Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus
- Abstract:
- 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. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.
- Authors:
- R Wray, H Paverd, I Machado, J Barbieri, F Easita, AR Edwards, FA Gallagher, IA Mendichovszky, TJ Mitchell, M de la Roche, JD Shields, S Ursprung, L Wallis, AY Warren, SJ Welsh, M Crispin-Ortuzar, GD Stewart, JO Jones, N Couper, LEM Hopcroft, R Hill, A Matakidou, C Caasi, J Watson, R Cross, SW Burge, A George, T Klatte, TF Aho, JN Armitage, SH Rossi, C Massie, S Anand, T Haddow, M Dodd, W Deng, E Martin, P Howden, S Wenlock, E Sala, S Symeonides, L Ho, J Baxter, S Leslie, D McLaren, J Brush, M O’Donnell, A Griffin, R Orr, C Cowan, T Powles, A Pejnovic, S Tincey, L Grant, M Nuttall, L Willsher, C Barnett, D Nicol, J Larkin, A Fielding, CG Smith, A Bex, E Boleti, J Carruthers, T Eisen, K Fife, A Godoy, A Hamid, A Laird, S Leung, J Malik, F Mumtaz, G Oades, AN Priest, ACP Riddick, B Venugopal, M Welsh, K Riddle, RJ Jones
- Journal:
- Nature Communications
- Citation info:
- 16(1)
- Publication date:
- 28th Apr 2025
- Full text
- DOI