Prognostic value of total metabolic tumour volume and therapy-response assessment by [${}^{18}$F]FDG PET/CT in patients with metastatic melanoma treated with BRAF/MEK inhibitors

Target therapy with BRAF/MEK inhibitors in metastatic melanoma is characterised by a high response rate; however, acquired resistance to treatment develops in many cases. We aimed to investigate if baseline total metabolic tumour volume (TMTV) and therapy-response assessment by [${}^{18}$F]FDG PET/CT have a prognostic role on progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma receiving BRAF ± MEK inhibitors. Fifty-seven patients who performed an [${}^{18}$F]FDG PET/CT at baseline and on treatment were retrospectively evaluated. A Cox proportional-hazard model was used to examine associations between OS and PFS with baseline clinical/PET parameters as well as for PET response. According to EORTC criteria, 34 patients were classified as responders (partial/complete metabolic response [PMR/CMR]) and 23 as non-responders (progressive/stable metabolic disease [PMD/SMD]). Baseline characteristics associated with a shorter PFS were more than two metastatic organ sites and TMTV > 56 cm${}^3$; the latter was the only independent feature at multivariate analysis. Patients achieving a CMR were associated with a prolonged PFS compared with those with PMR (median PFS 42.9 vs 8.8 months; p = 0.009). Disease progression occurred in new-onset disease sites in 87.5% of CMR, 7.1% of PMR and 34.8% of PMD/SMD (p < 0.001). High baseline TMTV and lack of treatment response were independent prognostic factors for OS, stratifying patients in three different prognostic classes (median OS 6.7, 18.3 and 102.2 months, respectively). Baseline TMTV and metabolic response may be useful prognostic indicators for PFS and OS in patients with advanced melanoma treated with BRAF/MEK inhibitors. In a retrospective cohort of 57 metastatic melanoma patients treated with BRAF/MEK inhibitors, a TMTV > 56 cm${}^3$ at baseline [${}^{18}$F]FDG PET/CT was significantly correlated with a shorter PFS and OS. The combined use of baseline TMTV along with PET response during treatment allowed for the identification of three groups of patients with very different median OS.