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

Nemes K, Johann PD, Steinbügl M, Gruhle M, Bens S, Kachanov D, Teleshova M, Hauser P, Simon T, Tippelt S, Eberl W, Chada M, Lopez VSM, Grigull L, Hernáiz-Driever P, Eyrich M, Pears J, Milde T, Reinhard H, Leipold A, van de Wetering M, Gil-Da-costa MJ, Ebetsberger-Dachs G, Kerl K, Lemmer A, Boztug H, Furtwängler R, Kordes U, Vokuhl C, Hasselblatt M, Bison B, Kröncke T, Melchior P, Timmermann B, Gerss J, Siebert R, Frühwald MC (2022)

Publication Type: Journal article

Publication year: 2022


Book Volume: 14

Article Number: 2185

Journal Issue: 9

DOI: 10.3390/cancers14092185


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.

Involved external institutions

Universitätsklinikum Augsburg DE Germany (DE) Städtisches Klinikum Braunschweig DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Münster DE Germany (DE) Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology / Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии имени Дмитрия Рогачева RU Russian Federation (RU) Hospital Sant Joan de Déu Barcelona ES Spain (ES) Charité - Universitätsmedizin Berlin DE Germany (DE) HELIOS Kliniken DE Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) Princess Máxima Center NL Netherlands (NL) Asklepios Kinderklinik Sankt Augustin DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Temple Street Children's University Hospital / Children's Health Ireland (CHI) IE Ireland (IE) Johannes Kepler Universität (JKU) Linz AT Austria (AT) Hopp-Kindertumorzentrum Heidelberg - KiTZ DE Germany (DE) Hospital de São João / Saint John Hospital PT Portugal (PT) Julius-Maximilians-Universität Würzburg DE Germany (DE) Medizinische Universität Wien AT Austria (AT) Kinder- und Jugendkrankenhaus "Auf der Bult" DE Germany (DE) Städtisches Klinikum Karlsruhe DE Germany (DE) Borsod-Abaúj-Zemplén County Teaching Hospital HU Hungary (HU) Universitätsklinikum Bonn DE Germany (DE)

How to cite


Nemes, K., Johann, P.D., Steinbügl, M., Gruhle, M., Bens, S., Kachanov, D.,... Frühwald, M.C. (2022). 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. Cancers, 14(9).


Nemes, Karolina, et al. "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." Cancers 14.9 (2022).

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