CT radiomics to predict checkpoint inhibitors treatment outcomes in patients with advanced cutaneous melanoma

Introduction Predicting checkpoint inhibitors treatment outcomes in melanoma is a relevant task, due to the unpredictable and potentially fatal toxicity and high costs for society. However, accurate biomarkers for treatment outcomes are lacking. Radiomics are a technique to quantitatively capture tumor characteristics on readily available computed tomography (CT) imaging. The purpose of this study was to investigate the added value of radiomics for predicting durable clinical benefit from checkpoint inhibitors in melanoma in a large, multicenter cohort. Methods Patients who received first-line anti-PD1 with or without anti-CTLA4 treatment for advanced cutaneous melanoma were retrospectively identified from nine participating hospitals. For every patient, up to five representative lesions were segmented on baseline CT and radiomics features were extracted. A machine learning pipeline was trained on the radiomics features to predict durable clinical benefit, defined as stable disease for more than six months or response per RECIST 1.1 criteria. This approach was evaluated using a leave-one-center-out cross validation and compared to a model based on previously discovered clinical predictors. Lastly, a combination model was built on the radiomics and clinical model. Results A total of 620 patients were included, of which 59.2% experienced durable clinical benefit. The radiomics model achieved an area under the receiver operator characteristic curve (AUROC) of 0.607 [95%CI 0.562-0.652], lower than that of the clinical model (AUROC=0.646 [95%CI 0.600-0.692]). The combination model yielded no improvement over the clinical model in terms of discrimination (AUROC=0.636 [95%CI 0.592-0.680]) or calibration. The output of the radiomics model was significantly correlated with three out of five input variables of the clinical model (p < 0.001). Discussion The radiomics model achieved a moderate predictive value of durable clinical benefit, which was statistically significant. However, a radiomics approach was unable to add value to a simpler clinical model, most likely due to the overlap in predictive information learned by both models. Future research should focus on the application of deep learning, spectral CT derived radiomics and a multimodal approach for accurately predicting benefit to checkpoint inhibitor treatment in advanced melanoma.