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
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