Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations.

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.

[Mediastinal haematoma: A little known complication of ultrasound-guided trans-bronchial lymph node aspiration (EBUS-TBNA)]. / Un hématome médiastinal : complication méconnue d'une ponction transbronchique échoguidée.

INTRODUCTION: Endobronchial ultrasound-guided trans-bronchial needle aspiration (EBUS-TBNA) has emerged as a minimally invasive, highly accurate technique for sampling intrathoracic lymph nodes. The complication rate after EBUS-TBNA is estimated at between 0.22% to 1.44%. Analysis of the different series of EBUS-TBNA reveals that mediastinal haematoma has not been described as a complication. CASE REPORT: We describe the case of a 65-year-old-man who underwent an EBUS-TBNA of a subcarinal lymph node. Few days later the patient presented with haemoptysis of average amount associated with a haematoma in the subcarinal area seen on CT-scan. It was suggested that puncture of a bronchial artery occurred during passage of the needle. This complication occurred during the change from treatment by low molecular weight heparin to antivitamine K. The patient was monitored in the intensive care unit and received medical treatment only. CONCLUSIONS: This patient developed a complication after an EBUS-TBNA that is rarely described and probably under diagnosed. This complication occurred during the change between two anticoagulant treatments, which requires special attention in this particular context.

CT-texture analysis of subsolid nodules for differentiating invasive from in-situ and minimally invasive lung adenocarcinoma subtypes.

PURPOSE: The purpose of this study was to evaluate the usefulness of computed tomography-texture analysis (CTTA) in differentiating between in-situ and minimally-invasive from invasive adenocarcinomas in subsolid lung nodules (SSLNs). MATERIAL AND METHODS: Two radiologists retrospectively reviewed 49 SSLNs in 44 patients. There were 27 men and 17 women with a mean age of 63±7 (SD) years (range: 47-78years). For each SSLN, type (pure ground-glass or part-solid) was assessed by consensus and CTTA was conducted independently by each observer using a filtration-histogram technique. Different filters were used before histogram quantification: no filtration, fine, medium and coarse, followed by histogram quantification using mean intensity, standard deviation (SD), entropy, mean positive pixels (MPP), skewness and kurtosis. RESULTS: We analyzed 13 pure ground-glass and 36 part-solid nodules corresponding to 16 adenocarcinomas in-situ (AIS), 5 minimally invasive adenocarcinomas (MIA) and 28 invasive adenocarcinomas (IVA). At uni- and multivariate analysis CTTA allowed discriminating between IVAs and AIS/MIA (P<0.05 and P=0.025, respectively) with the following histogram parameters: skewness using fine textures and kurtosis using coarse filtration for pure ground-glass nodules, and SD without filtration for part-solid nodules. CONCLUSION: CTTA has the potential to differentiate AIS and MIA from IVA among SSLNs. However, our results require further validation on a larger cohort.

[Predictive factors of complications during CT-guided transthoracic biopsy]. / Facteurs prédictifs de complications des ponctions transpariétales thoraciques.

INTRODUCTION: CT-guided transthoracic core-needle biopsy (TTNB) is frequently used for the diagnosis of lung nodules. The aim of this study is to describe TTNBs' complications and to investigate predictive factors of complications. METHODS: All consecutive TTNBs performed in three centers between 2006 and 2012 were included. Binary logistic regression was used for multivariate analysis. RESULTS: Overall, 970 TTNBs were performed in 929 patients. The complication rate was 34% (life-threatening complication in 6%). The most frequent complications were pneumothorax (29% included 4% which required chest-tube) and hemoptysis (5%). The mortality rate was 0.1% (n=1). In multivariate analysis, predictive factor for a complication was small target size (AOR=0.984; 95% CI [0.976-0.992]; P<0.001). This predictive factor was also found for occurrence of life-threatening complication (AOR=0.982; [0.965-0.999]; P=0.037), of pneumothorax (AOR=0.987; [0.978-0.995]; P=0.002) and of hemoptysis (AOR=0.973; [0.951-0.997]; P=0.024). CONCLUSION: One complication occurred in one-third of TTNBs. The proportion of life-threatening complication was 6%. A small lesion size was predictive of complication occurrence.

Lung adenocarcinomas: correlation of computed tomography and pathology findings.

Adenocarcinoma is the most common histologic type of lung cancer. Recent lung adenocarcinoma classifications from the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society (IASLC/ETS/ERS, 2011) and World Health Organization (WHO, 2015) define a wide range of adenocarcinoma types and subtypes featuring different prognosis and management. This spectrum of lesions translates into various CT presentations and features, which generally show good correlation with histopathology, stressing the key role of the radiologist in the diagnosis and management of those patients. This review aims at helping radiologists to understand the basics of the up-to-date adenocarcinoma pathological classifications, radio-pathological correlations and how to use them in the clinical setting, as well as other imaging-related correlations (radiogenomics, quantitative analysis, PET-CT).

Personalized chemotherapy of lung cancer: What the radiologist should know.

Lung cancer is the leading cause of deaths due to cancer in France. More than half of lung cancers are discovered at an advanced-stage. New anticancer treatment strategies (i.e., the so-called personalized or targeted therapy) have recently been introduced and validated for non-small-cell lung cancer (NSCLC), in addition to or in association with standard chemotherapy. Personalized therapy includes tyrosine kinase inhibitors (TKIs), antiangiogenic treatments and immunotherapy. Because these treatments may be responsible for atypical thoracic adverse effects and responses as compared to standard chemotherapy, RECIST 1.1 criteria may be inadequate to evaluate the responses to these agents. The goal of this article was to review personalized treatment strategies for NSCLC, to consider the therapy-specific responses and thoracic complications induced by these new therapeutic agents and finally to discuss future directions for the personalized assessment of tumor response.

The new classification of lung adenocarcinomas: implications for pathologists and radiologists.

The present manuscript is a summary of two lectures which were given respectively by B. Weynand and G.R. Ferretti. The new classification of lung adenocarcinomas has changed the view of the radiologists and the pathologists especially regarding the former bronchiolo-alveolar carcinoma (BAC). The aim of this paper is to correlate radiological and histopathological images according to the 2011 classification for lung adenocarcinoma proposed by the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society and to draw attention to the way these lesions can be approached preoperatively.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

CT characteristics of resolving ground-glass opacities in a lung cancer screening programme.

PURPOSE: This study aimed at evaluating the computed tomography (CT) characteristics of resolving localized ground-glass opacities (GGOs) in a screening programme for lung cancer. MATERIAL AND METHODS: 280 patients at high-risk for lung cancer (221 men, 59 women; mean age, 58.6 years), divided into four groups (lung cancer history (n = 83), head and neck cancer history (n = 63), symptomatic (n = 88) and asymptomatic (n = 46) cigarette smokers), were included in a prospective trial with annual low-dose CT for lung cancer screening. We retrospectively reviewed all localized GGOs, analyzed the CT characteristics on initial CT scans and changes during follow-up (median 29.1 months). Variables associated with resolution of GGOs were tested using chi-square or Mann-Whitney tests. RESULTS: A total of 75 GGOs were detected in 37 patients; 54.7% were present at baseline and 45.3% appeared on annual CT. During follow-up, 56.2% persisted and 43.8% disappeared. The resolving localized GGOs were significantly more often lobular GGOs (p = 0.006), polygonal in shape (p = 0.02), mixed (p = 0.003) and larger (p < 0.0001) than non-resolving localized GGOs. CONCLUSION: Localized GGOs are frequent and many disappeared on follow-up. CT characteristics of resolving GGOs show significant differences compared to persistent ones. This study emphasizes the importance of short-term CT follow-up in subjects with localized GGOs.

Imaging of a case of extramedullary solitary plasmacytoma of the trachea.

We describe a case of extramedullary tracheal plasmacytoma that was incidentally discovered in a 73-year-old man on a PET scan performed for assessing the extent of colon cancer. CT scan showed the tumor; multiplanar reformation coupled with virtual bronchoscopy allowed proper treatment planning. The tracheal tumor was resected during rigid bronchoscopy. Relevant investigations excluded multiple myeloma. Follow-up CT showed persistent thickening of the tracheal wall, but there has been no recurrence after one-year followup.

[Volumetric CT scanning: 2D and 3D reconstruction]. / Tomodensitométrie volumique : reconstructions 2D et 3D.

This review aims to present the 2D and 3D reconstructions derived from high-resolution volume CT acquisitions and to illustrate their thoracic applications, as well as showing the interest and limitations of these techniques. We present new applications for computer-assisted detection (CAD) and tools for quantification of pulmonary lesions.

Imaging of tumors of the trachea and central bronchi.

Tumors of the trachea and central bronchi can be benign or malignant. Clinical presentation may be confusing, particularly in benign tumors that can be misdiagnosed as asthma or chronic bronchitis. Chest radiography has many limitations and is often considered unremarkable in patients with tumors of the central airways; therefore, multidetector CT (MDCT) has become the most useful noninvasive method for diagnosing and assessing the central airways. The purpose of this article is to provide a review of imaging of the tumors of the trachea and central bronchi. We emphasize the crucial role of MDCT and postprocessing techniques in assessing neoplasms of the central airways.

Imaging of tumors of the trachea and central bronchi.

Tumors of the trachea and central bronchi can be benign or malignant. Clinical presentation may be confusing, particularly in benign tumors that can be misdiagnosed as asthma or chronic bronchitis. Chest radiography has many limitations and is often considered unremarkable in patients with tumors of the central airways; therefore, multidetector CT (MDCT) has become the most useful noninvasive method for diagnosing and assessing the central airways. The purpose of this article is to provide a review of imaging of the tumors of the trachea and central bronchi. We emphasize the crucial role of MDCT and postprocessing techniques in assessing neoplasms of the central airways.

Unusual cystic presentation of pulmonary nodular amyloidosis associated with MALT-type lymphoma.

The case reported herein consists of nodular pulmonary amyloidosis presenting with unusual cystic radiological features which reveal a pulmonary localisation of an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). The present case is the first to report a radiological presentation of nodular pulmonary amyloidosis in the absence of Sjögren's syndrome. Although transthoracic fine-needle biopsy was helpful for the diagnostic of amyloidosis, final diagnosis of associated MALT-type lymphoma required an open lung biopsy. This emphasises the importance of performing surgical investigations in pulmonary nodular amyloidosis in order to depict the presence of underlying lung tumours or lymphoproliferative disorders.

[Volume CT: recent advances in acquired abnormalities of the trachea]. / Tomodensitométrie volumique: avancées récentes en pathologie trachéale acquise.

OBJECTIVES: To show the recent improvements in CT imaging of the trachea due to the introduction of multidetector computed tomography (MDCT). MATERIAL AND METHODS: MDCT technology, which was introduced in the early 00's, allows acquiring the entire airways within few seconds while using low dose parameters thanks to the natural high contrast of the airways. RESULTS: Volume acquisition with isotropic voxels offers an excellent anatomical resolution in all directions, improving the quality of multiplanar reformations and 3D reconstructions, including virtual bronchoscopy. Therefore, the ability of CT for detecting and localizing tracheal abnormalities are improved, which is useful for planning endoscopy or open surgery, or assess their results. Dynamic acquisition during expiration is the last refinement permitted by MDCT, which is of value to detect tracheomalacia. CONCLUSIONS: MDCT is a non-invasive technique to image the trachea. Its applications are numerous, such as depiction of anatomical or functional abnormalities, evaluation of local extent of the disease, planning and assessing open surgery or interventional endoscopy.

Non-conform diagnostic management of pulmonary embolism suspected patients is responsible for a higher risk of thrombotic event occurrence.

The aim of this 3-month follow-up prospective pragmatic study was to evaluate the implementation of a pulmonary embolism (PE) diagnostic strategy in clinical practice. One thousand and one hundred thirty-four consecutive in- and outpatients with clinically suspected PE were enrolled into a sequential diagnostic algorithm in which vascular medical unit plays a pivotal role in advising physicians and suggesting the most appropriate tests according to the diagnostic algorithm. In this observational study, patients that followed the proposed work-up were attributed to a so-called "conform group". Patients in whom diagnostic work-up was not according to protocol were attributed to a "non-conform group". Nine hundred and ninety-seven patients (87.9%) had a conform work-up, and 137 patients a non-conform work-up according to the proposed diagnostic algorithm. The non-conform work-up directly increased in relation to the age of the referred patients. PE was ruled out in 907 (80%) patients of whom 787 (86.8%) were in the conform group. Of the 797 patients who did not receive anticoagulant drugs, follow-up was obtained in 792 (99.4%). Among these patients, the incidence of acute thromboembolic events during the 3-month follow-up period was different in the group of patients that had a conform work-up (1%, [95% CI, 0.5-2.1%]) from the non-conform group patients (4.5%, [95% CI, 2-10.2%]. Therefore patients from the non-conform group have an independent increased risk to develop a thromboembolic event during the follow-up, adjusted odds ratio 3.3 [1.1-10, 95% CI]. Therefore we demonstrated that a non-conform diagnostic management strategy is associated with a higher risk of thrombotic event occurrence.