SMARCA4/BRG1-deficient non-small cell lung cancer: clinical, imaging, pathological features, and follow-up results of 23 patients.

Abstract

Background: SMARCA4/BRG1-deficient non-small cell lung cancer (S/B-d NSCLC) is a rare subtype of non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical, imaging, serum tumor marker, and pathological features of S/B-d NSCLC, particularly computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan features.

Methods: Our analysis included 23 patients with pathologically confirmed S/B-d NSCLC from January 2021 to December 2023. A retrospective analysis of clinical, serum tumor markers, imaging [including CT, FDG PET/CT, magnetic resonance imaging (MRI)], pathological features, treatment protocols, and follow-up results was performed. Independent samples t-tests were used to assess statistical differences in short diameters and maximum standardized uptake value (SUV_max) between groups.

Results: S/B-d NSCLC occurs predominantly in male patients with a history of smoking and a mean age of 62.78 years (39-77 years). S/B-d NSCLC was found incidentally during physical examination in 56.52% of patients. The CT scan features were as follows: predominantly tumors (72.73%), peripheral in the lungs (77.27%), round or roundish morphology (81.28%), pleural or vascular invasion (95.46%), and moderately to severely enhanced (59.09%). The FDG PET/CT showed FDG-avid with mean SUV_max of 14.78±9.57. Lung cancer-related serum tumor markers had high positivity rates for carcinoembryonic antigen (CEA) (66.67%), recombinant cytokeratin fragment antigen 21-1 (CYFRA21-1) (61.91%), and carbohydrate antigen 125 (CA125) (57.14%). Pathological features are often characterized by grading (poor differentiation, 100%), tumor spread through the air space (STAS, 85.71%), and vascular invasion (85.71%). Immunohistochemistry showed that SMARCA4 (BRG1) was absent, and P40, P63, ALK-Ventana ALK (D5F3), and p-TRK were often negative. Genetic tests showed that the positivity rate of TP53 (76.92%) and KEAP1 (53.85%) was high. Despite diverse treatment options being available, high rates of progression during treatment and poor prognosis were observed. Among CT features (N=22), the short diameter of CT-diagnosed metastatic lymph nodes (LNs) was larger than that of non-metastatic LNs, and the difference was statistically significant (P=0.02). Among the FDG PET/CT features (N=12), SUV_max was larger in tumor group than lesion group, SUV_max was larger in M1 group than M0 group, and the difference was statistically significant in both groups (P=0.001 and P=0.04).

Conclusions: S/B-d NSCLC has distinct features in epidemiology, serum tumor markers, imaging, and pathology. In particular, FDG-avid is evident in the FDG PET/CT scan. The size of the lesion and the degree of FDG avidity provide information about the degree of malignancy and the high probability of distant metastasis in S/B-d NSCLC. FDG PET/CT is recommended when S/B-d NSCLC is suspected based on CT features, especially for large lesions. The FDG PET/CT scan can help with accurate staging and individual treatment planning.