{
  "abstract": "Introduction Patients with bone metastases (BM) from non-small cell lung cancer (NSCLC) derive less clinical benefit from immune checkpoint inhibitors (ICIs) than those without skeletal involvement. We aimed to characterize bone-specific disease control profiles under first-line ICI therapy and explore the association of denosumab with clinical outcomes. Methods We conducted a multicenter retrospective study in BM-NSCLC patients, naïve to systemic therapy, treated with first-line ICI monotherapy, with or without denosumab. Radiological response in soft tissue and bone compartments was assessed at 6 months using iRECIST. Disease control (DCR: iCR, iPR, or iSD) and dissociated response (discordant DCR between compartments) were predefined. Denosumab impact was evaluated using logistic regression and Cox models. Results Sixty-one patients were included (16 women [26%]; mean age 65.8 ± 9.6 years). Soft tissue DCR was 64% and bone DCR was 62% at M6. Dissociated response occurred in 21% (n = 13), associated with female sex, KRAS mutations, and elevated C-reactive protein (all p < 0.05). Denosumab did not alter bone DCR (73% vs. 60%; adjusted OR 0.64; 95% CI: 0.12–2.99; p = 0.582) but was associated with improved progression-free survival (log-rank p = 0.06) and reduced hazard of progression or death (adjusted HR 0.28; 95% CI: 0.06–1.33; p = 0.110). Conclusion ICI-driven immune activation does not translate uniformly across compartments. Female sex, KRAS mutation, and systemic inflammation are potential determinants of bone-specific resistance. While denosumab did not significantly modify bone DCR, its trend toward association with improved progression-free survival and reduced risk of progression or death generates the hypothesis of an immunomodulatory effect warranting prospective evaluation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "Emmanuel Massy"
    },
    {
      "name": "Nicolas Stacoffe"
    },
    {
      "name": "Fauvernier, M."
    },
    {
      "name": "Michaël Duruisseaux"
    },
    {
      "name": "E. Grolleau"
    },
    {
      "name": "M. Lamkhioued"
    },
    {
      "name": "M. Pérol"
    },
    {
      "name": "Charlotte Domblides"
    },
    {
      "name": "Mathieu Roche"
    },
    {
      "name": "A. Stuani"
    },
    {
      "name": "Philippe Clezardin"
    },
    {
      "name": "E. Bonnelye"
    },
    {
      "name": "Jean-Baptiste Pialat"
    },
    {
      "name": "N. Girard"
    },
    {
      "name": "C. Confavreux"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6t1axbma156wr.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbo.2026.100797",
  "fulltext_url": null,
  "id": "6t1axbma156wr",
  "issns": [
    "2212-1374"
  ],
  "landing_url": "https://hal.science/hal-05761691v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2730|Bone health and treatments"
    ]
  ],
  "openalex": "W7203628880",
  "pdf_url": "https://hal.science/hal-05761691/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": "Amsterdam : Elsevier, c2012-",
  "ris": "https://research.draconitic.com/paper/6t1axbma156wr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "hal-05761691",
      "source": "hal",
      "url": "https://hal.science/hal-05761691v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Bone health and treatments",
      "subfield": "oncology"
    }
  ],
  "title": "Dissociated skeletal response to first-line immunotherapy in synchronous bone metastatic non-small cell lung cancer patients: Clinical profiles and survival benefit of denosumab adjunction",
  "title_text": "Dissociated skeletal response to first-line immunotherapy in synchronous bone metastatic non-small cell lung cancer patients: Clinical profiles and survival benefit of denosumab adjunction",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/6t1axbma156wr",
  "venue": "Journal of Bone Oncology",
  "versions": []
}