Imaging Proliferation of Stage IV Cutaneous Melanoma With 18 F-FLT PET/CT : A Potential Noninvasive Tool for Predicting Treatment Resistance to Targeted Therapy?

Abstract

PATIENTS AND METHODS

This explorative side study of the phase II multicenter REPOSIT trial included 19 patients with stage IV BRAF V600E/K-mutated cutaneous melanoma who underwent optional 18 F-FLT PET/CT. 18 F-FLT PET/CT was performed at baseline and after 2 weeks of treatment to evaluate baseline uptake and early changes in metabolic activity. 18 F-FDG PET/CT was performed at baseline for comparison. Ki67 expression was assessed in metastatic tissue samples. Analyses included: (1) visual comparison of baseline 18 F-FLT and 18 F-FDG uptake, (2) correlation of 18 F-FLT uptake with Ki-67, (3) semiquantitative analysis of baseline 18 F-FLT uptake, and (4) evaluation of percentage change in 18 F-FLT uptake after 2 weeks.

RESULTS

Patients with consistently lower 18 F-FLT than 18 F-FDG uptake in metastases had longer progression-free survival (PFS; median 9.6 months, range: 3.4 to 32.3) compared with those with equal/higher or heterogeneous 18 F-FLT uptake (3.5 to 5.3 mo). Baseline 18 F-FLT SULpeak did not correlate with Ki67 expression ( P = 0.601), nor was Ki67 associated with PFS ( P = 0.39). No significant PFS difference was observed between patients with baseline 18 F-FLT SULpeak below or above the median ( P = 0.601). However, a greater percentage decrease in 18 F-FLT uptake at 2 weeks was associated with longer PFS (median: 13.9 vs 4.3 mo, P = 0.005).

BACKGROUND

18 F-FLT PET/CT visualizes cellular proliferation and may correlate more directly with tumor aggressiveness and treatment response than 18 F-FDG PET/CT in melanoma patients treated with BRAF/MEK inhibitors. We aimed to assess whether 18 F-FLT PET/CT can predict early resistance to BRAF/MEK inhibitors in addition to current clinical tools in patients with BRAF-mutated metastatic melanoma.

CONCLUSIONS

Baseline 18 F-FLT uptake patterns relative to 18 F-FDG, and early changes in 18 F-FLT uptake, were associated with PFS in patients treated with BRAF/MEK inhibitors. These explorative findings suggest that 18 F-FLT PET/CT may have predictive value, warranting confirmation in larger prospective studies.