ABSTRACT
BACKGROUND: BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Melanoma , Bayes Theorem , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Treatment Outcome , Vemurafenib/therapeutic useABSTRACT
INTRODUCTION: Intrathoracic textiloma is a rare complication possibly leading to misdiagnosis. It could present as haemoptysis, lung abscess, pseudo-tumour or a chronic cough. CASE REPORT: A 65-year-old patient with a history of multiple cardiac problems and needing long-term anticoagulation, complained since 2007 of recurrent haemoptysis of increasing abundance, the etiological investigation of which was negative. A thoracic CT-scan revealed a lesion in the lingula in contact with the pericardial plates of an implanted automatic defibrillator dating from 1989. In 2016, after two failures of arterial embolization, a diagnostic and therapeutic surgical exploration was undertaken on this patient who was a high operative risk. A segmental resection revealed an intra-pulmonary textiloma on pathological examination. CONCLUSION: The diagnosis of intrathoracic textiloma remains rare and its late presentation is non specific. Radiological imaging with a CT-scan and/or MRI could lead to the diagnosis. Surgery remains the reference treatment for the diagnosis and cure of intrathoracic textiloma with pathological examination, essential for confirmation. A means of prevention has to be developed because swab count is not totally reliable.
Subject(s)
Foreign Bodies/diagnosis , Hemoptysis/diagnosis , Lung/pathology , Surgical Mesh/adverse effects , Thoracic Surgical Procedures/adverse effects , Aged , Diagnosis, Differential , Foreign Bodies/complications , Foreign Bodies/pathology , Hemoptysis/etiology , Humans , Late Onset Disorders/diagnosis , Late Onset Disorders/etiology , Late Onset Disorders/pathology , Male , Time FactorsABSTRACT
Currently about 50% of cases of haemoptysis are thought to be cryptogenic. Haemorrhage from the pulmonary arterial system is rare and usually due to aneurysms or pseudoaneurysms, the radiological diagnosis of which is often difficult. We report here the case of a patient admitted with a heavy haemoptysis in whom the thoracic CT scan did not reveal the diagnosis. Bronchoscopy with endobronchial ultrasound showed a vascular malformation of a branch of the pulmonary artery allowing a radiological embolisation. This case underlines the importance of bronchoscopy and the role of ultrasound in the diagnosis of haemoptysis, considered ideopathic, complicating vascular malformations.
