Predictive value of 3′-deoxy-3′- 18 F-fluorothymidine PET in the early response to anti-programmed death-1 therapy in patients with advanced non-small cell lung cancer

Abstract

Background Anti-programmed death-1 (anti-PD-1) therapy has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). However, it is difficult to evaluate the early response to anti-PD-1 therapy. We determined whether changes in 3′-deoxy-3′-[ 18 F]-fluorothymidine (18 F-FLT) PET parameters before and soon after treatment initiation predicted the therapeutic effect of anti-PD-1 antibody. Methods Twenty-six patients with advanced NSCLC treated with anti-PD-1 antibody were enrolled prospectively and underwent 18 F-FLT PET before and at 2 and 6 weeks after treatment initiation. Changes in maximal standardized uptake value (I "SUV max), proliferative tumor volume (I "PTV) and total lesion proliferation (I "TLP) of the lesions 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 TLP at 2 weeks, and decreased SUV max, PTV, and TLP at 6 weeks, compared with those with PD, while three of eight (37.5%) patients who responded had increased TLP from baseline at 2 weeks (ie, pseudoprogression). Among the parameters that changed between baseline and 2 weeks, I "PTV0-2 and I "TLP0-2 had the highest accuracy (76.0%) to predict PD. Among the parameters that changed between baseline and 6 weeks, I "SUV max 0-6, I "PTV0-6 and I "TLP0-6 had the highest accuracy (90.9%) to predict PD. I "TLP0-2 (≥60%, HR 3.41, 95% CI 1.34-8.65, p=0.010) and I "TLP0-6 (≥50%, HR 31.4, 95% CI 3.55 to 276.7, p=0.0019) were indicators of shorter progression-free survival. Conclusions Changes in 18 F-FLT PET parameters may have value as an early predictive biomarker for the response to anti-PD-1 therapy in patients with NSCLC. However, it should be noted that pseudoprogression was observed in 18 F-FLT PET imaging at 2 weeks after treatment initiation. Trial registration number jRCTs051180147.