{
  "abstract": "Background: Transcriptomic FOLFIRINOX-component sensitivity signatures have been clinically evaluated in resected and advanced PDAC, but their relevance and longitudinal stability in the neoadjuvant BR/LA setting are unknown. Patients and methods: We retrospectively studied 77 patients with borderline resectable or locally advanced PDAC treated with neoadjuvant FOLFIRINOX followed by resection. Pretreatment sensitivity to 5-fluorouracil, oxaliplatin and irinotecan was determined using previously developed locked transcriptomic classifiers and integrated into a regimen-level FOLFIRINOX classification. The primary molecular cohort comprised 53 patients whose pretreatment biopsies had [≥]10% tumour cellularity. Cox models assessed associations with survival. Longitudinal changes were assessed in 35 paired tumours. Results: Thirty-one pretreatment tumours were classified as FOLFIRINOX-sensitive (FFX-Sens), and 22 were not classified as FOLFIRINOX-sensitive (FFX-Res). FFX-Sens status was associated with longer overall survival (OS; hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25-0.93; p=0.029). In the complete-case model adjusted for baseline carbohydrate antigen 19-9 (CA19-9) and tumour size (n=50), the association with OS persisted (adjusted HR 0.47, 95% CI 0.23-0.96; p=0.037), whereas the adjusted association with disease-free survival was not statistically significant (adjusted HR 0.55, 95% CI 0.28-1.10; p=0.090). Among paired tumours, 15 changed from FFX-Sens to FFX-Res and four in the opposite direction (exact McNemar p=0.019). The OS association also persisted after adjustment for postoperative pathological factors (adjusted HR 0.40; p=0.015). Conclusions: Pretreatment FOLFIRINOX sensitivity was associated with OS under neoadjuvant FOLFIRINOX, while matched pretreatment and residual-tumour analyses revealed significant directional reclassification after treatment. These findings extend the clinical evaluation of validated drug-specific FOLFIRINOX sensitivity classifiers to the neoadjuvant setting and provide a longitudinal assessment of their stability during treatment. They support prospective evaluation of both pretreatment stratification and molecular reassessment of residual disease.",
  "abstract_shown": true,
  "affiliations": [
    "CRCM INSERM U.1068"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "C. Gaucher"
    },
    {
      "name": "M. Kaya"
    },
    {
      "name": "J. Garnier"
    },
    {
      "name": "A. Barthelemy"
    },
    {
      "name": "P. Rochigneux"
    },
    {
      "name": "F. Poizat"
    },
    {
      "name": "M. Rubis"
    },
    {
      "name": "P. Moussard"
    },
    {
      "name": "J. Roques"
    },
    {
      "name": "N. Fraunhoffer"
    },
    {
      "affs": [
        0
      ],
      "name": "N. J. Dusetti"
    },
    {
      "name": "B. Chanez"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6n4a2chdb4ysa.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.07.749857",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749857v1.full",
  "id": "6n4a2chdb4ysa",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749857v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7212002263",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749857v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6n4a2chdb4ysa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:37Z",
      "native_id": "10.64898/2026.09.07.749857",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749857v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Transcriptomic FOLFIRINOX sensitivity signatures stratify overall survival and reveal directional reclassification after neoadjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic cancer",
  "title_text": "Transcriptomic FOLFIRINOX sensitivity signatures stratify overall survival and reveal directional reclassification after neoadjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:37Z",
  "url": "https://research.draconitic.com/paper/6n4a2chdb4ysa",
  "venue": "bioRxiv",
  "versions": []
}