Treatment and Survival of Malignant Extracranial Germ Cell Tumours in the Paediatric Population: A Systematic Review and Meta-Analysis

Abstract

Objective: This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies. Methods: The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients. Results: The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I–II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy. Conclusions: This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival.

Extracranial Germ Cell Tumors in Children: Ten Years of Experience in Three Children’s Medical Centers in Shanghai

“…The treatment for patients at a high risk of recurrence still needs to be improved. Several studies have explored the clinical factors conferring a survival disadvantage to pediatric MGCT patients, including an AFP level > 10,000 ng/mL, primary extragonadal tumors, an age greater than 11 years, a clinical stage of IV and residual disease after surgery [15][16][17]. Similar conclusions were obtained, except for children older than 11 years old.…”

Pediatric Germ Cell Tumors- Pathological Variations and Challenges

“…Likewise, in this study chemotherapy was given in 6 patients post operatively with predominant stage III & IV disease which had residual disease after surgical excision 12 .…”

“…the type of surgery and the need of adjuvant and neo adjuvant chemotherapy depends on the clinical stage of the disease. Traditionally treatment of Germ Cell tumour with clinical stage I (localized disease) is en bloc surgical resection 12 . Hence, in this study, all patients presenting at stage I tumour underwent surgical excision.…”

Primary non-gestational mediastinal choriocarcinoma metastatic to the brainstem

“…Primary extragonadal non-gestational mediastinal choriocarcinoma is a highly aggressive tumour primarily seen in young men associated with a poor prognosis 1–4 8–12. Patients with primary mediastinal germ cell tumours fare worse than those with tumours at other locations 1 8 9 11 13–17. Malignant germ cell tumours emerge from a totipotent cell; thus, accounting for the wide variety of primary anatomic sites, including gonadal, sacrococcygeal, mediastinal, retroperitoneal and other paraxial locations 18.…”