Predictive value of ¹⁸F-FDG PET/CT and serum tumor markers for tumor mutational burden in patients with non-small cell lung cancer

Purpose: To investigate the correlations between metabolic parameters (MPs) of F-18-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT), serum tumor markers (STMs), and tumor mutational burden (TMB) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, we enrolled 129 patients with NSCLC (males, 78; females, 51) who underwent baseline TMB and STM tests and F-18-FDG PET/CT scans before treatment between March 2018 and September 2022. Patients were categorized into TMB-high (TMB >= 10 mutations/Mb; n = 27 [20.9%]) and non-TMB-high (TMB <10 mutations/Mb; n = 102 [79.1%]) groups. Binary logistic regression analyses were performed to determine independent predictors of TMB-high. Univariate and multivariate linear regression analyses were performed to determine independent predictors of TMB level on a log scale. Subgroup analyses for adenocarcinoma (ADC), ADC with EGFR+, ADC with EGFR-, and squamous cell carcinoma (SCC) were performed. Results: For ADC, all MPs (SULpeak, SULmax, SULmean, MTV, and TLG) were significantly higher in the TMB-high group than the non-TMB-high group; smoker (odds ratio [OR] = 27.08, p = 0.018), EGFR+ (OR = 0.03, p = 0.033), KRAS+ (OR = 7.98, p = 0.083), high CEA (OR = 33.56, p = 0.029), and high CA125 (OR = 13.68, p = 0.030) were independent predictors of TMB-high; and all MPs showed significant positive linear correlations with TMB on a log scale, with SULpeak as an independent predictor. However, no significant correlation was observed for SCC. Conclusion: MPs and STMs can predict the TMB level for patients with ADC, and may serve as potential substitutes for TMB with increased value and easy implementation in guiding immunotherapy through noninvasive methods.