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Pancreatic Neoplasms: HELP
Articles by Johanna W. Wilmink
Based on 19 articles published since 2008
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Between 2008 and 2019, J. W. Wilmink wrote the following 19 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 Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. 2018

Versteijne, E / Vogel, J A / Besselink, M G / Busch, O R C / Wilmink, J W / Daams, J G / van Eijck, C H J / Groot Koerkamp, B / Rasch, C R N / van Tienhoven, G / Anonymous2681013. ·Department of Radiation Oncology, Cancer Centre Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Surgery, Cancer Centre Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Centre Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. · Medical Library, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Centre, Erasmus University Rotterdam, Rotterdam, The Netherlands. ·Br J Surg · Pubmed #29708592.

ABSTRACT: BACKGROUND: Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. METHODS: MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. RESULTS: In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. CONCLUSION: Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.

3 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.

4 Review Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer. 2016

Rombouts, Steffi J / Walma, Marieke S / Vogel, Jantien A / van Rijssen, Lennart B / Wilmink, Johanna W / Mohammad, Nadia Haj / van Santvoort, Hjalmar C / Molenaar, I Quintus / Besselink, Marc G. ·Department of Surgery, University Medical Centre Utrecht Cancer Center, Utrecht, The Netherlands. · Department of Surgery, G4-196, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Medical Oncology, University Medical Centre Utrecht Cancer Center, Utrecht, The Netherlands. · Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands. · Department of Surgery, G4-196, Academic Medical Centre, Amsterdam, The Netherlands. m.g.besselink@amc.uva.nl. ·Ann Surg Oncol · Pubmed #27370653.

ABSTRACT: BACKGROUND: FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC. METHODS: The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate. RESULTS: Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity. CONCLUSIONS: Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.

5 Clinical Trial Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial. 2015

Kordes, Sil / Pollak, Michael N / Zwinderman, Aeilko H / Mathôt, Ron A / Weterman, Mariëtte J / Beeker, Aart / Punt, Cornelis J / Richel, Dick J / Wilmink, Johanna W. ·Department of Medical Oncology, Academic Medical Centre, Amsterdam, Netherlands. · Department of Oncology, McGill University, Montreal, QC, Canada. · Department of Statistics, Academic Medical Centre, Amsterdam, Netherlands. · Department of Hospital Pharmacy, Academic Medical Centre, Amsterdam, Netherlands. · Department of Internal Medicine, Spaarne Hospital, Hoofddorp, Netherlands. · Department of Medical Oncology, Academic Medical Centre, Amsterdam, Netherlands. Electronic address: j.w.wilmink@amc.uva.nl. ·Lancet Oncol · Pubmed #26067687.

ABSTRACT: BACKGROUND: In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication. METHODS: We did this double-blind, randomised, placebo-controlled phase 2 trial at four centres in the Netherlands. Patients aged 18 years or older with advanced pancreatic cancer were randomly assigned (1:1), via a permutated computer-generated block allocation scheme (block size of six) to receive intravenous gemcitabine (1000 mg/m(2)) on days 1, 8, and 15 every 4 weeks and oral erlotinib (100mg) once daily in combination with either oral metformin or placebo twice daily. Metformin dose was escalated from 500 mg (in the first week) to 1000 mg twice daily in the second week. Randomisation was stratified by hospital, diabetes status, and tumour stage. The primary endpoint was overall survival at 6 months in the intention-to-treat population. This trial is complete and is registered with ClinicalTrials.gov, number NCT01210911. FINDINGS: Between May 31, 2010, and Jan 3, 2014, we randomly assigned 121 patients to receive gemcitabine and erlotinib with either placebo (n=61) or metformin (n=60). Overall survival at 6 months was 63·9% (95% CI 51·9-75·9) in the placebo group and 56·7% (44·1-69·2) in the metformin group (p=0·41). There was no difference in overall survival between groups (median 7·6 months [95% CI 6·1-9·1] vs 6·8 months [95% CI 5·1-8·5] in the metformin group; hazard ratio [HR] 1·056 [95% CI 0·72-1·55]; log-rank p=0·78). The most frequent grade 3-4 toxic effects were neutropenia (15 [25%] patients in placebo group vs 15 [25%] in metformin group), skin rash (six [10%] vs four [7%]), diarrhoea (three [5%] vs six [10%]), and fatigue (two [3%] vs six [10%]). INTERPRETATION: Addition of a conventional anti-diabetic dose of metformin does not improve outcome in patients with advanced pancreatic cancer treated with gemcitabine and erlotinib. Future research should include studies of more potent biguanides, and should focus on patients with hyperinsulinaemia and patients with tumours showing markers of sensitivity to energetic stress, such as loss of function of AMP kinase, a key regulator of cellular energy homoeostasis. FUNDING: Academic Medical Centre, Amsterdam, and The Terry Fox Foundation, Vancouver, Canada.

6 Clinical Trial Phase I Clinical Trial to Determine the Feasibility and Maximum Tolerated Dose of Panitumumab to Standard Gemcitabine-Based Chemoradiation in Locally Advanced Pancreatic Cancer. 2015

van Zweeden, Annette A / van der Vliet, Hans J / Wilmink, Johanna W / Meijerink, Martijn R / Meijer, Otto W M / Bruynzeel, Anna M E / van Tienhoven, Geertjan / Giovannetti, Elisa / Kazemier, Geert / Jacobs, Maarten A J M / Verheul, Henk M W. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. · Department of Radiation Oncology, VU University Medical Center, Amsterdam, the Netherlands. · Department of Radiation Oncology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands. · Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands. · Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands. h.verheul@vumc.nl. ·Clin Cancer Res · Pubmed #26056353.

ABSTRACT: PURPOSE: Epidermal growth factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the nonoverlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety, and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer (LAPC). EXPERIMENTAL DESIGN: Patients with LAPC and WHO performance status 0 to 1 were treated with weekly panitumumab at four dose levels (1-2.5 mg/kg), combined with weekly gemcitabine 300 mg/m(2) and radiotherapy (50.4 Gy in 28 fractions) for 6 weeks, followed by gemcitabine 1,000 mg/m(2) weekly for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. Each cohort was monitored during the combination therapy to establish dose limiting toxicity. Tumor evaluation was performed after CRT and during gemcitabine monotherapy. RESULTS: Fourteen patients were enrolled; 14 were evaluable for toxicity and 13 for response. The MTD for panitumumab was 1.5 mg/kg. Three of the 6 patients, treated at MTD, experienced grade 3 adverse events during the combination therapy; neutropenia (n = 2; 33%), fatigue (n = 1; 17%), nausea (n = 1; 17%), and vomiting (n = 1; 17%). Partial response was achieved by 3 patients (23%), 1 in each dose cohort. Median progression free survival of the three cohorts together was 8.9 months. CONCLUSIONS: The addition of panitumumab to gemcitabine-based chemoradiotherapy in LAPC has manageable toxicity and potential clinical efficacy.

7 Clinical Trial Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer. 2015

Kordes, S / Klümpen, H J / Weterman, M J / Schellens, J H M / Richel, D J / Wilmink, J W. ·Department of Medical Oncology, Academic Medical Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands, silkordes@gmail.com. ·Cancer Chemother Pharmacol · Pubmed #25822310.

ABSTRACT: PURPOSE: The combination of an mTOR inhibitor with 5-fluorouracil-based anticancer therapy is attractive because of preclinical evidence of synergy between these drugs. According to our phase I study, the combination of capecitabine and everolimus is safe and feasible, with potential activity in pancreatic cancer patients. METHODS: Patients with advanced adenocarcinoma of the pancreas were enrolled. Eligible patients had a WHO performance status 0-2 and adequate hepatic and renal functions. The treatment regimen consisted of capecitabine 1000 mg/m(2) BID day 1-14 and everolimus 10 mg daily (5 mg BID) in a continuous 21-day schedule. Tumor assessment was performed with CT-scan every three cycles. Primary endpoint was response rate (RR) according to RECIST 1.0. Secondary endpoints were progression-free survival, overall survival and 1-year survival rate. RESULTS: In total, 31 patients were enrolled. Median (range) treatment duration with everolimus was 76 days (1-431). Principal grade 3/4 toxicities were hyperglycemia (45 %), hand-foot syndrome (16 %), diarrhea (6 %) and mucositis (3 %). Prominent grade 1/2 toxicities were anemia (81 %), rash (65 %), mucositis (58 %) and fatigue (55 %). RR was 6 %. Ten patients (32 %) had stable disease resulting in a disease control rate of 38 %. Median overall survival was 8.9 months (95 % CI 4.6-13.1). Progression-free survival was 3.6 months (95 % CI 1.9-5.3). CONCLUSIONS: The oral regimen with the combination of capecitabine and everolimus is a moderately active treatment for patients with advanced pancreatic cancer, with an acceptable toxicity profile at the applied dose level.

8 Clinical Trial A phase I/II, non-randomized, feasibility/safety and efficacy study of the combination of everolimus, cetuximab and capecitabine in patients with advanced pancreatic cancer. 2013

Kordes, Sil / Richel, Dick J / Klümpen, Heinz-Josef / Weterman, Mariëtte J / Stevens, Arnoldus J W M / Wilmink, Johanna W. ·Department of Medical Oncology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. s.kordes@amc.uva.nl ·Invest New Drugs · Pubmed #22367239.

ABSTRACT: BACKGROUND: Improvements in knowledge of molecular mechanisms in cancer are the basis for new studies combining chemotherapy with targeted drugs. Inhibition of the epidermal growth factor receptor (EGFR) by erlotinib or cetuximab has limited or no activity, respectively, in pancreatic cancer. The crosstalk between EGFR and mammalian target of rapamycin (mTOR) pathways is a potential mechanism of resistance; therefore we conducted a study to explore safety and efficacy of multiple pathway inhibition by cetuximab and everolimus in combination with capecitabine. METHODS: Safety and efficacy of fixed standard dose cetuximab in combination with various dose levels of everolimus (5-10 mg/day) and capecitabine (600-800 mg/m(2) bid, 2 weeks every 3 weeks) were investigated in a phase I/II study in patients with advanced pancreatic cancer. The primary endpoint was objective response. RESULTS: Sixteen patients were treated in the phase I part at two dose levels. Mucositis, rash and hand-foot syndrome were dose-limiting toxicities. Dose level 1 (everolimus 5 mg/day, capecitabine 600 mg/m(2) bid for 2 weeks every 3 weeks and cetuximab 250 mg/m(2) weekly) was considered the maximum tolerated dose (MTD). Of 31 patients in the phase II part, partial response was documented in two patients (6.5%) and five (16.1%) had stable disease. Median overall survival was 5.0 months (CI 3.1-6.8). CONCLUSION: The schedule of capecitabine, everolimus and cetuximab resulted in considerable epidermal and mucosal toxicities and prevented escalation to optimal dose levels. Because of toxicity and low efficacy this treatment combination cannot be recommended for treatment in pancreatic cancer patients.

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 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.

12 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.

13 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

14 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.

15 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).

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 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.

18 Article Protease-activated receptor-1 drives pancreatic cancer progression and chemoresistance. 2014

Queiroz, Karla C S / Shi, Kun / Duitman, JanWillem / Aberson, Hella L / Wilmink, Johanna W / van Noesel, Carel J M / Richel, Dick J / Spek, C Arnold. ·Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ·Int J Cancer · Pubmed #24436106.

ABSTRACT: Protease activated receptor (PAR)-1 expression in tumor cells is associated with disease progression and overall survival in a variety of cancers of epithelial origin; however, the importance of PAR-1 in the tumor microenvironment remains unexplored. Utilizing an orthotopic pancreatic cancer model in which tumor cells are PAR-1 positive whereas stromal cells are PAR-1 negative, we show that PAR-1 expression in the microenvironment drives progression and induces chemoresistance of pancreatic cancer. PAR-1 enhances monocyte recruitment into the tumor microenvironment by regulating monocyte migration and fibroblast dependent chemokine production thereby inducing chemoresistance. Overall, our data identify a novel role of PAR-1 in the pancreatic tumor microenvironment and suggest that PAR-1 may be an attractive target to reduce drug resistance in pancreatic cancer.

19 Minor The Khorana score for the prediction of venous thromboembolism in patients with pancreatic cancer. 2017

van Es, N / Franke, V F / Middeldorp, S / Wilmink, J W / Büller, H R. ·Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: n.vanes@amc.nl. · Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. ·Thromb Res · Pubmed #28002757.

ABSTRACT: BACKGROUND: The Khorana score is a clinical prediction score developed to identify ambulatory cancer patients at high risk of venous thromboembolism (VTE), who may be eligible for thromboprophylaxis. This score has been validated in various populations with cancer, but its performance in patients with pancreatic cancer is less clear. PATIENTS AND METHODS: This is a single center, retrospective cohort study in which consecutive, ambulatory patients with pancreatic adenocarcinoma, who started neoadjuvant or palliative chemotherapy at our center between 2003 and 2014 were included. At baseline, the Khorana score classified patients as 'intermediate risk' (2 points) or 'high risk' (≥3 points) for VTE. The primary outcome was the composite of objectively confirmed symptomatic or incidental lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE) during 2-year follow-up. RESULTS: The study group comprised 178 patients. The mean age was 62years and 62% had distant metastasis. Overall, 22 of 178 patients (12.4%) developed lower extremity DVT or PE. The estimated cumulative incidence at 6months was 8.2% in 'intermediate risk' patients and 9.5% in the 'high risk' patients (subhazard ratio for first 6months: 1.23; 95% CI: 0.41-3.65). At 2years, the cumulative incidence was higher in 'intermediate risk' patients (15.3%) than in 'high risk' patients (10.1%). CONCLUSIONS: In the present study, the Khorana score was not able to discriminate between pancreatic cancer patients at intermediate risk and high risk of VTE. Physicians should have a low threshold of considering thromboprophylaxis in patients with pancreatic cancer given the high absolute VTE risk.