[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Artificial intelligence solution to classify pulmonary nodules on CT.

PURPOSE: The purpose of this study was to create an algorithm to detect and classify pulmonary nodules in two categories based on their volume greater than 100 mm3 or not, using machine learning and deep learning techniques. MATERIALS AND METHOD: The dataset used to train the model was provided by the organization team of the SFR (French Radiological Society) Data Challenge 2019. An asynchronous and parallel 3-stages pipeline was developed to process all the data (a data "pre-processing" stage; a "nodule detection" stage; a "classifier" stage). Lung segmentation was achieved using 3D U-NET algorithm; nodule detection was done using 3D Retina-UNET and classifier stage with a support vector machine algorithm on selected features. Performances were assessed using area under receiver operating characteristics curve (AUROC). RESULTS: The pipeline showed good performance for pathological nodule detection and patient diagnosis. With the preparation dataset, an AUROC of 0.9058 (95% confidence interval [CI]: 0.8746-0.9362) was obtained, 87% yielding accuracy (95% CI: 84.83%-91.03%) for the "nodule detection" stage, corresponding to 86% specificity (95% CI: 82%-92%) and 89% sensitivity (95% CI: 84.83%-91.03%). CONCLUSION: A fully functional pipeline using 3D U-NET, 3D Retina-UNET and classifier stage with a support vector machine algorithm was developed, resulting in high capabilities for pulmonary nodule classification.

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.

Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.

BACKGROUND: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). PATIENTS AND METHODS: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. RESULTS: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. CONCLUSIONS: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. CLINICAL TRIAL NUMBER: NCT02034981.

[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).

[Prediction of the efficiency of endoscopic lung volume reduction by valves in severe emphysema]. / Prédiction de l'efficacité de la réduction endoscopique d'emphysème pulmonaire par valve.

INTRODUCTION: In severe emphysema, endoscopic lung volume reduction with valves is an alternative to surgery with less morbidity and mortality. In 2015, selection of patients who will respond to this technique is based on emphysema heterogeneity, a complete fissure visible on the CT-scan and absence of collateral ventilation between lobes. Our case report highlights that individualized prediction is possible. CASE REPORT: A 58-year-old woman had severe, disabling pulmonary emphysema. A high resolution thoracic computed tomography scan showed that the emphysema was heterogeneous, predominantly in the upper lobes, integrity of the left greater fissure and no collateral ventilation with the left lower lobe. A valve was inserted in the left upper lobe bronchus. At one year, clinical and functional benefits were significant with complete atelectasis of the treated lobe. CONCLUSION: The success of endoscopic lung volume reduction with a valve can be predicted, an example of personalized medicine.

Adacolumn Granulocyte-Apheresis for Alcoholic Hepatitis: Preliminary Study.

INTRODUCTION: Alcoholic hepatitis (AH) is an acute-on-chronic inflammatory response affecting the liver. It has been recognized that white blood cells (WBCs) are involved in the pathogenesis and in the prognosis of AH. The aim of study was to use Adacolumn, which can selectively adsorb myeloid linage leucocytes (granulocytes and monocytes/macrophages) from the blood in the column and improve the clinical status of patients. MATERIALS: Six patients with a diagnosis of AH were treated with Adacolumn granulocyte-apheresis therapy. INCLUSION CRITERIA: patients not responders to corticosteroids therapy with Maddrey Discriminant Function (MDF) >32 and MELD score 20-26. The patients underwent five 1-hour sessions for 5 consecutive days with a follow-up at 28 days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. Liver parameters, WBC count, proinflammatory cytokines, coagulation, and predictive scores were valued before and after the cycle of apheresis treatment. RESULTS: After 5 days, the findings showed a significant improvement of WBC count (P < .014) and cytokines such as interleukin (IL)-6 (P < .019), tumor necrosis factor α (TNFα) (P < .02), and IL-8 (P < .029). The results probably determined a reduction of aspartate transaminase (AST; P < .02) and alanine transaminase (ALT; P < .011), although we did not observe a significant improve in bilirubin, prothrombin time (PT), and Maddrey score. The improvement of MELD score, depending on an improvement of international normalized ratio for administration of plasma, was not considered. At day 28 of follow-up, PT, IL-6, TNFα, AST and ALT results significantly improved. CONCLUSIONS: The Adacolumn apheresis was safe and was able to determine an improvement of clinical status of patients with reduction of inflammatory markers. More patients are needed to validate these results.

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.

Solitary fibrous tumor of the pleura: Can computed tomography features help predict malignancy? A series of 56 patients with histopathological correlates.

OBJECTIVE: To identify computed tomography (CT) predictors of malignancy, from a retrospective study of preoperative CT scans of patients with solitary fibrous tumors (SFT) of the pleura. PATIENTS AND METHODS: The CT scans of 56 patients with histopathologically confirmed SFT (33 women and 23 men; mean age, 60years) who underwent surgery between December 2004 and November 2012 were retrospectively analyzed by three radiologists working in consensus, blinded to the final histological diagnosis. RESULTS: SFT was asymptomatic and incidentally discovered in 22 patients (45.8%). Resection specimen analysis (R0 resection in all cases) revealed that 23 tumors (41%) were malignant. The CT features, which significantly differed between malignant and benign SFTs were tumor size (P=0.002) with a discriminative threshold value of 10cm, tumor heterogeneity before (P=0.02) and after (P=0.03) intravenous administration of iodinated contrast material, presence of intratumoral hydric attenuation areas (P=0.01), pleural effusion (P=0.01), measurable intratumoral vessels (P=0.02), hypervascularization with visible intratumoral vessels and/or marked enhancement (P=0.001). Presence of intratumoral calcifications (P=0.2) and maximum post-contrast enhancement value (P=0.6) were not significantly different between the two groups. CONCLUSION: A size greater than or equal to 10cm, hypervascularization, attenuation heterogeneity and association with pleural effusion are individual variables that suggest malignant SFT on CT.