Abstract A051: Prediction of clinical outcomes of cancer patients treated with anti-PD-1/PD-L1 using a radiomics-based imaging score of immune infiltrate
Authors: Sun Roger , Limkin Elaine Johanna , Dercle Laurent , Reuzé Sylvain , Champiat Stéphane , Brandao David , Verlingue Loic , Ammari Samy , Aspeslagh Sandrine , Hollebecque Antoine , Massard Christophe , Marabelle Aurélien , Scoazec Jean-Yves , Robert Charlotte , Soria Jean-Charles , Deutsch Eric , Ferté Charles 
Published: August 2018

Abstract
Background: The discovery of biomarkers identifying responders to immunotherapy is a major challenge. Tumor and peritumoral immune infiltration has been shown to be associated with response to anti-PD-1/PD-L1. The aim of this study was to develop a radiomics-based imaging tool of tumor immune infiltrate and to assess whether such a tool could predict clinical outcomes of patients treated with anti-PD1/PDL1.
Methods: A predictive radiomics-based model of tumor-infiltrating CD8+ T cells was trained using data from the head and neck cohort of The Cancer Imaging Archive (HNSC-TCIA). Two cohorts from our institute were used for validation. Contrast-enhanced CTs of 57 patients from the HNSC-TCIA were manually segmented (tumor and surrounding tissue) and 76 radiomics features extracted. A radiomics-based score was build using radiomics features to predict tumor-infiltrating CD8+ T-cells' abundance, which was estimated using RNA-sequencing data from The Cancer Genome Atlas, and the Microenvironment Cell Populations-counter signature. As a first validation, this signature was applied to an independent cohort of 100 patients for whom the pathologic tumor immune infiltrate was postulated as either favorable (lymphoma, melanoma, lung, bladder, renal, MSI+ cancers, and adenopathy; 70 patients) or unfavorable (adenoid cystic carcinoma, low-grade neuroendocrine tumors, uterine leiomyoma; 30 patients). The signature was then applied on baseline-CTs of a second external cohort of 139 patients prospectively enrolled in anti PD-1/PD-L1 phase 1 trials. The median of the radiomics-based CD8+ score was used to separate patients into two groups (high and low score). Survival was estimated using Cox-proportional hazards model.
Results: We developed a radiomics-based CD8+ signature using the six radiomics features that had highest performance on random forest. In the first external cohort, the radiomics-based CD8 T-cells score was associated with the postulated tumor immune infiltrate (Wilcoxon test, P &lt; 0.001). In the second external cohort of patients treated with anti-PD-1/anti-PD-L1, median (±SD) radiomics score was 109.6±61.3. Patients with high-predicted score had significantly better OS (HR= 0.55, 95%CI=0.36-0.86, P= 0.009). The radiomics-based CD8+ predicted score remained significant in a multivariate Cox regression analysis including RMH score (HR= 0.50, 95%CI=0.32-0.78, P= 0.003).
Conclusions: The radiomics-based signature of CD8+ T cells appears as a promising tool to estimate tumor immune infiltrate and to infer the outcome of patients treated with anti-PD-1/PD-L1.
Citation Format: Roger Sun, Elaine Johanna Limkin, Laurent Dercle, Sylvain Reuzé, Stéphane Champiat, David Brandao, Loic Verlingue, Samy Ammari, Sandrine Aspeslagh, Antoine Hollebecque, Christophe Massard, Aurélien Marabelle, Jean-Yves Scoazec, Charlotte Robert, Jean-Charles Soria, Eric Deutsch, Charles Ferté. Prediction of clinical outcomes of cancer patients treated with anti-PD-1/PD-L1 using a radiomics-based imaging score of immune infiltrate [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A051.