Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK)

Karolina Nemes, Susanne Bens, Denis Kachanov, Margarita Teleshova, Peter Hauser, Thorsten Simon, Stephan Tippelt, Wilhelm Woessmann, Olaf Beck, Christian Flotho, Lorenz Grigull, Pablo H Driever, Paul-Gerhardt Schlegel, Claudia Khurana, Kathrin Hering, Reinhard Kolb, Alfred Leipold, Floor Abbink, Maria J Gil-Da-Costa, Martin BeneschKornelius Kerl, Stephen Lowis, Carmen H Marques, Norbert Graf, Karsten Nysom, Christian Vokuhl, Patrick Melchior, Thomas Kröncke, Reinhard Schneppenheim, Uwe Kordes, Joachim Gerss, Reiner Siebert, Rhoikos Furtwängler, Michael C Frühwald


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.

TidsskriftEuropean journal of cancer (Oxford, England : 1990)
Sider (fra-til)112-122
Antal sider11
StatusUdgivet - jan. 2021


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