Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
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 inspire...
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001429.full |
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| author | Jean-Charles Soria Charles Ferte Christophe Massard Roger Sun Guillaume Louvel Eric Deutsch Benjamin Frey Markus Hecht Rainer Fietkau Nora Sundahl Florian Putz Andrea Lancia Angela Rouyar Marina Milic Alexandre Carré Enzo Battistella Emilie Alvarez Andres Stéphane Niyoteka Edouard Romano Jérôme Durand-Labrunie Sophie Bockel Rastilav Bahleda Charlotte Robert Celine Boutros Maria Vakalopoulou Nikos Paragios Piet Ost Udo Gaipl |
| author_facet | Jean-Charles Soria Charles Ferte Christophe Massard Roger Sun Guillaume Louvel Eric Deutsch Benjamin Frey Markus Hecht Rainer Fietkau Nora Sundahl Florian Putz Andrea Lancia Angela Rouyar Marina Milic Alexandre Carré Enzo Battistella Emilie Alvarez Andres Stéphane Niyoteka Edouard Romano Jérôme Durand-Labrunie Sophie Bockel Rastilav Bahleda Charlotte Robert Celine Boutros Maria Vakalopoulou Nikos Paragios Piet Ost Udo Gaipl |
| author_sort | Jean-Charles Soria |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-231cb0065627444ebd7c169e765aa1cb |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-231cb0065627444ebd7c169e765aa1cb2025-08-20T02:14:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001429Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cellsJean-Charles Soria0Charles Ferte1Christophe Massard2Roger Sun3Guillaume Louvel4Eric Deutsch5Benjamin Frey6Markus Hecht7Rainer Fietkau8Nora Sundahl9Florian Putz10Andrea Lancia11Angela Rouyar12Marina Milic13Alexandre Carré14Enzo Battistella15Emilie Alvarez Andres16Stéphane Niyoteka17Edouard Romano18Jérôme Durand-Labrunie19Sophie Bockel20Rastilav Bahleda21Charlotte Robert22Celine Boutros23Maria Vakalopoulou24Nikos Paragios25Piet Ost26Udo Gaipl274 Oncology Research and Development, AstraZeneca, Gaithersburg, Maryland, USA9 Departement of Medicine, Gustave Roussy, Villejuif, Île-de-France, FrancePalliative Care Unit, Gustave Roussy Institute, Villejuif, France5 Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, FranceAff1 0000 0001 2284 9388grid.14925.3bDepartment of RadiotherapyGustave Roussy Cancer Campus 94800 Villejuif France1 INSERM U1030, Molecular Radiotherapy, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France5 Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Saarland University Medical Center, Homburg, Germany2 Comprehensive Cancer Center Erlangen-EMN, Erlangen, Bayern, Germany4 Department of Radiation Oncology, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium5 Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany6 Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy2 Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France2 Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France1 Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France2 Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France2 Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France2 Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France1 Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France1 Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France1 Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France5Gustave Roussy, Villejuif, Ile de France, France2 Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France9 Departement of Medicine, Gustave Roussy, Villejuif, Île-de-France, France10 CentraleSupélec, Gif-sur-Yvette, Île-de-France, France7 TheraPanacea, Paris, France4 Department of Radiation Oncology, University Hospital Ghent, Gent, Oost-Vlaanderen, BelgiumTranslational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen & Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyBackground 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.https://jitc.bmj.com/content/8/2/e001429.full |
| spellingShingle | Jean-Charles Soria Charles Ferte Christophe Massard Roger Sun Guillaume Louvel Eric Deutsch Benjamin Frey Markus Hecht Rainer Fietkau Nora Sundahl Florian Putz Andrea Lancia Angela Rouyar Marina Milic Alexandre Carré Enzo Battistella Emilie Alvarez Andres Stéphane Niyoteka Edouard Romano Jérôme Durand-Labrunie Sophie Bockel Rastilav Bahleda Charlotte Robert Celine Boutros Maria Vakalopoulou Nikos Paragios Piet Ost Udo Gaipl Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells Journal for ImmunoTherapy of Cancer |
| 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 |
| title_full | Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells |
| title_fullStr | Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells |
| title_full_unstemmed | Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells |
| title_short | Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells |
| title_sort | radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of cd8 cells |
| url | https://jitc.bmj.com/content/8/2/e001429.full |
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