1. Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States.
- Author
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Frazier AL, Hale JP, Rodriguez-Galindo C, Dang H, Olson T, Murray MJ, Amatruda JF, Thornton C, Arul GS, Billmire D, Shaikh F, Pashankar F, Stoneham S, Krailo M, and Nicholson JC
- Subjects
- Adolescent, Age Factors, Biomarkers, Tumor analysis, Child, Child, Preschool, Clinical Trials as Topic, Disease-Free Survival, Endodermal Sinus Tumor epidemiology, Endodermal Sinus Tumor etiology, Evidence-Based Medicine, Female, Humans, Male, Neoplasm Staging, Neoplasms, Germ Cell and Embryonal mortality, Neoplasms, Germ Cell and Embryonal pathology, Predictive Value of Tests, Prognosis, Retrospective Studies, Risk Assessment, Risk Factors, United Kingdom epidemiology, United States epidemiology, alpha-Fetoproteins analysis, Models, Statistical, Neoplasms, Germ Cell and Embryonal epidemiology, Neoplasms, Germ Cell and Embryonal etiology
- Abstract
Purpose: To risk stratify malignant extracranial pediatric germ cell tumors (GCTs)., 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 data set of patients with stage II to 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 estimate the percentage of patients who achieved 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 multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications., Conclusion: Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy., (© 2014 by American Society of Clinical Oncology.)
- Published
- 2015
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