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Eur J Cancer. 2019 Sep;118:49-57. doi: 10.1016/j.ejca.2019.05.001. Epub 2019 Jul 12.

Results from the UK Children's Cancer and Leukaemia Group study of extracranial germ cell tumours in children and adolescents (GCIII).

Author information

Children's Cancer Team, Cancer Research Clinical Trials Unit, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address:
Children and Young Persons Cancer Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, UK. Electronic address:
Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Statistics and Data Centre, Children's Oncology Group, Monrovia, CA, USA. Electronic address:
Statistics and Data Centre, Children's Oncology Group, Monrovia, CA, USA. Electronic address:
Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Electronic address:



For extracranial malignant germ cell tumours (MGCTs) in the UK, the GCII study used carboplatin-based chemotherapy (JEb) and demonstrated equivalent survival to cisplatin-containing protocols. GCIII, a single-arm observational study, used new risk stratification, replaced consolidation chemotherapy with a standard number of cycles and introduced surveillance for all stage I MGCTs. Pure teratomas were registered to understand their natural history.


Patients with MGCTs were stratified to three risk groups - low risk (LR), intermediate risk (IR) and high risk (HR), using stage and prognostic factors. Patients with alpha fetoprotein (AFP) >10,000 kU/L, stage IV disease (except testis <5 years and all germinomas) or stage II-IV mediastinal tumour were classified HR. Stage I tumours (LR) received chemotherapy only if disease progressed. IR and HR patients received 4 and 6 JEB cycles, respectively. Carboplatin dose was calculated using glomerular filtration rate to give an area under the curve of 7.9 ml/m2.min.


Eighty-six patients with MGCTs were enrolled from 2005 to 2009: 59% female, median age, 5.7 years. Twenty-five patients were LR, 21 IR and 38 HR. Seven LR patients had disease progression; all were successfully treated with chemotherapy. Overall survival (OS) for the whole group was 97%; 5-year event-free survival for JEb-treated patients was 92%, and OS, 95%. JEb was well tolerated with no observed significant hearing or renal side-effects. There was no discernible difference in carboplatin dose whether calculated by body surface area or creatinine clearance. Forty-seven patients with teratoma were managed with surgery and one had malignant transformation.


Carboplatin-based chemotherapy as part of a risk-stratified approach leads to excellent survival in paediatric MGCTs, minimising potential burden of long-term effects.


Carboplatin; Germ cell; Late effects; Paediatric


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