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Prognostic Factors in Children With Extragonadal Malignant Germ Cell Tumors: A Pediatric Intergroup Study

Neyssa Marina, Wendy B. London, A. Lindsay Frazier, Stephen Lauer, Frederick Rescorla, Barbara Cushing, Marcio H. Malogolowkin, Robert P. Castleberry, Richard B. Womer, Thomas Olson

From the Stanford University Medical Center, Stanford, CA; University of Florida and Children's Oncology Group Statistics and Data Center, Gainesville, FL; Dana-Farber Cancer Center, Boston, MA; Children's Healthcare of Atlanta at Egleston, Atlanta, GA; Indiana University Riley Children's Hospital, Indianapolis, IN; Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI; Children's Hospital Los Angeles, Los Angeles, CA; University of Alabama at Birmingham, AL; and the Children's Hospital of Philadelphia, Philadelphia, PA

Address reprint requests to Neyssa Marina, MD, Stanford University Medical Center, 1000 Welch Rd, Suite 300, Stanford, CA 94304-1812; e-mail: neyssa.marina{at}stanford.edu

PURPOSE: To investigate prognostic factors for pediatric extragonadal malignant germ cell tumors (PEMGCT).

MATERIALS AND METHODS: Between 1990 and 1996, patients with stage I through IV PEMGCT were eligible for a trial of cisplatin dose intensity. We retrospectively investigated prognostic factors for PEMGCT, including age, stage, primary site, treatment, and elevated alfa fetoprotein by univariate and multivariate analysis.

RESULTS: The 165 patients had a median age of 1.9 years (range, 3 days to 18.5 years); 109 were female; and 99 had alfa fetoprotein 10,000. There were 30 stage I/II, 61 stage III, and 74 stage IV tumors; primary sites included 88 sacrococcygeal, 39 thoracic, and 38 others. The 5-year overall survival (OS) and event-free survival (EFS) rates with standard deviations were 83.4% ± 3.7% and 79.0% ± 4.1%, respectively. Univariate analysis identified age 12 years as a highly significant prognostic factor for EFS (5-year EFS, 48.9% ± 15.6% v 84.1% ± 3.9%; P < .0001) and for OS (5-year OS, 53.7% ± 14.9% v 88.5% ± 3.4%; P < .0001), whereas treatment was of borderline significance (P = .0777). Multivariate Cox proportional hazards regression identified only age 12 years as a significant prognostic factor for EFS (P = .0002). In multivariate Cox regression for OS, the combination of age and primary site was highly significant (P < .0001). Patients 12 years of age with thoracic tumors had six times the risk of death compared with patients younger than 12 years with other primaries.

CONCLUSION: Age is the most predictive factor of EFS in PEMGCT. There is a significant interaction between age and primary site, suggesting that patients 12 years of age with thoracic tumors are a biologically distinct group.

Presented in part at the 33rd Annual Meeting of the International Society of Pediatric Oncology, Brisbane, Australia, October 10-13, 2001.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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