Challenges and developments of pediatric extracranial germ cell tumors management

Abstract

Germ cell tumors (GCTs) are a group of tumors that arise not only from the gonads but also from various organs, mainly around the midline. The histological subtypes differ depending on the age and the primary site, as do the response to the treatment. As the GCTs treated by pediatric oncologists are highly diverse, they must evaluate the tumor based on the appropriate tumor staging system and find the best option for the patient. Typical tumor markers include lactate dehydrogenase, alfa-fetoprotein, and human chorionic gonadotropin. Recently, serum miRNAs (miR371-373, miR302-367 clusters) have been reported to impact the treatment of GCTs significantly.

In 2015, the Malignant Germ Cell International Consortium (MaGIC) proposed a new pediatric extracranial germ cell tumor risk stratification with age ≥11 years, extragonadal origin, and Stage IV as risk factors. Based on this new stratification, a clinical trial, AGCT1531, is now underway worldwide to evaluate the usefulness of active surveillance for the low-risk group and carboplatin for the standard-risk group. In addition to the above-mentioned serum miRNA, analysis of genetic information of tumors is also gradually accumulating knowledge, and stratification based on these is expected in the future. The prognosis of GCTs has improved the most among the malignant tumors during the 20th century. However, the standard therapy for immature teratomas or high-risk patients has not yet been established, and we must develop new treatments. Furthermore, GCTs are rare, and tackling them with multi-disciplinary collaboration like MaGIC in Japan is necessary.