Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
Open Access
- 1 January 2020
- journal article
- research article
- Published by BMJ in Journal for ImmunoTherapy of Cancer
- Vol. 8 (2), e001429
- https://doi.org/10.1136/jitc-2020-001429
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'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.Funding Information
- Amazon AWS grant
- SIRIC-SOCRATE 2.0 (grant INCa-DGOS-INSERM_12551)
- Fondation ARC pour la Recherche sur le Cancer (grant SIGN'IT20181007805)
- Fondation pour la Recherche Médicale (grant DIC20161236437)
- INSERM in partnership with Fondation Bettencourt Schueller (CCA-INSERM-BETTENCOURT)
This publication has 32 references indexed in Scilit:
- Optimising efficacy and reducing toxicity of anticancer radioimmunotherapyThe Lancet Oncology, 2019
- Time to abandon single-site irradiation for inducing abscopal effectsNature Reviews Clinical Oncology, 2018
- Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapiesStrahlentherapie und Onkologie, 2018
- Immunomodulation by ionizing radiation-impact for design of radio-immunotherapies and for treatment of inflammatory diseasesImmunological Reviews, 2017
- Elements of cancer immunity and the cancer–immune set pointNature, 2017
- Radiotherapy and immunotherapy: a beneficial liaison?Nature Reviews Clinical Oncology, 2017
- Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2016
- Pembrolizumab versus Ipilimumab in Advanced MelanomaThe New England Journal of Medicine, 2015
- Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancerNature, 2015
- Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediatedInternational Journal of Radiation Oncology*Biology*Physics, 2004