Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Hanneke W. M. van Laarhoven
Based on 21 articles published since 2008
||||

Between 2008 and 2019, H. W. van Laarhoven wrote the following 21 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
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 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.

7 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.

8 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.

9 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

10 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.

11 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).

12 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.

13 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.

14 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

15 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.

16 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.

17 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.

18 Article Feasibility and repeatability of PET with the hypoxia tracer [(18)F]HX4 in oesophageal and pancreatic cancer. 2015

Klaassen, Remy / Bennink, Roelof J / van Tienhoven, Geertjan / Bijlsma, Maarten F / Besselink, Marc G H / van Berge Henegouwen, Mark I / Wilmink, Johanna W / Nederveen, Aart J / Windhorst, Albert D / Hulshof, Maarten C C M / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands; LEXOR (Laboratory for Experimental Oncology and Radiobiology), Academic Medical Center, Amsterdam, The Netherlands. Electronic address: r.klaassen@amc.uva.nl. · Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands. · LEXOR (Laboratory for Experimental Oncology and Radiobiology), Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands. ·Radiother Oncol · Pubmed #26049919.

ABSTRACT: BACKGROUND AND PURPOSE: To investigate the feasibility and to determine the repeatability of recurrent [(18)F]HX4 PET scans in patients with oesophageal (EC) and pancreatic (PC) cancer. MATERIALS AND METHODS: 32 patients were scanned in total; seven patients (4 EC/3 PC) were scanned 2, 3 and 4h post injection (PI) of [(18)F]HX4 and 25 patients (15 EC/10 PC) were scanned twice 3.5h PI, on two separate days (median 4, range 1-9days). Maximum tumour to background ratio (TBRmax) and the tumour hypoxic volume (HV) (TBR>1.0) were calculated. Repeatability was assessed using Bland-Altman analysis. Agreement in localization was calculated as the distance between the centres of mass in the HVs. RESULTS: For EC, the TBRmax in the tumour (mean±SD) was 1.87±0.46 with a coefficient of repeatability (CoR) of 0.53 (28% of mean). The HV ranged from 3.4 to 98.8ml with a CoR of 5.1ml. For PC, the TBRmax was 1.72±0.23 with a CoR of 0.27 (16% of mean). The HV ranged from 4.6 to 104.0ml with a CoR of 7.8ml. The distance between the centres of mass in the HV was 2.2±1.3mm for EC and 2.1±1.5mm for PC. CONCLUSIONS: PET scanning with [(18)F]HX4 was feasible in both EC and PC patients. Amount and location of elevated [(18)F]HX4 uptake showed good repeatability, suggesting [(18)F]HX4 PET could be a promising tool for radiation therapy planning and treatment response monitoring in EC and PC patients.

19 Article Blocking Hedgehog release from pancreatic cancer cells increases paracrine signaling potency. 2015

Damhofer, Helene / Veenstra, Veronique L / Tol, Johanna A M G / van Laarhoven, Hanneke W M / Medema, Jan Paul / Bijlsma, Maarten F. ·Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. · Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. · Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands m.f.bijlsma@amc.uva.nl. ·J Cell Sci · Pubmed #25359882.

ABSTRACT: Members of the Hedgehog (Hh) family of morphogens play crucial roles in development but are also involved in the progression of certain types of cancer. Despite being synthesized as hydrophobic dually lipid-modified molecules, and thus being strongly membrane-associated, Hh ligands are able to spread through tissues and act on target cells several cell diameters away. Various mechanisms that mediate Hh release have been discussed in recent years; however, little is known about dispersion of this ligand from cancer cells. Using co-culture models in conjunction with a newly developed reporter system, we were able to show that different members of the ADAM family of metalloproteinases strongly contribute to the release of endogenous bioactive Hh from pancreatic cancer cells, but that this solubilization decreases the potency of cancer cells to signal to adjacent stromal cells in direct co-culture models. These findings imply that under certain conditions, cancer-cell-tethered Hh molecules are the more potent signaling activators and that retaining Hh on the surface of cancer cells can unexpectedly increase the effective signaling range of this ligand, depending on tissue context.

20 Article Ten weeks to live: a population-based study on treatment and survival of patients with metastatic pancreatic cancer in the south of the Netherlands. 2015

Bernards, Nienke / Haj Mohammad, Nadia / Creemers, Geert-Jan / de Hingh, Ignace H J T / van Laarhoven, Hanneke W M / Lemmens, Valery E P P. ·Netherlands Cancer Registry, Comprehensive Cancer Center Netherlands , Eindhoven , The Netherlands. ·Acta Oncol · Pubmed #25263080.

ABSTRACT: BACKGROUND: A large proportion of patients with pancreatic cancer presents with metastatic disease. We conducted a population-based study to evaluate trends in treatment and survival of patients with metastatic pancreatic cancer. METHODS: We included all patients diagnosed with pancreatic cancer between 1993 and 2010 in the South of the Netherlands (N=3099). Multivariable logistic regression analysis was conducted to evaluate trends in treatment with chemotherapy. Crude overall survival according to period of diagnosis was analyzed, and independent risk factors for death were identified. RESULTS: Forty-eight percent of the patients (N=1494) were diagnosed with metastatic disease. The percentage of patients being diagnosed with metastatic disease increased during the study period from 35% in 1993-1996 to 59% in 2009-2010 (p<0.0001). Overall, 18% of these patients received chemotherapy. The prescription of palliative chemotherapy almost tripled from 10% to 27% (p<0.0001). Treatment largely depended on age, ranging from 38% among patients aged <50 years [compared to 60-69 years: adjusted odds ratio (ORadj) 2.5 (95% CI 1.4-4.2)] to 1% among patients aged ≥80 years [compared to 60-69 years: ORadj 0.04 (95% CI 0.0-0.2)]. Patients were more likely to receive chemotherapy if they had a high socioeconomic status [ORadj 2.0 (95% CI 1.3-3.1)], and if diagnosis was pathologically verified [no verification vs. verification: ORadj 0.3 (95% CI 0.2-0.5)]. The administration of chemotherapy varied widely between 10 hospitals (5-34%, p<0.0001). The median overall survival of patients with metastatic pancreatic cancer remained 9-11 weeks. CONCLUSION: A growing proportion of pancreatic cancer patients presented with metastatic disease. Usage of palliative chemotherapy increased over time, but median survival remained 9-11 weeks. In the near future, it should be evaluated if the recently introduced regimens have an impact on population-based survival.

21 Minor Streptozotocin-induced diabetic ketoacidosis in a patient with metastatic islet-cell carcinoma. 2013

Berends, M / Lesterhuis, W J / van Laarhoven, H W M. ·Department of Internal Medicine, Maasziekenhuis Pantein, Boxmeer, the Netherlands. ·Neth J Med · Pubmed #24394744.

ABSTRACT: Here we report a severe life-threatening complication of treatment with streptozotocin in a patient with pancreatic island-cell carcinoma. The patient was admitted to the intensive care unit with severe diabetic ketoacidosis which needed aggressive fluid resuscitation and insulin therapy. We believe it is critical to be aware of the symptoms of diabetic ketoacidosis and monitor glucose levels during streptozotocin treatment.