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

Abstract

RESULTS

Patients with consistently lower 18F-FLT than 18F-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 18F-FLT uptake (3.5 to 5.3 mo). Baseline 18F-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 18F-FLT SULpeak below or above the median (P= 0.601). However, a greater percentage decrease in 18F-FLT uptake at 2 weeks was associated with longer PFS (median: 13.9 vs 4.3 mo, P= 0.005).

BACKGROUND

18F-FLT PET/CT visualizes cellular proliferation and may correlate more directly with tumor aggressiveness and treatment response than 18F-FDG PET/CT in melanoma patients treated with BRAF/MEK inhibitors. We aimed to assess whether 18F-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 18F-FLT uptake patterns relative to 18F-FDG, and early changes in 18F-FLT uptake, were associated with PFS in patients treated with BRAF/MEK inhibitors. These explorative findings suggest that 18F-FLT PET/CT may have predictive value, warranting confirmation in larger prospective studies.

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 18F-FLT PET/CT. 18F-FLT PET/CT was performed at baseline and after 2 weeks of treatment to evaluate baseline uptake and early changes in metabolic activity. 18F-FDG PET/CT was performed at baseline for comparison. Ki67 expression was assessed in metastatic tissue samples. Analyses included: (1) visual comparison of baseline 18F-FLT and 18F-FDG uptake, (2) correlation of 18F-FLT uptake with Ki-67, (3) semiquantitative analysis of baseline 18F-FLT uptake, and (4) evaluation of percentage change in 18F-FLT uptake after 2 weeks.