Are there imaging characteristics that can distinguish separate primary lung carcinomas from intrapulmonary metastases using next-generation sequencing as a gold standard?

Objectives: Distinguishing separate primary lung carcinomas (SPLCs) from intrapulmonary metastases (IPMs) in non-small cell lung cancer (NSCLC) patients is a challenging dilemma in clinical practice. Next-generation sequencing (NGS) was recently shown to represent a robust molecular method for clonal discrimination in this setting. In this study, using clonal relationships established by comprehensive NGS as the ground truth, we investigated whether NSCLC patients with SPLCs versus IPMs exhibit distinct imaging characteristics.

Material and methods: This retrospective study included patients who underwent pre-treatment computed tomography (CT) and/or positron emission tomography/CT (PET/CT) imaging followed by surgical resection for >1 NSCLC. Nodular, parenchymal, pleural, and ancillary CT features, as well as maximum standardized uptake values (SUVs) on PET/CT were recorded. Rao-Scott chi-square, Wilcoxon rank-sum, and Fisher's exact tests were used in patient- and lesion-level comparisons.

Results: This study included 60 patients (median age = 69 years, 68 % female) with 127 individual tumors comprising 51 SPLC vs 23 IPM tumor pairs based on NGS profiling. SPLCs were associated with subsolid consistency (P = 0.005) and spiculated contours (P < 0.001), while IPMs were associated with greater difference of size between lesions (P = 0.017) or pure solid consistency of the smaller lesion (P = 0.011). Lymph node involvement was more frequent in IPMs than SPLCs (P = 0.036). SUV measurements were not useful for differentiation (P > 0.05).

Conclusion: Selected preoperative CT features are distributed differentially in SPLCs and IPMs, suggesting that imaging may have a role in distinguishing clonal relationships of tumors in patients with >1 NSCLC.