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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

1
Children's Cancer Team, Cancer Research Clinical Trials Unit, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address: s.depani@bham.ac.uk.
2
Children and Young Persons Cancer Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, UK. Electronic address: Sara.stoneham@nhs.net.
3
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: mkrailo@childrensoncologygroup.org.
4
Statistics and Data Centre, Children's Oncology Group, Monrovia, CA, USA. Electronic address: cxia@childrensoncologygroup.org.
5
Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Electronic address: james.nicholson@addenbrookes.nhs.uk.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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

KEYWORDS:

Carboplatin; Germ cell; Late effects; Paediatric

PMID:
31306943
DOI:
10.1016/j.ejca.2019.05.001

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