Impact of age on survival according to molecular tumor findings in children and adolescents with soft-tissue and bone sarcoma: The BIOSCA project

Emmanuel Desandes; Eve Lapouble; Brigitte Lacour; Sandra Guissou; Stéphanie Goujon; Anne-Sophie Defachelles; Valérie Marechal; Nathalie Gaspar; Anne Gomez-Mascard; Marie Karanian; Perrine Marec-Berard; Véronique Minard-Colin; Daniel Orbach; Marie-Dominique Tabone; Olivier Delattre; Gaelle Pierron

doi:10.1016/j.canep.2023.102398

Impact of age on survival according to molecular tumor findings in children and adolescents with soft-tissue and bone sarcoma: The BIOSCA project

Cancer Epidemiol. 2023 Jun 23:102398. doi: 10.1016/j.canep.2023.102398. Online ahead of print.

Authors

Emmanuel Desandes¹, Eve Lapouble², Brigitte Lacour³, Sandra Guissou³, Stéphanie Goujon⁴, Anne-Sophie Defachelles⁵, Valérie Marechal², Nathalie Gaspar⁶, Anne Gomez-Mascard⁷, Marie Karanian⁸, Perrine Marec-Berard⁹, Véronique Minard-Colin⁶, Daniel Orbach¹⁰, Marie-Dominique Tabone¹¹, Olivier Delattre¹², Gaelle Pierron²

Affiliations

¹ Registre National des cancers de l'Enfant, Registre National des Tumeurs Solides de l'Enfant, CHRU Nancy, Vandœuvre-lès-Nancy, France; Epidemiology of childhood and adolescent cancers, CRESS, INSERM, UMR1153, Université Paris-Cité, Paris, France. Electronic address: emmanuel.desandes@univ-lorraine.fr.
² Unité de Génétique Somatique, Département de génétique, Institut Curie, Paris, France.
³ Registre National des cancers de l'Enfant, Registre National des Tumeurs Solides de l'Enfant, CHRU Nancy, Vandœuvre-lès-Nancy, France; Epidemiology of childhood and adolescent cancers, CRESS, INSERM, UMR1153, Université Paris-Cité, Paris, France.
⁴ Epidemiology of childhood and adolescent cancers, CRESS, INSERM, UMR1153, Université Paris-Cité, Paris, France; Registre National des Cancers de l'Enfant, Hôpital Paul Brousse, Groupe Hospitalier Universitaire Paris-Sud, Assistance Publique Hôpitaux de Paris (AP-HP), Villejuif, and Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France.
⁵ Department of Pediatric, Adolescents and Young Adults Oncology, Centre Oscar Lambret, Lille, France.
⁶ Department of Oncology for Child and Adolescent, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
⁷ Laboratoire d'anatomie et cytologie pathologiques, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
⁸ Departments of Biopathology, Centre Léon Bérard, Lyon, France; Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Cancer Research of Lyon, Lyon, France.
⁹ Département d'hémato-oncologie pédiatrique, IHOPe/Centre Leon Berard, Lyon, France.
¹⁰ SIREDO oncology center (Care, Innovation and Research for Children, Adolescents and young Adults with Cancer), Institut Curie, PSL University, Paris, France.
¹¹ Department of Pediatric Hemato-Oncology, Armand-Trousseau Sorbonne University Hospital, AP-HP, Paris, France.
¹² Unité de Génétique Somatique, Département de génétique, Institut Curie, Paris, France; INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France.

PMID: 37357067
DOI: 10.1016/j.canep.2023.102398

Abstract

Background: Adolescents (15-19 years) with sarcoma are known to have significantly worse survival than children (0-14 years). One possible reason may be that the adolescent sarcomas exhibit specific biological characteristics resulting in differences in clinical presentation and treatment resistance behaviors. The BIOSCA project aims to further explore these age-related differences in survival accounting for molecular tumor characteristic in children and adolescents with sarcoma.

Methods: A retrospective national population-based observational study with documented somatic genetic analyses was conducted between 2011 and 2016 of all patients aged from 0 to 17 years with a diagnosis of sarcoma using the National Registry of Childhood Cancers Database.

Results: A total of 1637 children (0-9years: 40%), preadolescents (10-14years: 35%) and adolescents (15-17 years: 25%) with a diagnosis of bone (N = 845) or soft-tissue (N = 792) sarcoma were included. Adolescents had significantly worse outcome for undifferentiated small round cell sarcoma (USRCS), alveolar rhabdomyosarcoma (ARMS), and epithelioid sarcoma. Five-year overall survivals were worse among CIC-rearranged USRCS cases (47% [95%CI:21-69]) as compared to other USRCS, and PAX3::FOXO1 ARMS patients (44% [95%CI:32-55]) as compared to other ARMS. Adjusting for stage and genomic-profiling status, adolescents with USRCS were 1.6-fold more likely to die than children (P = 0.05), while the difference in survival between age of ARMS patients was weaken. Indeed, the prevalence of PAX3::FOXO1 increased significantly with age.

Conclusion: Age was an independent prognostic factor of outcome only in patients with USRCS, while the association between age and survival of patients with ARMS could be partly explained by differences in prevalence of PAX3::FOXO1.

Keywords: Adolescents; Children; Molecular biomarker; Sarcoma; Survival.