B Fresneau1, D Orbach2, C Faure-Conter3, H Sudour-Bonnange4, C Vérité5, V Gandemer6, M Pasquet7, S Fasola8, A Rome9, S Raimbault10, H Martelli11, D Frappaz3, G Le Teuff12, C Patte10. 1. Gustave Roussy, Université Paris-Saclay, Department of Pediatric Oncology, Villejuif, F-94805, France; Paris-Saclay University, Paris-Sud University, CESP, INSERM, Villejuif, France. Electronic address: brice.fresneau@gustaveroussy.fr. 2. SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris, France. 3. Institut D'Hemato-oncologie Pediatrique, Department of Pediatric Oncology, Lyon, France. 4. Centre Oscar Lambret, Department of Pediatric Oncology, Lille, France. 5. Centre Hospitalier Universitaire, Department of Pediatric Onco-hematology, Bordeaux, France. 6. Centre Hospitalier Universitaire, Department of Pediatric Onco-hematology, Rennes, France. 7. Centre Hospitalier Universitaire, Department of Pediatric Onco-hematology, Toulouse, France. 8. Centre Hospitalier Universitaire, Department of Pediatric Onco-hematology, Hôpital Trousseau, AP-HP, France. 9. Centre Hospitalier Universitaire, Department of Pediatric Oncology, Marseille, France. 10. Gustave Roussy, Université Paris-Saclay, Department of Pediatric Oncology, Villejuif, F-94805, France. 11. Centre Hospitalier Universitaire, Department of Pediatric Surgery, Le Kremlin-Bicêtre, France. 12. Paris-Saclay University, Paris-Sud University, CESP, INSERM, Villejuif, France; Gustave Roussy, Department of Biostatistics, F94805 Villejuif, France.
Abstract
PURPOSE: In adults' non-seminomatous germ cell tumours (NS-GCT), alpha-fetoprotein (AFP) decline was identified as an important prognostic factor. We investigated its prognostic value in the French TGM95 study for childhood NS-GCT. PATIENTS AND METHODS: Three risk groups were defined: low risk (LR: localised and completely resected pS1, AFP<15000 ng/ml), with a 'wait-and-see' strategy; intermediate-risk (IR: localised incompletely resected, AFP<15000 ng/ml) with 3-5 vinblastine-bleomycine-cisplatin courses; high risk (HiR: AFP≥15000 ng/ml and/or metastatic) with 4-6 etoposide-ifosfamide-cisplatin courses. The multivariable prognostic analysis for progression-free survival (PFS) included age (±10 years), primary tumour site (1-testis, 2-ovary, 3-extragonadal), extent of disease (1-pS1, 2-loco-regional dissemination, 3-metastasis) and AFP (±10,000 ng/ml). AFP decline prognostic value was investigated in IR + HiR groups using predicted time to normalisation (TTN), AFP change, and difference between observed and expected (based on AFP half-life) area under the curve (O-E AUC). RESULTS: From January 1995 to December 2005, 239 patients (median age = 3years, 60 LR, 65 IR, 114 HiR) were included. Main sites were testis (n = 66), ovary (n = 77) and sacrococcygeal (n = 57). Five-year PFS and OS were 85% (95% confidence interval [CI] = 80-89%) and 93% (89-95%), respectively. Age ≥ 10 years (hazard ratio [HR] = 4.6, 95% CI = 2.1-10.1, p = 0.0001) and extragonadal primary (HR = 6.3, 95% CI = 2.0-19.9, p = 0.005) were significant prognostic factors. In AFP decline analysis (n = 151, 17 events), TTN (p = 0.61) and AFP change (p = 0.10) were not prognostic, whereas we showed a significant effect of O-E AUC (HR = 2.1, 95% CI = 1.0-4.2, p = 0.05). CONCLUSION: Age ≥ 10 years and extragonadal tumours remain as poor prognostic factors. Contrary to adults, TTN is not reliable in paediatric NS-GCT. The prognostic value of O-E AUC should be investigated in larger studies.
PURPOSE: In adults' non-seminomatous germ cell tumours (NS-GCT), alpha-fetoprotein (AFP) decline was identified as an important prognostic factor. We investigated its prognostic value in the French TGM95 study for childhood NS-GCT. PATIENTS AND METHODS: Three risk groups were defined: low risk (LR: localised and completely resected pS1, AFP<15000 ng/ml), with a 'wait-and-see' strategy; intermediate-risk (IR: localised incompletely resected, AFP<15000 ng/ml) with 3-5 vinblastine-bleomycine-cisplatin courses; high risk (HiR: AFP≥15000 ng/ml and/or metastatic) with 4-6 etoposide-ifosfamide-cisplatin courses. The multivariable prognostic analysis for progression-free survival (PFS) included age (±10 years), primary tumour site (1-testis, 2-ovary, 3-extragonadal), extent of disease (1-pS1, 2-loco-regional dissemination, 3-metastasis) and AFP (±10,000 ng/ml). AFP decline prognostic value was investigated in IR + HiR groups using predicted time to normalisation (TTN), AFP change, and difference between observed and expected (based on AFP half-life) area under the curve (O-E AUC). RESULTS: From January 1995 to December 2005, 239 patients (median age = 3years, 60 LR, 65 IR, 114 HiR) were included. Main sites were testis (n = 66), ovary (n = 77) and sacrococcygeal (n = 57). Five-year PFS and OS were 85% (95% confidence interval [CI] = 80-89%) and 93% (89-95%), respectively. Age ≥ 10 years (hazard ratio [HR] = 4.6, 95% CI = 2.1-10.1, p = 0.0001) and extragonadal primary (HR = 6.3, 95% CI = 2.0-19.9, p = 0.005) were significant prognostic factors. In AFP decline analysis (n = 151, 17 events), TTN (p = 0.61) and AFP change (p = 0.10) were not prognostic, whereas we showed a significant effect of O-E AUC (HR = 2.1, 95% CI = 1.0-4.2, p = 0.05). CONCLUSION: Age ≥ 10 years and extragonadal tumours remain as poor prognostic factors. Contrary to adults, TTN is not reliable in paediatric NS-GCT. The prognostic value of O-E AUC should be investigated in larger studies.
Authors: Bo Ci; Donghan M Yang; Mark Krailo; Caihong Xia; Bo Yao; Danni Luo; Qinbo Zhou; Guanghua Xiao; Lin Xu; Stephen X Skapek; Matthew M Murray; James F Amatruda; Lindsay Klosterkemper; Furqan Shaikh; Cecile Faure-Conter; Brice Fresneau; Samuel L Volchenboum; Sara Stoneham; Luiz Fernando Lopes; James Nicholson; A Lindsay Frazier; Yang Xie Journal: JCO Clin Cancer Inform Date: 2020-06