Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data from the United Kingdom and United States
View / Open Files
Authors
Frazier, A Lindsay
Hale, Juliet P
Rodriguez-Galindo, Carlos
Dang, Ha
Olson, Thomas
Amatruda, James F
Thornton, Claire
Arul, G Suren
Billmire, Deborah
Shaikh, Furqan
Pashankar, Farzana
Stoneham, Sara
Krailo, Mark
Nicholson, James C
Publication Date
2014-12-01Journal Title
Journal of Clinical Oncology
ISSN
0732-183X
Publisher
American Society of Clinical Oncology
Type
Article
Metadata
Show full item recordCitation
Frazier, A. L., Hale, J. P., Rodriguez-Galindo, C., Dang, H., Olson, T., Murray, M., Amatruda, J. F., et al. (2014). Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data from the United Kingdom and United States. Journal of Clinical Oncology https://doi.org/10.1200/JCO.2014.58.3369
Abstract
Purpose
Risk stratification of malignant extracranial pediatric germ cell tumors (GCT).
Patients and methods
Data from seven GCT trials conducted by the Children’s Oncology Group (United States) or the Children’s Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a dataset of patients with stage II-IV disease, treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and to estimate the percentage of patients who achieve long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method.
Results:
In multivariate analysis of 519 GCT patients, stage IV disease (p=0.001), age >11y (p <0.0001), and tumor site (p<0.0001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) >10,000 ng/ml was associated with worse outcome whereas pure YST was associated with better outcome although neither met criteria for statistical significance.. The analysis identified a group of patients over age 11 with either stage III/IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival of<70%. A bootstrap procedure showed retention of age, tumor site and stage in >94%, AFP in 12%, and YST in 27% of the replications.
Conclusions:
Clinical trial data from two large national pediatric clinical trials organizations has produced a new evidence-based risk stratification of malignant pediatric GCT that identifies a poor-risk group who warrant intensified therapy.
Sponsorship
Financial Support: Bridging the Gap Fund, Dana Farber Cancer Institute; atie Walker Cancer Trust; Teenage Cancer Trust; William Guy Forbeck Foundation
Identifiers
External DOI: https://doi.org/10.1200/JCO.2014.58.3369
This record's URL: https://www.repository.cam.ac.uk/handle/1810/254450
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved