Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
Roger Sun
(1)
,
Nora Sundahl
(2)
,
Markus Hecht
(3)
,
Florian Putz
(3)
,
Andrea Lancia
(4)
,
Angela Rouyar
(1)
,
Marina Milic
(1)
,
Alexandre Carré
(1)
,
Enzo Battistella
(1)
,
Emilie Alvarez Andres
(1)
,
Stéphane Niyoteka
(1)
,
Edouard Romano
(5)
,
Guillaume Louvel
(5)
,
Jérôme Durand-Labrunie
(5)
,
Sophie Bockel
(5)
,
Rastilav Bahleda
(6)
,
Charlotte Robert
(5)
,
Celine Boutros
(7)
,
Maria Vakalopoulou
(8, 9)
,
Nikos Paragios
(10)
,
Benjamin Frey
(3)
,
Jean-Charles Soria
(7)
,
Christophe Massard
(6)
,
Charles Ferté
(7)
,
Rainer Fietkau
(3)
,
Piet Ost
(2)
,
Udo Gaipl
(3)
,
Eric Deutsch
(1)
1
RaMo-IT -
Radiothérapie Moléculaire et Innovation Thérapeutique
2 Ghent University Hospital
3 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
4 Fondazione IRCCS Policlinico San Matteo [Pavia]
5 Département de radiothérapie [Gustave Roussy]
6 DITEP - Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy]
7 Département de médecine oncologique [Gustave Roussy]
8 OPIS - OPtimisation Imagerie et Santé
9 MICS - Mathématiques et Informatique pour la Complexité et les Systèmes
10 TheraPanacea [Paris]
2 Ghent University Hospital
3 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
4 Fondazione IRCCS Policlinico San Matteo [Pavia]
5 Département de radiothérapie [Gustave Roussy]
6 DITEP - Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy]
7 Département de médecine oncologique [Gustave Roussy]
8 OPIS - OPtimisation Imagerie et Santé
9 MICS - Mathématiques et Informatique pour la Complexité et les Systèmes
10 TheraPanacea [Paris]
Charlotte Robert
- Fonction : Auteur
- PersonId : 747236
- IdHAL : charlotte-robert
- ORCID : 0000-0001-8838-1343
Maria Vakalopoulou
- Fonction : Auteur
- PersonId : 752265
- IdHAL : maria-vakalopoulou
- ORCID : 0000-0003-0791-1264
Christophe Massard
- Fonction : Auteur
- PersonId : 761366
- ORCID : 0000-0001-5505-0564
Eric Deutsch
- Fonction : Auteur
- PersonId : 766720
- ORCID : 0000-0002-8223-3697
- IdRef : 157876403
Résumé
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.
ResultsA 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.ConclusionsThese 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 du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
|
Résumé |
en
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.
ResultsA 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.ConclusionsThese 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.
|
Auteur(s) |
Roger Sun
1
, Nora Sundahl
2
, Markus Hecht
3
, Florian Putz
3
, Andrea Lancia
4
, Angela Rouyar
1
, Marina Milic
1
, Alexandre Carré
1
, Enzo Battistella
1
, Emilie Alvarez Andres
1
, Stéphane Niyoteka
1
, Edouard Romano
5
, Guillaume Louvel
5
, Jérôme Durand-Labrunie
5
, Sophie Bockel
5
, Rastilav Bahleda
6
, Charlotte Robert
5
, Celine Boutros
7
, Maria Vakalopoulou
8, 9
, Nikos Paragios
10
, Benjamin Frey
3
, Jean-Charles Soria
7
, Christophe Massard
6
, Charles Ferté
7
, Rainer Fietkau
3
, Piet Ost
2
, Udo Gaipl
3
, Eric Deutsch
1
1
RaMo-IT -
Radiothérapie Moléculaire et Innovation Thérapeutique
( 1041775 )
- Institut Gustave Roussy, 114 rue Edouard Vaillant,
94800
Villejuif
- France
2
Ghent University Hospital
( 334659 )
- De Pintelaan 185, 9000 Gent, Belgium
- Belgique
3
FAU -
Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
( 311714 )
- Schlossplatz 4, 91054 Erlangen, Germany
- Allemagne
4
Fondazione IRCCS Policlinico San Matteo [Pavia]
( 236413 )
- Viale Camillo Golgi, 19, 27100 Pavia PV, Italie
- Italie
5
Département de radiothérapie [Gustave Roussy]
( 26449 )
- Gustave Roussy. 114, rue Édouard-Vaillant 94805 Villejuif Cedex -France
- France
6
DITEP -
Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy]
( 252201 )
- Gustave Roussy. 114, rue Édouard-Vaillant. 94805 Villejuif Cedex - France
- France
7
Département de médecine oncologique [Gustave Roussy]
( 28519 )
- Gustave Roussy. 114, rue Édouard-Vaillant 94805 Villejuif Cedex -France
- France
8
OPIS -
OPtimisation Imagerie et Santé
( 1043517 )
- France
9
MICS -
Mathématiques et Informatique pour la Complexité et les Systèmes
( 1042590 )
- Plateau de Moulon 3 rue Joliot Curie 91192 GIF SUR YVETTE CEDEX
- France
10
TheraPanacea [Paris]
( 573968 )
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2020-11-13
|
Volume |
8
|
Numéro |
2
|
Page/Identifiant |
e001429
|
Domaine(s) |
|
DOI | 10.1136/jitc-2020-001429 |
PubMed Central | PMC7668366 |
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