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A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice

Newton, C; Murali, K; Ahmad, A; Hockings, H; Graham, R; Liberale, V; Sarker, S-J; ... Lockley, M; + view all (2019) A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice. European Journal of Cancer , 113 pp. 19-27. 10.1016/j.ejca.2019.03.001. Green open access

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Abstract

BACKGROUND: Adult guidelines recommend BEP (bleomycin, etoposide, cisplatin) for all ovarian germ cell tumours, causing debilitating toxicities in young patients who will survive long term. Paediatricians successfully reduce toxicities by using lower bleomycin doses and substituting carboplatin for cisplatin, while testicular and paediatric immature teratomas (ITs) are safely managed with surgery alone. AIM: The aim was to determine whether reduced-toxicity treatment could rationally be extended to patients older than 18 years. // METHODS: Multicentre cohort study was carried out in four large UK cancer centres over 12 years. // RESULTS: One hundred thirty-eight patients were enrolled. Overall survival was 93%, and event-free survival (EFS) was 72%. Neoadjuvant/ adjuvant chemotherapy (82% BEP) caused 27 potentially chronic toxicities, and one patient subsequently died from acute lymphoblastic leukaemia. There was no difference in histology, stage or grade in patients ≤/>18 years, and EFS was not different in these age groups (≤18:28% and >18:28%; log-rank P = 0.96). Histological subtype powerfully predicted EFS (log-rank P = 4.9 × 10-7). Neoadjuvant/adjuvant chemotherapy reduced future relapse/progression in dysgerminoma (n = 37, chemo:0% vs. no chemo:20%), yolk sac tumour (n = 23, 26.3% vs.75%) and mixed germ cell tumour (n = 32, 40%vs.70%) but not in IT (n = 42, 33% vs.15%). Additionally, we observed no radiological responses to chemotherapy in ITs, pathological IT grade did not predict EFS (univariate hazard ratio 0.82, 95% confidence interval: 0.57-1.19, P = 0.94) and there were no deaths in this subtype. // CONCLUSION: Survival was excellent but chemotherapy toxicities were severe, implying significant overtreatment. Our data support the extension of reduced-toxicity, paediatric regimens to adults. Our practice-changing findings that IT was chemotherapy resistant and pathological grade uninformative strongly endorse exclusive surgical management of ovarian ITs at all ages.

Type: Article
Title: A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejca.2019.03.001
Publisher version: https://doi.org/10.1016/j.ejca.2019.03.001
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/ licenses/ by/4.0/.
Keywords: BEP, Dysgerminoma, Immature teratoma, Mixed germ cell tumour, Ovarian germ cell cancer, Yolk sac tumour
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > UCL Medical School
URI: https://discovery.ucl.ac.uk/id/eprint/10072648
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