BACKGROUND: Refined therapy has helped to improve survival rates in rhabdoid tumors (RT). Prognosis for patients with chemoresistant, recurrent, or progressive RT remains dismal. Although decitabine, an epigenetically active agent, has mainly been evaluated in the management of hematologic malignancies in adults, safety in children has also been demonstrated repeatedly. MATERIALS AND METHODS: A retrospective series of patients who received decitabine upon relapse or progression following therapy according to the EU-RHAB regimen is presented. Due to the retrospective nature of analyses, response was defined as measurable regression of at least one lesion on imaging. 850k methylation profiling was done whenever tumor tissue was available. RESULTS: A total of 22 patients with RT of any anatomical localization were included. Most patients (19/22) presented with metastases. All received low-dose decitabine with or preceding conventional chemotherapy. Patients received a median of two (1-6) courses of decitabine; 27.3% (6/22) demonstrated a radiological response. Molecular analyses revealed increased methylation levels in tumors from responders. No excessive toxicity was observed. Clinical benefits for responders included eligibility for early phase trials or local therapy. Responders showed prolonged time to progression and overall survival. Due to small sample size, statistical correction for survivorship bias demonstrated no significant effect on survival for responders. CONCLUSIONS: Patients with RT demonstrate promising signs of antitumor activity after multiagent relapse therapy including decitabine. Analyses of methylation data suggest a specific effect on an epigenetic level. We propose to consider decitabine and other epigenetic drugs as candidates for further clinical investigations in RT.

Department of Diagnostic and Interventional Radiology University Medical Center Augsburg Germany

Department of General Pediatrics Hematology and Oncology Children's University Hospital Tübingen Germany

Department of Paediatrics and Adolescent Medicine Rigshospitalet Copenhagen Denmark

Department of Pediatric Hematology and Oncology University Children's Hospital Münster Münster Germany

Department of Pediatric Hematology and Oncology University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Pediatric Hematology Oncology and Stem Cell Transplantation University Hospital of Regensburg Regensburg Germany

Department of Pediatric Oncology 2nd Department of Pediatrics Semmelweis University Budapest Hungary

Department of Pediatrics Asklepios Kinderklinik Sankt Augustin Sankt Augustin Germany

Division of Pediatric Hematology and Oncology Department of Pediatric and Adolescent Medicine University Medical Center Freiburg University of Freiburg Freiburg Germany

Hopp Children's Cancer Center Heidelberg and Heidelberg University Hospital Heidelberg Germany

Institute of Biostatistics and Clinical Research University of Münster Muenster Germany

Institute of Human Genetics University of Ulm and Ulm University Hospital Ulm Germany

Institute of Neuropathology University Hospital Münster Münster Germany

Institute of Neuropathology University Medical Center Hamburg Eppendorf Hamburg Germany

Pediatric Hematology and Oncology Division University Hospital S João Alameda Hernani Monteiro Porto Portugal

Research Institute Children's Cancer Center Hamburg Hamburg Germany

University Medical Center Augsburg Paediatric and Adolescent Medicine Swabian Children's Cancer Center Augsburg Germany

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