Abstract
We investigated the relationship between tumor 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans and thymidylate synthase (TS) expression. In addition, we evaluated the value of FDG uptake in predicting treatment response and prognosis when combined with TS expression in patients with advanced non-small cell lung cancer (NSCLC). We measured the maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of tumor lesions on pretreatment scan in 234 patients (age: 60.1 ± 9.4 years; males: 56.4%) with stage IV non-squamous NSCLC who were enrolled in the prospective phase II clinical trial. We investigated the correlation of the parameters with TS expression and the predictive values of the parameters compared with other clinical factors. Among these parameters, TLG was the most relevant parameter that had a significant correlation with TS expression (ρ = 0.192, P = 0.008). A multivariable Cox proportional-hazards model revealed that high TLG was a significant independent predictor for treatment response (hazard ratio [HR]: 2.05; P = 0.027), progression-free survival (HR: 1.39; P = 0.043), and overall survival (HR: 1.65; P = 0.035) with other factors. In patients with advanced non-squamous NSCLC, tumor TLG on pretreatment PET/CT scan has predictive and prognostic value.
Highlights
Www.nature.com/scientificreports both primary and metastatic tumors, even if an adequate specimen is not obtained
total lesion glycolysis (TLG) of tumor on pretreatment positron emission tomography/computed tomography (PET/CT) scan was an independent predictor of thymidylate synthase (TS) expression, treatment response, and clinical outcome
As the evidence indicating an association between TS expression and clinical outcomes in patients who received pemetrexed-based therapy has grown[4,6,7], there have been attempts to identify a biomarker related to TS expression[8,16]
Summary
Www.nature.com/scientificreports both primary and metastatic tumors, even if an adequate specimen is not obtained. A previous study demonstrated that TS expression was significantly correlated with glucose transporter 1 (Glut1) and hypoxia-inducible factor-1α (HIF-1α), key elements for determining the amount of FDG uptake within tumor cells, in patients with primary lung cancer[16]. With respect to TS expression and TS inhibitor treatment, the role of tumor FDG uptake in prediction and prognosis remains unclear. We investigated the relationship between tumor FDG uptake and TS expression in the prospectively collected dataset for our previous stratified randomized phase II clinical trial[4] and assessed the value of tumor FDG uptake in predicting treatment response to TS inhibitors and the prognosis of the patients who were stratified by TS expression level
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