Seminoma and dysgerminoma: evidence for alignment of clinical trials and de-escalation of systemic chemotherapy

Frontiers in Oncology

Oncology

Nicola D. MacDonald¹  Christopher P. Bunting²  Daniel M. Berney³  Rupali Arora⁴  Jonathan Shamash⁵  Georgina E. Wood⁶  Constantine Alifrangis⁶  Mesel Veli⁶  Michelle Lockley⁷  Rowan E. Miller⁸  Sara Stoneham⁹ 

[1] Department of Gynaecology, University College London Hospital, London, United Kingdom;Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;Histopathology, Barts Health NHS Trust, London, United Kingdom;Histopathology, University College London Hospital, London, United Kingdom;Medical Oncology, Barts Health NHS Trust, London, United Kingdom;Medical Oncology, University College London Hospital, London, United Kingdom;Medical Oncology, University College London Hospital, London, United Kingdom;Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom;Medical Oncology, University College London Hospital, London, United Kingdom;Medical Oncology, Barts Health NHS Trust, London, United Kingdom;Paediatric Oncology, University College London Hospital, London, United Kingdom;

关键词: systemic chemotherapy;    carboplatin;    germ cell tumours;    seminoma;    dysgerminoma;    de-escalating chemotherapy;   

DOI  :  10.3389/fonc.2023.1271647

 received in 2023-08-02, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

Malignant germ cell tumours are a group of rare cancers whose incidence peaks in late adolescence and early adulthood. Dysgerminomas of the ovary and seminomas of the testis are analogous diseases, but seminomas have a 10-fold higher incidence. The two tumours are morphologically identical and are only differentiated by surrounding organ-specific tissue or testicular germ cell neoplasia in situ. They share genetic features including KIT and RAS mutations, amplification of chromosome 12p, and expression of pluripotency markers (NANOG (Nanog homeobox), OCT3/4 (Octamer-binding transcription factor 3/4), and SAL4 (Spalt-like trascription factor 4)). Both histologies are exquisitely sensitive to platinum chemotherapy, and the combination of bleomycin, etoposide, and cisplatin (BEP) yields survival rates greater than 90%. However, BEP causes significant, lifelong toxicity (cardiovascular, renal, respiratory, and neurological) in these young patients with an expectation of cure. Here, we comprehensively review the biological features of dysgerminoma and seminoma to demonstrate that they are biologically analogous diseases. We present available clinical trial data supporting de-escalation of chemotherapy treatment. Finally, we propose that future trials should enrol men, women, and children to benefit all patients regardless of age or sex.

【 授权许可】

Unknown   
Copyright © 2023 Wood, Bunting, Veli, Arora, Berney, Alifrangis, MacDonald, Miller, Shamash, Stoneham and Lockley