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<p>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.</p>

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Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月28日

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  • Rebecca Wray,
  • Hania Paverd,
  • Ines Machado,
  • Johanna Barbieri,
  • Farhana Easita,
  • Abigail R. Edwards,
  • Ferdia A. Gallagher,
  • Iosif A. Mendichovszky,
  • Thomas J. Mitchell,
  • Maike de la Roche,
  • Jacqueline D. Shields,
  • Stephan Ursprung,
  • Lauren Wallis,
  • Anne Y. Warren,
  • Sarah J. Welsh,
  • Mireia Crispin-Ortuzar,
  • Grant D. Stewart,
  • James O. Jones,
  • Niki Couper,
  • Lisa E. M. Hopcroft,
  • Robert Hill,
  • Athena Matakidou,
  • Cara Caasi,
  • James Watson,
  • Ruby Cross,
  • Sarah W. Burge,
  • Anne George,
  • Tobias Klatte,
  • Tevita F. Aho,
  • James N. Armitage,
  • Sabrina Helena Rossi,
  • Charlie Massie,
  • Shubha Anand,
  • Tiffany Haddow,
  • Marc Dodd,
  • Wenhan Deng,
  • Ezequiel Martin,
  • Philip Howden,
  • Stephanie Wenlock,
  • Evis Sala,
  • Stefan Symeonides,
  • Lynn Ho,
  • Jennifer Baxter,
  • Stuart Leslie,
  • Duncan McLaren,
  • John Brush,
  • Marie O’Donnell,
  • Alisa Griffin,
  • Ruth Orr,
  • Catriona Cowan,
  • Thomas Powles,
  • Anna Pejnovic,
  • Sophia Tincey,
  • Lee Grant,
  • Martin Nuttall,
  • Lucy Willsher,
  • Christian Barnett,
  • David Nicol,
  • James Larkin,
  • Alison Fielding,
  • Christopher G. Smith,
  • Axel Bex,
  • Ekaterini Boleti,
  • Jade Carruthers,
  • Tim Eisen,
  • Kate Fife,
  • Angela Godoy,
  • Abdel Hamid,
  • Alexander Laird,
  • Steve Leung,
  • Jahangeer Malik,
  • Faiz Mumtaz,
  • Grenville Oades,
  • Andrew N. Priest,
  • Antony C. P. Riddick,
  • Balaji Venugopal,
  • Michelle Welsh,
  • Kathleen Riddle,
  • Robert J. Jones

摘要

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.