INTRODUCTION: Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established. METHODS: CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC. High risk was defined as choroid plexus carcinoma (CPC), incompletely resected APP, and all metastatic CPT. From 2000 until 2010, 158 CPT patients from 23 countries were enrolled. RESULTS: For randomized CPC, the 5/10 year progression free survival (PFS) of patients on CarbEV (n = 20) were 62%/47%, respectively, compared to 27%/18%, on CycEV (n = 15), (intention-to-treat, HR 2.6, p = 0.032). Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n = 54) 65%/51% and 41%/39%, respectively. Without irradiation, 12 out of 33 patients with CPC younger than three years were alive for a median of 8.52 years. Extent of surgery and metastases were not independent prognosticators. CONCLUSIONS: Chemotherapy for Choroid Plexus Carcinoma is feasible and effective. CarbEV is superior to CycEV. A subset of CPC can be cured without irradiation.

2nd Department of Pediatrics Semmelweis University Budapest Hungary

Department of Neuroradiology University Hospital of Augsburg Augsburg Germany

Department of Particle Therapy University Hospital Essen West German Proton Therapy Centre Essen Essen Germany

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

Department of Pediatric Oncology Hacettepe University Medical School and Cancer Institute Ankara Turkey

Department of Pediatric Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Departments of Neuropathology and Neuroradiology MD Anderson Cancer Center Houston USA

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

IOZK Immune Oncological Centre Cologne Cologne Germany

Neuro Oncology Program Institute of Neurological Research FLENI Buenos Aires Argentina

Oncology Development AbbVie Chicago IL USA

Pediatric Hematology Oncology Oncology Institute Istanbul University Istanbul Turkey

University of Regensburg Regensburg Germany

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Activation of Wnt/β-catenin signaling is critical for the tumorigenesis of choroid plexus