A comprehensive clinico-pathological review of a series of pediatric, adolescents and young adults with high-grade osteosarcoma: from clinics to biomarker discovery.
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BACKGROUND: We analyzed clinical and immunohistochemical characteristics of pediatric, adolescents and young adults with high-grade osteosarcoma (HGOS) to validate prognostic factors, identify targetable and prognostic biomarkers and define management of multiple relapses. METHODS: Retrospective analysis of 67 patients with HGOS between 2001 and 2020 was studied. BTN3A2, HSP90 and GLYPICAN1 were further analyzed based on their high expression on in silico model. RESULTS: Conventional osteosarcoma was the most frequent histology subtype (89.5%); 26.9% of patients had metastases at diagnosis. Proportion of limb-sparing surgery and R0 resection increased before and after 2011 (66.6% vs. 96.2%; 78.5% vs 87.5% respectively), while no treatment-related deaths occurred after 2011. 5-year OS and EFS were 61% and 56.6%, (5.4-year median follow-up (0.20-17.40). In multivariate analysis, metastatic disease was the sole independent prognostic factor. 5-year EFS and OS for patients with 1st, 2nd, and 3rd relapse were 8-12%, 0-5%, and 11.1-11.1% respectively. BTN3A2 was highly expressed at diagnosis, surgery, and relapse. CONCLUSION: Metastatic disease remains the most important prognosis factor in HGOS. Improvements in surgical procedures and reduction in treatment-related mortality were observed. Survival after multiple relapses remains poor; we define figures to be used for benchmarking in clinical trials. BTN3A2 is a potential therapeutic target.