{
  "abstract": "BackgroundImmune checkpoint inhibition is increasingly integrated with thoracic radiotherapy in esophageal squamous cell carcinoma (ESCC), but checkpoint inhibitor pneumonitis (CIP) remains a clinically important toxicity. Whether baseline systemic inflammation modifies the association between lung radiation dose and clinically significant CIP is unclear.MethodsThis single-center retrospective cohort included 268 patients with ESCC treated with PD-1/PD-L1 inhibitors; 154 subsequently received thoracic radiotherapy. Baseline systemic inflammation was assessed using the systemic immune-inflammation index (SII) from a complete blood count obtained within 7 days before the first immunotherapy dose. The primary endpoint was grade ≥2 CIP according to CTCAE v5.0; grade ≥1 and grade ≥3 CIP were secondary endpoints. Multivariable Cox models evaluated clinical risk factors, and SII-by-V20 interaction analyses were performed in the radiotherapy subgroup. The grade ≥2 nomogram underwent 10-fold cross-validation, 1,000-resample bootstrap validation/calibration, and decision-curve analysis.ResultsIn the overall cohort, 77/268 (28.7%), 29/268 (10.8%), and 19/268 (7.1%) patients developed grade ≥1, grade ≥2, and grade ≥3 CIP, respectively. In the radiotherapy subgroup, the corresponding event counts were 54/154 (35.1%), 20/154 (13.0%), and 13/154 (8.4%). High SII, thoracic radiotherapy, and COPD were independently associated with CIP, while higher BMI was protective. The association of V20 with CIP was concentrated in the high-SII subgroup, with significant SII×V20 interactions across severity thresholds. The nomogram had a C-index of 0.758 (95% CI, 0.680–0.836); the mean 10-fold cross-validated C-index was 0.74 (95% CI, 0.69–0.79), and the bootstrap optimism-corrected C-index was 0.73. Calibration and decision-curve analyses supported acceptable internal performance and potential clinical utility.ConclusionsBaseline systemic inflammation was associated with heterogeneity in the relationship between lung V20 and subsequent CIP risk. These findings support a hypothesis-generating host–dosimetry framework for risk stratification but do not establish a validated V20 threshold for treatment modification. Independent external validation and mechanistic studies are required before clinical implementation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Shuai Qie"
    },
    {
      "name": "Yasong Shi"
    },
    {
      "name": "Wenfan Sun"
    },
    {
      "name": "Yaning Wei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3fphspwrc9wam.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1826446",
  "fulltext_url": null,
  "id": "3fphspwrc9wam",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826446",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3fphspwrc9wam.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:47Z",
      "native_id": "10.3389/fimmu.2026.1826446",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826446"
    },
    {
      "first_seen": "2026-11-04T12:21:26Z",
      "native_id": "10.3389/fimmu.2026.1826446",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826446/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Risk stratification for immune-related pneumonitis in esophageal cancer: differential roles of systemic inflammation across severity grades and additive effect of radiation",
  "title_text": "Risk stratification for immune-related pneumonitis in esophageal cancer: differential roles of systemic inflammation across severity grades and additive effect of radiation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:18Z",
  "url": "https://research.draconitic.com/paper/3fphspwrc9wam",
  "venue": "Frontiers in Immunology",
  "versions": []
}