title: Feasibility of intensive multimodal therapy in infants affected by rhabdoid tumors - experience of the EU-RHAB registry.
abstract: Rhabdoid tumors mainly affect infants and other very young children with a marked vulnerability towards intensive therapy such as invasive surgery, high dose chemotherapy (HDCT) and dose intense radiotherapy. Radiotherapy (RT) is a promising option in rhabdoid tumors but its application in infants remains controversial. Neurocognitive and vascular side effects occur even long after completion of therapy. Therapeutic recommendations suggested by the European Rhabdoid Registry including RT, high dose chemotherapy (HDCT) and methotrexate (MTX) were developed by a consensus committee. Unique to our EU-RHAB database is the ability to analyze data of 64 of 81 registered infants (under one year of age) separate from older children. 20 (age at diagnoses 2-12 months) of these had received radiotherapy. To our knowledge, this is the first report specifically analyzing treatment data of infants suffering from malignant rhabdoid tumors. Our results suggest that radiotherapy significantly increases the mean survival time as well as the 3 year overall survival in infants. We detected a doubling of survival times in infants who received RT. Overall, our results suggest that infants benefit from RT with tolerable acute side effects. Severe long term sequelae likely due to intraventricular MTX and/or RT were reported in 4 patients (leukoencephalopathy). No differences in chemotherapy-related toxicity were observed between infants and children. We suggest that a nihilistic therapeutic approach towards young infants is not warranted and that RT may not be a priori rejected as a therapeutic option in infants.
authors.affiliation: Swabian Children's Cancer Center, Children's Hospital Augsburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Seeringer
authors.affiliation: Swabian Children's Cancer Center, Children's Hospital Augsburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bartelheim
authors.affiliation: Hematology and Oncology, University Children's Hospital Münster, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kerl
authors.affiliation: Neuropathology, University Hospital Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hasselblatt
authors.affiliation: Institute of Pathology Christian-Albrechts-University Kiel, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Leuschner
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rutkowski
authors.affiliation: Westgerman Protontherapycenter Essen, University Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Timmermann
authors.affiliation: Radiooncology, University Hospital Leipzig, Germany.
authors.forename: R-D
authors.initials: RD
authors.lastname: Kortmann
authors.affiliation: Pediatric Hematology and Oncology, Olgahospital Stuttgart, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Koscielniak
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schneppenheim
authors.affiliation: Neuroradiology, University of Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Warmuth-Metz
authors.affiliation: Institute of Biometry and Clinical Research, University of Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gerß
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Pediatric Hematology and Oncology, University Hospital Homburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.affiliation: Hematology and Oncology, University Children's Hospital Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Boos
authors.affiliation: Swabian Children's Cancer Center, Children's Hospital Augsburg, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Frühwald
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D005240:Feasibility Studies; D005858:Germany; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D057967:Infusions, Intraventricular; D033183:Interdisciplinary Communication; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012042:Registries; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate
chemical_list: D003609:Dactinomycin; D008727:Methotrexate