Published July 2021
| Version v1
Journal article
Circulating tumor DNA in advanced non-small-cell lung cancer patients with HIV is associated with shorter overall survival: Results from a Phase II trial (IFCT-1001 CHIVA)
Creators
- Wislez, Marie
- Domblides, Charlotte
- Greillier, Laurent
- Mazières, Julien
- Monnet, Isabelle
- Kiakouama-Maleka, Lize
- Quantin, Xavier
- Spano, Jean Philippe
- Ricordel, Charles
- Fraisse, Philippe
- Janicot, Henri
- Audigier-Valette, Clarisse
- Amour, Elodie
- Langlais, Alexandra
- Rabbe, Nathalie
- Makinson, Alain
- Cadranel, Jacques
- Laurent-Puig, Pierre
- Lavolé, Armelle
- Blons, Hélène
Contributors
Others:
- Hôpital Cochin [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)) ; École Pratique des Hautes Études (EPHE) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)
- Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)
- Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle (ImmunoConcept) ; Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO) ; Centre Inria d'Université Côte d'Azur (CRISAM) ; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM) ; Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC) ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC) ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
- Service de Pneumologie [CHI Créteil] ; CHI Créteil
- Hôpital de la Croix-Rousse [CHU - HCL] ; Hospices Civils de Lyon (HCL)
- Institut régional de Cancérologie de Montpellier (ICM)
- CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Service de pneumologie [Rennes] = Pneumology [Rennes] ; Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
- Nouvel Hôpital Civil de Strasbourg ; Les Hôpitaux Universitaires de Strasbourg (HUS)
- Service Pneumologie / Allergologie [CHU Clermont-Ferrand] ; Pôle RHEUNNIRS [CHU Clermont-Ferrand] ; CHU Gabriel Montpied [Clermont-Ferrand] ; CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand] ; CHU Clermont-Ferrand-CHU Clermont-Ferrand
- Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse
- Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT)
- CHU Montpellier = Montpellier University Hospital ; Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan) ; Sorbonne Université (SU)
- This work was supported by Prix Alain Depierre IFCT.
Description
IntroductionHIV is an exclusion criterion for most lung cancer (LC) trials, however LC is the most common non-AIDS-defined malignancy in people living with HIV (PLHIV), poorer prognosis than the general population. Circulating tumor DNA (ctDNA) was a prognostic marker in LC patients from the general population. This study assessed ctDNA's prognostic value in PLHIV from a dedicated phase II trial.MethodsOverall, 61 PLHIV with advanced non-squamous non-small-cell lung cancer (NSCLC) participated in the IFCT Phase II trial evaluating first-line four-cycle carboplatin (Ca) AUC5 pemetrexed (P) 500 mg/m2 induction therapy every 3 weeks, followed by P maintenance therapy. Blood samples collected before treatment were analyzed to detect ctDNA using ultra-deep targeted next-generation-sequencing (NGS).ResultsAppropriate samples were available from 55 PLVIH and analyzed for ctDNA detection. Including 42 males (76.4 %), 52.9 years median age, 51 smokers (92.7 %), five with non-squamous NSCLC Stage III (9%), 50 Stage IV (91 %), and performance status (PS) 0−2. ctDNA was detected in 35 patients (64 %), 22 with high and 13 with low ctDNA levels. Overall, 77 % were positive for TP53, 29 % for KRAS, and 11 % for STK11 mutations, more than one alteration was detected in 43 % of samples. Multivariate analysis showed that positive ctDNA was significantly associated with shorter PFS (HR, 4.31, 95 %CI: 2.06−8.99, p < 0.0001), and shorter OS (HR, 3.52, 95 %CI: 1.72−7.19, p < 0.001). Moreover, OS was significantly longer for patients with low ctDNA levels at diagnosis as compared to high (p = 0.01).ConclusionWe show that ctDNA detection using ultra-deep NGS is an independent prognostic factor in PLHIV with advanced NSCLC.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://inria.hal.science/hal-03526372
- URN
- urn:oai:HAL:hal-03526372v1
Origin repository
- Origin repository
- UNICA