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Pancreatic Neoplasms: HELP
Articles by Chris Verslype
Based on 10 articles published since 2010
(Why 10 articles?)

Between 2010 and 2020, C. Verslype wrote the following 10 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 Guideline New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. 2012

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

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

3 Review Scleroderma-like cutaneous lesions during treatment with paclitaxel and gemcitabine in a patient with pancreatic adenocarcinoma. Review of literature. 2018

Verhulst, Lien / Noë, Esther / Morren, Marie-Anne / Verslype, Chris / Van Cutsem, Eric / Van den Oord, Joost J / De Haes, Petra. ·Department of Dermatology, AZ Delta Hospital and private practice, Roeselare, Belgium. · Department of Dermatology, UZ Leuven, Leuven, Belgium. · Department of Digestive Oncology, UZ Leuven and KULeuven, Leuven, Belgium. · Department of Pathology, UZ Leuven, Leuven, Belgium. ·Int J Dermatol · Pubmed #29938783.

ABSTRACT: BACKGROUND: Chemotherapy-induced skin sclerosis is generally not associated with other manifestations of systemic sclerosis. It is featured by skin sclerosis without visceral involvement (i.e., Raynaud's phenomenon, esophageal dysmotility, and pulmonary fibrosis), temporal association with chemotherapy administration, and the absence of detectable autoantibodies. The clinical course of scleroderma-like changes induced by paclitaxel or gemcitabine are refractory to treatment and commonly progressive, even after discontinuation of the triggering drugs. OBJECTIVE: Report a case of scleroderma-like cutaneous lesions during combination treatment with nab-paclitaxel and gemcitabine in a patient with pancreatic adenocarcinoma and determine other published cases of scleroderma-like skin changes following treatment with nab-paclitaxel, paclitaxel, or gemcitabine through the period from 2002 to 2018. METHODS: Literature search from the year 2002 onwards using combinations of "Scleroderma" AND "paclitaxel," AND/OR "gemcitabine." RESULTS: Additional to our case report we reviewed 14 other cases in the literature. Most of these cases share three prominent features: skin sclerosis without systemic involvement, temporal association with chemotherapy administration, and absence of detectable scleroderma-specific autoantibodies. CONCLUSION: To our knowledge, this is the first case report of scleroderma-like cutaneous lesions during combination treatment with nab-paclitaxel and gemcitabine in a patient with pancreatic adenocarcinoma. However, given the current literature, these scleroderma-like lesions are most likely induced by nab-paclitaxel or paclitaxel, rather than by gemcitabine.

4 Clinical Trial Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. 2018

Van Cutsem, Eric / Hidalgo, Manuel / Canon, Jean-Luc / Macarulla, Teresa / Bazin, Igor / Poddubskaya, Elena / Manojlovic, Nebojsa / Radenkovic, Dejan / Verslype, Chris / Raymond, Eric / Cubillo, Antonio / Schueler, Armin / Zhao, Charles / Hammel, Pascal. ·Gastroenterology/Digestive Oncology, University Hospitals Gasthuisberg/Leuven & KULeuven, Leuven, Belgium. · Centro Nacional Investigaciones Oncologicas, Madrid, Spain and START Madrid, Madrid, Spain. · Service d'Oncologie-Hématologie, Grand Hopital de Charleroi, Charleroi, Belgium. · Gastrointestinal Cancer Unit, Oncology Department, Vall d'Hebron University Hospital and Institute of Oncology, Barcelona, Spain. · Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center, and I.M. Sechenov First Moscow State Medical University, Moscow, Russia. · Clinic for Gastroenterology and Hepatology, Military Medical Academy of Serbia, Belgrade, Serbia. · First Surgical Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. · Medical Oncology Département, Saint Joseph Hospital, Paris, France. · HM Universitario Sanchinarro, Centro Integral Oncológico Clara Campal (HM-CIOCC), and Departamento de Ciencias Médicas Clínicas, Universidad CEU San Pablo, Madrid, Spain. · Biostatistics, Merck KGaA, Darmstadt, Germany. · Clinical Oncology Early Development, EMD Serono, Billerica, MA. · Digestive Oncology Unit, Hôpital Beaujon, Clichy, France. ·Int J Cancer · Pubmed #29756206.

ABSTRACT: The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m

5 Clinical Trial Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. 2018

Hurwitz, Herbert / Van Cutsem, Eric / Bendell, Johanna / Hidalgo, Manuel / Li, Chung-Pin / Salvo, Marcelo Garrido / Macarulla, Teresa / Sahai, Vaibhav / Sama, Ashwin / Greeno, Edward / Yu, Kenneth H / Verslype, Chris / Dawkins, Fitzroy / Walker, Chris / Clark, Jason / O'Reilly, Eileen M. ·Duke University Medical Center, Campus mail 439 Seeley-mudd Bldg, 10 Bryan Searle Drive, Duke University M, Durham, NC, 27710, USA. · Clinical Digestive Oncology, University Hospitals Leuven and KU Leuven, UZ Herestraat 49, 3000, Leuven, Belgium. · Sarah Cannon Research Institute/Tennessee Oncology, 250 25th Ave N, Nashville, TN, 37203, USA. · Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA. · Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan. · School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Street, Beitou District, Taipei, 112, Taiwan. · Pontificia Universidad Católica de Chile, Av Libertador Bernardo O'Higgins, 340, Santiago, Región Metropolitana, Chile. · Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital (HUVH), Passeig de la Vall d'Hebron, 119-129, 08035, Barcelona, Spain. · Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Cancer Center Floor B1 Reception E, 1500 E Medical Center Dr SPC 5912, Ann Arbor, MI, 48109-5912, USA. · Thomas Jefferson University Hospital, 925 Chestnut Street, Suite 320A, Philadelphia, PA, 19107, USA. · Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, MMC 480, Minneapolis, MN, 55455, USA. · Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA. · Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE, 19803, USA. · Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA. oreillye@mskcc.org. · Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA. oreillye@mskcc.org. ·Invest New Drugs · Pubmed #29508247.

ABSTRACT: Background Ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor, plus capecitabine improved overall survival (OS) vs capecitabine in a subgroup analysis of patients with metastatic pancreatic cancer and systemic inflammation (C-reactive protein [CRP] >13 mg/dL) in the randomized phase II RECAP study. We report results from two randomized phase III studies, JANUS 1 (NCT02117479) and JANUS 2 (NCT02119663). Patients and Methods Adults with advanced/metastatic pancreatic cancer, one prior chemotherapy regimen and CRP >10 mg/L were randomized 1:1 (stratified by modified Glasgow Prognostic Score [1 vs 2] and Eastern Cooperative Oncology Group performance status [0/1 vs 2]) to 21-day cycles of ruxolitinib 15 mg twice daily plus capecitabine 2000 mg/m

6 Clinical Trial A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. 2016

Fazio, Nicola / Buzzoni, Roberto / Baudin, Eric / Antonuzzo, Lorenzo / Hubner, Richard A / Lahner, Harald / DE Herder, Wouter W / Raderer, Markus / Teulé, Alexandre / Capdevila, Jaume / Libutti, Steven K / Kulke, Matthew H / Shah, Manisha / Dey, Debarshi / Turri, Sabine / Aimone, Paola / Massacesi, Cristian / Verslype, Chris. ·European Institute of Oncology, Milan, Italy nicola.fazio@ieo.it. · IRCCS National Tumor Institute, Milan, Italy. · Institut Gustave Roussy, Villejuif, France. · Careggi University Hospital, Florence, Italy. · The Christie NHS Foundation Trust, Manchester, U.K. · University of Duisburg-Essen, Essen, Germany. · Erasmus MC, Rotterdam, the Netherlands. · University Hospital of Vienna, Vienna, Austria. · Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. · Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY, U.S.A. · Dana-Farber Cancer Institute, Boston, MA, U.S.A. · The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, U.S.A. · Novartis Healthcare Private Limited, Hyderabad, India. · Novartis Pharma AG, Basel, Switzerland. · Novartis Oncology, Paris, France. · University Hospitals Leuven, Leuven, Belgium. ·Anticancer Res · Pubmed #26851029.

ABSTRACT: BACKGROUND: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436). PATIENTS AND METHODS: In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progression-free survival (PFS) rate of ≥60% in stage 1. RESULTS: As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%). CONCLUSION: BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2.

7 Article A new intraductal radiofrequency ablation device for inoperable biliopancreatic tumors complicated by obstructive jaundice: the IGNITE-1 study. 2017

Laleman, Wim / van der Merwe, Schalk / Verbeke, Len / Vanbeckevoort, Dirk / Aerts, Raymond / Prenen, Hans / Van Cutsem, Eric / Verslype, Chris. ·Department of Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. · Department of Radiology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. · Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium. ·Endoscopy · Pubmed #28732391.


8 Article Clinical characteristics and management of insulin-producing neuroendocrine carcinomas. 2016

Lowette, K / Verslype, C / Van Cutsem, E. · ·Acta Gastroenterol Belg · Pubmed #27821028.

ABSTRACT: BACKGROUND AND AIMS: Due to rarity of insulin-producing pancreatic neuroendocrine carcinomas, no large, nor randomized studies of the clinical course, treatment options and outcome are available. Therefore, we want to share our personal experience and we retrospectively reviewed a cohort of five patients. PATIENTS AND METHODS: This study reports on the clinical characteristics, disease course, management and outcome of five patients with an advanced pancreatic neuroendocrine carcinoma with insulin production, which we followed recently in our center (between 2006 and 2015). Extraordinary for our cohort is that, except for one patient, which was diagnosed with a de novo malignant insulinoma, all other patients were diagnosed with a non-functional pancreatic neuroendocrine tumor which evolved during the disease course to a malignant insulinoma. RESULTS: Although various treatment strategies, both surgical and medical, are used to prolong survival and prevent hypoglycemic events, long-term prognosis of these patients remains poor, especially after transformation of a non-functional pancreatic neuroendocrine tumor to an insulin-producing neuroendocrine carcinoma. Of all five patients, only one is still alive, the other four died 25, 17, 3 and 1 month(s) after diagnosis of the malignant insulinoma. In general, prognosis is determined by early diagnosis and treatment, and by resectability of the tumor and its biological behavior. CONCLUSION: Management of a malignant insulinoma is very challenging and a better understanding of the underlying mechanisms of this disease entity and its biological behavior is absolutely necessary to improve diagnostic tools, treatment and outcome in the future. (Acta gastro-enterol. belg., 2016, 79, 321-327).

9 Article Successful application of endoscopic ultrasound-guided fine needle biopsy to establish pancreatic patient-derived tumor xenografts: a pilot study. 2016

Hermans, Els / Van der Merwe, Schalk W / Depreeuw, Jeroen / Dekervel, Jeroen / Radaelli, Enrico / Roskams, Tania / van Pelt Jos, Jos / Topal, Baki / Verslype, Chris / Prenen, Hans / Van Steenbergen, Werner / Nevens, Frederik / Lambrechts, Diether / Amant, Frédéric. ·Laboratory of Gynecologic Oncology, Department of Oncology, University of Leuven, Leuven, Belgium. · Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium. · Center for the Biology of Disease, KU Leuven Center for Human Genetics - InfraMouse, VIB, University of Leuven, Leuven, Belgium. · Division of Translational Cell & Tissue Research, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium. · Department of Abdominal Surgery, University of Leuven, Leuven, Belgium. · Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium. ·Endoscopy · Pubmed #27626319.


10 Article VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. 2012

Lambrechts, Diether / Claes, Bart / Delmar, Paul / Reumers, Joke / Mazzone, Massimiliano / Yesilyurt, Betül T / Devlieger, Roland / Verslype, Chris / Tejpar, Sabine / Wildiers, Hans / de Haas, Sanne / Carmeliet, Peter / Scherer, Stefan J / Van Cutsem, Eric. ·Laboratory of Translational Genetics, Vesalius Research Center, VIB and KULeuven, Leuven, Belgium. diether.lambrechts@vibkuleuven.be ·Lancet Oncol · Pubmed #22608783.

ABSTRACT: BACKGROUND: No biomarkers that could guide patient selection for treatment with the anti-VEGF monoclonal antibody bevacizumab have been identified. We assessed whether genetic variants in the VEGF pathway could act as biomarkers for bevacizumab treatment outcome. METHODS: We investigated DNA from white patients from two phase 3 randomised studies. In AViTA, patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine and erlotinib plus either bevacizumab or placebo. In AVOREN, patients with metastatic renal-cell carcinoma were randomly assigned to receive interferon alfa-2a plus either bevacizumab or placebo. We assessed the correlation of 138 SNPs in the VEGF pathway with progression-free survival and overall survival in a subpopulation of patients from AViTA. Significant findings were confirmed in a subpopulation of patients from AVOREN and functionally studied at the molecular level. FINDINGS: We investigated DNA of 154 patients from AViTA, of whom 77 received bevacizumab, and 110 patients from AVOREN, of whom 59 received bevacizumab. Only rs9582036, a SNP in VEGF receptor 1 (VEGFR1 or FLT1), was significantly associated with overall survival in the bevacizumab group of AViTA after correction for multiplicity (per-allele hazard ratio [HR] 2·1, 95% CI 1·45-3·06, p=0·00014). This SNP was also associated with progression-free survival (per-allele HR 1·89, 1·31-2·71, p=0·00081) in bevacizumab-treated patients from AViTA. AC and CC carriers of this SNP exhibited HRs for overall survival of 2·0 (1·19-3·36; p=0·0091) and 4·72 (2·08-10·68; p=0·0002) relative to AA carriers. No effects were seen in placebo-treated patients and a significant genotype by treatment interaction (p=0·041) was recorded, indicating that the VEGFR1 locus containing this SNP serves as a predictive marker for bevacizumab treatment outcome in AViTA. Fine-mapping experiments of this locus identified rs7993418, a synonymous SNP affecting tyrosine 1213 in the VEGFR1 tyrosine-kinase domain, as the functional variant underlying the association. This SNP causes a shift in codon usage, leading to increased VEGFR1 expression and downstream VEGFR1 signalling. This VEGFR1 locus correlated significantly with progression-free survival (HR 1·81, 1·08-3·05; p=0·033) but not overall survival (HR 0·91, 0·45-1·82, p=0·78) in the bevacizumab group in AVOREN. INTERPRETATION: A locus in VEGFR1 correlates with increased VEGFR1 expression and poor outcome of bevacizumab treatment. Prospective assessment is underway to validate the predictive value of this novel biomarker. FUNDING: F Hoffmann-La Roche.