Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States.

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.

• Authors: A Lindsay Frazier, Juliet P Hale, Carlos Rodriguez-Galindo, Ha Dang, Thomas Olson, Matthew J Murray, James F Amatruda, Claire Thornton, G Suren Arul, Deborah Billmire, Furqan Shaikh, Farzana Pashankar, Sara Stoneham, Mark Krailo, James C Nicholson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 2 Pg. 195-201 (Jan 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25452439 (Publication Type: Journal Article, Validation Study)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Biomarkers, Tumor
• alpha-Fetoproteins

Topics

• Adolescent
• Age Factors
• Biomarkers, Tumor (analysis)
• Child
• Child, Preschool
• Clinical Trials as Topic
• Disease-Free Survival
• Endodermal Sinus Tumor (epidemiology, etiology)
• Evidence-Based Medicine
• Female
• Humans
• Male
• Models, Statistical
• Neoplasm Staging
• Neoplasms, Germ Cell and Embryonal (epidemiology, etiology, mortality, pathology)
• Predictive Value of Tests
• Prognosis
• Retrospective Studies
• Risk Assessment
• Risk Factors
• United Kingdom (epidemiology)
• United States (epidemiology)
• alpha-Fetoproteins (analysis)