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

Abstract

Objectives: 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 [¹⁸F]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.

Methods: Fifty-seven patients who performed an [¹⁸F]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.

Results: 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 cm³; 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).

Conclusions: Baseline TMTV and metabolic response may be useful prognostic indicators for PFS and OS in patients with advanced melanoma treated with BRAF/MEK inhibitors.

Key points: • In a retrospective cohort of 57 metastatic melanoma patients treated with BRAF/MEK inhibitors, a TMTV > 56 cm³ at baseline [¹⁸F]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.

Keywords: Melanoma; Mitogen-activated protein kinases; Patient outcome assessment; Positron emission tomography computed tomography; Proto-oncogene proteins B-raf.