@article{NemesJohannSteinbuegletal.2022,
  author    = {Nemes, Karolina and Johann, Pascal D. and Steinb{\"u}gl, Mona and Gruhle, Miriam and Bens, Susanne and Kachanov, Denis and Teleshova, Margarita and Hauser, Peter and Simon, Thorsten and Tippelt, Stephan and Eberl, Wolfgang and Chada, Martin and Lopez, Vicente Santa-Maria and Grigull, Lorenz and Hern{\´a}iz-Driever, Pablo and Eyrich, Matthias and Pears, Jane and Milde, Till and Reinhard, Harald and Leipold, Alfred and van de Wetering, Marianne and Gil-da-Costa, Maria Jo{\~a}o and Ebetsberger-Dachs, Georg and Kerl, Kornelius and Lemmer, Andreas and Boztug, Heidrun and Furtw{\"a}ngler, Rhoikos and Kordes, Uwe and Vokuhl, Christian and Hasselblatt, Martin and Bison, Brigitte and Kr{\"o}ncke, Thomas and Melchior, Patrick and Timmermann, Beate and Gerss, Joachim and Siebert, Reiner and Fr{\"u}hwald, Michael C.},
  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},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {9},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14092185},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270730},
  year      = {2022},
  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.},
  language  = {en}
}
@article{BartelheimNemesSeeringeretal.2016,
  author    = {Bartelheim, Kerstin and Nemes, Karolina and Seeringer, Angela and Kerl, Kornelius and Buechner, Jochen and Boos, Joachim and Graf, Norbert and D{\"u}rken, Matthias and Gerss, Joachim and Hasselblatt, Martin and Kortmann, Rolf-Dieter and Teichert von Luettichau, Irene and Nagel, Inga and Nygaard, Randi and Oyen, Florian and Quiroga, Eduardo and Schlegel, Paul-Gerhardt and Schmid, Irene and Schneppenheim, Reinhard and Siebert, Reiner and Solano-Paez, Palma and Timmermann, Beate and Warmuth-Metz, Monika and Fr{\"u}hwald, Michael Christoph},
  title     = {Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007},
  series = {Cancer Medicine},
  volume    = {5},
  journal   = {Cancer Medicine},
  number    = {8},
  doi       = {10.1002/cam4.741},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164799},
  pages     = {1765-1775},
  year      = {2016},
  abstract  = {Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64\% (genetic analyses, FISH, MLPA, sequencing) up to 97\% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46\% (±0.10) and 45\% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.},
  language  = {en}
}