title: Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: A population-based study.
abstract: BACKGROUND
  The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown.
  
  
  METHODS
  This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database.
  
  
  RESULTS
  At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes.
  
  
  CONCLUSIONS
  The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients.
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
authors.forename: Rahul
authors.initials: R
authors.lastname: Krishnatry
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Program in Genetics and Genome Biology, University of Toronto, Toronto, Canada.|Pediatric Oncology Group of Ontario, Toronto, Canada.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Zhukova
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Guerreiro Stucklin
authors.affiliation: Pediatric Oncology Group of Ontario, Toronto, Canada.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Pole
authors.affiliation: Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Program in Genetics and Genome Biology, University of Toronto, Toronto, Canada.|Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Mistry
authors.affiliation: Hadassah Medical Centre, Jerusalem, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Fried
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramaswamy
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Ute
authors.initials: U
authors.lastname: Bartels
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Huang
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
authors.forename: Normand
authors.initials: N
authors.lastname: Laperriere
authors.affiliation: Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Division of Neurosurgery, University of Toronto, Toronto, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Dirks
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Pediatric Oncology Group of Ontario, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Greenberg
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Program in Genetics and Genome Biology, University of Toronto, Toronto, Canada.|Pediatric Oncology Group of Ontario, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Malkin
authors.affiliation: Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Division of Pathology, University of Toronto, Toronto, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Pratiti
authors.initials: P
authors.lastname: Bandopadhayay
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Manley
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Canada.|Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada.|Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, Canada.|Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001932:Brain Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009864:Ontario; D016016:Proportional Hazards Models; D012042:Registries; D012044:Regression Analysis; D012189:Retrospective Studies; D012737:Sex Factors; D016019:Survival Analysis; D017741:Survivors; D013997:Time Factors; D055815:Young Adult
keywords: children; glioma; low-grade; neurofibromatosis type 1 (NF1); outcome; radiation