@article {Sune001429, author = {Roger Sun and Nora Sundahl and Markus Hecht and Florian Putz and Andrea Lancia and Angela Rouyar and Marina Milic and Alexandre Carr{\'e} and Enzo Battistella and Emilie Alvarez Andres and St{\'e}phane Niyoteka and Edouard Romano and Guillaume Louvel and J{\'e}r{\^o}me Durand-Labrunie and Sophie Bockel and Rastilav Bahleda and Charlotte Robert and Celine Boutros and Maria Vakalopoulou and Nikos Paragios and Benjamin Frey and Jean-Charles Soria and Christophe Massard and Charles Fert{\'e} and Rainer Fietkau and Piet Ost and Udo Gaipl and Eric Deutsch}, title = {Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells}, volume = {8}, number = {2}, elocation-id = {e001429}, year = {2020}, doi = {10.1136/jitc-2020-001429}, publisher = {BMJ Specialist Journals}, abstract = {Background Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions.Methods Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30\%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient{\textquoteright}s response.Results A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables.Conclusions These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.}, URL = {https://jitc.bmj.com/content/8/2/e001429}, eprint = {https://jitc.bmj.com/content/8/2/e001429.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }