Predictive value of integrated <sup>18</sup>F-FDG PET/MRI in the early response to nivolumab in patients with previously treated non-small cell lung cancer
Yukihiro Umeda, Miwa Morikawa, Masaki Anzai, Shingo Ameshima, Maiko Kadowaki, Yuko Waseda, Hiroko Shigemi, Tetsuya Tsujikawa, Yasushi Kiyono, Hidehiko Okazawa, Tamotsu Ishizuka
Abstract
Background The early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI ( 18 F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC). Methods Twenty-five patients with previously treated NSCLC were enrolled prospectively and underwent 18 F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy. Results The disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADC mean (ie, negative ΔADC mean ) and lower ΔTLG+ΔADC mean than patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADC mean had the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADC mean value <16.5 was significantly associated with longer median progression-free survival (9.0 vs 1.8 months, p<0.00001) and overall survival (23.6 vs 4.7 months, p=0.0001) compared with ΔTLG+ΔADC mean value ≥16.5. A multivariate Cox model revealed that ≥16.5 ΔTLG+ΔADC mean was an independent predictor of shorter progression-free survival (HR 37.7) and overall survival (HR 9.29). Conclusions A combination of ΔTLG and ΔADC mean measured by integrated 18 F-FDG PET/MRI may have value as a predictor of the response and survival of patients with NSCLC following nivolumab therapy. Trial registration number UMIN 000020707.