Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy
| العنوان: | Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy |
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| المؤلفون: | Hendrik Everaert, Danielle Lienard, Bart Neyns, Gil Awada, Simon Planken, Marleen Keyaerts, Hakim El Housni, Véronique Del Marmol, Pierre Heimann, Hassane Njimi, Mélanie Delaunoy, Julia Katharina Schwarze, Teofila Seremet, Yanina Jansen |
| المساهمون: | Surgery, Faculty of Medicine and Pharmacy, Clinical sciences, Internal Medicine, Supporting clinical sciences, Medical Imaging, Nuclear Medicine, Medical Oncology, Laboratory for Medical and Molecular Oncology, Laboratory of Molecullar and Cellular Therapy |
| المصدر: | Journal of Translational Medicine Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-13 (2019) Journal of translational medicine, 17 (1 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Central Nervous System, Male, 0301 basic medicine, Oncology, medicine.medical_treatment, Programmed Cell Death 1 Receptor, lcsh:Medicine, Kaplan-Meier Estimate, 0302 clinical medicine, Cost of Illness, Favorable outcome, Neoplasm Metastasis, Anti pd1, Melanoma, NRAS mutations monitoring, Medicine(all), Hazard ratio, General Medicine, Sciences bio-médicales et agricoles, Middle Aged, Treatment Outcome, Circulating tumor DNA, 030220 oncology & carcinogenesis, Female, Immunotherapy, Biologie, Adult, medicine.medical_specialty, Monitoring, Metastatic melanoma, medicine.drug_class, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, BRAF, 03 medical and health sciences, Internal medicine, BRAF/NRAS mutations monitoring, medicine, Humans, Liquid biopsy, Aged, business.industry, Research, lcsh:R, Translational research, 030104 developmental biology, Multivariate Analysis, Mutation, business, Follow-Up Studies |
| الوصف: | Background: Treatment with anti-PD1 monoclonal antibodies improves the survival of metastatic melanoma patients but only a subgroup of patients benefits from durable disease control. Predictive biomarkers for durable benefit could improve the clinical management of patients. Methods: Plasma samples were collected from patients receiving anti-PD1 therapy for ctDNA quantitative assessment of BRAF V600 and NRAS Q61/G12/G13 mutations. Results: After a median follow-up of 84 weeks 457 samples from 85 patients were analyzed. Patients with undetectable ctDNA at baseline had a better PFS (Hazard ratio (HR) = 0.47, median 26 weeks versus 9 weeks, p = 0.01) and OS (HR = 0.37, median not reached versus 21.3 weeks, p = 0.005) than patients with detectable ctDNA. Additionally, the HR for death was lower after the ctDNA level became undetectable during follow-up (adjusted HR: 0.16 (95% CI 0.07-0.36), p-value < 0.001). ctDNA levels > 500 copies/ml at baseline or week 3 were associated with poor clinical outcome. Patients progressive exclusively in the central nervous system (CNS) had undetectable ctDNA at baseline and at subsequent assessments. In multivariate analysis adjusted for LDH, CRP, ECOG and number of metastatic sites, the ctDNA remained significant for PFS and OS. A positive correlation was observed between ctDNA levels and total metabolic tumor volume (TMTV), number of metastatic sites and total tumor burden. Conclusions: Assessment of ctDNA baseline and during therapy was predictive for tumor response and clinical outcome in metastatic melanoma patients and reflected the tumor burden. ctDNA evaluation provided reliable complementary information during anti-PD1 antibody therapy. SCOPUS: ar.j info:eu-repo/semantics/published |
| وصف الملف: | 1 full-text file(s): application/pdf |
| تدمد: | 1479-5876 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a6bbc4e61b7332e00b567ee9e5508abTest https://doi.org/10.1186/s12967-019-2051-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9a6bbc4e61b7332e00b567ee9e5508ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14795876 |
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