Please use this identifier to cite or link to this item:
doi:10.22028/D291-36142
Title: | 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 |
Author(s): | Nemes, Karolina Johann, Pascal D. Steinbügl, Mona Gruhle, Miriam Bens, Susanne Kachanov, Denis Teleshova, Margarita Hauser, Peter Simon, Thorsten Tippelt, Stephan Eberl, Wolfgang Chada, Martin Lopez, Vicente Santa-Maria Grigull, Lorenz Hernáiz-Driever, Pablo Eyrich, Matthias Pears, Jane Milde, Till Reinhard, Harald Leipold, Alfred van de Wetering, Marianne Gil-da-Costa, Maria João Ebetsberger-Dachs, Georg Kerl, Kornelius Lemmer, Andreas Boztug, Heidrun Furtwängler, Rhoikos Kordes, Uwe Vokuhl, Christian Hasselblatt, Martin Bison, Brigitte Kröncke, Thomas Melchior, Patrick Timmermann, Beate Gerss, Joachim Siebert, Reiner Frühwald, Michael C. |
Language: | English |
Title: | Cancers |
Volume: | 14 |
Issue: | 9 |
Publisher/Platform: | MDPI |
Year of Publication: | 2022 |
Free key words: | SMARCB1 atypical teratoid rhabdoid tumors extracranial malignant rhabdoid tumor RTPS1 RTPS2 germline mutation EU-RHAB registry |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | 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. |
DOI of the first publication: | 10.3390/cancers14092185 |
Link to this record: | urn:nbn:de:bsz:291--ds-361423 hdl:20.500.11880/32950 http://dx.doi.org/10.22028/D291-36142 |
ISSN: | 2072-6694 |
Date of registration: | 30-May-2022 |
Description of the related object: | Supplementary Materials |
Related object: | https://www.mdpi.com/article/10.3390/cancers14092185/s1 |
Faculty: | M - Medizinische Fakultät |
Department: | M - Pädiatrie M - Radiologie |
Professorship: | M - Keiner Professur zugeordnet |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
---|---|---|---|---|
cancers-14-02185-v4.pdf | 3,3 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License