Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration

Abstract

During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.

Fig 1.

Potential strategies for future treatment of malignant extracranial germ cell tumors on the basis of risk stratification from Malignant Germ Cell International Collaborative (MaGIC) pediatric data set and adult germ cell studies. The MaGIC data set will be expanded and analyzed. In addition, all studies will emphasize coordination of the collection of tumor material for biologic studies. BEJ, carboplatin, etoposide, and bleomycin (administered once per week); BEP, cisplatin, etoposide, and bleomycin (administered once per week); CCLG, Children's Cancer and Leukemia and Cancer Group; COG, Children's Oncology Group; GOG, Gynecology Oncology Group; IGCCC, International Germ Cell Consensus Classification; JEb, carboplatin, etoposide, and bleomycin only with cycle; PEb, cisplatin, etoposide, and bleomycin only with cycle; TIGER, Randomized Phase III Trial of Initial Salvage Chemotherapy for Patients with Germ Cell Tumors.