and insufficient treatment options, PDAC is predicted to soon become one of the leading causes of cancer-related death. Although intensified cytostatic combinations, particularly gemcitabine plus nab-paclitaxel and the folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) protocol, provide some improvement in efficacy and survival compared with gemcitabine alone, a breakthrough in the treatment of metastatic pancreatic cancer remains out of sight. Nevertheless, recent translational research activities propose that either modulation of the immune response or pharmacological targeting of epigenetic modifications alone, or in combination with chemotherapy, might open highly powerful therapeutic avenues in GI cancer entities, including pancreatic cancer. Deregulation of key epigenetic factors and chromatin-modifying proteins, particularly those responsible for the addition, removal or recognition of post-translational histone modifications, are frequently found in human pancreatic cancer and hence constitute particularly exciting treatment opportunities. This review summarises both current clinical trial activities and discovery programmes initiated throughout the biopharma landscape, and critically discusses the chances, hurdles and limitations of epigenetic-based therapy in future PDAC treatment.

9 Review Pancreatic cancer chemoradiotherapy. 2016

Brunner, Thomas B / Seufferlein, Thomas. ·Department of Radiation Oncology, University Medical Center Freiburg, Robert-Koch-Str. 3, Freiburg, Germany; German Cancer Consortium (DKTK), Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: thomas.brunner@uniklinik-freiburg.de. · Department of Internal Medicine I, Ulm University, Albert-Einstein-Allee 23, D-89081, Ulm, Germany. Electronic address: thomas.seufferlein@uniklinik-ulm.de. ·Best Pract Res Clin Gastroenterol · Pubmed #27644909.

ABSTRACT: Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15-20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery.

10 Review A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection. 2016

Dumstrei, Karin / Chen, Hongda / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. · European Molecular Biology Organization (EMBO), D-69117 Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), D-69120 Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. ·Oncotarget · Pubmed #26840568.

ABSTRACT: Pancreatic cancer is a leading cause of cancer-related deaths in the western world. Patients with pancreatic cancer have poor prognosis, partly due to difficulties in detecting it at early stages. While different markers have been associated with pancreatic cancer, many of them show suboptimal sensitivity and specificity. Serum autoantibodies against tumor-associated antigens have recently emerged as early stage biomarkers for different types of cancers. Given the urgent need for early and reliable biomarkers for pancreatic cancer, we undertook a systematic review of the published literature to identify primary articles that evaluated serum autoantibodies in pancreatic cancer detection by searching PubMed and ISI Web of Knowledge. Two reviewers extracted data on study characteristics and results independently. Overall, 31 studies evaluating 124 individual serum autoantibodies in pancreatic cancer detection met the inclusion criteria. In general, single autoantibody markers showed relatively low sensitivities at high specificity. A combination of markers, either multiple serum autoantibodies or serum autoantibodies combined with tumor-associated markers, led to a better diagnostic performance. However, most of the analyzed autoantibodies have only been reported in single studies and therefore need to be independently validated. We conclude that serum autoantibodies might present an option as biomarkers for early detection of pancreatic cancer, but more work is needed to identify and validate autoantibody signatures that are associated with early stage pancreatic cancer.

11 Review The Promise of Gene Therapy for Pancreatic Cancer. 2016

Vassaux, Georges / Angelova, Assia / Baril, Patrick / Midoux, Patrick / Rommelaere, Jean / Cordelier, Pierre. ·1 Université de Nice Sophia Antipolis , Nice, France . · 2 Laboratoire TIRO , UMRE 4320, CEA, Nice, France . · 3 German Cancer Research Center (DKFZ) , Tumor Virology/F010, Heidelberg, Germany . · 4 Centre de Biophysique Moléculaire, CNRS UPR4301 and University of Orléans , Orléans, France . · 5 INSERM , UMR1037 CRCT, F-31000 Toulouse, France . · 6 Université Toulouse III-Paul Sabatier , F-31000 Toulouse, France . ·Hum Gene Ther · Pubmed #26603492.

ABSTRACT: Unlike for other digestive cancer entities, chemotherapy, radiotherapy, and targeted therapies have, so far, largely failed to improve patient survival in pancreatic adenocarcinoma (PDAC), which remains the fourth leading cause of cancer-related death in Europe and the United States. In this context, gene therapy may offer a new avenue for patients with PDAC. In this review, we explore the research currently ongoing in French laboratories aimed at defeating PDAC using nonviral therapeutic gene delivery, targeted transgene expression, or oncolytic virotherapy that recently or will soon bridge the gap between experimental models of cancer and clinical trials. These studies are likely to change clinical practice or thinking about PDAC management, as they represent a major advance not only for PDAC but may also significantly influence the field of gene-based molecular treatment of cancer.

12 Review MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies. 2016

Hessmann, E / Schneider, G / Ellenrieder, V / Siveke, J T. ·Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany. · Department of Internal Medicine II, Medizinische Klinik, Klinikum rechts der Isar, Technische Universität, Munich, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Oncogene · Pubmed #26119937.

ABSTRACT: Owing to its aggressiveness, late detection and marginal therapeutic accessibility, pancreatic ductal adenocarcinoma (PDAC) remains a most challenging malignant disease. Despite scientific progress in the understanding of the mechanisms that underly PDAC initiation and progression, the successful translation of experimental findings into effective new therapeutic strategies remains a largely unmet need. The oncogene MYC is activated in many PDAC cases and is a master regulator of vital cellular processes. Excellent recent studies have shed new light on the tremendous functions of MYC in cancer and identified inhibition of MYC as a likewise beneficial and demanding effort. This review will focus on mechanisms that contribute to deregulation of MYC expression in pancreatic carcinogenesis and progression and will summarize novel biological findings from recent in vivo models. Finally, we provide a perspective, how regulation of MYC in PDAC may contribute to the development of new therapeutic approaches.

13 Review Perspectives in the treatment of pancreatic adenocarcinoma. 2015

Cid-Arregui, Angel / Juarez, Victoria. ·Angel Cid-Arregui, German Cancer Research Center, Translational Immunology, Tumor Immunology Program, 69120 Heidelberg, Germany. ·World J Gastroenterol · Pubmed #26309356.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages, when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize, which involve essential adaptive changes in cellular metabolism, signaling, adhesion and immunoediting. In addition, PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades, gemcitabine has been the reference for the systemic treatment of PDAC. However, recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC, with survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over single-agent gemcitabine. With the pending issue of their higher toxicities, these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past, with only one drug (erlotinib) approved to date. Besides, a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise, immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the treatment of advanced PDAC.

14 Review Gene and cell therapy for pancreatic cancer. 2015

Singh, Hans Martin / Ungerechts, Guy / Tsimberidou, Apostolia M. ·National Center for Tumor Diseases and German Cancer Research Center, Department of Translational Oncology , Heidelberg , Germany. ·Expert Opin Biol Ther · Pubmed #25582170.

ABSTRACT: INTRODUCTION: The clinical outcomes of patients with pancreatic cancer are poor, and the limited success of classical chemotherapy underscores the need for new, targeted approaches for this disease. The delivery of genetic material to cells allows for a variety of therapeutic concepts. Engineered agents based on synthetic biology are under clinical investigation in various cancers, including pancreatic cancer. AREAS COVERED: This review focuses on Phase I - III clinical trials of gene and cell therapy for pancreatic cancer and on future implications of recent translational research. Trials available in the US National Library of Medicine (www.clinicaltrials.gov) until February 2014 were reviewed and relevant published results of preclinical and clinical studies were retrieved from www.pubmed.gov . EXPERT OPINION: In pancreatic cancer, gene and cell therapies are feasible and may have synergistic antitumor activity with standard treatment and/or immunotherapy. Challenges are related to application safety, manufacturing costs, and a new spectrum of adverse events. Further studies are needed to evaluate available agents in carefully designed protocols and combination regimens. Enabling personalized cancer therapy, insights from molecular diagnostic technologies will guide the development and selection of new gene-based drugs. The evolving preclinical and clinical data on gene-based therapies can lay the foundation for future avenues improving patient care in pancreatic cancer.

15 Review SIBLINGs and SPARC families: their emerging roles in pancreatic cancer. 2014

Kaleağasıoğlu, Ferda / Berger, Martin R. ·Ferda Kaleağasıoğlu, Visiting Scientist at Toxicology and Chemotherapy Unit, German Cancer Research Center, D-69120 Heidelberg, Germany. ·World J Gastroenterol · Pubmed #25356037.

ABSTRACT: Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the "small integrin binding ligand N-linked glycoproteins" (SIBLINGs) and "secreted protein acidic and rich in cysteine" (SPARC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPARC family of modular extracellular proteins is comprised of SPARC/osteonectin (ON) and SPARC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.

16 Review Oncogenic KRAS signalling in pancreatic cancer. 2014

Eser, S / Schnieke, A / Schneider, G / Saur, D. ·1] Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany [2] German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. · Livestock Biotechnology, Technische Universität München, Liesel-Beckmann Str. 1., 85354 Freising, Germany. · Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany. ·Br J Cancer · Pubmed #24755884.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal. The annual number of deaths equals the number of newly diagnosed cases, despite maximal treatment. The overall 5-year survival rate of <5% has remained stubbornly unchanged over the last 30 years, despite tremendous efforts in preclinical and clinical science. There is unquestionably an urgent need to further improve our understanding of pancreatic cancer biology, treatment response and relapse, and to identify novel therapeutic targets. Rigorous research in the field has uncovered genetic aberrations that occur during PDAC development and progression. In most cases, PDAC is initiated by oncogenic mutant KRAS, which has been shown to drive pancreatic neoplasia. However, all attempts to target KRAS directly have failed in the clinic and KRAS is widely assumed to be undruggable. This has led to intense efforts to identify druggable critical downstream targets and nodes orchestrated by mutationally activated KRAS. This includes context-specific KRAS effector pathways, synthetic lethal interaction partners and KRAS-driven metabolic changes. Here, we review recent advances in oncogenic KRAS signalling and discuss how these might benefit PDAC treatment in the future.

17 Review [Diffusion-weighted imaging of the pancreas]. 2011

Grünberg, K / Grenacher, L / Klauss, M. ·Abteilung Radiologie, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Im Neuenheimer Feld 280, Heidelberg, Germany. k.gruenberg@dkfz.de ·Radiologe · Pubmed #21305263.

ABSTRACT: Diffusion-weighted imaging (DWI) has increasingly gained in importance over the last 10 years especially in cancer imaging for differentiation of malignant and benign lesions. Through development of fast magnetic resonance imaging (MRI) sequences DWI is not only applicable in neuroradiology but also in abdominal imaging. As a diagnostic tool of the pancreas DWI enables a differentiation between normal tissue, cancer and chronic pancreatitis. The ADC values (apparent diffusion coefficient, the so-called effective diffusion coefficient) reported in the literature for healthy pancreatic tissue are in the range from 1.49 to 1.9×10(-3) mm(2)/s, for pancreatic cancer in the range from 1.24 to 1.46×10(-3) mm(2)/s and for autoimmune pancreatitis an average ADC value of 1.012×10(-3) mm(2)/s. There are controversial data in the literature concerning the differentiation between chronic pancreatitis and pancreatic cancer. Using DWI-derived IVIM (intravoxel incoherent motion) the parameter f (perfusion fraction) seems to be advantageous but it is important to use several b values. In the literature the mean f value in chronic pancreatitis is around 16%, in pancreatic cancer 8% and in healthy pancreatic tissue around 25%. So far, DWI has not been helpful for differentiating cystic lesions of the pancreas. There are many references with other tumor entities and in animal models which indicate that there is a possible benefit of DWI in monitoring therapy of pancreatic cancer but so far no original work has been published.

18 Review Inverse system perturbations as a new methodology for identifying transcriptomic signaling participants in balanced biological processes. 2009

Hauser, Kai / Abdollahi, Amir / Huber, Peter E. ·Radiation Oncology, German Cancer Research Center (DKFZ)/University Hospital Center, Heidelberg, Germany. ·Cell Cycle · Pubmed #19652537.

ABSTRACT: We devise a novel, systems-biology approach for identifying genetic participants in homeostatic biological processes. The central idea is that genes which are inversely regulated in alignment with positive and negative system perturbation are strong candidates for significant regulatory involvement in a given homeostatic process. This allows us to integrate known genetic participants together with hitherto unknown ones into a signaling network. We illustrate this concept and justify the underlying rationale in the exemplary case of the formation of blood vessels (angiogenesis) in the progression of pancreatic cancer where we have introduced a gene regulatory network governing the shift from a non angiogenic phenotype to an angiogenic phenotype in pancreatic tissue ('angiogenic switch'). The envisaged pay-off of our approach is an improved understanding of signaling networks as well as the discovery of yet unknown genetic agents for diagnostic and therapeutic purposes. Subject to mild constraints, the same algorithm for the identification of signalling components can in principle be implemented across a wide spectrum of homeostatic processes including, e.g., apoptosis and fibrogenesis.

19 Review Identification of malignancy factors by analyzing cystic tumors of the pancreas. 2009

Bauer, Andrea / Kleeff, Jörg / Bier, Melanie / Wirtz, Martin / Kayed, Hany / Esposito, Irene / Korc, Murray / Hafner, Mathias / Hoheisel, Jörg D / Friess, Helmut. ·Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany. andrea.bauer@dkfz.de ·Pancreatology · Pubmed #19077453.

ABSTRACT: AIM: The diversity in the aggressiveness of cystic tumors of the pancreas - ranging from the usually benign serous cystadenoma to lesions of variable degrees of malignancy - was utilized for the identification of molecular factors that are involved in the occurrence of malignancy. METHODS: We analyzed the transcript profiles of different cystic tumor types. The results were confirmed at the protein level by immunohistochemistry. Also, functional studies with siRNA silencing were performed. RESULTS: Expression variations at the RNA and protein level were identified that are closely correlated with the degree of malignancy. Besides, all tumors could be classified effectively by this means. Many of the identified factors had not previously been known to be associated with malignant cystic lesions. siRNA silencing of the gene with the most prominent variation - the anti-apoptotic factor FASTK (Fas-activated serine/threonine kinase) - revealed a regulative effect on several genes known to be relevant to the development of tumors. CONCLUSION: By a molecular analysis of rare types of pancreatic cancer, which are less frequent in terms of disease, variations could be identified that could be critical for the regulation of malignancy and thus relevant to the treatment of also the majority of pancreatic tumors.

20 Review Stool testing for the early detection of pancreatic cancer: rationale and current evidence. 2008

Haug, Ulrike / Wente, Moritz N / Seiler, Christoph M / Jesenofsky, Ralf / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Bergheimer Street 20, Heidelberg 69115, Germany. u.haug@dkfz.de ·Expert Rev Mol Diagn · Pubmed #18999925.

ABSTRACT: The development of effective tools for the early detection of pancreatic cancer, or its precursors, in high-risk subjects could play a key role in reducing the burden of this disease, which is the most lethal among solid gastrointestinal tumors. Given the poor accessibility of the pancreas due to its anatomic site, and given the limitations of imaging modalities, biomarker screening might be a promising diagnostic option. This review focuses on the rationale of using stool markers for the early detection of pancreatic cancer, and systematically summarizes current evidence. Despite several potential advantages of stool testing for pancreatic cancer and its biological plausibility, only six studies investigating two genetic markers in stool (the K-ras and the p53 gene) could be identified. Even though these studies were limited in size and could hardly approximate the screening setting, both markers appear to lack sensitivity and, in particular, specificity. The investigation of further marker candidates (e.g., epigenetic markers) in adequately designed studies represents an important next step to explore the potential of stool testing for pancreatic cancer. Pertinent studies could greatly benefit from recent methodological advances gained in connection with stool testing for colorectal cancer.

21 Clinical Trial Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the 'Arbeitsgemeinschaft Internistische Onkologie'. 2018

Haas, M / Siveke, J T / Schenk, M / Lerch, M M / Caca, K / Freiberg-Richter, J / Fischer von Weikersthal, L / Kullmann, F / Reinacher-Schick, A / Fuchs, M / Kanzler, S / Kunzmann, V / Ettrich, T J / Kruger, S / Westphalen, C B / Held, S / Heinemann, V / Boeck, S. ·Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. Electronic address: michael.haas@med.lmu.de. · 2nd Medical Department, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Solid Tumor Translational Oncology (DKTK, Partner Site Essen), West German Cancer Center, University Hospital Essen, Essen, Germany. · Department of Haematology and Oncology, Hospital Barmherzige Brüder, Regensburg, Germany. · Department of Medicine A, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt University, Greifswald, Germany. · Department of Internal Medicine I, Klinikum Ludwigsburg, Ludwigsburg, Germany. · Practice for Haematology and Oncology, Dresden, Germany. · Department of Oncology, Gesundheitszentrum St. Marien, Amberg, Germany. · Department of Medicine I, Klinikum Weiden, Weiden, Germany. · Department of Haematology and Oncology, St. Josef-Hospital, Ruhr University, Bochum, Germany. · Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Klinikum Bogenhausen, Munich, Germany. · Department of Internal Medicine II, Leopoldina Krankenhaus Schweinfurt, Schweinfurt, Germany. · Department of Medical Oncology, University Hospital of Wuerzburg, Wuerzburg, Germany. · Department of Internal Medicine I, University of Ulm, Ulm, Germany. · Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. · ClinAssess GmbH, Leverkusen, Germany. ·Eur J Cancer · Pubmed #29549862.

ABSTRACT: INTRODUCTION: In metastatic pancreatic ductal adenocarcinoma (mPDAC) treatment, erlotinib is known to be more effective in patients developing skin rash. Treatment with the FOLFIRINOX regimen is only performed in fit patients following defined inclusion criteria. The present study investigates the efficacy of gemcitabine plus erlotinib (gem/erlotinib) in rash-positive patients fit for FOLFIRINOX. PATIENTS AND METHODS: For this prospective phase II study, 150 patients were recruited in 20 centres. All patients received gem/erlotinib for 4 weeks (run-in phase); the subsequent treatment was determined by the development of skin rash: patients with rash grades 1-4 continued with gem/erlotinib, rash-negative patients were switched to FOLFIRINOX. Primary study end-point was to achieve a 1-year survival rate in rash-positive patients ≥40%. RESULTS: Ninety patients were deemed positive for skin rash by the end of the run-in phase, showing a 1-year survival rate of 40.0% (95% confidence interval [CI] 29.8-50.9). Median overall survival (OS) was 10.1 months, progression-free survival (PFS) was 3.8 months and overall response rate (ORR) was 23.3%. Patients switched to FOLFIRINOX (n = 27) had a 1-year survival rate of 48.1% (95% CI 28.7-68.1), a median OS of 10.9 months, a median PFS of 6.6 months and an ORR of 33.3%. Rash-negative patients had a lower quality of life at baseline but seemed to experience an improved control of pain during FOLFIRINOX. CONCLUSIONS: First-line treatment with gem/erlotinib was effective in fit, rash-positive mPDAC patients achieving a 1-year survival rate comparable to previous reports for FOLFIRINOX. The study was registered at clinicaltrials.gov (NCT0172948) and Eudra-CT (2011-005471-17).

22 Clinical Trial A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol. 2017

Hajda, Jacek / Lehmann, Monika / Krebs, Ottheinz / Kieser, Meinhard / Geletneky, Karsten / Jäger, Dirk / Dahm, Michael / Huber, Bernard / Schöning, Tilman / Sedlaczek, Oliver / Stenzinger, Albrecht / Halama, Niels / Daniel, Volker / Leuchs, Barbara / Angelova, Assia / Rommelaere, Jean / Engeland, Christine E / Springfeld, Christoph / Ungerechts, Guy. ·Coordination Centre for Clinical Trials, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. Jacek.Hajda@med.uni-heidelberg.de. · Coordination Centre for Clinical Trials, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. · Oryx GmbH & Co KG, Marktplatz 1, 85598, Baldham, Germany. · Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. · Department of Neurosurgery, Klinikum Darmstadt, Grafenstraße 9, 64283, Darmstadt, Germany. · Department of Medical Oncology, National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. · Central Pharmacy, University Hospital Heidelberg, Im Neuenheimer Feld 670, 69120, Heidelberg, Germany. · Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. · Department of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. · Tissue Imaging & Analysis Center (TIGA), University Heidelberg - BioQuant, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany. · Institute of Immunology, Transplantation Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. · Department of Applied Tumor Virology, German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany. ·BMC Cancer · Pubmed #28851316.

ABSTRACT: BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy. METHODS: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug. DISCUSSION: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.

23 Clinical Trial The Impact of SMAD4 Loss on Outcome in Patients with Advanced Pancreatic Cancer Treated with Systemic Chemotherapy. 2017

Ormanns, Steffen / Haas, Michael / Remold, Anna / Kruger, Stephan / Holdenrieder, Stefan / Kirchner, Thomas / Heinemann, Volker / Boeck, Stefan. ·Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany. steffen.ormanns@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. michael.haas@med.uni-muenchen.de. · Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany. annaremold@yahoo.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. annaremold@yahoo.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. stephan.kruger@med.uni-muenchen.de. · Institute of Laboratory Medicine, German Heart Centre Munich, Technische Universität München, 80333 Munich, Germany. holdenrieder@dhm.mhn.de. · Institute of Clinical Chemistry and Clinical Pharmacology, Universitätsklinikum Bonn, 53127 Bonn, Germany. holdenrieder@dhm.mhn.de. · Institute of Pathology, Ludwig-Maximilians Universität München, Thalkirchner Str. 36, 80337 Munich, Germany. thomas.kirchner@med.uni-muenchen.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK, German Cancer Consortium), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. thomas.kirchner@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. volker.heinemann@med.uni-muenchen.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK, German Cancer Consortium), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. volker.heinemann@med.uni-muenchen.de. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians Universität München, Marchioninistr. 15, 81377 Munich, Germany. stefan.boeck@med.uni-muenchen.de. · Deutsches Konsortium für Translationale Krebsforschung (DKTK, German Cancer Consortium), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. stefan.boeck@med.uni-muenchen.de. ·Int J Mol Sci · Pubmed #28534865.

ABSTRACT: The role of the tumor suppressor mothers against decapentaplegic homolog 4 (SMAD4) has not yet been defined in patients (pts) with advanced pancreatic cancer (aPC). This translational research study was designed to evaluate the impact of tumoral SMAD4 loss on clinicopathological parameters and outcome in PC patients receiving palliative chemotherapy. Using immunohistochemistry, we examined SMAD4 expression in tumor tissue of 143 aPC pts treated within completed prospective clinical and biomarker trials. In uni- and multivariate analyses, SMAD4 expression status was correlated to clinicopathological patient characteristics and outcome. At chemotherapy initiation, 128 pts had metastatic PC; most pts (

24 Clinical Trial Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis. 2017

Pelzer, Uwe / Blanc, Jean-Frédéric / Melisi, Davide / Cubillo, Antonio / Von Hoff, Daniel D / Wang-Gillam, Andrea / Chen, Li-Tzong / Siveke, Jens T / Wan, Yin / Solem, Caitlyn T / Botteman, Marc F / Yang, Yoojung / de Jong, Floris A / Hubner, Richard A. ·Department of Hematology/Oncology/Tumorimmunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. · Service d'Hépato-Gastroentérologie et Oncologie Digestive, Hôpital Haut-Lévêque, CHU de Bordeaux, Inserm UMR 1053, Université de Bordeaux, Bordeaux, France. · Digestive Molecular Clinical Oncology Unit, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy. · Servicio de Oncologia Médica, Centro Integral Oncológico Clara Campal (CIOCC), Hospital Universitario Madrid Sanchinarro, Calle Oña, 10, 28050 Madrid, Spain. · Virginia G. Piper Cancer Center at HonorHealth/TGen, 10460N 92nd St #206, Scottsdale, AZ 85258, USA. · Division of Oncology, Washington University in St Louis, 660 South Euclid Avenue, St Louis, MO 63110, USA. · National Institute of Cancer Research, National Health Research Institutes, 2F, No. 367, Sheng-Li Road, Tainan 70456, Taiwan. · Division of Solid Tumor Translational Oncology, DKTK Partner Site Essen, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pharmerit International, 4350 East-West Hwy #430, Bethesda, MD 20814, USA. · Shire, Plc, 650 East Kendal St, Cambridge, MA 02142, USA. · Department of Global Medical Affairs Oncology, Shire GmbH, Zählerweg 10, 6300 Zug, Switzerland. · Department of Medical Oncology, Christie Hospital NHS Foundation Trust, 550 Wilmslow Rd, Manchester M20 4BX, UK. ·Br J Cancer · Pubmed #28350787.

ABSTRACT: BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. RESULTS: Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). CONCLUSIONS: Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

25 Clinical Trial Optimization of carbon ion and proton treatment plans using the raster-scanning technique for patients with unresectable pancreatic cancer. 2015

Dreher, Constantin / Habermehl, Daniel / Ecker, Swantje / Brons, Stephan / El-Shafie, Rami / Jäkel, Oliver / Debus, Jürgen / Combs, Stephanie E. ·Department of Radiation Oncology, University Hospital of Heidelberg, INF 400, 69120, Heidelberg, Germany. Constantin.Dreher@stud.uni-heidelberg.de. · Department of Radiooncology, Klinikum rechts der Isar, Ismaninger Str. 22, 81675, Munich, Germany. daniel.habermehl@tum.de. · Heidelberg Ion Beam Therapy Center (HIT), INF 450, 69120, Heidelberg, Germany. Swantje.Ecker@med.uni-heidelberg.de. · Heidelberg Ion Beam Therapy Center (HIT), INF 450, 69120, Heidelberg, Germany. stephan.brons@med.uni-heidelberg.de. · Department of Radiation Oncology, University Hospital of Heidelberg, INF 400, 69120, Heidelberg, Germany. rami.elshafie@med.uni-heidelberg.de. · Heidelberg Ion Beam Therapy Center (HIT), INF 450, 69120, Heidelberg, Germany. o.jaekel@dkfz-heidelberg.de. · Department of Medical Physics in Radiation Oncology, German Cancer Research Center, INF 280, 69120, Heidelberg, Germany. o.jaekel@dkfz-heidelberg.de. · Department of Radiation Oncology, University Hospital of Heidelberg, INF 400, 69120, Heidelberg, Germany. Juergen.Debus@med.uni-heidelberg.de. · Department of Radiooncology, Klinikum rechts der Isar, Ismaninger Str. 22, 81675, Munich, Germany. stephanie.combs@tum.de. ·Radiat Oncol · Pubmed #26590103.

ABSTRACT: BACKGROUND: The aim of the thesis is to improve radiation plans of patients with locally advanced, unresectable pancreatic cancer by using carbon ion and proton beams. PATIENTS AND METHODS: Using the treatment planning system Syngo RT Planning (Siemens, Erlangen, Germany) a total of 50 treatment plans have been created for five patients with the dose schedule 15 × 3 Gy(RBE). With reference to the anatomy, five field configurations were considered to be relevant. The plans were analyzed with respect to dose distribution and individual anatomy, and compared using a customized index. RESULTS: Within the index the three-field configurations yielded the best results, though with a high variety of score points (field setup 5, carbon ion: median 74 (range 48-101)). The maximum dose in the myelon is low (e.g. case 3, carbon ion: 21.5 Gy(RBE)). A single posterior field generally spares the organs at risk, but the maximum dose in the myelon is high (e.g. case 3, carbon ion: 32.9 Gy(RBE)). Two oblique posterior fields resulted in acceptable maximum doses in the myelon (e.g. case 3, carbon ion: 26.9 Gy(RBE)). The single-field configuration and the two oblique posterior fields had a small score dispersion (carbon ion: median 66 and 58 (range 62-72 and 40-69)). In cases with topographic proximity of the organs at risk to the target volume, the single-field configuration scored as well as the three-field configurations. CONCLUSION: In summary, the three-field configurations showed the best dose distributions. A single posterior field seems to be robust and beneficial in case of difficult topographical conditions and topographical proximity of organs at risk to the target volume. A setup with two oblique posterior fields is a reasonable compromise between three-field and single-field configurations.

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