Development and Validation of a Predictive Model for Metastatic Melanoma Patients Treated with Pembrolizumab Based on Automated Analysis of Whole-Body [F-18]FDG PET/CT Imaging and Clinical Features

Background: Antibodies that inhibit the programmed cell death protein 1 (PD-1) receptor offer a significant survival benefit, potentially cure (i.e., durable disease-free survival following treatment discontinuation), a substantial proportion of patients with advanced melanoma. Most patients however fail to respond to such treatment or acquire resistance. Previously, we reported that baseline total metabolic tumour volume (TMTV) determined by whole-body [F-18]FDG PET/CT was independently correlated with survival and able to predict the futility of treatment. Manual delineation of [F-18]FDG-avid lesions is however labour intensive and not suitable for routine use. A predictive survival model is proposed based on automated analysis of baseline, whole-body [F-18]FDG images. Methods: Lesions were segmented on [F-18]FDG PET/CT using a deep-learning approach and derived features were investigated through Kaplan-Meier survival estimates with univariate logrank test and Cox regression analyses. Selected parameters were evaluated in multivariate Cox survival regressors. Results: In the development set of 69 patients, overall survival prediction based on TMTV, lactate dehydrogenase levels and presence of brain metastases achieved an area under the curve of 0.78 at one year, 0.70 at two years. No statistically significant difference was observed with respect to using manually segmented lesions. Internal validation on 31 patients yielded scores of 0.76 for one year and 0.74 for two years. Conclusions: Automatically extracted TMTV based on whole-body [F-18]FDG PET/CT can aid in building predictive models that can support therapeutic decisions in patients treated with immune-checkpoint blockade.