Natural growth and disease progression of non-small cell lung cancer evaluated with ¹⁸F-fluorodeoxyglucose PET/CT

Purpose: The aims of this study were to: (1) estimate the volumetric and metabolic growth rate of non-small cell lung cancer (NSCLC), (2) evaluate disease progression prior to treatment, and (3) explore the effects of tumor growth rate and time to treatment (TTT) on survival outcome. Methods: Patients with inoperable stages I-III NSCLC with serial pre-treatment PET/CT scans were eligible for this study. PET-derived metabolic tumor volumes (PET-MTV) and CT-derived gross tumor volumes (CT-GTV) were contoured using PET/CT information. Normalized standardized uptake values (NSUV) in tumors including the NSUVmean and NSUVmax were measured. Tumor growth rates expressed as doubling time (DT) were estimated using an exponential model. Pre-treatment disease progression defined as the development of any new site of disease on PET/CT and change in TNM stage (AJCC 7th ed.) were recorded. Growth rate and tumor progression were analyzed with respect to overall (OS) and progression free survival (PFS). Results: Thirty-four patients with a median inter-scan interval (ISI) of 43 days and TTT of 48 days were analyzed. Tumor volumes showed remarkable inter-scan growth while NSUV did not increase significantly. The DT for PET-MTV, CT-GTV, NSUVmean and NSUVmax were 124, 139, 597, and 333 days, respectively. Pre-treatment disease progression occurred in 20.6% patients with longer ISI being a significant risk factor (OR = 1.027, p= 0.02). The optimal threshold ISI to predict progression was 58 days (4.8% vs. 46.2%, p= 0.007). Neither tumor growth rates nor TTT were significantly correlated to OS or PFS. Conclusions: NSCLC displays rapid tumor volume growth whereas NSUVmean and NSUVmax are relatively stable over the same time period. Longer delays before initiation of treatment are associated with higher risk of pre-treatment disease progression.