Angiogenic and Immune Predictors of Neoadjuvant Axitinib Response in Renal Cell Carcinoma with Venous Tumour Thrombus

ABSTRACT: Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10-15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. We conducted a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders had higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predicted response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features included plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281304 | GEO | 2025/01/30

REPOSITORIES: GEO