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Background <p>Combining high-dose stereotactic body radiation therapy (SBRT) with FOLFIRINOX (FFX) is promising as neoadjuvant strategy for pancreatic ductal adenocarcinoma (PDAC). This study provides an in-depth histo-molecular characterisation of resected PDAC samples from patients treated with FFX ± SBRT.</p> Methods <p>Residual tumour tissues from 56 non-metastatic PDAC patients were analysed: seventeen underwent upfront surgery, seventeen received neoadjuvant FFX alone and twenty-two FFX followed by radiotherapy (sixteen SBRT, six radiochemotherapy [RT-CT]). Samples were assessed using RNAseq and immunohistochemistry/fluorescence, including multiplex.</p> Results <p>Addition of SBRT to FFX favourably remodelled PDAC, influencing stromal, immune, metabolic and molecular features. Unlike RT-CT, SBRT counteracted several detrimental effects induced by FFX alone. Notably, FFX + SBRT enriched tumours with ‘Classical’ and ‘Inactive stroma’ signatures—linked to better prognosis - while reducing ‘Basal-like’ cell enrichment. SBRT promoted COL1A1-driven stromal remodelling while globally preserving T-lymphocyte infiltration, including cytotoxic T cells, which maintained close proximity to tumour cells despite increased desmoplasia. Key transcriptional alterations induced by SBRT were identified, offering targets for future combination therapies.</p> Conclusions <p>Highlighting a more favourable stromal and molecular profile after integration of high-dose SBRT to FFX, this study supports the development, rationale and validation in prospective trials of using this treatment combination in non-metastatic PDAC.</p> <p></p>

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Favorable histo-molecular remodeling of pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX followed by high-dose stereotactic body radiotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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  • Christelle Bouchart,
  • Oier Azurmendi Senar,
  • Julie Navez,
  • Laurine Verset,
  • Anaïs Boisson,
  • Matthieu Hein,
  • Kosta Stosic,
  • Eric Quertinmont,
  • Vjola Tafciu,
  • Shulin Zhao,
  • Léo Mas,
  • Nicky D’Haene,
  • Dirk Van Gestel,
  • Luigi Moretti,
  • Ellis Michiels,
  • Ilse Rooman,
  • Vincent Detours,
  • Jean-Baptiste Bachet,
  • Pieter Demetter,
  • Karen Willard-Gallo,
  • Rémy Nicolle,
  • Tatjana Arsenijevic,
  • Jean-Luc Van Laethem

摘要

Background

Combining high-dose stereotactic body radiation therapy (SBRT) with FOLFIRINOX (FFX) is promising as neoadjuvant strategy for pancreatic ductal adenocarcinoma (PDAC). This study provides an in-depth histo-molecular characterisation of resected PDAC samples from patients treated with FFX ± SBRT.

Methods

Residual tumour tissues from 56 non-metastatic PDAC patients were analysed: seventeen underwent upfront surgery, seventeen received neoadjuvant FFX alone and twenty-two FFX followed by radiotherapy (sixteen SBRT, six radiochemotherapy [RT-CT]). Samples were assessed using RNAseq and immunohistochemistry/fluorescence, including multiplex.

Results

Addition of SBRT to FFX favourably remodelled PDAC, influencing stromal, immune, metabolic and molecular features. Unlike RT-CT, SBRT counteracted several detrimental effects induced by FFX alone. Notably, FFX + SBRT enriched tumours with ‘Classical’ and ‘Inactive stroma’ signatures—linked to better prognosis - while reducing ‘Basal-like’ cell enrichment. SBRT promoted COL1A1-driven stromal remodelling while globally preserving T-lymphocyte infiltration, including cytotoxic T cells, which maintained close proximity to tumour cells despite increased desmoplasia. Key transcriptional alterations induced by SBRT were identified, offering targets for future combination therapies.

Conclusions

Highlighting a more favourable stromal and molecular profile after integration of high-dose SBRT to FFX, this study supports the development, rationale and validation in prospective trials of using this treatment combination in non-metastatic PDAC.