Infants and newborns with atypical teratoid rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors (eMRT) in the EU-RHAB Registry: a unique and challenging population
Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, t...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2022
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| In: |
Cancers
Year: 2022, Volume: 14, Issue: 9, Pages: 1-16 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers14092185 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14092185 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/9/2185 
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| Author Notes: | 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 and Michael C. Frühwald |
| Summary: | Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005-2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option. |
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| Item Description: | Published: 27 April 2022 Gesehen am 29.06.2022 |
| Physical Description: | Online Resource |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers14092185 |