Karolina Nemes1, Susanne Bens2, Denis Kachanov3, Margarita Teleshova3, Peter Hauser4, Thorsten Simon5, Stephan Tippelt6, Wilhelm Woessmann7, Olaf Beck8, Christian Flotho9, Lorenz Grigull10, Pablo H Driever11, Paul-Gerhardt Schlegel12, Claudia Khurana13, Kathrin Hering14, Reinhard Kolb15, Alfred Leipold16, Floor Abbink17, Maria J Gil-Da-Costa18, Martin Benesch19, Kornelius Kerl20, Stephen Lowis21, Carmen H Marques22, Norbert Graf23, Karsten Nysom24, Christian Vokuhl25, Patrick Melchior26, Thomas Kröncke27, Reinhard Schneppenheim28, Uwe Kordes28, Joachim Gerss29, Reiner Siebert2, Rhoikos Furtwängler23, Michael C Frühwald30. 1. Paediatrics and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg, Germany. 2. Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany. 3. National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russian Federation. 4. Department of Pediatric Oncology, 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary. 5. Department of Pediatric Hematology and Oncology, University Children's Hospital of Cologne, Cologne, Germany. 6. Department of Pediatric Hematology and Oncology, Pediatrics III, University Hospital of Essen, Essen, Germany. 7. Department of Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 8. Department of Pediatric Hematology, Oncology & Hemostaseology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany. 9. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium, Heidelberg, Germany. 10. Department of Pediatric Hematology and Oncology, Children's Hospital of Hannover, Hannover, Germany. 11. Department of Pediatric Oncology and Hematology, Charité - University Hospital Berlin, Corporate Member of Free University Berlin, Humboldt-University Berlin, and Berlin Institute of Health, Berlin, Germany. 12. Department of Pediatric Hematology and Oncology, University Würzburg, Würzburg, Germany. 13. Department of Pediatric Hematology and Oncology, Children's Hospital of Bielefeld, Germany. 14. Department of Radiotherapy and Radiation Oncology, Leipzig University, Leipzig, Germany. 15. Department of Pediatrics, Children's Center, Hospital of Oldenburg, Oldenburg, Germany. 16. Children's Hospital Karlsruhe, Karlsruhe, Germany. 17. Department of Pediatric Hematology and Oncology, VU University Medical Center, Amsterdam, the Netherlands. 18. Pediatric Hemathology and Oncology Division, University Hospital S. João Alameda Hernani Monteiro, Porto, Portugal. 19. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. 20. Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany. 21. School of Clinical Sciences, University of Bristol, London, UK. 22. Pediatric Onco-hematology Unit, Niño Jesús Hospital, Madrid, Spain. 23. Department of Pediatric Hematology and Oncology, University of Saarland, Homburg, Germany. 24. Department of Paediatrics and Adolescent Medicine, Neuroscience Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 25. Department of Pathology, Section of Pediatric Pathology, University Hospital Bonn, Bonn, Germany. 26. Department of Radiation Oncology, University of Saarland, Homburg, Germany. 27. Department of Diagnostic and Interventional Radiology, University Hospital Augsburg, Augsburg, Germany. 28. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 29. Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany. 30. Paediatrics and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg, Germany. Electronic address: Michael.fruehwald@uk-augsburg.de.
Abstract
INTRODUCTION: Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework. METHODS: We evaluated 100 patients recruited within EU-RHAB (2009-2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics. RESULTS: A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/100), localised disease (M0) with (LN+) and without (LN-) loco-regional lymph node involvement in 65% (65/100). SMARCB1 germline mutations (GLM) were detected in 21% (17/81 evaluable) of patients. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.8 ± 5.4% and 35.2 ± 5.1%, respectively. On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes. In an adjusted multivariate model presence of a GLM, M+ and lack of a GTR were the strongest significant negative predictors of outcome. CONCLUSIONS: We suggest to stratify patients with localised disease (M0), GTR+ and without proof of a GLM (5-year OS 72.2 ± 9.9%) as 'standard risk'. Patients presenting with one of the features M+ and/or GTR- and/or GLM+ belong to a high risk group (5-year, OS 32.5 ± 6.2%). These patients need novel therapeutic strategies such as combinations of targeted agents with conventional chemotherapy or novel experimental approaches ideally within international phase I/II trials.
INTRODUCTION: Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumourpatients treated according to the EU-RHAB therapeutic framework. METHODS: We evaluated 100 patients recruited within EU-RHAB (2009-2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics. RESULTS: A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/100), localised disease (M0) with (LN+) and without (LN-) loco-regional lymph node involvement in 65% (65/100). SMARCB1 germline mutations (GLM) were detected in 21% (17/81 evaluable) of patients. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.8 ± 5.4% and 35.2 ± 5.1%, respectively. On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes. In an adjusted multivariate model presence of a GLM, M+ and lack of a GTR were the strongest significant negative predictors of outcome. CONCLUSIONS: We suggest to stratify patients with localised disease (M0), GTR+ and without proof of a GLM (5-year OS 72.2 ± 9.9%) as 'standard risk'. Patients presenting with one of the features M+ and/or GTR- and/or GLM+ belong to a high risk group (5-year, OS 32.5 ± 6.2%). These patients need novel therapeutic strategies such as combinations of targeted agents with conventional chemotherapy or novel experimental approaches ideally within international phase I/II trials.
Authors: Karolina Nemes; Pascal D Johann; Mona Steinbügl; Miriam Gruhle; Susanne Bens; Denis Kachanov; Margarita Teleshova; Peter Hauser; Thorsten Simon; Stephan Tippelt; Wolfgang Eberl; Martin Chada; Vicente Santa-Maria Lopez; Lorenz Grigull; Pablo Hernáiz-Driever; Matthias Eyrich; Jane Pears; Till Milde; Harald Reinhard; Alfred Leipold; Marianne van de Wetering; Maria João Gil-da-Costa; Georg Ebetsberger-Dachs; Kornelius Kerl; Andreas Lemmer; Heidrun Boztug; Rhoikos Furtwängler; Uwe Kordes; Christian Vokuhl; Martin Hasselblatt; Brigitte Bison; Thomas Kröncke; Patrick Melchior; Beate Timmermann; Joachim Gerss; Reiner Siebert; Michael C Frühwald Journal: Cancers (Basel) Date: 2022-04-27 Impact factor: 6.575
Authors: Karolina Nemes; Pascal D Johann; Stefanie Tüchert; Patrick Melchior; Christian Vokuhl; Reiner Siebert; Rhoikos Furtwängler; Michael C Frühwald Journal: Cancer Manag Res Date: 2022-02-09 Impact factor: 3.989