title: Description of the EuroTARGET cohort: A European collaborative project on TArgeted therapy in renal cell cancer-GEnetic- and tumor-related biomarkers for response and toxicity.
abstract: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort.
  
  
  
  EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses.
  
  
  
  In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5-30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and methylome data (Illumina Infinium HumanMethylation450 BeadChip) were created for 116 RCC tissues (and 23 normal kidney tissues). For 73 out of the 920 patients, all platform data types were generated. In addition, 40 patients were included in a pharmacokinetic/pharmacodynamic phase IV substudy.
  
  
  
  Analysis of EuroTARGET cohort data will contribute to personalization of therapy for patients with mRCC. The extensive clinical data and multiplatform EuroTARGET data will be freely available.
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Loes F M
authors.initials: LFM
authors.lastname: van der Zanden
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Sita H
authors.initials: SH
authors.lastname: Vermeulen
authors.affiliation: deCODE Genetics/Amgen, Reykjavik, Iceland.
authors.forename: Arna
authors.initials: A
authors.lastname: Oskarsdottir
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Jake S F
authors.initials: JSF
authors.lastname: Maurits
authors.affiliation: Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Meta H M
authors.initials: MHM
authors.lastname: Diekstra
authors.affiliation: University of Medicine and Pharmacy Carol Davila, Bucaresti, Romania, Bucuresti, Romania.
authors.forename: Valentin
authors.initials: V
authors.lastname: Ambert
authors.affiliation: Epidemiology and analyses in public health, Joint Unit 1027, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III Paul Sabatier, Faculty of Medicine, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cambon-Thomsen
authors.affiliation: Medical Oncology Department, Hospital Universitario 12 de Octubre, I+12 Research Institute, (CiberOnc), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Fritsch
authors.affiliation: Medical Oncology, HM Hospitales-Centro Integral Oncológico HM Clara Campal, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Garcia Donas
authors.affiliation: Anatomía Patológica, Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guarch Troyas
authors.affiliation: Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.affiliation: Department of Pathology, University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Christina
authors.initials: C
authors.lastname: Hulsbergen-van de Kaa
authors.affiliation: Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaehde
authors.affiliation: Clinic of Urology and Paediatric Urology, Saarland University, Homburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Junker
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Martinez-Cardus
authors.affiliation: deCODE Genetics/Amgen, Reykjavik, Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Oosterwijk-Wakka
authors.affiliation: University of Medicine and Pharmacy Carol Davila, Bucaresti, Romania, Bucuresti, Romania.
authors.forename: Marius T
authors.initials: MT
authors.lastname: Radu
authors.affiliation: deCODE Genetics/Amgen, Reykjavik, Iceland.
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.affiliation: Hereditary Endorine Cancer Group, Spanish National Cancer Research Centre (CNIO) and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodriguez-Antona
authors.affiliation: CESAR central office, CESAR Central European Society for Anticancer Drug Research-EWIV, Vienna, Austria.
authors.forename: Max
authors.initials: M
authors.lastname: Roessler
authors.affiliation: PamGene International B.V., 's-Hertogenbosch, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Ruijtenbeek
authors.affiliation: deCODE Genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.affiliation: Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Warren
authors.affiliation: Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Lodewyk
authors.initials: L
authors.lastname: Wessels
authors.affiliation: Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. Electronic address: Bart.Kiemeney@radboudumc.nl.
authors.forename: Lambertus A L M
authors.initials: LALM
authors.lastname: Kiemeney
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib; D000077210:Sunitinib
keywords: Biomarker; Genomics; Metastatic renal cell carcinoma; Therapy response; Transcriptomics; Tyrosine kinase inhibitor