title: Benefits and adverse events in younger versus older patients receiving neoadjuvant chemotherapy for osteosarcoma: findings from a meta-analysis.
abstract: OBJECTIVE
  The LIVESTRONG Young Adult Alliance has conducted a meta-analysis of individual patient data from prospective neoadjuvant chemotherapy osteosarcoma studies and registries to examine the relationships of sex, age, and toxicity on survival.
  
  
  METHODS
  Suitable data sets were identified by a survey of published data reported in PubMed. The final pooled data set comprised 4,838 patients from five international cooperative groups.
  
  
  RESULTS
  After accounting for important variables known at study entry such as tumor location and histology, females experienced higher overall survival rates than males (P = .005) and children fared better than adolescents and adults (P = .002). Multivariate landmark analysis following surgery indicated that a higher rate of chemotherapy-induced tumor necrosis was associated with longer survival (P < .001), as was female sex (P = .004) and the incidence of grade 3 or 4 mucositis (P = .03). Age group was not statistically significant in this landmark analysis (P = .12). Females reported higher rates of grade 3 or 4 thrombocytopenia relative to males (P < .001). Children reported the highest rates of grade 3 or 4 neutropenia (P < .001) and thrombocytopenia (P < .001). The achievement of good tumor necrosis was higher for females than for males (P = .002) and for children than for adults (P < .001).
  
  
  CONCLUSIONS
  These results suggest fundamental differences in the way chemotherapy is handled by females compared with males and by children compared with older populations. These differences may influence survival in a disease in which chemotherapy is critical to overall outcomes.
authors.affiliation: Peter MacCallum Cancer Centre and Australasian Sarcoma Study Group, Melbourne, Australia.
authors.forename: Marnie
authors.initials: M
authors.lastname: Collins
authors.forename: Miriam
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Rachel
authors.initials: R
authors.lastname: Conyers
authors.forename: Alan
authors.initials: A
authors.lastname: Herschtal
authors.forename: Jeremy
authors.initials: J
authors.lastname: Whelan
authors.forename: Stefan
authors.initials: S
authors.lastname: Bielack
authors.forename: Leo
authors.initials: L
authors.lastname: Kager
authors.forename: Thomas
authors.initials: T
authors.lastname: Kühne
authors.forename: Matthew
authors.initials: M
authors.lastname: Sydes
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Smeland
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.forename: Antonio Sérgio
authors.initials: AS
authors.lastname: Petrilli
authors.forename: Archie
authors.initials: A
authors.lastname: Bleyer
authors.forename: David M
authors.initials: DM
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002648:Child; D003131:Combined Modality Therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009503:Neutropenia / Q000139:chemically induced; D012516:Osteosarcoma / Q000188:drug therapy* / Q000601:surgery; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011446:Prospective Studies; D012044:Regression Analysis; D012737:Sex Factors; D013921:Thrombocytopenia / Q000139:chemically induced; D055815:Young Adult