Loes F M van der Zanden1, Sita H Vermeulen1, Arna Oskarsdottir2, Jake S F Maurits1, Meta H M Diekstra3, Valentin Ambert4, Anne Cambon-Thomsen5, Daniel Castellano6, Achim Fritsch7, Jesus Garcia Donas8, Rosa Guarch Troyas9, Henk-Jan Guchelaar3, Arndt Hartmann10, Christina Hulsbergen-van de Kaa11, Ulrich Jaehde7, Kerstin Junker12, Anna Martinez-Cardus13, Gisli Masson2, Jeannette Oosterwijk-Wakka14, Marius T Radu4, Thorunn Rafnar2, Cristina Rodriguez-Antona15, Max Roessler16, Rob Ruijtenbeek17, Kari Stefansson18, Anne Warren19, Lodewyk Wessels20, Tim Eisen21, Lambertus A L M Kiemeney22, Egbert Oosterwijk14. 1. Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. 2. deCODE Genetics/Amgen, Reykjavik, Iceland. 3. Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands. 4. University of Medicine and Pharmacy Carol Davila, Bucaresti, Romania, Bucuresti, Romania. 5. 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. 6. Medical Oncology Department, Hospital Universitario 12 de Octubre, I+12 Research Institute, (CiberOnc), Madrid, Spain. 7. Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn, Germany. 8. Medical Oncology, HM Hospitales-Centro Integral Oncológico HM Clara Campal, Madrid, Spain. 9. Anatomía Patológica, Complejo Hospitalario de Navarra, Pamplona, Spain. 10. Department of Pathology, University Erlangen-Nürnberg, Erlangen, Germany. 11. Department of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands. 12. Clinic of Urology and Paediatric Urology, Saarland University, Homburg, Germany. 13. Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain. 14. Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands. 15. Hereditary Endorine Cancer Group, Spanish National Cancer Research Centre (CNIO) and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 16. CESAR central office, CESAR Central European Society for Anticancer Drug Research-EWIV, Vienna, Austria. 17. PamGene International B.V., 's-Hertogenbosch, The Netherlands. 18. deCODE Genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 19. Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK. 20. Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 21. Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK. 22. Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. Electronic address: Bart.Kiemeney@radboudumc.nl.
Abstract
OBJECTIVE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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: Daniel J George; Jean-Francois Martini; Michael Staehler; Robert J Motzer; Ahmed Magheli; Frede Donskov; Bernard Escudier; Sherry Li; Michelle Casey; Olga Valota; Brigitte Laguerre; Allan J Pantuck; Hardev S Pandha; Anup Patel; Maria Lechuga; Alain Ravaud Journal: Clin Cancer Res Date: 2018-11-06 Impact factor: 12.531
Authors: Meta H M Diekstra; Jesse J Swen; Loes F M van der Zanden; Sita H Vermeulen; Epie Boven; Ron H J Mathijssen; Koya Fukunaga; Taisei Mushiroda; Fumiya Hongo; Egbert Oosterwijk; Anne Cambon-Thomsen; Daniel Castellano; Achim Fritsch; Jesus Garcia Donas; Cristina Rodriguez-Antona; Rob Ruijtenbeek; Marius T Radu; Tim Eisen; Kerstin Junker; Max Roessler; Ulrich Jaehde; Tsuneharu Miki; Stefan Böhringer; Michiaki Kubo; Lambertus A L M Kiemeney; Henk-Jan Guchelaar Journal: Cancers (Basel) Date: 2022-06-08 Impact factor: 6.575
Authors: Carmen Garrigós; Marta Espinosa; Ana Salinas; Ignacio Osman; Rafael Medina; Miguel Taron; Sonia Molina-Pinelo; Ignacio Duran Journal: Oncotarget Date: 2017-11-20
Authors: M H Diekstra; A Fritsch; F Kanefendt; J J Swen; Djar Moes; F Sörgel; M Kinzig; C Stelzer; D Schindele; T Gauler; S Hauser; D Houtsma; M Roessler; B Moritz; K Mross; L Bergmann; E Oosterwijk; L A Kiemeney; H J Guchelaar; U Jaehde Journal: CPT Pharmacometrics Syst Pharmacol Date: 2017-07-13