{
  "abstract": "Introduction An association between systemic sclerosis (SSc) and lung cancer has been shown in population-based cohort studies, however, a Mendelian randomization analysis refutes causality. Herein, we analyzed lung cancer risk in an inception cohort of SSc patients with long-term follow-up, complemented by a systematic review and meta-analysis of published dataMaterial and Methods All patients evaluated in our center within 12 months of SSc onset, between January 1995 and December 2020, with regular follow-up until December 2024, were included. Clinical manifestations, laboratory parameters, treatments and comorbidities were prospectively recorded. Age-standardized incidence ratio (SIR) of lung cancer in our cohort was estimated based on lung cancer data in the general Greek population according to the Global Cancer Observatory database. Logistic regression models were applied to assess determinants of lung cancer. A systematic literature search for the association between SSc and cancer, and a meta-analysis of lung cancer SIRs from eligible studies was conducted.Results A total of 180 SSc patients (151 female, aged 49±14 years old, 77 with diffuse SSc, 96 anti-topoisomerase positive) were followed-up for 11.7±6.4 years and 2,110 patient-years were analyzed. Lung cancer was diagnosed in 12 patients (non-small- and small- cell lung cancer in 10 and 2 patients, respectively) aged 59.4±10.8 years (range 43-77) and with SSc duration of 10.2±5.9 years (range 2-20) at the time of cancer diagnosis; 3/12 cases had SSc for less than 3 years. SIR of lung cancer was 5.1 for the entire inception cohort (95% CI 4.7-5.4), 3.8 (95% CI 3.5-4.1) for males and 9.5 (95% CI 8.7-10.3) for females, respectively. Multivariate analysis showed that diffuse subtype [OR 4.9 (95% CI 1.2-20.4)] and prolonged immunosuppression (>5 years) [OR 4.3 (95% CI 1.02-17.7)] were associated with lung cancer development, while digital ulcers were negatively associated [OR 0.21 (95% CI 0.05- 0.89)]. Our meta-analysis included 15 studies with 20,408 SSc patients and estimated a pooled lung cancer age-SIR of 3.90 [95% CI (2.59 – 5.85), p<0.001].Conclusions Our results show an increased lung cancer risk by 5-fold in SSc and this risk is more than double in contemporary female than male patients. Diffuse SSc and prolonged immunosuppression, probably reflecting more severe disease forms, are associated with the highest risk of lung cancer. Further studies to inform screening strategies are warranted.",
  "authors": [
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Anastasios Makris"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Vasiliki Poulia"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Vasiliki-Kalliop Bournia"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Kalliopi Fragiadaki"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Maria G Tektonidou"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Petros P Sfikakis"
    },
    {
      "affiliations": [
        "First Department of Propaedeutic and Internal Medicine, National and Kapodistrian university, Medical School, Athens, Greece"
      ],
      "name": "Stylianos Panopoulos"
    }
  ],
  "title": "P.367 Lung cancer risk is highly increased in female patients with systemic sclerosis: data from an inception cohort and meta-analysis of published studies",
  "uid": "ca0deb57-5377-50c9-82a5-9146feaef2d6"
}