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Bone Tumors and Orthopedics

(P 71) GERMLINE POLYMORPHISMS IN THE VEGF PATHWAY AS PROGNOSTIC BIOMARKERS IN LOCALIZED HIGH-GRADE OSTEOSARCOMA: A STUDY BASED ON DATA FROM THE GEIS-33 PROTOCOL

Objective: The VEGF pathway influences angiogenesis, which impacts tumor progression and patient outcomes. This study aimed to evaluate whether genetic polymorphisms in the vascular endothelial growth factor (VEGF) pathway are associated with relapse-free survival (RFS) and overall survival (OS) in patients with localised high-grade osteosarcoma.

Methods: 68 patients with localised high-grade osteosarcoma enrolled in the GEIS 33 protocol were included. All patients received two cycles of MAP (methotrexate, doxorubicin, cisplatin) chemotherapy followed by surgery, with adjuvant treatment tailored to histological response and P-glycoprotein expression. DNA was extracted from peripheral blood samples and genotyped for specific variants in the VEGFA, VEGFR1, and VEGFR2 genes. Clinical and genetic data were correlated with survival outcomes.

Results: median follow-up was 62.4 months. The 5-year RFS was 71%, and the 5-year OS was 72%. Among clinical factors, only surgical margins (wide/radical vs. marginal) were significantly associated with RFS (P = 0.04), while age, gender, tumor site, and histological response did not correlate with OS.
For the VEGFR1 rs7993418 variant, the 5-year RFS was 89% for AA genotype carriers, 48% for heterozygotes, and 50% for GG genotype (P = 0.03). The 5-year OS was 79% for AA genotype, 68% for heterozygotes, and 33% for GG genotype (P = 0.01).
For the VEGFR2 rs9582036 variant, AA genotype had a 5-year RFS of 92%, compared to 24% for carriers of the C allele (P = 0.02). The 5-year OS was 68% for AA genotype, 46% for C allele carriers (P = 0.03).
In the multivariate Cox regression analysis conducted for each SNP, where surgical margins were included as covariate, these polymorphisms remained statistically significant.

Conclusion: Germline polymorphisms in the VEGF pathway may help predict RFS and OS in high grade localised osteosarcoma patients treated with chemotherapy. Their role as predictive/prognostic biomarkers in osteosarcoma patients treated with antiangiogenic drugs should be explored.