Academic Journal
Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression
| العنوان: | Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression |
|---|---|
| المؤلفون: | Giroux Leprieur, Étienne, Hélias-Rodzewicz, Zofia, Takam Kamga, Paul, Costantini, Adrien, Julie, Catherine, Corjon, Alexandre, Dumenil, Coraline, Dumoulin, Jennifer, Giraud, Violaine, Labrune, Sylvie I., Garinet, Simon, Chinet, Thierry C., Emile, Jean François J.F. |
| المساهمون: | Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré AP-HP, Service de pathologie CHU Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré AP-HP, Hôpital Européen Georges Pompidou APHP (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO) |
| المصدر: | ISSN: 2051-1426 ; Journal for Immunotherapy of Cancer ; https://hal.science/hal-02889991 ; Journal for Immunotherapy of Cancer, 2020, 8 (1), ⟨10.1136/jitc-2020-000527⟩. |
| بيانات النشر: | HAL CCSD BMJ Publishing Group |
| سنة النشر: | 2020 |
| المجموعة: | Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| مصطلحات موضوعية: | biomarkers, tumor, lung neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; BACKGROUND: Despite prolonged tumor response to immune checkpoint inhibitors (ICIs) for a subset of patients with advanced non-small cell lung cancer (NSCLC), a secondary resistance will occur for a majority of these patients. The understanding of late progression mechanisms with ICIs is important to improve future treatment strategies. METHODS: We performed whole-exome sequencing (WES) on circulating tumor DNA and compared molecular profiles between the beginning of ICI treatment and tumor progression in patients with advanced NSCLC treated with ICIs and who had initial and prolonged tumor response with secondary progression, after at least 6 months of treatment. RESULTS: We identified eight patients who experienced initial and durable tumor response, and secondary tumor progression after 6 months of treatment, with available paired blood samples (diagnosis and progression). All had lung adenocarcinoma, three had programmed-death ligand-1 expression ≥50% in immunohistochemistry and all presented low blood tumor mutational burden (bTMB). Seven patients received nivolumab in second-line or more, and one received pembrolizumab as first-line treatment. WES at progression showed clonal selection with molecular alterations of Wnt pathway-related genes, increase of copy number aberrations in cancer-related genes and loss of tumor-suppressor genes (such as PTEN) or of genes associated with immune response (such as B2M). No difference in term of bTMB was observed at progression. CONCLUSIONS: This is the first study describing putative molecular mechanisms associated with late progression under ICI in lung cancer. Studies on treatment strategies adapted to these mechanisms are needed. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/32581058; hal-02889991; https://hal.science/hal-02889991; https://hal.science/hal-02889991/document; https://hal.science/hal-02889991/file/e000527.full.pdf; PUBMED: 32581058; PUBMEDCENTRAL: PMC7319709 |
| DOI: | 10.1136/jitc-2020-000527 |
| الاتاحة: | https://hal.science/hal-02889991 https://hal.science/hal-02889991/document https://hal.science/hal-02889991/file/e000527.full.pdf https://doi.org/10.1136/jitc-2020-000527 |
| Rights: | http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.F61D5AF4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/jitc-2020-000527 |
|---|