Early metabolic responses on FDG PET-CT in 7 days correlate with progression-free survival (PFS) in patients with metastatic melanomas after initiation of targeted therapy

Objectives This study is designed to evaluate PET-CT parameters as measures of melanoma metabolic responses to dasatinib, a broad-spectrum ATP-competitive inhibitor of oncogenic tyrosine kinases/kinase families. The hypothesis is that early metabolic changes detected on PET-CT after 7 days of dasainib therapy correlate with clinical outcomes.

Methods Under an-IRB approved protocol, melanoma patients underwent F-18 FDG PET-CT before and after 7 daily oral doses of 100 mg without concurrent chemotherapy nor radiotherapy. Image parameters include SUV max (Smax), SUV mean (Smean), metabolic tumor volume (MTV) at 42% threshold and total lesion glyscolysis (TLG). Baseline and Day-8 (D8) Smax, Smean, MTV, TLG, interval changes (Δ) as well as fractional changes (%Δ) from baseline were analysed against clinical measures including PFS using correlation coefficients without (rank correlation) and with assumption of normal data distribution.

Results Over 26 months, 18 consecutive eligible patients were accrued, of which 10 were evaluable with completed baseline and D8 PET-CT and PFS (median=8 weeks). Significant rank correlation (Spearman's rho) were found between PFS and Smax, Smean and TLG on D8 but not at baseline, nor with MTV nor interval changes(Δ). Significant correlation coefficient (CC) were found only between PFS and 4 fractional changes (%Δ), potential uses of which require scrutiny to establish their normal data distribution.

Conclusions After 7 days of targeted therapy, PET-CT Smax, Smean and TLG correlate with PFS in this study of small sample size. They should be further evaluated to explore their roles to serve as early imaging markers in cancer therapy and to avoid futile therapy. Fractional metabolic changes in PET-CT should also be further studied as potential imaging markers.

Research Support Bristol-Myers Squibb