title: Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data.
abstract: Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors.
  
  
  
  Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates.
  
  
  
  Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients.
  
  
  
  Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Mynarek
authors.affiliation: Oncology Unit, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Pizer
authors.affiliation: Brain Tumor Programme, Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Dannis
authors.initials: D
authors.lastname: van Vuurden
authors.affiliation: Second Department of Pediatrics, School of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Miklos
authors.initials: M
authors.lastname: Garami
authors.affiliation: Department of Pediatrics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Fangusaro
authors.affiliation: Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Davidson
authors.affiliation: Department of Pediatric Hematoncology, University Hospital de São João, Porto, Portugal.
authors.forename: Maria Joao
authors.initials: MJ
authors.lastname: Gil-da-Costa
authors.affiliation: Pediatric Oncology Department, University Hospital Brno, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Sterba
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.affiliation: Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gerber
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: B Ole
authors.initials: BO
authors.lastname: Juhnke
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Kwiecien
authors.affiliation: Department of Neuropathology, University of Bonn, Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Clifford
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.affiliation: Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.|IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Netherlands.|Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.affiliation: Department of Pathology (Neuropathology), Children's Hospital Los Angeles and the University of Southern California, Los Angeles, California, USA.
authors.forename: Floyd
authors.initials: F
authors.lastname: Gilles
authors.affiliation: Telethon Kids Institute, Subiaco, Western Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gottardo
authors.affiliation: Department of Pediatrics, Division of Hematology, Oncology and BMT, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016208:Databases, Factual; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010870:Pineal Gland / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D010871:Pinealoma / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000628:therapy*; D011446:Prospective Studies; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: high-dose chemotherapy; pediatric; pineoblastoma; radiotherapy; treatment