The authors Laetitia Padovani, Aurelie Baret and Dominique Barbolosi equally participated in this work.Objective: Positron emission tomography with 18 F fludeoxyglucose integrated with CT ( 18 F-FDG PET/CT) is a recommended imaging procedure in the evaluation of non-small-cell lung cancers (NSCLCs). Radiochemotherapy (RCT) is a mainstay for treatment of locally advanced NSCLC, for which overall survival still remains poor. Early evaluation of treatment response may help in decisionmaking to complete radiotherapy (RT) or to switch to other treatment modalities. The present study aimed to evaluate the performance of new metabolic parameters based on a simplified kinetic analysis on a single time point (SKA-S)-derived mathematical method, as compared with standardized uptake value (SUV) measurement during RT. Methods: Four patients treated with RT or RCT for NSCLC were evaluated using 18 F-FDG PET/CT during RT and after treatment completion. Whole-body 18 F-FDG PET/CT was performed followed by four additional list-mode acquisitions centered over the target lesion. Response was evaluated at four times (i.e. PET1-PET4) by calculating standard SUV values and T80%, the time taken to reach 80% of 18 F-FDG metabolized fraction using a SKA-S-derived mathematical method. Results: Data from SUV and T80% calculations were found to be controversial. T80% was found to be more predictive of clinical outcome. Conclusion: Although results from this pilot study should be further confirmed in a large prospective study, the data suggest that T80% is a promising metabolic biomarker for assessing early response to RT. Advances in knowledge: In this proof of concept study, we show that T80% defined from a mathematic model taking into account the net influx rate constant and vascular volume could be consider as a promising biomarker as compared with the maximum SUV.