title: Parents' and Adolescents' Preferences for Intensified or Reduced Treatment in Randomized Lymphoblastic Leukemia Trials.
abstract: BACKGROUND
  When offered participation in clinical trials, families of children with cancer face a delicate balance between cure and toxicity. Since parents and children may perceive this balance differently, this paper explores whether adolescent patients have different enrollment patterns compared to younger children in trials with different toxicity profiles.
  
  
  METHODS
  Age-dependent participation rates in three consecutive, randomized childhood leukemia trials conducted by the Nordic Society of Paediatric Haematology and Oncology were evaluated. The ALL2000 dexamethasone/vincristine (Dx/VCR) trial tested treatment intensifications to improve cure, and the back-to-back ALL2008 6-mercaptopurine (6MP) and ALL2008 PEG-asparaginase (ASP) trials tested treatment intensifications (6MP) and toxicity reduction without compromising survival (ASP). Patient randomization and toxicity data were prospectively registered by the treating physicians.
  
  
  RESULTS
  Parents of young children favored treatment intensifications (Dx/VCR: 12% refusal; 6MP: 14%; ASP: 21%), whereas parents of adolescents favored treatment reductions (Dx/VCR: 52% refusal; 6MP: 30%; ASP: 8%). Adolescents were more likely to refuse intensification trials than young children (adjusted ORs 6.3; P < 0.01 [Dx/VCR] and 2.1; P = 0.04 [6MP]). Adolescents were less likely to refuse the ASP trial, with varying effect size depending on the length of the preceding consolidation treatment (adjusted OR for median consolidation length 0.15; P = 0.01). Younger children participated more frequently in only 6MP than in only ASP (14% vs. 5%), and adolescents vice versa (2% vs. 17%; P = 0.001).
  
  
  CONCLUSIONS
  Parents' and adolescents' divergent inclinations toward intensified or reduced therapy emphasize the necessity of actively involving adolescents in the informed consent process, which should also address motives for trial participation.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Tulstrup
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne Baekgaard
authors.initials: HB
authors.lastname: Larsen
authors.affiliation: Department of Pediatrics, Section of Pediatric Oncology/Hematology, Lund University Hospital, Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Castor
authors.affiliation: Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossel
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.|Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Kathrine
authors.initials: K
authors.lastname: Grell
authors.affiliation: Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.affiliation: Department of Clinical Sciences, Queen Silvia's Children's Hospital, Gothenburg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.affiliation: Childhood Cancer Research Unit, Department of Women and Child Health, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderhäll
authors.affiliation: Department of Pediatrics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Ann
authors.initials: A
authors.lastname: Åsberg
authors.affiliation: Department of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland.
authors.forename: Olafur Gisli
authors.initials: OG
authors.lastname: Jonsson
authors.affiliation: Department of Paediatrics, University of Tampere, Finland.
authors.forename: Kim
authors.initials: K
authors.lastname: Vettenranta
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas Leth
authors.initials: TL
authors.lastname: Frandsen
authors.affiliation: Department of Pediatric Oncology, Skejby Hospital, Aarhus, Denmark.
authors.forename: Birgitte Klug
authors.initials: BK
authors.lastname: Albertsen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.|Institute of Clinical Medicine, University of Copenhagen, Denmark.|Division of Pediatric Hematology/Oncology, Perlmutter Cancer Center, NYU Langone Medical Center, New York City, New York.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010290:Parents / Q000523:psychology; D057240:Patient Preference / Q000523:psychology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000523:psychology; D015996:Survival Rate; D016312:Treatment Refusal / Q000523:psychology*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011092:Polyethylene Glycols; D014750:Vincristine; C042705:pegaspargase; D003907:Dexamethasone; D015122:Mercaptopurine; D001215:Asparaginase
keywords: acute lymphoblastic leukemia; adolescent; child; clinical trials as topic; decision making; research ethics