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.

Pediatric malignant germ cell tumors: A comparison of the neuro‐oncology and solid tumor experience

“…A clinical trial of active surveillance of females with stage I malignant ovarian GCTs from the Children's Oncology Group showed that despite a 4‐year EFS of only 52%, OS was maintained at 99% after standard first‐line chemotherapy . Future studies are planned to evaluate surveillance strategies after complete resection for extragonadal sites and all histologies …”

“…A phase II study of 107 relapsed patients treated with paclitaxel and ifosfamide followed by high‐dose carboplatin and etoposide and subsequent ASCR had a 5‐year EFS of 47% and OS of 52% . Currently, there is an ongoing phase III randomized control trial comparing paclitaxel, ifosfamide, and cisplatin (TIP) versus TI‐CE (TIGER Study/Alliance 0311102/EORTC 1407) with tandem autologous transplants for refractory or recurrent GCTs …”

Involvement and comfort of gynecologic oncologists in the treatment of pediatric, adolescent, and young adult patients with gynecologic malignancies

“…Similarly, collaboration between providers and institutions has been stressed recently. Olson et al . examined collaborations in gynecologic cancer clinical trials and noted that this is expanding; pediatric and adult oncologists, surgeons, and other sub‐specialists including gynecologic oncology were included in this study.…”

Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study

“…Patients are treated at pediatric departments as well as gynecology units. An initial surgery may also sometimes be managed at nonspecialized centers, and inadequate surgical staging is common . Luckily, the survival rates for children with malignant germ cell tumors (GCT) generally have greatly improved.…”