A comprehensive clinico-pathological review of a series of pediatric, adolescents and young adults with high-grade osteosarcoma: from clinics to biomarker discovery.

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.