TY - JOUR
T1 - Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK)
AU - Nemes, Karolina
AU - Bens, Susanne
AU - Kachanov, Denis
AU - Teleshova, Margarita
AU - Hauser, Peter
AU - Simon, Thorsten
AU - Tippelt, Stephan
AU - Woessmann, Wilhelm
AU - Beck, Olaf
AU - Flotho, Christian
AU - Grigull, Lorenz
AU - Driever, Pablo H.
AU - Schlegel, Paul-Gerhardt
AU - Khurana, Claudia
AU - Hering, Kathrin
AU - Kolb, Reinhard
AU - Leipold, Alfred
AU - Abbink, Floor
AU - Gil-da-Costa, Maria J.
AU - Benesch, Martin
AU - Kerl, Kornelius
AU - Lowis, Stephen
AU - Marques, Carmen H.
AU - Graf, Norbert
AU - Nysom, Karsten
AU - Vokuhl, Christian
AU - Melchior, Patrick
AU - Kröncke, Thomas
AU - Schneppenheim, Reinhard
AU - Kordes, Uwe
AU - Gerss, Joachim
AU - Siebert, Reiner
AU - Furtwängler, Rhoikos
AU - Frühwald, Michael C.
N1 - Funding Information: MCF is supported by the ?Deutsche Kinderkrebsstiftung? DKKS A2016/34 04.2014 and ?Deutsche Forschungsgemeinschaft? DFG FR 1516/4-1. RSch's research is supported by the F?rdergemeinschaft Kinderkrebszentrum Hamburg e.V. RS received grant support for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. We thank P. Neumayer for expert assistance in data acquisition and the teams of the tumour genetic laboratories at the Institutes of Human Genetics in Kiel and Ulm for expert assistance. Funding Information: Pablo Hernáiz Driever has received travel grants from Novartis. Reiner Siebert has received speaker's honoraries from Astra Zeneca und Roche. None of the other authors declare any conflict of interest. Publisher Copyright: © 2020 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - EU-RHAB Registry
KW - RTK
KW - Risk stratification
KW - SMARCB1
KW - eMRT
UR - http://www.scopus.com/inward/record.url?scp=85096862544&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejca.2020.10.004
DO - https://doi.org/10.1016/j.ejca.2020.10.004
M3 - Article
C2 - 33249395
SN - 0959-8049
VL - 142
SP - 112
EP - 122
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -