Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis

Evgenia Papakonstantinou; Kleoniki I Athanasiadou; Georgios Markozannes; Vassiliki Tzotzola; Evdoxia Bouka; Margarita Baka; Maria Moschovi; Sophia Polychronopoulou; Emmanuel Hatzipantelis; Vasiliki Galani; Kalliopi Stefanaki; Katerina Strantzia; Maria Vousvouki; Panagiota Kourou; Evgenia Magkou; Maria Nikita; Christos Zambakides; John Michelarakis; Aikaterini Alexopoulou; Maro Gavra; Astero Malama; Evangelia E Ntzani; Eleni Th Petridou

doi:10.1016/j.canep.2024.102551

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis

Cancer Epidemiol. 2024 Mar 5:90:102551. doi: 10.1016/j.canep.2024.102551. Online ahead of print.

Authors

Evgenia Papakonstantinou¹, Kleoniki I Athanasiadou², Georgios Markozannes³, Vassiliki Tzotzola⁴, Evdoxia Bouka⁵, Margarita Baka⁶, Maria Moschovi⁷, Sophia Polychronopoulou⁸, Emmanuel Hatzipantelis⁹, Vasiliki Galani¹⁰, Kalliopi Stefanaki¹¹, Katerina Strantzia¹², Maria Vousvouki¹³, Panagiota Kourou¹⁴, Evgenia Magkou¹⁵, Maria Nikita¹⁵, Christos Zambakides¹⁶, John Michelarakis¹⁷, Aikaterini Alexopoulou¹⁸, Maro Gavra¹⁹, Astero Malama¹⁹, Evangelia E Ntzani²⁰, Eleni Th Petridou²¹

Affiliations

¹ Department of Pediatric Oncology, Ippokratio General Hospital, 49 Konstantinoupoleos Street, Thessaloniki 54642, Greece. Electronic address: e.papakonstantinou@ippokratio.gr.
² Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 Vasilisis Sophias Avenue, Athens 11528, Greece. Electronic address: drklea@med.uoa.gr.
³ Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
⁴ Department of Pediatric Hematology-Oncology (TAO), Aghia Sophia Children's Hospital, Thivon and Livadias, Goudi, Athens 11527, Greece.
⁵ Hellenic Society for Social Pediatrics and Health Promotion, Athens, Greece.
⁶ Department of Oncology, "Pan. & Agl. Kyriakou", Thivon and Papadiamantopoulou Str, Athens 11527, Greece.
⁷ Haematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Thivon and Levadias, Goudi, Athens 11527, Greece. Electronic address: mmoschov@med.uoa.gr.
⁸ Department of Pediatric Hematology-Oncology (TAO), Aghia Sophia Children's Hospital, Thivon and Livadias, Goudi, Athens 11527, Greece. Electronic address: sophpol@otenet.gr.
⁹ Children's & Adolescents Hematology-Oncology Unit, 2nd Paediatric Department, School of Medicine, Aristotle University of Thessaloniki, Greece. Electronic address: hatzip@auth.gr.
¹⁰ Paediatric and Adolescent Oncology Clinic, Children's Hospital "MITERA", Athens, Greece.
¹¹ Histopathology Department, Aghia Sophia Children's Hospital, Thivon and Levadias, Goudi, Athens 11527, Greece. Electronic address: kalstef@otenet.gr.
¹² Histopathology Department, "Pan. & Agl. Kyriakou" Children's Hospital, Thivon and Papadiamantopoulou Str, Athens 11527, Greece.
¹³ Childhood & Adolescent Hematology Oncology Unit, 2nd Pediatric Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA Hospital, Greece.
¹⁴ Pediatric Hematology-Oncology Unit, First Department of Pediatrics, Thivon and Levadias, Goudi, Athens 11527, Greece.
¹⁵ Department of Pediatric Hematology-Oncology, "Pan. & Agl. Kyriakou" Children's Hospital, Thivon and Papadiamantopoulou Str, Athens 11527, Greece.
¹⁶ 1st Orthopedic Clinic, "Pan. & Agl. Kyriakou" Children's Hospital, Thivon and Papadiamantopoulou Str, Athens 11527, Greece. Electronic address: chrzam@otenet.gr.
¹⁷ 2nd Orthopedic Clinic, "Pan. & Agl. Kyriakou" Children's Hospital, Thivon and Papadiamantopoulou Str, Athens 11527, Greece.
¹⁸ Children's & Adolescents Radiotherapy Department, "Pan. & Agl. Kyriakou" Children's Hospital, Thivon and Papadiamantopoulou Str, Athens 11527, Greece.
¹⁹ Department of Medical Imaging and Interventional Radiology, Aghia Soﬁa Children's Hospital, Thivon and Levadias, Goudi, Athens 11527, Greece.
²⁰ Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina 45110, Greece; Center for Evidence Synthesis in Health, Brown University School of Public Health, Providence, RI 02903, USA. Electronic address: entzani@uoi.gr.
²¹ Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str, Athens 11527, Greece. Electronic address: epetrid@gmail.com.

PMID: 38447251
DOI: 10.1016/j.canep.2024.102551

Abstract

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR _{females/males}: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR _{18+/<10 years}: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Keywords: NARECHEM-ST; Neoadjuvant chemotherapy; Osteosarcoma; Pediatric cancer; Survival.