Correlation of baseline 18F-FDG-PET/CT parameters with the outcome of advanced melanoma patients treated with the pd-1 blocking monoclonal antibody pembrolizumab

Background: Advanced Melanoma is a condition with a poor long-term prognosis and although the last few years there has been an enormous improvement due to the Immune Checkpoint Inhibitors (ICI), only a subset of patients benefit. Biomarkers to better guide treatment decisions are being investigated. In this study we aimed to investigate the role of pre-treatment 18F-FDG PET/CT as a predictor of survival after pembrolizumab treatment. Methods: Between Sep 2014 and Apr 2016, 141 patients where selected for therapy with pembrolizumab (2 mg/kg q3wks). Of those patients, 69 had undergone 18F-FDG PET/CT within 6 weeks prior to treatment initiation and were eligible for analysis. In these patients, the Total Metabolic Tumor Volume (TMTV) and the Total Lesional Glycolysis (TLG) was measured. A log rank was performed to correlate TMTV, TLG, LDH and presence of brain metastasis to overall survival (OS) and progression free survival (PFS) after pembrolizumab administration. Multivariate analysis was conducted for selected parameters. For each parameter, treshold values were determined to dichotomize the patients, prior to analysis. Results: The analyses showed that the TMTV (higher than 90 ml vs lower) is the best independent predictor of the OS and PFS in this patient cohort. The subgroup with a volume higher than 90 ml had a median OS of 26 weeks, whereas in the other group, the median OS was not yet reached. The one-year survival was 72,5% and 0% respectively. The difference in OS was significant (p<0.001). Presence of brain metastasis proved to be of additional predictive value. Conclusion: TMTV with threshold of 90 ml was the best predictive parameter for the response on pembrolizumab treatment in our patient cohort. Confirmation in an independent patient group is planned.