Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors


Key Points

  • A high-risk group consisted of patients aged ≥11 years with stage IV ovarian germ cell tumors, stage II to III extragonadal germ cell tumors, or stage IV extragonadal disease.
  • Bootstrap analysis showed that that age, tumor site, and stage were retained as adverse factors in > 94% of 1,000 replications.

In a study reported in the Journal of Clinical Oncology, Frazier et al used data from U.S. and UK clinical trials to identify a high-risk group of patients with pediatric extracranial germ cell tumors.

Study Details

The study involved data from seven germ cell tumor trials conducted by the Children’s Oncology Group (U.S.) or the Children’s Cancer and Leukemia Group (UK) between 1985 and 2009, used to generate a data set of 519 patients with stage II to IV disease treated with platinum-based therapy.

There were more female patients (66%), and the majority of the patients were aged < 4 years (53%), with the 10 to 14 year age group being second largest (21%). The most common histology was yolk sac tumor (55%) followed by mixed malignant germ cell tumors (40%), serum alpha-fetoprotein was ≥ 10,000 ng/mL in 49% of patients, 79% had stage III or IV disease, and 26% received a carboplatin-based regimen.

Factors Associated With Poor Outcome

In multivariate analysis, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001 for ovarian and extragonadal vs testicular) were significant predictors of worse long-term disease-free survival. Elevated serum alpha-fetoprotein was associated with worse outcome (P = .45) and pure yolk sac tumor was associated with better outcome (P = .06), but neither factor was statistically significant.

Long-term disease-free survival (ie, cure) ranged from 99% for boys aged < 11 years with stage II to III testicular germ cell tumors to 40% for patients aged ≥ 11 years with stage IV extragonadal germ cell tumors. A poor-risk group was identified with long-term disease-free survival < 70%, consisting of patients aged ≥ 11 years with stage IV ovarian germ cell tumors (67%), stage II to III extragonadal germ cell tumors (65%), or stage IV extragonadal disease (40%).

Validation using bootstrap methods showed that stage IV disease was an adverse prognostic factor in 94.1% of 1,000 replications, age ≥ 11 years an adverse factor in 99.8%, and tumor site an adverse factor in 98%, with serum alpha-fetoprotein retained in the model as an adverse factor in only 12% and yolk sac tumor predicting better outcome in only 28%.

The investigators concluded: “Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric [germ cell tumors] that identifies a poor-risk group warranting intensified therapy.”

The study was supported by the Bridging the Gap Fund, Dana-Farber Cancer Institute, Katie Walker Cancer Trust, Teenage Cancer Trust, and William Guy Forbeck Foundation.

Lindsay, Frazier, MD, ScM, of Dana-Farber Cancer Institute and Boston Children’s Hospital, is the corresponding author for the Journal of Clinical Oncology article.

The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.