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

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

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.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage*
  • Carboplatin / adverse effects
  • Chemotherapy, Adjuvant
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Neoplasm Staging
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Orchiectomy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovariectomy
  • Progression-Free Survival
  • Risk Assessment
  • Risk Factors
  • Teratoma / drug therapy*
  • Teratoma / mortality
  • Teratoma / pathology
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / pathology
  • Time Factors
  • United Kingdom

Substances

  • Carboplatin
  • Cisplatin