Objective   To assess the clinical significance of combining the risk score model based on ferroptosis-related genes from circulating tumor cells (CTCs) with tumor metabolic load using positron emission tomography/computed tomography (PET/CT) for prognostic stratification of advanced non-small cell lung cancer (NSCLC).

  Methods  From January 2019 to January 2022, 101 patients with stage Ⅲ–Ⅳ NSCLC at Tangshan People's Hospital (Tangshan Cancer Hospital) were selected for research. The metabolic tumor volume (MTV) and total glycolytic lesion (TLG) were quantitatively evaluated using PET/CT. CTCs isolated from the peripheral blood of the patients, and the expression of ferroptosis-related genes (ALOX5, TFRC, PHKG2, FADS2, and NOX1) detected using polymerase chain reaction (PCR) were used to construct the risk score.

  Results  Based on the median risk score, patients were assigned into the low-risk score group (≤0.70, n=51) and the high-risk score group (>0.70, n=50). Compared with patients with low-risk scores, patients with high-risk scores showed significantly higher MTV and TLG values (P<0.05). A significant positive correlation existed between risk score and MTV and TLG values (r=0.618, 0.462, both P<0.001). The median progression-free survival (PFS) and overall survival (OS) of patients with low MTV and low-risk scores were higher than those with low MTV and high-risk scores (P<0.001). The median PFS and OS of patients with low TLG and low-risk scores were higher than those with low TLG and high-risk scores (P<0.001). Multivariate Cox regression analysis showed that the hazard ratio (HR) of OS was significantly higher in the high-risk score group than in the low-risk score group (HR=3.22, P=0.001). After adjusting for MTV and TLG in multivariate analysis, the HR of high-risk scores was similar in patients with NSCLC (P<0.01).

  Conclusions  A low-risk score with low MTV or TLG shows a better prognosis than a low-risk score with high MTV or TLG.