A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort study

Because responses of patients with cancer to immunotherapy can vary in success, innovative predictors of response to treatment are urgently needed to improve treatment outcomes. We aimed to develop and independently validate a radiomics-based biomarker of tumour-infiltrating CD8 cells in patients in...

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Bibliographic Details
Published in:The lancet oncology 2018-09, Vol.19 (9), p.1180-1191
Main Authors: Sun, Roger, Limkin, Elaine Johanna, Vakalopoulou, Maria, Dercle, Laurent, Champiat, Stéphane, Han, Shan Rong, Verlingue, Loïc, Brandao, David, Lancia, Andrea, Ammari, Samy, Hollebecque, Antoine, Scoazec, Jean-Yves, Marabelle, Aurélien, Massard, Christophe, Soria, Jean-Charles, Robert, Charlotte, Paragios, Nikos, Deutsch, Eric, Ferté, Charles
Format: Article
Language:English
Subjects:
Apoptosis
Archives & records
Bioengineering
Bioinformatics
Biomarkers
Cancer
CD8 antigen
Cell death
Clinical trials
Computed tomography
Computer Science
Data processing
Datasets
Gene expression
Genomes
Genotype & phenotype
Gynecology
Immunotherapy
Inflammation
Learning algorithms
Life Sciences
Ligands
Liver
Lymphoma
Medical records
Melanoma
Metastases
Patients
PD-1 protein
PD-L1 protein
Phenotypes
Radiomics
Ribonucleic acid
RNA
Solid tumors
Studies
Tumors
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Summary:Because responses of patients with cancer to immunotherapy can vary in success, innovative predictors of response to treatment are urgently needed to improve treatment outcomes. We aimed to develop and independently validate a radiomics-based biomarker of tumour-infiltrating CD8 cells in patients included in phase 1 trials of anti-programmed cell death protein (PD)-1 or anti-programmed cell death ligand 1 (PD-L1) monotherapy. We also aimed to evaluate the association between the biomarker, and tumour immune phenotype and clinical outcomes of these patients. In this retrospective multicohort study, we used four independent cohorts of patients with advanced solid tumours to develop and validate a radiomic signature predictive of immunotherapy response by combining contrast-enhanced CT images and RNA-seq genomic data from tumour biopsies to assess CD8 cell tumour infiltration. To develop the radiomic signature of CD8 cells, we used the CT images and RNA sequencing data of 135 patients with advanced solid malignant tumours who had been enrolled into the MOSCATO trial between May 1, 2012, and March 31, 2016, in France (training set). The genomic data, which are based on the CD8B gene, were used to estimate the abundance of CD8 cells in the samples and data were then aligned with the images to generate the radiomic signatures. The concordance of the radiomic signature (primary endpoint) was validated in a Cancer Genome Atlas [TGCA] database dataset including 119 patients who had available baseline preoperative imaging data and corresponding transcriptomic data on June 30, 2017. From 84 input variables used for the machine-learning method (78 radiomic features, five location variables, and one technical variable), a radiomics-based predictor of the CD8 cell expression signature was built by use of machine learning (elastic-net regularised regression method). Two other independent cohorts of patients with advanced solid tumours were used to evaluate this predictor. The immune phenotype internal cohort (n=100), were randomly selected from the Gustave Roussy Cancer Campus database of patient medical records based on previously described, extreme tumour-immune phenotypes: immune-inflamed (with dense CD8 cell infiltration) or immune-desert (with low CD8 cell infiltration), irrespective of treatment delivered; these data were used to analyse the correlation of the immune phenotype with this biomarker. Finally, the immunotherapy-treated dataset (n=137) of patients recru
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(18)30413-3