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Pancreatic Neoplasms: HELP
Articles by Hanneke W. M. van Laarhoven
Based on 30 articles published since 2009
(Why 30 articles?)
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Between 2009 and 2019, H. van Laarhoven wrote the following 30 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
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 Review Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis. 2017

Creemers, A / Krausz, S / Strijker, M / van der Wel, M J / Soer, E C / Reinten, R J / Besselink, M G / Wilmink, J W / van de Vijver, M J / van Noesel, C J M / Verheij, J / Meijer, S L / Dijk, F / Bijlsma, M F / van Oijen, M G H / van Laarhoven, H W M. ·Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. Electronic address: a.creemers@amc.uva.nl. · Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. · Department of Surgery, AMC, The Netherlands. · Department of Pathology, AMC, The Netherlands. · Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands. · Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. ·Biochim Biophys Acta Rev Cancer · Pubmed #28801248.

ABSTRACT: BACKGROUND: The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. METHODS: PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed. RESULTS: A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n=10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15-3.22, p=0.01). CONCLUSION: The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.

3 Review Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies. 2017

Le Large, T Y S / Bijlsma, M F / Kazemier, G / van Laarhoven, H W M / Giovannetti, E / Jimenez, C R. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, Pisa, Italy; CNR-Nano, Institute of Nanoscience and Nanotechnology, Pisa, Italy. · Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: c.jimenez@vumc.nl. ·Semin Cancer Biol · Pubmed #28366542.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.

4 Review Prognostic value of lymph node metastases detected during surgical exploration for pancreatic or periampullary cancer: a systematic review and meta-analysis. 2016

van Rijssen, Lennart B / Narwade, Poorvi / van Huijgevoort, Nadine C M / Tseng, Dorine S J / van Santvoort, Hjalmar C / Molenaar, Isaac Q / van Laarhoven, Hanneke W M / van Eijck, Casper H J / Busch, Olivier R C / Besselink, Marc G H / Anonymous11900872. ·Department of Surgery, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Utrecht Medical Center, Utrecht, Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, Netherlands; Department of Surgery, St. Antonius Hospital, Nieuwegein, Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, Netherlands. Electronic address: m.g.besselink@amc.nl. ·HPB (Oxford) · Pubmed #27346135.

ABSTRACT: BACKGROUND: Hepatic-artery and para-aortic lymph node metastases (LNM) may be detected during surgical exploration for pancreatic (PDAC) or periampullary cancer. Some surgeons will continue the resection while others abort the exploration. METHODS: A systematic search was performed in PubMed, EMBASE and Cochrane Library for studies investigating survival in patients with intra-operatively detected hepatic-artery or para-aortic LNM. Survival was stratified for node positive (N1) disease. RESULTS: After screening 3088 studies, 13 studies with 2045 patients undergoing pancreatoduodenectomy were included. No study reported survival data after detection of LNM and aborted surgical exploration. In 110 patients with hepatic-artery LNM, median survival ranged between 7 and 17 months. Estimated pooled mean survival in 84 patients with hepatic-artery LNM was 15 [95%CI 12-18] months (13 months in PDAC), compared to 19 [16-22] months in 270 patients with N1-disease without hepatic-artery LNM (p = 0.020). In 192 patients with para-aortic LNM, median survival ranged between 5 and 32 months. Estimated pooled mean survival in 169 patients with para-aortic LNM was 13 [8-17] months (11 months in PDAC), compared to 17 (6-27) months in 506 patients with N1-disease without para-aortic LNM (p < 0.001). Data on the impact of (neo)adjuvant therapy on survival were lacking. CONCLUSION: Survival after pancreatoduodenectomy in patients with intra-operatively detected hepatic-artery and especially para-aortic LNM is inferior to patients undergoing pancreatoduodenectomy with other N1 disease. It remains unclear what the consequence of this should be since data on (neo-)adjuvant therapy and survival after aborted exploration are lacking.

5 Review The conflicting roles of tumor stroma in pancreatic cancer and their contribution to the failure of clinical trials: a systematic review and critical appraisal. 2015

Bijlsma, Maarten F / van Laarhoven, Hanneke W M. ·Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. ·Cancer Metastasis Rev · Pubmed #25566685.

ABSTRACT: A nearly universal feature of pancreatic ductal adenocarcinoma (PDAC) is an extensive presence of activated stroma. This stroma is thought to aid in various tumor-promoting processes and hampers response to therapy. Here, we aim to evaluate the evidence that supports this role of the stroma in PDAC with functional experiments in relevant models, discuss the clinical trials that have aimed to target the stroma in this disease, and examine recent work that explains why these clinical trials based on stroma-targeting strategies have thus far not achieved the expected success. We systematically searched PubMed through August 2014 with no restrictions to identify published peer-reviewed research articles assessing the effect of targeting the stroma on tumor growth or metastases in preclinical animal models. Five hundred and thirty articles were extracted of which 31 were included in the analysis. Unfortunately, due to the large variety in models and outcome measures, we could not perform a meta-analysis of our data. We find that despite an abundance of positive outcomes reported in previous studies on stroma targeting, a strong discrepancy exists with the outcomes of clinical trials and the more recent preclinical work that is in line with these trials. We explain the incongruities by the duration of stroma targeting and propose that chronic stroma targeting treatment is possibly detrimental in the treatment of this disease.

6 Article A novel amplitude binning strategy to handle irregular breathing during 4DMRI acquisition: improved imaging for radiotherapy purposes. 2019

van Kesteren, Z / van der Horst, A / Gurney-Champion, O J / Bones, I / Tekelenburg, D / Alderliesten, T / van Tienhoven, G / Klaassen, R / van Laarhoven, H W M / Bel, A. ·Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. z.vankesteren@amc.uva.nl. · Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. · Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. · Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK, SM2 5NG, UK. · Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. ·Radiat Oncol · Pubmed #31088490.

ABSTRACT: BACKGROUND: For radiotherapy of abdominal cancer, four-dimensional magnetic resonance imaging (4DMRI) is desirable for tumor definition and the assessment of tumor and organ motion. However, irregular breathing gives rise to image artifacts. We developed a outlier rejection strategy resulting in a 4DMRI with reduced image artifacts in the presence of irregular breathing. METHODS: We obtained 2D T2-weighted single-shot turbo spin echo images, with an interleaved 1D navigator acquisition to obtain the respiratory signal during free breathing imaging in 2 patients and 12 healthy volunteers. Prior to binning, upper and lower inclusion thresholds were chosen such that 95% of the acquired images were included, while minimizing the distance between the thresholds (inclusion range (IR)). We compared our strategy (Min95) with three commonly applied strategies: phase binning with all images included (Phase), amplitude binning with all images included (MaxIE), and amplitude binning with the thresholds set as the mean end-inhale and mean end-exhale diaphragm positions (MeanIE). We compared 4DMRI quality based on: Data included (DI); percentage of images remaining after outlier rejection. Reconstruction completeness (RC); percentage of bin-slice combinations containing at least one image after binning. Intra-bin variation (IBV); interquartile range of the diaphragm position within the bin-slice combination, averaged over three central slices and ten respiratory bins. IR. Image smoothness (S); quantified by fitting a parabola to the diaphragm profile in a sagittal plane of the reconstructed 4DMRI. A two-sided Wilcoxon's signed-rank test was used to test for significance in differences between the Min95 strategy and the Phase, MaxIE, and MeanIE strategies. RESULTS: Based on the fourteen subjects, the Min95 binning strategy outperformed the other strategies with a mean RC of 95.5%, mean IBV of 1.6 mm, mean IR of 15.1 mm and a mean S of 0.90. The Phase strategy showed a poor mean IBV of 6.2 mm and the MaxIE strategy showed a poor mean RC of 85.6%, resulting in image artifacts (mean S of 0.76). The MeanIE strategy demonstrated a mean DI of 85.6%. CONCLUSIONS: Our Min95 reconstruction strategy resulted in a 4DMRI with less artifacts and more precise diaphragm position reconstruction compared to the other strategies. TRIAL REGISTRATION: Volunteers: protocol W15_373#16.007; patients: protocol NL47713.018.14.

7 Article Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer. 2019

Strijker, M / Chen, J W / Mungroop, T H / Jamieson, N B / van Eijck, C H / Steyerberg, E W / Wilmink, J W / Groot Koerkamp, B / van Laarhoven, H W / Besselink, M G. ·Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK. · Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · Department of Surgery, Erasmus Medical Centre, Rotterdam, the Netherlands. · Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, the Netherlands. · Department of Medical Oncology, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. ·Br J Surg · Pubmed #30758855.

ABSTRACT: BACKGROUND: As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared decision-making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking. METHODS: This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10 per cent of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically. RESULTS: After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The C-statistic/area under the curve values ranged from 0·57 to 0·90. Based on study design, validation methods and the availability of web-based calculators, two models were identified as the most promising. CONCLUSION: Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decision-making.

8 Article Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2019

Campa, Daniele / Matarazzi, Martina / Greenhalf, William / Bijlsma, Maarten / Saum, Kai-Uwe / Pasquali, Claudio / van Laarhoven, Hanneke / Szentesi, Andrea / Federici, Francesca / Vodicka, Pavel / Funel, Niccola / Pezzilli, Raffaele / Bueno-de-Mesquita, H Bas / Vodickova, Ludmila / Basso, Daniela / Obazee, Ofure / Hackert, Thilo / Soucek, Pavel / Cuk, Katarina / Kaiser, Jörg / Sperti, Cosimo / Lovecek, Martin / Capurso, Gabriele / Mohelnikova-Duchonova, Beatrice / Khaw, Kay-Tee / König, Anna-Katharina / Kupcinskas, Juozas / Kaaks, Rudolf / Bambi, Franco / Archibugi, Livia / Mambrini, Andrea / Cavestro, Giulia Martina / Landi, Stefano / Hegyi, Péter / Izbicki, Jakob R / Gioffreda, Domenica / Zambon, Carlo Federico / Tavano, Francesca / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Key, Timothy J / Fave, Gianfranco Delle / Strobel, Oliver / Jonaitis, Laimas / Andriulli, Angelo / Lawlor, Rita T / Pirozzi, Felice / Katzke, Verena / Valsuani, Chiara / Vashist, Yogesh K / Brenner, Hermann / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · First Department of Medicine, University of Szeged, Szeged, Hungary. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University, Rome, Italy. · PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. · Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. · University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET, University and Hospital Trust of Verona, Verona, Italy. · Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30325019.

ABSTRACT: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10

9 Article Association of the location of pancreatic ductal adenocarcinoma (head, body, tail) with tumor stage, treatment, and survival: a population-based analysis. 2018

van Erning, Felice N / Mackay, Tara M / van der Geest, Lydia G M / Groot Koerkamp, B / van Laarhoven, Hanneke W M / Bonsing, Bert A / Wilmink, Johanna W / van Santvoort, Hjalmar C / de Vos-Geelen, Judith / van Eijck, Casper H J / Busch, Olivier R / Lemmens, Valery E / Besselink, Marc G / Anonymous2081202. ·a Department of Research , Netherlands Comprehensive Cancer Organisation (IKNL) , Utrecht , Netherlands. · b Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC , University of Amsterdam , Amsterdam , Netherlands. · c Department of Surgery , Erasmus Medical Center , Rotterdam , the Netherlands. · d Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC , University of Amsterdam , Amsterdam , the Netherlands. · e Department of Surgery , Leiden University Medical Center , Leiden , the Netherlands. · f Department of Surgery, Regional Academic Cancer Center Utrecht , University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein , Nieuwegein , the Netherlands. · g Department of Internal Medicine, Division of Medical Oncology , GROW - School for Oncology and Developmental Biology, Maastricht UMC+ , Maastricht , the Netherlands. · h Department of Public Health , Erasmus Medical Center , Rotterdam , the Netherlands. ·Acta Oncol · Pubmed #30264642.

ABSTRACT: BACKGROUND: The association between pancreatic ductal adenocarcinoma (PDAC) location (head, body, tail) and tumor stage, treatment and overall survival (OS) is unclear. METHODS: Patients with PDAC diagnosed between 2005 and 2015 were included from the population-based Netherlands Cancer Registry. Patient, tumor and treatment characteristics were compared with the tumor locations. Multivariable logistic and Cox regression analyses were used. RESULTS: Overall, 19,023 patients were included. PDAC locations were 13,451 (71%) head, 2429 (13%) body and 3143 (16%) tail. Differences were found regarding metastasized disease (head 42%, body 69%, tail 84%, p < .001), size (>4 cm: 21%, 40%, 51%, p < .001) and resection rate (17%, 4%, 7%, p < .001). For patients without metastases, median OS did not differ between head, body, tail (after resection: 16.8, 15.0, 17.3 months, without resection: 5.2, 6.1, 4.6 months, respectively). For patients with metastases, median OS differed slightly (2.6, 2.4, 1.9 months, respectively, adjusted HR body versus head 1.17 (95%CI 1.10-1.23), tail versus head 1.35 (95%CI 1.29-1.41)). CONCLUSIONS: PDAC locations in body and tail are larger, more often metastasized and less often resectable than in the pancreatic head. Whereas survival is similar after resection, survival in metastasized disease is somewhat less for PDAC in the pancreatic body and tail.

10 Article Evaluation of Six Diffusion-weighted MRI Models for Assessing Effects of Neoadjuvant Chemoradiation in Pancreatic Cancer Patients. 2018

Klaassen, Remy / Gurney-Champion, Oliver J / Engelbrecht, Marc R W / Stoker, Jaap / Wilmink, Johanna W / Besselink, Marc G / Bel, Arjan / van Tienhoven, Geertjan / van Laarhoven, Hanneke W M / Nederveen, Aart J. ·Cancer Center Amsterdam, Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands; Cancer Center Amsterdam, LEXOR (Laboratory for Experimental Oncology and Radiobiology), Academic Medical Center, Amsterdam, The Netherlands. Electronic address: r.klaassen@amc.uva.nl. · Department of Radiology & Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiology & Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. · Cancer Center Amsterdam, Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands. ·Int J Radiat Oncol Biol Phys · Pubmed #29891208.

ABSTRACT: PURPOSE: To compare 6 diffusion-weighted imaging (DWI) MRI models for response evaluation in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: DWI images were acquired at 3T for b = 0-600 s/mm RESULTS: The mono-exponential model had the lowest goodness of fit in both tumor (R CONCLUSIONS: Individual treatment evaluation is possible with all investigated DWI models, with treatment associated changes exceeding the repeatability. The double monoexponential fit with ADC

11 Article Patient characteristics and treatment considerations in pancreatic cancer: a population based study in the Netherlands. 2018

Zijlstra, Myrte / van der Geest, Lydia G M / van Laarhoven, Hanneke W M / Lemmens, Valery E P P / van de Poll-Franse, Lonneke V / Raijmakers, Natasja J H. ·a Netherlands Comprehensive Cancer Organisation , Utrecht , The Netherlands. · b Department of Medical Oncology , Radboud MC , Nijmegen , The Netherlands. · c Department of Medical Oncology , Academic MC , Amsterdam , The Netherlands. · d Department of Public Health , Erasmus MC , Rotterdam , The Netherlands. · e CoRPS - Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology , Tilburg University , Tilburg , The Netherlands. · f Division of Psychosocial Research and Epidemiology , The Netherlands Cancer Institute , Amsterdam , The Netherlands. ·Acta Oncol · Pubmed #29741436.

ABSTRACT: BACKGROUND: Pancreatic cancer carries a poor prognosis. To date, there has been little research devoted to decision-making regarding treatment options in pancreatic cancer, including the rationale for choosing to withhold tumor targeting treatment (TTT). This study aims to gain insight into the characteristics of patients receiving no TTT, the reasons for this decision and their survival. METHODS: All patients diagnosed in the Netherlands between 1 January 2014 and 30 June 2015 with a proven pancreatic adenocarcinoma or a pathologically unverified pancreatic tumor were identified in the Netherlands Cancer Registry. Information on initial management, patient characteristics, main reasons for no TTT (as reported in medical charts) and survival were analyzed. RESULTS: A total of 3090 patients was included. Of these patients, 1818 (59%) received no TTT. Median age of no TTT patients was 74 years (range 35-99) versus 66 years (30-87) for TTT patients. In the no TTT group 77% had a clinical stage III/IV versus 57% of patients who received TTT. Main reasons for not starting TTT were patient's choice (27%) and extensive disease (21%). Median survival of patients who did not receive TTT was 1.9 months, ranging from a median survival of 0.8 months (when main reason to withhold TTT was short life expectancy) to 4.4 months (main reason to withhold TTT: old age). In the latter group, a relatively large proportion of clinical stage I tumors was present (37%). CONCLUSION: The majority of patients with pancreatic cancer received no TTT and had a very poor median survival. In most patients, patient's choice not to start treatment was the main reason for withholding treatment, suggesting patient's involvement in decision-making.

12 Article Comparison of six fit algorithms for the intra-voxel incoherent motion model of diffusion-weighted magnetic resonance imaging data of pancreatic cancer patients. 2018

Gurney-Champion, Oliver J / Klaassen, Remy / Froeling, Martijn / Barbieri, Sebastiano / Stoker, Jaap / Engelbrecht, Marc R W / Wilmink, Johanna W / Besselink, Marc G / Bel, Arjan / van Laarhoven, Hanneke W M / Nederveen, Aart J. ·Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom. · Department of Medical Oncology, Academic Medical Center, Amsterdam, Netherlands. · Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands. · Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands. · Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. · Department of Internal Medicine, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, Netherlands. · Department Radiation Oncology, Academic Medical Center, Amsterdam, Netherlands. ·PLoS One · Pubmed #29617445.

ABSTRACT: The intravoxel incoherent motion (IVIM) model for diffusion-weighted imaging (DWI) MRI data bears much promise as a tool for visualizing tumours and monitoring treatment response. To improve the currently poor precision of IVIM, several fit algorithms have been suggested. In this work, we compared the performance of two Bayesian IVIM fit algorithms and four other IVIM fit algorithms for pancreatic cancer imaging. DWI data were acquired in 14 pancreatic cancer patients during two MRI examinations. Three different measures of performance of the fitting algorithms were assessed: (i) uniqueness of fit parameters (Spearman's rho); (ii) precision (within-subject coefficient of variation, wCV); and (iii) contrast between tumour and normal-appearing pancreatic tissue. For the diffusivity D and perfusion fraction f, a Bayesian fit (IVIM-Bayesian-lin) offered the best trade-off between tumour contrast and precision. With the exception for IVIM-Bayesian-lin, all algorithms resulted in a very poor precision of the pseudo-diffusion coefficient D* with a wCV of more than 50%. The pseudo-diffusion coefficient D* of the Bayesian approaches were, however, significantly correlated with D and f. Therefore, the added value of fitting D* was considered limited in pancreatic cancer patients. The easier implemented least squares fit with fixed D* (IVIM-fixed) performed similar to IVIM-Bayesian-lin for f and D. In conclusion, the best performing IVIM fit algorithm was IVM-Bayesian-lin, but an easier to implement least squares fit with fixed D* performs similarly in pancreatic cancer patients.

13 Article The Dutch Pancreas Biobank Within the Parelsnoer Institute: A Nationwide Biobank of Pancreatic and Periampullary Diseases. 2018

Strijker, Marin / Gerritsen, Arja / van Hilst, Jony / Bijlsma, Maarten F / Bonsing, Bert A / Brosens, Lodewijk A / Bruno, Marco J / van Dam, Ronald M / Dijk, Frederike / van Eijck, Casper H / Farina Sarasqueta, Arantza / Fockens, Paul / Gerhards, Michael F / Groot Koerkamp, Bas / van der Harst, Erwin / de Hingh, Ignace H / van Hooft, Jeanin E / Huysentruyt, Clément J / Kazemier, Geert / Klaase, Joost M / van Laarhoven, Cornelis J / van Laarhoven, Hanneke W / Liem, Mike S / de Meijer, Vincent E / van Rijssen, L Bengt / van Santvoort, Hjalmar C / Suker, Mustafa / Verhagen, Judith H / Verheij, Joanne / Verspaget, Hein W / Wennink, Roos A / Wilmink, Johanna W / Molenaar, I Quintus / Boermeester, Marja A / Busch, Olivier R / Besselink, Marc G / Anonymous5040939. · ·Pancreas · Pubmed #29521943.

ABSTRACT: OBJECTIVES: Large biobanks with uniform collection of biomaterials and associated clinical data are essential for translational research. The Netherlands has traditionally been well organized in multicenter clinical research on pancreatic diseases, including the nationwide multidisciplinary Dutch Pancreatic Cancer Group and Dutch Pancreatitis Study Group. To enable high-quality translational research on pancreatic and periampullary diseases, these groups established the Dutch Pancreas Biobank. METHODS: The Dutch Pancreas Biobank is part of the Parelsnoer Institute and involves all 8 Dutch university medical centers and 5 nonacademic hospitals. Adult patients undergoing pancreatic surgery (all indications) are eligible for inclusion. Preoperative blood samples, tumor tissue from resected specimens, pancreatic cyst fluid, and follow-up blood samples are collected. Clinical parameters are collected in conjunction with the mandatory Dutch Pancreatic Cancer Audit. RESULTS: Between January 2015 and May 2017, 488 patients were included in the first 5 participating centers: 4 university medical centers and 1 nonacademic hospital. Over 2500 samples were collected: 1308 preoperative blood samples, 864 tissue samples, and 366 follow-up blood samples. CONCLUSIONS: Prospective collection of biomaterials and associated clinical data has started in the Dutch Pancreas Biobank. Subsequent translational research will aim to improve treatment decisions based on disease characteristics.

14 Article Repeatability and correlations of dynamic contrast enhanced and T2* MRI in patients with advanced pancreatic ductal adenocarcinoma. 2018

Klaassen, Remy / Gurney-Champion, Oliver J / Wilmink, Johanna W / Besselink, Marc G / Engelbrecht, Marc R W / Stoker, Jaap / Nederveen, Aart J / van Laarhoven, Hanneke W M. ·Cancer Center Amsterdam, Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands; Cancer Center Amsterdam, LEXOR (Laboratory for Experimental Oncology and Radiobiology), Academic Medical Center, Amsterdam, The Netherlands. Electronic address: r.klaassen@amc.uva.nl. · Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Cancer Center Amsterdam, Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. ·Magn Reson Imaging · Pubmed #29476781.

ABSTRACT: BACKGROUND: In current oncological practice of pancreatic ductal adenocarcinoma (PDAC), there is a great demand for response predictors and markers for early treatment evaluation. In this study, we investigated the repeatability and the interaction of dynamic contrast enhanced (DCE) and T2* MRI in patients with advanced PDAC to enable for such evaluation using these techniques. MATERIALS & METHODS: 15 PDAC patients underwent two DCE, T2* and anatomical 3 T MRI sessions before start of treatment. Parametric maps were calculated for the transfer constant (K RESULTS: PDAC K CONCLUSION: We showed good repeatability of DCE and T2* related MRI parameters in advanced PDAC patients. Furthermore, we have illustrated the relation of DCE K

15 Article Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy. 2018

van Veldhuisen, Eran / Vogel, Jantien A / Klompmaker, Sjors / Busch, Olivier R / van Laarhoven, Hanneke W M / van Lienden, Krijn P / Wilmink, Johanna W / Marsman, Hendrik A / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. · Department of Radiology, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. ·HPB (Oxford) · Pubmed #29475787.

ABSTRACT: BACKGROUND: Determining the resectability of locally advanced pancreatic cancer (LAPC) after induction chemotherapy is complex since CT-imaging cannot accurately portray tumor response. We hypothesized that CA19-9 response adds to RECIST-staging in predicting resectability of LAPC. METHODS: Post-hoc analysis within a prospective study on LAPC (>90° arterial or >270° venous involvement). CA19-9 response was determined after induction chemotherapy. Surgical exploration was performed in RECIST-stable or -regressive disease. The relation between CA19-9 response, resectability and survival was assessed. RESULTS: Restaging in 54 patients with LAPC after induction chemotherapy (mostly FOLFIRINOX) identified 6 RECIST-regressive, 32 RECIST-stable, and 16 patients with RECIST-progressive disease. The resection rate was 20.3% (11/54 patients). Sensitivity and specificity of RECIST-regression for resection were 40% and 87% whereas the positive predictive value (PPV) and negative predictive value (NPV) were 67% and 68%. Using a 30% decrease of CA19-9 as cut-off, 9/10 patients were correctly classified as resectable (90% sensitivity, PPV 43%) and 3/15 as unresectable (20% specificity, NPV 75%). In the total cohort, a CA19-9 decrease ≥30% was associated with improved survival (22.4 vs. 12.7 months, p = 0.02). CONCLUSION: Adding CA19-9 response after induction chemotherapy seems useful in determining which patients with RECIST non-progressive LAPC should undergo exploratory surgery.

16 Article The clinical benefit of hyperthermia in pancreatic cancer: a systematic review. 2018

van der Horst, Astrid / Versteijne, Eva / Besselink, Marc G H / Daams, Joost G / Bulle, Esther B / Bijlsma, Maarten F / Wilmink, Johanna W / van Delden, Otto M / van Hooft, Jeanin E / Franken, Nicolaas A P / van Laarhoven, Hanneke W M / Crezee, Johannes / van Tienhoven, Geertjan. ·a Department of Radiation Oncology and Hyperthermia , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. · b Department of Surgery , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. · c Medical Library , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. · d Laboratory for Experimental Oncology and Radiobiology (LEXOR) , Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. · e Department of Medical Oncology , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. · f Department of Radiology , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. · g Department of Gastroenterology and Hepatology , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands. ·Int J Hyperthermia · Pubmed #29168401.

ABSTRACT: OBJECTIVE: In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. METHODS AND MATERIALS: We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (m RESULTS: Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer m CONCLUSIONS: Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.

17 Article Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative. 2018

Coebergh van den Braak, R R J / van Rijssen, L B / van Kleef, J J / Vink, G R / Berbee, M / van Berge Henegouwen, M I / Bloemendal, H J / Bruno, M J / Burgmans, M C / Busch, O R C / Coene, P P L O / Coupé, V M H / Dekker, J W T / van Eijck, C H J / Elferink, M A G / Erdkamp, F L G / van Grevenstein, W M U / de Groot, J W B / van Grieken, N C T / de Hingh, I H J T / Hulshof, M C C M / Ijzermans, J N M / Kwakkenbos, L / Lemmens, V E P P / Los, M / Meijer, G A / Molenaar, I Q / Nieuwenhuijzen, G A P / de Noo, M E / van de Poll-Franse, L V / Punt, C J A / Rietbroek, R C / Roeloffzen, W W H / Rozema, T / Ruurda, J P / van Sandick, J W / Schiphorst, A H W / Schipper, H / Siersema, P D / Slingerland, M / Sommeijer, D W / Spaander, M C W / Sprangers, M A G / Stockmann, H B A C / Strijker, M / van Tienhoven, G / Timmermans, L M / Tjin-A-Ton, M L R / van der Velden, A M T / Verhaar, M J / Verkooijen, H M / Vles, W J / de Vos-Geelen, J M P G M / Wilmink, J W / Zimmerman, D D E / van Oijen, M G H / Koopman, M / Besselink, M G H / van Laarhoven, H W M / Anonymous3410913. ·a Department of Surgery , Erasmus MC University Medical Center , Rotterdam , The Netherlands. · b Department of Surgery , Academic Medical Center, Cancer Center Amsterdam , Amsterdam , The Netherlands. · c Department of Medical Oncology , Academic Medical Center , Amsterdam , The Netherlands. · d Netherlands Comprehensive Cancer Organization , Utrecht , The Netherlands. · e Department of Medical Oncology , University Medical Center Utrecht , Utrecht , The Netherlands. · f Department of Radiation Oncology , Maastro Clinic , Maastricht , The Netherlands. · g Department of Medical Oncology , Meander Medisch Centrum , Amersfoort , The Netherlands. · h Department of Gastroenterology and Hepatology , Erasmus MC University Medical Center , Rotterdam , The Netherlands. · i Department of Radiology , Leiden University Medical Center , Leiden , The Netherlands. · j Department of Surgery , Maasstad Hospital , Rotterdam , The Netherlands. · k Department of Epidemiology and Biostatistics , VU University Medical Center , Amsterdam , The Netherlands. · l Department of Surgery , Reinier de Graaf Hospital , Delft , The Netherlands. · m Department of Medical Oncology , Zuyderland Medisch Centrum , Heerlen , The Netherlands. · n Department of Surgery , University Medical Center Utrecht , Utrecht , The Netherlands. · o Department of Medical Oncology , Isala, Zwolle , The Netherlands. · p Department of Pathology , VU University Medical Center, Cancer Center Amsterdam , Amsterdam , The Netherlands. · q Department of Surgery , Catharina Hospital , Eindhoven , The Netherlands. · r Department of Radiotherapy , Academic Medical Center, Cancer Center Amsterdam , Amsterdam , The Netherlands. · s Living with Hope , Heemstede , The Netherlands. · t Department of Medical Oncology , St. Antonius Hospital , Nieuwegein , The Netherlands. · u Department of Pathology , Netherlands Cancer Institute , Amsterdam , The Netherlands. · v Department of Surgery , Deventer Hospital , Deventer , The Netherlands. · w Research Department , Tilburg University , Tilburg , The Netherlands. · x Department of Medical Oncology , Rode Kruis Hospital , Beverwijk , The Netherlands. · y Department of Medical Oncology , Treant Zorggroep , Hoogeveen , The Netherlands. · z Department of Radiotherapy , Instituut Verbeeten , Tilburg , The Netherlands. · aa Department of Surgery , Netherlands Cancer Institute - Antoni van Leeuwenhoek , Amsterdam , The Netherlands. · ab Department of Surgery , Diakonessenhuis , Utrecht , The Netherlands. · ac Stichting voor Patiënten met Kanker aan het Spijsverteringskanaal (SPKS) , Utrecht , The Netherlands. · ad Department of Gastroenterology , Radboud University Medical Center , Nijmegen , The Netherlands. · ae Department of Medical Oncology , Leiden University Medical Center , Leiden , The Netherlands. · af Department of Medical Oncology , Flevoziekenhuis , Almere , The Netherlands. · ag Department of Medical Psychology , Academic Medical Center , Amsterdam , The Netherlands. · ah Department of Surgery , Kennemer Gasthuis , Haarlem , The Netherlands. · ai Department of Medical Oncology , Hospital Rivierenland , Tiel , The Netherlands. · aj Department of Medical Oncology , Tergooi Hospital , Hilversum , The Netherlands. · ak Department of Medical Oncology , Zuwe Hofpoort Hospital , Woerden , The Netherlands. · al Department of Epidemiology , University Medical Center Utrecht , Utrecht , The Netherlands. · am Department of Surgery , Ikazia Hospital , Rotterdam , The Netherlands. · an Department of Medical Oncology , Maastricht University Medical Center , Maastricht , The Netherlands. · ao Department of Surgery , Elisabeth-Tweesteden Hospital , Tilburg , The Netherlands. ·Acta Oncol · Pubmed #28723307.

ABSTRACT: BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

18 Article Nationwide trends in chemotherapy use and survival of elderly patients with metastatic pancreatic cancer. 2017

van der Geest, Lydia G M / Haj Mohammad, Nadia / Besselink, Marc G H / Lemmens, Valery E P P / Portielje, Johanneke E A / van Laarhoven, Hanneke W M / Wilmink, J Hanneke W / Anonymous1231021. ·Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands. · Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Internal Medicine and Medical Oncology, Haga Hospital, The Hague, The Netherlands. · Foundation of Geriatric Oncology Netherlands (GeriOnNe), Eindhoven, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. ·Cancer Med · Pubmed #29035014.

ABSTRACT: Despite an aging population and underrepresentation of elderly patients in clinical trials, studies on elderly patients with metastatic pancreatic cancer are scarce. This study investigated the use of chemotherapy and survival in elderly patients with metastatic pancreatic cancer. From the Netherlands Cancer Registry, all 9407 patients diagnosed with primary metastatic pancreatic adenocarcinoma in 2005-2013 were selected to investigate chemotherapy use and overall survival (OS), using Kaplan-Meier and Cox proportional hazard regression analyses. Over time, chemotherapy use increased in all age groups (<70 years: from 26 to 43%, 70-74 years: 14 to 25%, 75-79 years: 5 to 13%, all P < 0.001, and ≥80 years: 2 to 3% P = 0.56). Median age of 2,180 patients who received chemotherapy was 63 years (range 21-86 years, 1.6% was ≥80 years). In chemotherapy-treated patients, with rising age (<70, 70-74, 75-79, ≥80 years), microscopic tumor verification occurred less frequently (91-88-87-77%, respectively, P = 0.009) and OS diminished (median 25-26-19-16 weeks, P = 0.003). After adjustment for confounding factors, worse survival of treated patients ≥75 years persisted. Despite limited chemotherapy use in elderly age, suggestive of strong selection, elderly patients (≥75 years) who received chemotherapy for metastatic pancreatic cancer exhibited a worse survival compared to younger patients receiving chemotherapy.

19 Article Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study. 2017

Vogel, Jantien A / Rombouts, Steffi J / de Rooij, Thijs / van Delden, Otto M / Dijkgraaf, Marcel G / van Gulik, Thomas M / van Hooft, Jeanin E / van Laarhoven, Hanneke W / Martin, Robert C / Schoorlemmer, Annuska / Wilmink, Johanna W / van Lienden, Krijn P / Busch, Olivier R / Besselink, Marc G. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. · Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, University of Louisville, Louisville, KY, USA. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. m.g.besselink@amc.nl. ·Ann Surg Oncol · Pubmed #28560601.

ABSTRACT: BACKGROUND: Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy. METHODS: This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3 months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors. RESULTS: Of 132 patients with LAPC, 70% (n = 93) started with chemotherapy (46% [n = 61] FOLFIRINOX). After 3 months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n = 16) of patients had Clavien-Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n = 4). With a median follow-up of 24 months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n = 30) was 34, 16, and 15 months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%. CONCLUSION: Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230).

20 Article Stromal SPOCK1 supports invasive pancreatic cancer growth. 2017

Veenstra, Veronique L / Damhofer, Helene / Waasdorp, Cynthia / Steins, Anne / Kocher, Hemant M / Medema, Jan P / van Laarhoven, Hanneke W / Bijlsma, Maarten F. ·Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Academic Medical Center and Cancer Center Amsterdam, The Netherlands. · Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, UK. · Department of Medical Oncology, Academic Medical Center, University of Amsterdam, the Netherlands. ·Mol Oncol · Pubmed #28486750.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is marked by an abundant stromal deposition. This stroma is suspected to harbor both tumor-promoting and tumor-suppressing properties. This is underscored by the disappointing results of stroma targeting in clinical studies. Given the complexity of tumor-stroma interaction in PDAC, there is a need to identify the stromal proteins that are predominantly tumor-promoting. One possible candidate is SPOCK1 that we previously identified in a screening effort in PDAC. We extensively mined PDAC gene expression datasets, and used species-specific transcript analysis in mixed-species models for PDAC to study the patterns and driver mechanisms of SPOCK1 expression in PDAC. Advanced organotypic coculture models with primary patient-derived tumor cells were used to further characterize the function of this protein. We found SPOCK1 expression to be predominantly stromal. Expression of SPOCK1 was associated with poor disease outcome. Coculture and ligand stimulation experiments revealed that SPOCK1 is expressed in response to tumor cell-derived transforming growth factor-beta. Functional assessment in cocultures demonstrated that SPOCK1 strongly affects the composition of the extracellular collagen matrix and by doing so, enables invasive tumor cell growth in PDAC. By defining the expression pattern and functional properties of SPOCK1 in pancreatic cancer, we have identified a stromal mediator of extracellular matrix remodeling that indirectly affects the aggressive behavior of PDAC cells. The recognition that stromal proteins actively contribute to the protumorigenic remodeling of the tumor microenvironment should aid the design of future clinical studies to target specific stromal targets.

21 Article Addition of MRI for CT-based pancreatic tumor delineation: a feasibility study. 2017

Gurney-Champion, Oliver J / Versteijne, Eva / van der Horst, Astrid / Lens, Eelco / Rütten, Heidi / Heerkens, Hanne D / Paardekooper, Gabriel M R M / Berbee, Maaike / Rasch, Coen R N / Stoker, Jaap / Engelbrecht, Marc R W / van Herk, Marcel / Nederveen, Aart J / Klaassen, Remy / van Laarhoven, Hanneke W M / van Tienhoven, Geertjan / Bel, Arjan. ·a Department of Radiation Oncology, Academic Medical Center , University of Amsterdam , Amsterdam , the Netherlands. · b Department of Radiology, Academic Medical Center , University of Amsterdam , Amsterdam , the Netherlands. · c Department of Radiation Oncology , Radboud University Medical Center , Nijmegen , the Netherlands. · d Department of Radiotherapy , University Medical Center Utrecht , Utrecht , the Netherlands. · e Department of Radiotherapy , Isala Clinics Zwolle , Zwolle , the Netherlands. · f Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology , Maastricht University Medical Centre , Maastricht , the Netherlands. · g Faculty of Biology, Medicine & Health, Division of Cancer Sciences , University of Manchester and Christie NHS Trust , Manchester , UK. · h Department of Medical Oncology, Academic Medical Center , University of Amsterdam , Amsterdam , the Netherlands. ·Acta Oncol · Pubmed #28375667.

ABSTRACT: PURPOSE: To assess the effect of additional magnetic resonance imaging (MRI) alongside the planning computed tomography (CT) scan on target volume delineation in pancreatic cancer patients. MATERIAL AND METHODS: Eight observers (radiation oncologists) from six institutions delineated the gross tumor volume (GTV) on 3DCT, and internal GTV (iGTV) on 4DCT of four pancreatic cancer patients, while MRI was available in a second window (CT + MRI). Variations in volume, generalized conformity index (CI RESULTS: The maximum ratios between delineated volumes within a patient were 6.1 and 22.4 for the GTV (3DCT) and iGTV (4DCT), respectively. The average (root-mean-square) overall observer variations were SD = 0.41 cm (GTV) and SD = 0.73 cm (iGTV). The mean CI CONCLUSIONS: The availability of MRI images during target delineation of pancreatic cancer on 3DCT and 4DCT resulted in smaller target volumes and reduced the interobserver variation in six out of eight delineated structures.

22 Article The use of adjuvant chemotherapy for pancreatic cancer varies widely between hospitals: a nationwide population-based analysis. 2016

Bakens, Maikel J / van der Geest, Lydia G / van Putten, Magreet / van Laarhoven, Hanneke W / Creemers, Geert-Jan / Besselink, Marc G / Lemmens, Valery E / de Hingh, Ignace H / Anonymous1051013. ·Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. · Netherlands Cancer Registry, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Oncology, Catharina Hospital, Eindhoven, the Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. Ignace.d.hingh@catharinaziekenhuis.nl. ·Cancer Med · Pubmed #27671746.

ABSTRACT: Adjuvant chemotherapy after pancreatoduodenectomy for pancreatic cancer is currently considered standard of care. In this nationwide study, we investigated which characteristics determine the likelihood of receiving adjuvant chemotherapy and its effect on overall survival. The data were obtained from the Netherlands Cancer Registry. All patients alive 90 days after pancreatoduodenectomy for M

23 Article Revisiting the Potential of Alternating Repetition Time Balanced Steady-State Free Precession Imaging of the Abdomen at 3 T. 2016

Gurney-Champion, Oliver J / Nederveen, Aart J / Klaassen, Remy / Engelbrecht, Marc R / Bel, Arjan / van Laarhoven, Hanneke W M / Stoker, Jaap / Goncalves, Sonia I. ·From the Departments of *Radiology, †Radiation Oncology, and ‡Medical Oncology, and §Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, the Netherlands; and ∥Institute for Biomedical Imaging and Life Sciences, University of Coimbra, Coimbra, Portugal. ·Invest Radiol · Pubmed #27071023.

ABSTRACT: OBJECTIVE: The aim was to investigate the value of optimized 3-dimensional alternating repetition time balanced steady-state free precession (ATR-SSFP), as an alternative to conventional segmented balanced steady-state free precession (bSSFP) with fat suppression prepulse (FS-bSSFP), in single breath-hold abdominal magnetic resonance imaging at 3 T. METHODS: Bloch simulations were performed to determine the optimal flip angle (FA = 1-90 degrees) and τ (1-3) with respect to signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between abdominal organs for ATR-SSFP. These were corroborated by phantom measurements for different T1/T2 values (5-47) as well as in a healthy volunteer. In addition, fat suppression efficiency was studied using phantom and volunteer measurements. The effect of resolution on image quality was studied in a healthy volunteer. Using the optimal settings, ATR-SSFP images as well as FS-bSSFP images were obtained in 15 pancreatic cancer patients. For 10 structures of interest, the signal ratio with respect to the pancreas was computed and compared between both sequences. Finally, 10 items on image quality (fat suppression, artifacts, and sharpness) and tissue conspicuity (ducts, vessels, and duodenum) were scored by 2 abdominal radiologists for both image sequences. RESULTS: The results of simulations, phantom measurements, and volunteer measurements showed that, considering scan time, fat suppression, and clinical relevance, the ideal settings for ATR-SSFP were as follows: τ = 3; TR1 = 3.46 milliseconds; radiofrequency phase cycling 0, 180, 180, 0 degrees; and FA = 13-16 degrees (highest SNR) and 24-26 degrees (highest CNR). The optimized feasible additional settings implemented for patient scans were FA = 18 degrees and resolution = 1.4 × 1.4 × 1.4 mm. In patients, the signal ratios of both ATR-SSFP and FS-bSSFP were comparable and had a T2-like contrast behavior, although more accentuated in ATR-SSFP. The ATR-SSFP scored significantly higher than FS-bSSFP for 9 of 10 items scored. CONCLUSIONS: For single breath-hold abdominal imaging at 3 T, ATR-SSFP performs best with τ = 3 and an FA between 13 degrees (highest SNR) and 26 degrees (highest CNR). The scoring of both abdominal radiologists indicated that, at τ = 3, FA = 18 degrees, and 1.4 × 1.4 × 1.4 mm resolution, ATR-SSFP was preferred over conventional FS-bSSFP with similar settings.

24 Article Volume matters in the systemic treatment of metastatic pancreatic cancer: a population-based study in the Netherlands. 2016

Haj Mohammad, N / Bernards, N / Besselink, M G H / Busch, O R / Wilmink, J W / Creemers, G J M / De Hingh, I H J T / Lemmens, V E P P / van Laarhoven, H W M. ·Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands. n.hajmohammad@amc.nl. · Department of Medical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. · Department of Research, Comprehensive Cancer Organisation The Netherlands/Netherlands Cancer Registry, Godebaldkwartier 419, 3511 DT, Utrecht, The Netherlands. · Department of Surgery, Academic Medical Center, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands. · Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. · Department of Public Health, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. ·J Cancer Res Clin Oncol · Pubmed #26995276.

ABSTRACT: PURPOSE: In pancreatic surgery, a relation between surgical volume and postoperative mortality and overall survival (OS) has been recognized, with high-volume centers reporting significantly better survival rates. We aimed to explore the influence of hospital volume on administration of palliative chemotherapy and OS in the Netherlands. METHODS: Patients diagnosed between 2007 and 2011 with metastatic pancreatic cancer were identified in the Netherlands Cancer Registry. Three types of high-volume centers were defined: high-volume (1) incidence center, based on the number of patients diagnosed with metastatic pancreatic cancer, (2) treatment center based on number of patients with metastatic pancreatic cancer who started treatment with palliative chemotherapy and (3) surgical center based on the number of resections with curative intent for pancreatic cancer. Independent predictors of administration of palliative chemotherapy were evaluated by means of logistic regression analysis. The multivariable Cox proportional hazard model was used to assess the impact of being diagnosed or treated in high-volume centers on survival. RESULTS: A total of 5385 patients presented with metastatic pancreatic cancer of which 24 % received palliative chemotherapy. Being treated with chemotherapy in a high-volume chemotherapy treatment center was associated with improved survival (HR 0.76, 95 % CI 0.67-0.87). Also, in all patients with metastatic pancreatic cancer, being diagnosed in a high-volume surgical center was associated with improved survival (HR 0.74, 95 % CI 0.66-0.83). CONCLUSIONS: Hospital volume of palliative chemotherapy for metastatic pancreatic cancer was associated with improved survival, demonstrating that a volume-outcome relationship, as described for pancreatic surgery, may also exist for pancreatic medical oncology.

25 Article Developing a core set of patient-reported outcomes in pancreatic cancer: A Delphi survey. 2016

Gerritsen, Arja / Jacobs, Marc / Henselmans, Inge / van Hattum, Jons / Efficace, Fabio / Creemers, Geert-Jan / de Hingh, Ignace H / Koopman, Miriam / Molenaar, I Quintus / Wilmink, Hanneke W / Busch, Olivier R / Besselink, Marc G / van Laarhoven, Hanneke W / Anonymous5130858. ·Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands; Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Medical Psychology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Data Center and Health Outcomes Research Unit, Italian Group for Adult Hematologic Diseases (GIMEMA), Rome, Italy. · Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands. · Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. · Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: h.vanlaarhoven@amc.nl. ·Eur J Cancer · Pubmed #26886181.

ABSTRACT: BACKGROUND: Patient-reported outcomes (PROs) are amongst the most relevant outcome measures in pancreatic cancer care and research. However, it is unknown which out of the numerous PROs are most important to patients and health care professionals (HCPs) in this setting. The aim of this study was to identify a core set of PROs to be incorporated in a nationwide prospective multidisciplinary pancreatic cancer registry. PATIENTS AND METHODS: We performed a two-round Delphi survey among 150 patients diagnosed with pancreatic or periampullary cancer (treated either with curative intent or in palliative setting) and 78 HCPs (surgeons, medical oncologists, gastroenterologists, radiotherapists, nurses, and dietitians) in The Netherlands. In round 1, participants were invited to rate the importance of 53 PROs, which were extracted from 17 different PRO measures and grouped into global domains, on a 1-9 Likert scale. PROs rated as very important (score 7-9) by the majority (≥ 80%) of curative and/or palliative patients as well as HCPs were considered sufficiently important to be incorporated in the core set. PROs not fulfilling these criteria in round 1 were presented again to the participants in round 2 along with individual and group feedback. RESULTS: A total of 97 patients (94%) in curative-intent setting, 38 patients (81%) in palliative setting and 73 HCPs (94%) completed both rounds 1 and 2. After the first round, 7 PROs were included in the core set: general quality of life, general health, physical ability, satisfaction with caregivers, satisfaction with services and care organisation, coping and defecation. After the second round, 10 additional PROs were added: appetite, ability to work/do usual activities, medication use, weight changes, fatigue, negative feelings, positive feelings, fear of recurrence, relationship with partner/family, and pancreatic enzyme replacement therapy use. CONCLUSION: This study provides a core set of PROs selected by patients and HCPs, which may be incorporated in pancreatic cancer care and research. Validation outside the Dutch context is recommended for generalisation and use in international studies.

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