The United Kingdom Children’s Cancer Study Group’s Second Germ Cell Tumor Study: Carboplatin, Etoposide, and Bleomycin Are Effective Treatment for Children With Malignant Extracranial Germ Cell Tumors, With Acceptable Toxicity

Mann, J R; Raafat, F.; Robinson, K.; Imeson, John; Gornall, P.; Sokal, M.; Gray, Elizabeth; McKeever, Patricia; Hale, Juliet; Bailey, Simon; Oakhill, A.

doi:10.1200/jco.2000.18.22.3809

Cited by 254 publications

(189 citation statements)

References 29 publications

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“…This view would be concordant with known clinical outcome data, which indicates that childhood MGCTs can be treated differently to their adult counterparts without adverse outcomes well into adolescence (Mann et al, 2000). Where the biological cut-off between childhood and adult MGCTs occurs, and what biology underpins this, has still to be elucidated.…”

Section: Discussionsupporting

confidence: 59%

Malignant germ cell tumours of childhood: new associations of genomic imbalance

et al. 2007

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Malignant germ cell tumours (MGCTs) of childhood are a rare group of neoplasms that comprise many histological subtypes and arise at numerous different sites. Genomic imbalances have been described in these tumours but, largely because of the paucity of cases reported in the literature, it is unclear how they relate to abnormalities in adult MGCTs and impact on potential systems for classifying GCTs. We have used metaphase-based comparative genomic hybridisation to analyse the largest series of paediatric MGCTs reported to date, representing 34 primary tumours (22 yolk sac tumours (YSTs), 11 germinomatous tumours and one metastatic embryonal carcinoma) occurring in children from birth to age 16, including 17 ovarian MGCTs. The large dataset enabled us to undertake statistical analysis, with the aim of identifying associations worthy of further investigation between patterns of genomic imbalance and clinicopathological parameters. The YSTs showed an increased frequency of 1p-(P ¼ 0.003), 3p þ (P ¼ 0.02), 4qÀ (P ¼ 0.07) and 6qÀ (P ¼ 0.004) compared to germinomatous tumours. Gain of 12p, which is invariably seen in adult MGCTs, was present in 53% of primary MGCTs of children aged 5 -16 and was also observed in four of 14 YSTs affecting children less than 5. Two of these cases (14% of MGCTs in children less than 5) showed gain of the 12p11 locus considered to be particularly relevant in adult MGCTs. Gain of 12p showed a significant association with gain of 12q. Conversely, MGCTs without 12p gain displayed a significantly increased frequency of loss on 16p (P ¼ 0.04), suggesting that this imbalance may contribute to tumour development in such cases. This data provides new insight into the biology of this under-investigated tumour group and will direct future studies on the significance of specific genetic abnormalities.

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Section: Discussionsupporting

confidence: 59%

Malignant germ cell tumours of childhood: new associations of genomic imbalance

et al. 2007

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“…For 137 children treated with JEB in this trial, the 5-year EFS was 88% and OS was 91%, which was comparable to the outcomes using PEb, but with no reports of sensorineural hearing loss. 48 These results suggested that carboplatin could be a potential alternative to cisplatin in children when used in sufficient doses. This hypothesis forms the basis of an upcoming collaborative trial.…”

Section: Staging and Risk Groupsmentioning

confidence: 82%

Paediatric extracranial germ-cell tumours

Shaikh

Murray

Amatruda

et al. 2016

The Lancet Oncology

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The management of paediatric extracranial germ cell tumours (GCTs) carries a unique set of challenges. GCTs are a heterogeneous group of neoplasms that present across a wide range of age, site, histology, and clinical behaviour. They are managed by a diverse variety of specialists. Correspondingly, their staging, risk-stratification, and treatment approaches have evolved disparately along multiple trajectories. Paediatric GCTs differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate evidence-based care. Suboptimal outcomes remain for several patient groups, and among survivors there are significant long-term toxicities.The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into better patient outcomes. Future trials will be characterised by improved riskstratification systems, biomarkers for response and toxicity, rational reduction of therapy for low-risk patients and novel approaches for highrisk patients, and improved international collaboration across paediatric and adult cooperative research groups. Correspondingly, their staging, risk-stratification, and treatment approaches have evolved disparately along multiple trajectories. Paediatric GCTs differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate evidence-based care.Suboptimal outcomes remain for several patient groups, and among survivors there are significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into better patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxicity, rational reduction of therapy for low-risk patients and novel approaches for high-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.

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“…For example, studies have reported similar outcomes in pediatric germ cell tumour patients treated using carboplatin, etoposide and bleomycin compared to treatment with cisplatin, etoposide and bleomycin but with less ototoxicity 53,54 and treatment with carboplatin, etoposide and bleomycin has been suggested as an alternative treatment in young children 55 . A possible role for carboplatin has also been suggested in the treatment of neuroblastoma, where one study reported similar survival between patients receiving cisplatin therapy and patients receiving partial substitution of cisplatin therapy with carboplatin 56 .…”

Section: How Should Patients Undergoing Cisplatin Therapy Be Managed mentioning

confidence: 83%

Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Lee

Pussegoda

Rassekh

et al. 2016

Therapeutic Drug Monitoring

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Abstract:Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field; (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment and management of cisplatin-induced hearing loss in children and adults; and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin based chemotherapy.

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The United Kingdom Children’s Cancer Study Group’s Second Germ Cell Tumor Study: Carboplatin, Etoposide, and Bleomycin Are Effective Treatment for Children With Malignant Extracranial Germ Cell Tumors, With Acceptable Toxicity

Abstract: Conservative surgery, a watch-and-wait approach after complete excision, and JEB for those requiring chemotherapy produced high cure rates and few serious complications.

Cited by 254 publications

References 29 publications

Malignant germ cell tumours of childhood: new associations of genomic imbalance

Malignant germ cell tumours of childhood: new associations of genomic imbalance

Paediatric extracranial germ-cell tumours

Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

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