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
| Autor: | Henk-Jan Guchelaar, Max Roessler, Arna Oskarsdottir, Thorunn Rafnar, Meta H M Diekstra, Valentin Ambert, Rosa Guarch Troyas, Lambertus A. Kiemeney, Kerstin Junker, Anna Martinez-Cardus, J.C. Oosterwijk-Wakka, Gisli Masson, Jesus Garcia Donas, Anne Cambon-Thomsen, Lodewyk F. A. Wessels, Tim Eisen, Cristina Rodríguez-Antona, Achim Fritsch, Ulrich Jaehde, Marius T. Radu, Arndt Hartmann, Sita H. Vermeulen, Daniel Castellano, Anne Y. Warren, Kari Stefansson, Loes F.M. van der Zanden, Jake S.F. Maurits, Egbert Oosterwijk, Christina A. Hulsbergen-van de Kaa, Rob Ruijtenbeek |
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| Přispěvatelé: | Unión Europea. Comisión Europea. 7 Programa Marco, MUMC+: DA KFT Medische Staf (9), RS: FHML non-thematic output |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Indoles medicine.medical_treatment Tyrosine kinase inhibitor Bioinformatics urologic and male genital diseases Targeted therapy Cohort Studies 0302 clinical medicine Sunitinib Molecular Targeted Therapy Prospective Studies Exome sequencing Aged 80 and over Sulfonamides Tissue microarray Genomics Middle Aged Sorafenib Kidney Neoplasms 3. Good health 030220 oncology & carcinogenesis Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] SURVIVAL Biomarker (medicine) Female medicine.drug Adult Niacinamide medicine.medical_specialty Indazoles CARCINOMA Urology Metastatic renal cell carcinoma Therapy response Antineoplastic Agents SUNITINIB Pazopanib 03 medical and health sciences Young Adult Internal medicine Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] medicine Carcinoma Biomarkers Tumor Humans Pyrroles Transcriptomics Carcinoma Renal Cell Protein Kinase Inhibitors Aged business.industry Phenylurea Compounds Biomarker medicine.disease POPULATION-BASED REGISTRY 030104 developmental biology Pyrimidines INTERFERON-ALPHA Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] business |
| Zdroj: | Urologic Oncology-Seminars and Original Investigations, 35, 8, pp. 529.e9-529.e16 Urologic Oncology-Seminars and Original Investigations, 35, 529.e9-529.e16 Urologic oncology-seminars and Original Investigations, 35(8):ARTN 529.e9. Elsevier Science Repisalud Instituto de Salud Carlos III (ISCIII) Urologic Oncology: Seminars and Original Investigations, 35(8) |
| ISSN: | 1078-1439 |
| Popis: | 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. We would like to thank all patients who participated and their treating physicians for inviting them. Sí |
| Databáze: | OpenAIRE |
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