Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC.

Introduction: Gene fusion testing of ALK, ROS1, RET, NTRK, and MET exon 14 skipping mutations is guideline recommended in nonsquamous NSCLC (NS-NSCLC). Nevertheless, assessment is often hindered by the limited availability of tissue and prolonged next-generation sequencing (NGS) testing, which can protract the initiation of a targeted therapy. Therefore, the development of faster gene fusion assessment is critical for optimal clinical decision-making. Here, we compared two ultrafast gene fusion assays (UFGFAs) using NGS (Genexus, Oncomine Precision Assay, Thermo Fisher Scientific) and a multiplex reverse-transcriptase polymerase chain reaction (Idylla, GeneFusion Assay, Biocartis) approach at diagnosis in a retrospective series of 195 NS-NSCLC cases and five extrapulmonary tumors with a known NTRK fusion. Methods: A total of 195 NS-NSCLC cases (113 known gene fusions and 82 wild-type tumors) were included retrospectively. To validate the detection of a NTRK fusion, we added five NTRK-positive extrathoracic tumors. The diagnostic performance of the two UFGFAs and standard procedures was compared. Results: The accuracy was 92.3% and 93.1% for Idylla and Genexus, respectively. Both systems improved the sensitivity for detection by including a 5'-3' imbalance analysis. Although detection of ROS1, MET exon 14 skipping, and RET was excellent with both systems, ALK fusion detection was reduced with sensitivities of 87% and 88%, respectively. Idylla had a limited sensitivity of 67% for NTRK fusions, in which only an imbalance assessment was used. Conclusions: UFGFA using NGS and reverse-transcriptase polymerase chain reaction approaches had an equal level of detection of gene fusion but with some technique-specific limitations. Nevertheless, UFGFA detection in routine clinical care is feasible with both systems allowing faster initiation of therapy and a broad degree of screening.

Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study).

BACKGROUND: There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database. METHODS: The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD. RESULTS: We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan-Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622-54,287) and the median annual cost per patient was €18,362 (6856-52,026), of which €11,784 (3003-42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests. CONCLUSIONS: This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842.

Assessment of the ITMIG Statement on the WHO Histological Classification and of the Eighth TNM Staging of Thymic Epithelial Tumors of a Series of 188 Thymic Epithelial Tumors.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare intrathoracic malignancies that are categorized histologically according to the WHO classification, which was recently updated in 2015 on the basis of a consensus statement of the International Thymic Malignancy Interest Group (ITMIG); at the same time, the standard Masaoka-Koga staging system is scheduled to be replaced by the eighth edition of the TNM staging classification by the American Joint Committee on Cancer/Union for International Cancer Control consortium. Our objectives were to analyze the feasibility of assessing ITMIG consensus major and minor morphological and immunohistochemical criteria and the eighth edition of the TNM staging classification in a routine practice setting. METHODS: This is a single-center study conducted at the Louis-Pradel Hospital of Lyon University, one of the largest centers for TETs in France. Overall, a large surgical series of 188 TETs diagnosed in 181 patients between 2000 and 2014 at our center were analyzed. RESULTS: There were 89 men (49%) and 92 women (51%); 57 patients (31%) presented with myasthenia gravis at time of diagnosis. According to the WHO classification, there were nine type A thymomas (5%), 67 type AB thymomas (36%), 19 type B1 thymomas (10%), 46 type B2 thymomas (24%), 27 type B3 thymomas (14%), and 20 thymic carcinomas (11%). ITMIG consensus major criteria were identified in 100% of type A, AB, B1, and B2 thymomas. After restaging according to the eighth edition of the TNM staging classification, there were 127 stage I (84%), three stage II (2%), 17 stage IIIa (11%), no stage IIIb, two stage IVa (1%), and three stage IVb (2%) thymomas. Significant correlation between histological type and stage at diagnosis was maintained after restaging according the TNM classification. CONCLUSION: Comprehensive analysis of our well-characterized surgical series of 188 TETs indicates the feasibility and the diagnostic value of the ITMIG consensus statement on WHO histological classification and highlights the major switch in staging when the eighth edition of the TNM staging classification is applied.