{
  "abstract": "Background The immunonutritional background has been deeply implicated in cancer behavior and clinical outcomes. In this study, we explored the prognostic impact of the Controlling Nutritional Status (CONUT) score through its correlation with blood immunophenotypes and cytokines to provide an easily available non-invasive tool to predict the survival benefit from first-line immune checkpoint inhibitors±chemotherapy (ICI±CHT) in patients affected by advanced non-small cell lung cancer (aNSCLC).Material and methods From a prospective cohort of patients with aNSCLC treated with first-line ICI±CHT, clinicopathological data and baseline blood samples for the assessment of CONUT score (albumin, lymphocytes, total cholesterol), relevant immunophenotypes (flow cytometry) and cytokines (multiplex array) were collected. Correlations of CONUT score with survival outcomes (progression-free/overall survival [PFS/OS]) and circulating immune-inflammatory benchmarks were analyzed.Results Among 178 patients enrolled in the AIRC (Italian Association for Cancer Research) project, 153 received ICI±CHT as first-line. Nutritional status tested by CONUT score was available in 137 cases and was <3, meaning good nutritional status, in 77 (56.2%), whereas scored ≥3 in 60 (43.8%), meaning an impaired nutritional status. At a median follow-up of 27.4 months (95% CI 22.9 to 32.0), patients with a CONUT score <3, compared to those with CONUT score ≥3, experienced significantly longer PFS (median PFS 8.03 vs 3.88 months, HR 0.58, 95% CI 0.40 to 0.84, p=0.004) and OS (median OS 22.24 vs 8.75 months, HR 0.61, 95% CI 0.40 to 0.94, p=0.03). The multivariable analysis, adjusting for age, histology, metastatic sites, sex, programmed death-ligand 1 (PD-L1), Eastern Cooperative Oncology Group Performance Status and treatment type, confirmed the prognostic impact of CONUT score in terms of PFS (HR 0.61, 95% CI 0.41 to 0.93, p=0.02) and OS (HR 0.60, 95% CI 0.38 to 0.96 p=0.03). Patients with CONUT score ≥3 displayed significantly higher blood levels of interleukin (IL)-1β, IL-12, IL-10, interferon-γ, IL-6, and soluble PD-L1 compared with those with CONUT score <3. A higher fraction of CD14+ cells (p=0.01) and CD8+Ki67+ (p<0.001) lymphocytes also characterized the blood of patients with CONUT score ≥3 compared with those with CONUT score <3.Conclusion A baseline good nutritional status (CONUT score <3) is associated with a distinct circulating immune-inflammatory profile and correlates with improved clinical outcomes in patients with aNSCLC treated with first-line ICI±CHT.",
  "authors": [
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Federica Pecci"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy",
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Giulia Mazzaschi"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy",
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Alessandra Dodi"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Prisca Tamarozzi"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Martina Manini"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Marianna Peroni"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Simona D’Agnelli"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Lucas Moron Dalla Tor"
    },
    {
      "affiliations": [
        "Department of Information Engineering, Polytechnic University of Marche Faculty of Engineering, Ancona, Marche, Italy"
      ],
      "name": "Giulia Bruschi"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Monica Pluchino"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Michela Verzè"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Roberta Minari"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Fabiana Perrone"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Paola Bordi"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Alessandro Leonetti"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy"
      ],
      "name": "Federico Quaini"
    },
    {
      "affiliations": [
        "Institute of Radiologic Science, University of Parma, Parma, Italy"
      ],
      "name": "Nicola Sverzellati"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy",
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Sebastiano Buti"
    },
    {
      "affiliations": [
        "Medicine and Surgery Department, University of Parma, Parma, Italy",
        "Medical Oncology Unit, University Hospital of Parma, Parma, Italy"
      ],
      "name": "Marcello Tiseo"
    }
  ],
  "title": "Dissecting the impact of Controlling Nutritional Status (CONUT) score on survival outcomes and immune-inflammatory profiles in patients with advanced NSCLC undergoing first-line immunotherapy",
  "uid": "d5e72dbb-b378-59a5-8922-631f3d27e37a"
}