Lung cancer in scleroderma: risk factors and outcomes

SESSION TITLE: Pulmonary Manifestations of Systemic Disease: Don't Forget About Breathing SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/09/2023 12:00 pm - 12:45 pm PURPOSE: Scleroderma (SSc) is associated with an increased risk of lung cancer. Although hypotheses for this association have been proposed, risk factors remain poorly defined, and screening guidelines are not established. Importantly, outcomes for those with lung cancer and comorbid SSc (SSc-CA) have yet to be determined. METHODS: A case-control study of SSc subjects with (cases) and without (controls) lung cancer was conducted at a single academic medical center. Our Scleroderma Program Patient Registry was used to identify age- and sex-matched controls. An additional retrospective control cohort of subjects with lung cancer without autoimmune disease was identified through a data repository at our institution to assess differences in histology and mortality. Clinical, radiologic, pathologic, and outcome data were compared using descriptive statistics and conditional logistic regression. A blinded thoracic radiologist reviewed chest computed tomography (CT) scans for presence and extent of interstitial lung disease (ILD) classified by the Goh algorithm. Locoregional disease was defined as localized disease with or without confirmed nodal involvement, and distant disease was defined as evidence of metastases. RESULTS: 27 cases and 54 matched controls were identified. The majority were female (81%) with an average age of 65 years (range, 50-90). Cases had increased odds of limited cutaneous disease (odds ratio [OR]=8.38, 95% confidence interval [CI] 1.89-37.2, p=0.005) despite also being more likely to have a topoisomerase (Scl70) autoantibody (OR=3.69, 95% CI 1.14-11.93, p=0.03). There was no difference in tobacco use between groups (cases 48% vs controls 32%, p=0.18). Cases were more likely to have had a longer duration of SSc (13.43 vs 6.93 years, p=0.029) and were less likely to have been treated with immunosuppression (OR=0.13, CI 0.04-0.46, p=0.002). All cases had ILD compared to 77% of controls (p=0.006), with a trend toward more severe radiologic disease in the cases (p=0.08). There was no difference in forced vital capacity (FVC) between groups. When compared to a lung cancer control cohort without autoimmune disease (N=219), SSc-CA cases were the same age at diagnosis (65 years) but were less likely to have used tobacco (48% vs 79%, p=0.001). Median survival (months) was similar for locoregional disease in SSc-CA (39.6, CI 34.0-54.0) compared to controls (36.5, CI 23.5-40.5) and for distant disease (19.09, CI 11.3-25.5 vs 8.0, CI 3.0-16.0, respectively). Tumor histology also did not differ; adenocarcinoma was identified in 74% of SSc-CA compared to 72% of lung cancer controls. CONCLUSIONS: Lung cancer in subjects with SSc was associated with limited cutaneous disease and with a Scl70 antibody. SSc-CA subjects were more likely than matched controls to have ILD although no significant difference was observed in FVC. Tobacco use was not a risk factor for lung cancer in our SSc cohort. Compared to those with lung cancer without autoimmune disease at our institution, the prevalence of adenocarcinoma and the median survival of those with SSc-CA was similar despite the presence of a comorbid inflammatory disease in the latter. CLINICAL IMPLICATIONS: While we describe phenotypic and serologic associations between SSc and lung cancer, further research is needed to identify a high-risk subpopulation who warrant screening. DISCLOSURES: No relevant relationships by Jane Dematte D Amico No relevant relationships by Anthony Esposito No relevant relationships by Ray Goodwin No relevant relationships by Jungwha Lee No relevant relationships by John Varga