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J Clin Oncol. 2015 Jan 10;33(2):195-201. doi: 10.1200/JCO.2014.58.3369. Epub 2014 Dec 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 information

1
A. Lindsay Frazier and Carlos Rodriguez-Galindo, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA; Juliet P. Hale, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle upon Tyne; Matthew J. Murray and James C. Nicholson, Cambridge University Hospitals NHS Foundation Trust; Matthew J. Murray, University of Cambridge, Cambridge; Claire Thornton, Royal Victoria Hospital, Belfast Health Trust, Belfast; G. Suren Arul, Birmingham Children's Hospital NHS Foundation Trust, Birgmingham; Sara Stoneham, Children's and Young Persons Cancer Services, University College London Hospital Trusts, London, United Kingdom; Ha Dang, Children's Oncology Group; Mark Krailo, University of Southern California, Los Angeles, CA; Thomas Olson, Children's Healthcare of Atlanta, Emory University, Atlanta, GA; James F. Amatruda, University of Texas Southwestern Medical Center and Children's Medical Center Dallas, Dallas, TX; Deborah Billmire, Riley Hospital for Children, Indianapolis, IN; Furqan Shaikh, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and Farzana Pashankar, Yale Cancer Center, New Haven, CT. lindsay_frazier@dfci.harvard.edu.
2
A. Lindsay Frazier and Carlos Rodriguez-Galindo, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA; Juliet P. Hale, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle upon Tyne; Matthew J. Murray and James C. Nicholson, Cambridge University Hospitals NHS Foundation Trust; Matthew J. Murray, University of Cambridge, Cambridge; Claire Thornton, Royal Victoria Hospital, Belfast Health Trust, Belfast; G. Suren Arul, Birmingham Children's Hospital NHS Foundation Trust, Birgmingham; Sara Stoneham, Children's and Young Persons Cancer Services, University College London Hospital Trusts, London, United Kingdom; Ha Dang, Children's Oncology Group; Mark Krailo, University of Southern California, Los Angeles, CA; Thomas Olson, Children's Healthcare of Atlanta, Emory University, Atlanta, GA; James F. Amatruda, University of Texas Southwestern Medical Center and Children's Medical Center Dallas, Dallas, TX; Deborah Billmire, Riley Hospital for Children, Indianapolis, IN; Furqan Shaikh, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and Farzana Pashankar, Yale Cancer Center, New Haven, CT.

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.

PMID:
25452439
PMCID:
PMC4279239
DOI:
10.1200/JCO.2014.58.3369
[Indexed for MEDLINE]
Free PMC Article

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