{
  "abstract": "Background\n\nCirculating cell-free DNA (cfDNA) offers a promising noninvasive way to predict resistance to immune-checkpoint inhibitors (ICI), for which robust biomarkers are still lacking.\n\nMethods\n\nThe SChISM (Size CfDNA Immunotherapy Signature Monitoring) proof-of-concept study (NCT05083494) collected baseline plasmatic cfDNA size profiles from 126 ICI-treated advanced carcinomas, quantified using the innovative, patented and standardized BIABooster device (Adelis). Fragmentome-derived variables and standard clinical variables (including neutrophils-to-lymphocyte ratio, NLR) were analyzed for univariable associations with early progression (EP, progression at first imaging) and progression-free survival (PFS). Multivariable analysis was carried through both unsupervised and supervised learning. Twenty-six variable selection methods combined with 11 models were benchmarked to derive a multivariable predictive model relying on a minimal subset of variables.\n\nResults\n\nHigher cfDNA concentration and high quantities of short fragments (111-240 base pairs (bp)) were associated with poor response and reduced PFS, unlike long fragments (> 300 bp). The proportion of fragments longer than 1650 bp exhibited the strongest association, with non-EP odds ratio = 0.39 [95% CI: 0.25-0.62] and PFS hazard ratio = 0.54 [95% CI: 0.42-0.68]. Unsupervised learning identified four patient clusters significantly associated with EP (p=0.004, Pearson’s Chi-squared test) and PFS (p=0.001, log-rank test). The multivariable machine learning analysis identified a subset of nine variables that shown greater performances in a logistic regression model:$$AUC_{signature}=88.5±3.3\\%$$ EP positive predictive value $$PPV_{signature}=69.4±7.49\\%$$ compared to single marker $$AUC_{R_{[>1650]}}=73.6±3.70\\%$$ $$PPV_{R_{[>1650]}}=55.8±7.46\\%$$ $$AUC_{NLR}=68.9±5.02\\%$$ $$PPV_{NLR}=52.6±8.75\\%$$.\n\nConclusion\n\ncfDNA size profiles significantly associated with progression and PFS during ICI, outperforming the routinely used markers.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2509.04939",
  "author_total": 13,
  "authors": [
    {
      "name": "Linh Nguyen Phuong"
    },
    {
      "name": "Frederic Fina"
    },
    {
      "name": "Laurent Greillier"
    },
    {
      "name": "Anastasiia Bakhmach"
    },
    {
      "name": "Pascale Tomasini"
    },
    {
      "name": "Jean-Laurent Deville"
    },
    {
      "name": "Romain Zakrasjek"
    },
    {
      "name": "Lucie Della-Negra"
    },
    {
      "name": "Audrey Boutonnet"
    },
    {
      "name": "Frédéric Ginot"
    },
    {
      "name": "Jean-Charles Garcia"
    },
    {
      "name": "Sébastien Benzekry"
    },
    {
      "name": "Sébastien Salas"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/26a4s7zz6s1jr.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": null,
  "id": "26a4s7zz6s1jr",
  "issns": [],
  "landing_url": "https://inria.hal.science/hal-05238567v4",
  "language": "en",
  "licence": "CC-BY-NC-SA-4.0",
  "licence_label": "CC BY-NC-SA 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-sa/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "hal",
      "1.sdv.bibs"
    ],
    [
      "hal",
      "1.sdv.can"
    ],
    [
      "hal",
      "1.sdv.sp"
    ],
    [
      "hal",
      "2.sdv.bbm.bm"
    ],
    [
      "hal",
      "2.sdv.sp.pharma"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://inria.hal.science/hal-05238567/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/26a4s7zz6s1jr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:54Z",
      "native_id": "hal-05238567",
      "source": "hal",
      "url": "https://inria.hal.science/hal-05238567v4"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.bm",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.bibs",
      "subfield": "bioinformatics"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.can",
      "subfield": "oncology"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.sp",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "The SChISM study: Circulating cell-free DNA size profiles as predictors of progression in advanced carcinoma treated with immune-checkpoint inhibitors",
  "title_text": "The SChISM study: Circulating cell-free DNA size profiles as predictors of progression in advanced carcinoma treated with immune-checkpoint inhibitors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:54Z",
  "url": "https://research.draconitic.com/paper/26a4s7zz6s1jr",
  "venue": "HAL",
  "versions": []
}