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
Creators: name: Nemes, Karolina
name: Johann, Pascal D.
name: Steinbügl, Mona
name: Gruhle, Miriam
name: Bens, Susanne
name: Kachanov, Denis
name: Teleshova, Margarita
name: Hauser, Peter
name: Simon, Thorsten
name: Tippelt, Stephan
name: Eberl, Wolfgang
name: Chada, Martin
name: Lopez, Vicente Santa-Maria
name: Grigull, Lorenz
name: Hernáiz-Driever, Pablo
name: Eyrich, Matthias
name: Pears, Jane
name: Milde, Till
name: Reinhard, Harald
name: Leipold, Alfred
name: Van De Wetering, Marianne
name: Gil-Da-Costa, Maria João
name: Ebetsberger-Dachs, Georg
name: Kerl, Kornelius
name: Lemmer, Andreas
name: Boztug, Heidrun
name: Furtwängler, Rhoikos
name: Kordes, Uwe
name: Vokuhl, Christian
name: Hasselblatt, Martin
name: Bison, Brigitte
name: Kröncke, Thomas
name: Melchior, Patrick
name: Timmermann, Beate
name: Gerss, Joachim
name: Siebert, Reiner
name: Frühwald, Michael C.
Publisher: name: Universität Ulm
Year: 2022
Subjects: subject: SMARCB1
subject: atypical teratoid rhabdoid tumors
subject: extracranial malignant rhabdoid tumor
subject: RTPS1
subject: RTPS2
subject: EU-RHAB registry
subject: DDC 610 / Medicine &amp; health
subject: Rhabdoid tumor; Genetics
subject: Teratoma; Genetics
subject: Germ-line mutation
subject: Infant
subject: Infant, Newborn
subject: Neugeborenes
subject: Kind
subject: Teratom

description: Simple Summary Malignant rhabdoid tumors (MRT) are deadly tumors that predominantly affect infants and young children. Even when considering the generally young age of these patients, the treatment of infants below the age of six months represents a particular challenge due to the vulnerability of this patient population. The aim of our retrospective study was to assess the available information on prognostic factors, genetics, toxicity of treatment and long-term outcomes of MRT. We confirmed that, in a cohort of homogenously treated infants with MRT, significant predictors of outcome were female sex, localized stage, absence of a GLM and maintenance therapy, and these significantly favorably influence prognosis. Stratification-based biomarker-driven tailored trials may be a key option to improve survival rates. Abstract 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.