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

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

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)195-201
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number2
DOIs
StatePublished - Oct 10 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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