title: Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.
abstract: OBJECTIVE
  The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4.
  
  
  METHODS
  After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine).
  
  
  RESULTS
  Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively).
  
  
  CONCLUSIONS
  Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.
authors: Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland. Electronic address: nicolas.gerber@kispi.uzh.ch.
authors: Nicolas U
authors: NU
authors: Gerber
authors: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Katja
authors: K
authors: von Hoff
authors: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Anika
authors: A
authors: Resch
authors: Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg, Germany.
authors: Holger
authors: H
authors: Ottensmeier
authors: Institute of Biostatistics and Clinical Research, University of Muenster, Germany.
authors: Robert
authors: R
authors: Kwiecien
authors: Institute of Biostatistics and Clinical Research, University of Muenster, Germany.
authors: Andreas
authors: A
authors: Faldum
authors: Department of Radiation Oncology, Medical Faculty, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany.
authors: Christiane
authors: C
authors: Matuschek
authors: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Dagmar
authors: D
authors: Hornung
authors: Institute for Radiation Therapy and Special Oncology, Hannover Medical School, Hannover, Germany.
authors: Michael
authors: M
authors: Bremer
authors: Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors: Martin
authors: M
authors: Benesch
authors: Department of Neuropathology, University of Bonn, Bonn, Germany.
authors: Torsten
authors: T
authors: Pietsch
authors: Department of Neuroradiology, University of Wuerzburg, Wuerzburg, Germany.
authors: Monika
authors: M
authors: Warmuth-Metz
authors: Department of Pediatric Oncology, University of Wuerzburg, Wuerzburg, Germany.
authors: Joachim
authors: J
authors: Kuehl
authors: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Stefan
authors: S
authors: Rutkowski
authors: Department of Radiation Oncology, University of Leipzig, Leipzig, Germany.
authors: Rolf D
authors: RD
authors: Kortmann
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term; D008606:Mental Processes; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D009483:Neuropsychological Tests; D010870:Pineal Gland; D010871:Pinealoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D011446:Prospective Studies; D012044:Regression Analysis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents