Nemes, Karolina, Johann, Pascal D., Steinbuegl, Mona, Gruhle, Miriam, Bens, Susanne, Kachanov, Denis, Teleshova, Margarita, Hauser, Peter, Simon, Thorsten ORCID: 0000-0002-3425-8451, Tippelt, Stephan, Eberl, Wolfgang, Chada, Martin, Lopez, Vicente Santa-Maria, Grigull, Lorenz ORCID: 0000-0001-8807-2874, Hernaiz-Driever, Pablo, Eyrich, Matthias ORCID: 0000-0002-8099-5903, Pears, Jane, Milde, Till ORCID: 0000-0002-7267-1052, Reinhard, Harald, Leipold, Alfred, van de Wetering, Marianne, Gil-da-Costa, Maria Joao, Ebetsberger-Dachs, Georg, Kerl, Kornelius, Lemmer, Andreas, Boztug, Heidrun, Furtwaengler, Rhoikos, Kordes, Uwe, Vokuhl, Christian, Hasselblatt, Martin, Bison, Brigitte, Kroencke, Thomas, Melchior, Patrick, Timmermann, Beate, Gerss, Joachim ORCID: 0000-0003-3489-683X, Siebert, Reiner and Fruehwald, Michael 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). BASEL: MDPI. ISSN 2072-6694

Full text not available from this repository.

Abstract

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. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nemes, KarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johann, Pascal D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinbuegl, MonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruhle, MiriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bens, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kachanov, DenisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teleshova, MargaritaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauser, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, ThorstenUNSPECIFIEDorcid.org/0000-0002-3425-8451UNSPECIFIED
Tippelt, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eberl, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chada, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez, Vicente Santa-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grigull, LorenzUNSPECIFIEDorcid.org/0000-0001-8807-2874UNSPECIFIED
Hernaiz-Driever, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eyrich, MatthiasUNSPECIFIEDorcid.org/0000-0002-8099-5903UNSPECIFIED
Pears, JaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milde, TillUNSPECIFIEDorcid.org/0000-0002-7267-1052UNSPECIFIED
Reinhard, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leipold, AlfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van de Wetering, MarianneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gil-da-Costa, Maria JoaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebetsberger-Dachs, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerl, KorneliusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lemmer, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boztug, HeidrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furtwaengler, RhoikosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kordes, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vokuhl, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hasselblatt, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bison, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroencke, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melchior, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timmermann, BeateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerss, JoachimUNSPECIFIEDorcid.org/0000-0003-3489-683XUNSPECIFIED
Siebert, ReinerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fruehwald, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-697627
DOI: 10.3390/cancers14092185
Journal or Publication Title: Cancers
Volume: 14
Number: 9
Date: 2022
Publisher: MDPI
Place of Publication: BASEL
ISSN: 2072-6694
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RISK-FACTORS; CHEMOTHERAPY; RADIATION; CHILDREN; THERAPY; AGEMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69762

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item