Paediatric extracranial germ-cell tumours

Abstract

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.

α‐Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium

“…5 The MaGIC risk categories are as follows: low risk (stage I disease of the testis, ovary, or extragonadal sites), standard risk 1 (SR1; age <11 years and stage II-IV disease of the testis, ovary, or extragonadal sites), standard risk 2 (SR2; age ≥11 years and stage II-IV disease of the testis meeting International Germ Cell Cancer Consensus Group good-risk criteria, stage II-III disease of the ovary, or stage II disease of extragonadal sites), and poor risk (age ≥11 years and stage II-IV disease of the testis meeting International Germ Cell Cancer Consensus Group intermediate-or poor-risk criteria, stage IV disease of the ovary, or stage III-IV disease of extragonadal sites). 5 The MaGIC risk categories are as follows: low risk (stage I disease of the testis, ovary, or extragonadal sites), standard risk 1 (SR1; age <11 years and stage II-IV disease of the testis, ovary, or extragonadal sites), standard risk 2 (SR2; age ≥11 years and stage II-IV disease of the testis meeting International Germ Cell Cancer Consensus Group good-risk criteria, stage II-III disease of the ovary, or stage II disease of extragonadal sites), and poor risk (age ≥11 years and stage II-IV disease of the testis meeting International Germ Cell Cancer Consensus Group intermediate-or poor-risk criteria, stage IV disease of the ovary, or stage III-IV disease of extragonadal sites).…”

“…2 Although event-free survival for pediatric patients remains excellent (>85% at 5 years) with modern multidisciplinary care, individuals with an advanced tumor stage and an age ≥11 years experience poor outcomes. [5][6][7] Certain nonseminomatous germ cell tumor histologies (yolk sac tumors, embryonal carcinomas, and teratomas) secrete α-fetoprotein (AFP), a 70-kDa protein, and this tumor marker is used as an indicator of disease response to chemotherapy and disease remission. [5][6][7] Certain nonseminomatous germ cell tumor histologies (yolk sac tumors, embryonal carcinomas, and teratomas) secrete α-fetoprotein (AFP), a 70-kDa protein, and this tumor marker is used as an indicator of disease response to chemotherapy and disease remission.…”

“…4 Although 50 to 70% of children with relapsed germ cell tumors can be successfully treated with salvage therapies, second-line treatments can be toxic, and the emotional toll of relapse substantial. [5][6][7] Certain nonseminomatous germ cell tumor histologies (yolk sac tumors, embryonal carcinomas, and teratomas) secrete α-fetoprotein (AFP), a 70-kDa protein, and this tumor marker is used as an indicator of disease response to chemotherapy and disease remission. Several studies of adult patients with germ cell tumors have shown that an unsatisfactory decline of elevated tumor markers after the initiation of therapy is associated with a poor prognosis.…”

Maternal Preeclampsia and Odds of Childhood Cancers in Offspring: A California Statewide Case–Control Study

“…Germ cell tumours are presumed to arise from pluripotent primordial germ cells and show a broad range of possible histologies . Both biological features and clinical presentation differ by histological subtype of germ cell tumours, which implies distinct aetiologies and necessitates subgroup analysis.…”

“…Germ cell tumours are presumed to arise from pluripotent primordial germ cells and show a broad range of possible histologies. 26 Both biological features and clinical presentation differ by histological subtype of germ cell tumours, which implies distinct aetiologies and necessitates subgroup analysis. Differential epigenetic changes, microRNA expression and signalling pathway activation were observed in certain subtypes of germ cell tumours, which provided potential biological evidence for distinct preeclampsia -germ cell tumour associations in epidemiological studies.…”