Comparing Changes in Solid Component Diameter and Mass for Detecting Invasive Adenocarcinoma in Sub-Solid Pulmonary Nodules (SSNs): the Summit Study

Abstract

Introduction and Objectives Evolution in size, density and morphology of sub-solid pulmonary nodules (SSNs) instigate conclusive management as they herald invasive adenocarcinoma (IA). Solid component diameter (SCD) correlates with the degree of invasion, but changes in SCD density and overall nodule mass (the product of nodule volume and density), are under-studied. We compare the accuracy of recommended thresholds (alone and in combination) for absolute SCD, and changes in SCD and mass, for detecting IA in SSNs. Methods Participants with persistent SSNs were monitored with Low-Dose Computed Tomography (LDCT) in the SUMMIT LDCT lung screening study (NCT03934866). Semiautomated segmentation provided volume and SCD measurements, and nodule mass (mg) derived by volume (mm ) x (Hounsfield Units + 1000)/1000]. Changes in SCD and mass from initial detection to either the last study scan or the final scan before intervention were compared against recommended thresholds of absolute SCD >= 8mm, SCD change >= 2mm and mass change >= 30%. Sensitivity, specificity, and AUROC for histologically proven IA were calculated. No proven IA was defined as absence of a lung cancer diagnosis in national cancer registries. Results In 590 participants with 813 SSNs 559 (68.8%) nonsolid, 254 (31.2%) part-solid, median overall diameter 10.2mm (IQR 7.6 14mm), follow-up 4.3 years (IQR 4.0 4.5years)], 54 (6.6%) had IA, and 759 (93.4%) had no proven IA. SCD change >=2mm and mass change -30% achieved sensitivities of 50% (95%CI 36 64%) and 52% (95%CI 38 66%) respectively, but SCD change was more specific (table 1). The absolute SCD threshold of >=8mm improved sensitivity to 63% (95%CI 49 76%); combining it with mass change >=30% or SCD change >=2mm for cases where SCD =8mm and SCD change >=2mm retained high specificity (92% (95%CI 90 94%)) and had the highest AUROC (0.84). Conclusion A combined strategy using SCD >= 8mm and SCD change >= 2mm in nodules under the 8mm threshold potentially provides the best balance of sensitivity, specificity and accuracy for diagnosing invasive adenocarcinoma in SSNs. While combining an SCD 8mm threshold with mass change - 30% optimised sensitivity, this came at the expense of specificity.