title: Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study.
abstract: Atypical choroid plexus papilloma (APP) represents a novel intermediate-grade subtype of choroid plexus tumor (CPT), the clinical outcome of which has not been described yet. We present the first analysis of a group of APP patients enrolled in the ongoing CPT-SIOP-2000 study of CPTs. A worldwide registration and a randomized trial for those patients who require chemotherapy started in 2000. For APP, maximal surgical resection was recommended. After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses (etoposide and vincristine, combined with either carboplatin or cyclophosphamide). Risk-adapted radiotherapy was given only to patients older than 3 years of age. Of the 106 patients with a centrally confirmed CPT histology, 30 had APP, 42 CPP and 34 CPC. APP patients were significantly younger (median = 0.7 years) than patients with CPP or CPC (both medians = 2.3 years). Complete resection was achieved in 68 (64%) patients (79% in CPP, 63% in APP, and 47% in CPC). Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients. All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease. In the observation group of 15 patients, one event was seen, and all patients were alive. In the treatment group, one patient with a metastasized tumor and incompletely resected APP died. While APP was defined histologically, median percentages of both the Ki-67/MIB-1 proliferation marker and the p53 tumor suppressor protein increased across the three histological subtypes (from CPP to APP and then CPC), suggesting that the subtypes comprise an ordinal categorization of increasingly severe CPT tumors. This ordering was reiterated by clinical outcome in the 92 patients treated per the study protocol, with 5-year EFS rates of 92% in 39 CPP patients, 83% in 24 APP patients, and 28% in 29 CPC patients. A similar ordering was seen when all 106 patients were evaluated for EFS. APP responded favorably to chemotherapy. The intermediate position of APP between CPP and CPC was supported by the clinical data.
authors: Department of Pediatric Oncology, St. Hedwig Children's Hospital, University of Regensburg, Regensburg, Germany.
authors: Brigitte
authors: B
authors: Wrede
authors: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors: Martin
authors: M
authors: Hasselblatt
authors: Department of Pediatric Oncology, St. Hedwig Children's Hospital, University of Regensburg, Regensburg, Germany.
authors: Ove
authors: O
authors: Peters
authors: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Peter F
authors: PF
authors: Thall
authors: Institute of Oncology, Hacettepe University, Ankara, Turkey.
authors: Tezer
authors: T
authors: Kutluk
authors: Department of Pediatrics, Sainte-Justine Hospital, Montreal, Canada.
authors: Albert
authors: A
authors: Moghrabi
authors: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Anita
authors: A
authors: Mahajan
authors: Department of Pediatric Hematology and Oncology, University of Hamburg-Eppendorf, Hamburg, Germany.
authors: Stefan
authors: S
authors: Rutkowski
authors: Neuro Oncology Program, Institute of Neurological Research, FLENI, Buenos Aires, Argentina.
authors: Blanca
authors: B
authors: Diez
authors: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Xuemei
authors: X
authors: Wang
authors: Institute for Neuropathology, University of Bonn, Bonn, Germany.
authors: Torsten
authors: T
authors: Pietsch
authors: Department of Radiotherapy, University of Leipzig, Leipzig, Germany.
authors: Rolf-Dieter
authors: RD
authors: Kortmann
authors: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors: Werner
authors: W
authors: Paulus
authors: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors: Astrid
authors: A
authors: Jeibmann
authors: Department of Pediatric Oncology, St. Hedwig Children's Hospital, University of Regensburg, Regensburg, Germany. jwolff@mdanderson.org.|Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. jwolff@mdanderson.org.|Department of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. jwolff@mdanderson.org.
authors: Johannes E A
authors: JEA
authors: Wolff
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005682:Gadolinium; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020288:Papilloma, Choroid Plexus / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D012042:Registries; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D005682:Gadolinium; D016190:Carboplatin