Correlations of ¹⁸F-FDG PET/CT metabolic parameters and systemic immune-inflammation index with distant metastasis of...

Although small-size (T1, solid nodule with maximum diameter <3 cm) non-small cell lung cancer (NSCLC) is generally associated with a favorable prognosis, a notable subset of patients present with distant metastasis, a paradox that conventional staging fails to address. Fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters and the systemic immune-inflammation index (SII) are linked to NSCLC progression, but their associations with distant metastasis in small-size NSCLC remain unclear. This study aimed to investigate these correlations to identify reliable metastatic risk factors for small-size NSCLC.

This retrospective study enrolled 243 cases of pathologically confirmed T1 solid NSCLC, including 114 with and 129 without distant metastasis, who underwent ¹⁸F-FDG PET/CT within two weeks before tumor resection or biopsy. PET/CT metabolic parameters including standardized uptake value peak (SUVpeak), standardized uptake value maximum (SUVmax), standardized uptake value mean (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and coefficient of variation (COV) at various SUV thresholds (1.0, 1.5, 2.0, and 2.5) were assessed for primary lesions. Inflammation factors including SII were measured one day prior to surgery or biopsy. Patients were randomized into modeling (n=182) and validation (n=61) cohorts (3:1). Univariate/multivariate logistic regression analyses identified independent risk factors for metastasis correlations between metabolic parameters and serum inflammation markers were analyzed.

In the modeling cohort, high SUVpeak, SUVmean, SUVmax, MTV, TLG, and COV were significantly associated with distant metastasis (all P<0.05), except COV at SUV 1.0 (P=0.65). Multivariate regression confirmed COV at an SUV threshold of 2.0 (COV2.0) >0.33 as an independent risk factor [hazard ratio (HR) =3.03, P=0.01]. SII >641.68 was also identified as an independent inflammation-related risk factor (HR =2.84, P=0.003). COV2.0 was positively correlated with SII [odds ratio (OR) =4.55, P=0.03]. The co-high COV2.0/SII status was identified as an independent risk factor for metastasis (HR =5.08, P<0.001). In the independent validation cohort, the metastasis rate in the co-high COV2.0/SII group was 84.20% (16/19), significantly higher than the non-metastasis rate (15.80%, 3/19, P=0.043). The metastasis rate in the co-low COV2.0/SII group was only 17.90% (5/28, P<0.001). No clinicopathological features (age, gender, histological subtype, tumor diameter, smoking history) were associated with metastasis (all P>0.05).

Enhanced glycolysis accompanied by a corresponding systemic immune response plays a critical role in T1 NSCLC metastasis. The combined assessment of ¹⁸F-FDG PET/CT-derived COV2.0 and serum SII may aid in evaluating the risk of distant metastasis in small-size NSCLC, thereby informing more rational treatment and follow-up strategies for lung cancer.