المؤلفون: Jordi Remon, Aurelie Swalduz, David Planchard, Sandra Ortiz-Cuaran, Laura Mezquita, Ludovic Lacroix, Cecile Jovelet, Etienne Rouleau, Camille Leonce, Frank De Kievit, Clive Morris, Greg Jones, Kelly Mercier, Karen Howarth, Emma Green, Maurice Pérol, Pierre Saintigny, Benjamin Besse

المصدر: PLoS ONE, Vol 15, Iss 6, p e0234302 (2020)

مصطلحات موضوعية: Medicine, Science

الوصف: Circulating tumor DNA (ctDNA)-based molecular profiling is rapidly gaining traction in clinical practice of advanced cancer patients with multi-gene next-generation sequencing (NGS) panels. However, clinical outcomes remain poorly described and deserve further validation with personalized treatment of patients with genomic alterations detected in plasma ctDNA. Here, we describe the outcomes, disease control rate (DCR) at 3 months and progression-free survival (PFS) in oncogenic-addicted advanced NSCLC patients with actionable alterations identified in plasma by ctDNA liquid biopsy assay, InVisionFirst®-Lung. A pooled retrospective analysis was completed of 81 advanced NSCLC patients with all classes of alterations predicting response to current FDA approved drugs: sensitizing common EGFR mutations (78%, n = 63) with T790M (73%, 46/63), ALK / ROS1 gene fusions (17%, n = 14) and BRAF V600E mutations (5%, n = 4). Actionable driver alterations detected in liquid biopsy were confirmed by prior tissue genomic profiling in all patients, and all patients received personalized treatment. Of 82 patients treated with matched targeted therapies, 10% were at first-line, 41% at second-line, and 49% beyond second-line. Acquired T790M at TKI relapse was detected in 73% (46/63) of patients, and all prospective patients (34/46) initiated osimertinib treatment based on ctDNA results. The 3-month DCR was 86% in 81 evaluable patients. The median PFS was of 14.8 months (12.1-22.9m). Baseline ctDNA allelic fraction of genomic driver did not correlate with the response rate of personalized treatment (p = 0.29). ctDNA molecular profiling is an accurate and reliable tool for the detection of clinically relevant molecular alterations in advanced NSCLC patients. Clinical outcomes with targeted therapies endorse the use of liquid biopsy by amplicon-based NGS ctDNA analysis in first line and relapse testing for advanced NSCLC patients.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/93ae8d067940452fb391568395e4fc0eTest

المؤلفون: Antoine Schernberg, Laura Mezquita, Angela Boros, Angela Botticella, Caroline Caramella, Benjamin Besse, Alexandre Escande, David Planchard, Cécile Le Péchoux, Eric Deutsch

المصدر: PLoS ONE, Vol 13, Iss 10, p e0204490 (2018)

مصطلحات موضوعية: Medicine, Science

الوصف: OBJECTIVE:To study the prognostic value of baseline leukocytosis or neutrophiliain two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients. MATERIALS AND METHODS:Clinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively. RESULTS:We identified 238 patients, displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC6179235?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/4164a803267e4c2980b1094e05918edcTest

المؤلفون: Cécile Jovelet, Jordan Madic, Jordi Remon, Aurélie Honoré, Romain Girard, Etienne Rouleau, Barbara André, Benjamin Besse, Magali Droniou, Ludovic Lacroix

المصدر: PLoS ONE, Vol 12, Iss 8, p e0183319 (2017)

مصطلحات موضوعية: Medicine, Science

الوصف: Over the past years, targeted therapies using tyrosine kinase inhibitors (TKI) have led to an increase in progression-free survival and response rate for a subgroup of non-small cell lung cancer (NSCLC) patients harbouring specific gene abnormalities compared with chemotherapy. However long-lasting tumor regression is rarely achieved, due to the development of resistant tumoral subclones, which requires alternative therapeutic approaches. Molecular profile at progressive disease is a challenge for making adaptive treatment decisions. The aim of this study was to monitor EGFR-mutant tumors over time based on the quantity of mutant DNA circulating in plasma (ctDNA), comparing two different methods, Crystal™ Digital™ PCR and Massive Parallel Sequencing (MPS). In plasma circulating cell free DNA (cfDNA) of 61 advanced NSCLC patients we found an overall correlation of 78% between mutated allelic fraction measured by Crystal Digital PCR and MPS. 7 additional samples with sensitizing mutations and 4 additional samples with the resistance mutation were detected with Crystal Digital PCR, but not with MPS. Monitoring levels of both mutation types over time showed a correlation between levels and trends of mutated ctDNA detected and clinical assessment of disease for the 6 patients tested. In conclusion, Crystal Digital PCR exhibited good performance for monitoring mutational status in plasma cfDNA, and also appeared as better suited to the detection of known mutations than MPS in terms of features such as time to results.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC5567481?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/23751c7a887c4ffe9f4476ab4cd61091Test

المؤلفون: Angela Botticella, David Planchard, Caroline Caramella, Eric Deutsch, A. Boros, Antoine Schernberg, Alexandre Escande, Benjamin Besse, Cécile Le Péchoux, Laura Mezquita

المصدر: PLoS ONE, Vol 13, Iss 10, p e0204490 (2018)
PLoS ONE

مصطلحات موضوعية: Male, 0301 basic medicine, Lung Neoplasms, Neutrophils, Leukocytosis, Cancer Treatment, lcsh:Medicine, Gastroenterology, Lung and Intrathoracic Tumors, Metastasis, Cohort Studies, Hematologic Cancers and Related Disorders, Leukocyte Count, White Blood Cells, chemistry.chemical_compound, 0302 clinical medicine, Animal Cells, Carcinoma, Non-Small-Cell Lung, Adenocarcinomas, Basic Cancer Research, Medicine and Health Sciences, Neoplasm Metastasis, lcsh:Science, Aged, 80 and over, education.field_of_study, Multidisciplinary, Pharmaceutics, Chemoradiotherapy, Hematology, Middle Aged, Prognosis, Oncology, 030220 oncology & carcinogenesis, Absolute neutrophil count, Female, Cellular Types, medicine.symptom, Research Article, Adult, Clinical Oncology, medicine.medical_specialty, Immune Cells, Immunology, Population, Adenocarcinoma of Lung, Antineoplastic Agents, Carcinomas, Cancer Chemotherapy, 03 medical and health sciences, Drug Therapy, Internal medicine, Biomarkers, Tumor, medicine, Humans, Chemotherapy, education, Survival analysis, Aged, Neoplasm Staging, Blood Cells, Myeloproliferative Disorders, business.industry, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, Induction chemotherapy, Cell Biology, medicine.disease, Survival Analysis, Neutrophilia, Carboplatin, Non-Small Cell Lung Cancer, respiratory tract diseases, 030104 developmental biology, chemistry, lcsh:Q, Clinical Medicine, business, Leukocyte Disorders, Brain metastasis

الوصف: Objective To study the prognostic value of baseline leukocytosis or neutrophiliain two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients. Materials and methods Clinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively. Results We identified 238 patients, displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5faddc02715e5ef3e50e83a01ffef8f5Test
https://doi.org/10.1371/journal.pone.0204490Test