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Introduction Tumor mutational burden (TMB) has been proposed as a novel predictive biomarker for the stratification of patients with NSCLC undergoing immune checkpoint inhibitor (ICI) treatment. The assessment of TMB has recently been established using large targeted sequencing panels, and numerous studies are ongoing to harmonize TMB assessment. "Correlation" or the coefficient of determination has generally been used to evaluate the association between different panels. We hypothesized that these metrics might overestimate the comparability, especially for lower TMB values. Methods A total of 30 samples from patients with NSCLC undergoing ICI treatment were consecutively sequenced using the following three large, targeted sequencing panels: FoundationOne, Oncomine TML, and QiaSeq TMB. The TMB values were compared in the whole patient population and in a subset of patients in which the TMB assessed by FoundationOne was between 5 and 25 mutations/Mb. Prediction of durable clinical benefit (>6 mo with no progression) was assessed using receiver operator characteristics, and optimal cutoff values were calculated using the Youden J statistic. Results Correlation between the three targeted sequencing panels was strong in the whole patient population (R2 > 0.79) but was dramatically reduced in the subset of patients with TMB of 5 to 25 mutations/Mb. The agreement assessed using the Bland-Altman method was also very low. All panels were able to predict durable clinical benefit in the TMB-high population. Conclusions Assessment of TMB using the three targeted sequencing panels was possible and predictive of response to ICI treatment, but correlation was an inappropriate measurement to assess the association between the respective panels.

BackgroundReliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors.MethodsMaximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD).ResultsA high MTV and a high TLG were significantly associated with a lower OS (p3) was 10.5 months (95% CI: 6.2 to upper limit: unreached), while the median OS in patients with MTV below the median was not reached. Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI: 0.65 to 0.87 and 0.72, 95% CI: 0.62 to 0.84, respectively).ConclusionMTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.

At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One of the most recent has drawn worldwide hype to the possible benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of these articles evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss some pros and cons concerning the current therapeutic options targeting this process.

Background NGS from plasma samples in non-squamous cell lung carcinoma (NSCC) can aid in the detection of actionable genomic alterations. However, the absolute clinical value of NGS in liquid biopsy (LB) made at baseline is currently uncertain. We assessed the impact of plasma-based NGS using an in-house test and an outsourced test in comparison to a routine molecular pathology workflow. Methods Twenty-four advanced/metastatic treatment-naïve NSCC patients were prospectively included. NGS analyses were conducted both in-house using the Oncomine cfTNA Panel and in an external testing center using the Foundation Liquid assay. NGS analysis and/or specific molecular based assays were conducted in parallel on tissue or cytological samples. Results Both LB tests were well correlated. Tissue NGS results were obtained in 67% of patients and demonstrated good correlation with LB assays. Activating EGFR mutations were detected using LB tests in three patients. PD-L1 expression assessed in tissue sections enabled the initiation of pembrolizumab treatment in five patients. Conclusion NGS from LB is feasible in routine clinical practice using an in-house or an outsourced test at baseline. However, the impact on therapy selection was limited in this small series of patients and LB was not able to replace tissue-based testing in our hands.

Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations.

International audience; Background - The introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). Patients and methods - A total of 345 samples were analyzed using the US Food and Drug Administration-approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients. Results - Cobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable. Conclusion - PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.

Summary It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P = 0.01) and a better OS (HR = 2, P = 0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR = 0.4, 95% CI [0.19; 0.8], P = 0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having ≥ 2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.

Resume Introduction La bronchopneumopathie chronique obstructive (BPCO) est une pathologie frequente qui, bien que pouvant sembler banale, est susceptible de dissimuler d’autres diagnostics a meme d’accelerer son histoire naturelle ou a meme de la simuler. Nous presentons le cas de quatre patients, suivis pour BPCO emphysemateuse, mais dont certaines caracteristiques cliniques et radiologiques ont conduit a reconsiderer le diagnostic. Observations Une femme de 52 ans, non fumeuse et non menopausee, suivie pour emphyseme, qui presentait finalement une lymphangioleiomyomatose decelee par imagerie sous-diaphragmatique revelant des angiomyolipomes renaux ; un homme de 44 ans, tabagique, suivi pour un emphyseme tres rapidement evolutif, presentant finalement une histiocytose langheransienne decelee sur un scanner realise quatre ans plus tot revelant des « nodules troues » ; un ancien avitailleur d’aeroport de 73 ans, non-fumeur, presentant un emphyseme severe, revelant un deficit en alpha-1 antitrypsine ; un homme de 54 ans, non-fumeur, presentant un trouble ventilatoire obstructif severe, une hypo-attenuation multilobaire et des bronchectasies de meme topographie, revelant une forme severe de syndrome de Swyer-James- MacLeod. Conclusion Les quatre observations presentees illustrent la necessite de savoir remettre en question le diagnostic de BPCO lorsque certaines caracteristiques phenotypiques sont decelees.

Background Management of large numbers of reverse transcriptase-polymerase chain reactions (RT-PCR) for diagnosis of coronavirus 2019 disease (COVID-19) requires robust infrastructures, located in dedicated premises with a high standard of biosafety procedures, and well-trained personnel. The handling of a "run-of-river sample" to obtain rapid reporting of results is challenging. Methods We studied the clinical performance of the Idylla™ SARS-CoV-2 Test (index test) on a platform capable of fully automated nucleic acid testing including extraction, amplification, and detection in a single-use cartridge to establish the diagnosis of COVID-19. The study was conducted on a prospective cohort of 112 volunteers with recent symptoms and an unknown SARS-CoV-2 status who came to free screening centers of the Nice metropolitan area. All subjects underwent bilateral nasopharyngeal sampling. One sample was processed using the index test, the other using the standard of care RT-PCR. Samples were treated blind. Results Most of the participants (70%) were sampled within 4 days of symptom onset. Forty-five (40.2%) were positive for COVID-19. No clinical symptoms were distinguished between SARS-CoV-2 RT-PCR positive and negative subjects except anosmia and dysgeusia. Positive and negative agreement between the index and the standard of care test was 100%. Conclusions The Idylla™ SARS-CoV-2 Test is very sensitive, specific, rapid and easy to use in a near-patient RT-PCR approach to distinguish between symptomatic SARS-CoV-2 positive and negative patients in selected settings.

Introduction The detection of a ROS1 rearrangement in advanced and metastatic lung adenocarcinoma (LUAD) led to a targeted treatment with tyrosine kinase inhibitors with favorable progression-free survival and overall survival of the patients. Thus, it is mandatory to screen for the ROS1 rearrangement in all these patients. ROS1 rearrangements can be detected using break-apart fluorescence in situ hybridization (FISH), which is the gold standard; however, ROS1 immunohistochemistry (IHC) can be used as a screening test because it is widely available, easy and rapid to perform, and cost-effective. Methods We evaluated the diagnostic accuracy and interpathologist agreement of two anti-ROS1 IHC clones, SP384 (Ventana, Tucson, Arizona) and D4D6 (Cell Signaling, Danvers, Massachusetts), in a training cohort of 51 positive ROS1 FISH LUAD cases, and then in a large validation cohort of 714 consecutive cases of LUAD from six routine molecular pathology platforms. Results In the two cohorts, the SP384 and D4D6 clones show variable sensitivity and specificity rates on the basis of two cutoff points greater than or equal to 1+ (all % tumor cells) and greater than or equal to 2+ (>30% stained tumor cells). In the validation cohort, the D4D6 yielded the best accuracy for the presence of a ROS1 rearrangement by FISH. Interpathologist agreement was moderate to good (interclass correlation 0.722–0.874) for the D4D6 clone and good to excellent (interclass correlation: 0.830–0.956) for the SP384 clone. Conclusions ROS1 IHC is an effective screening tool for the presence of ROS1 rearrangements. However, users must be acutely aware of the variable diagnostic performance of different anti-ROS1 antibodies before implementation into routine clinical practice.

Histopathology is the fundamental tool of pathology used for more than a century to establish the final diagnosis of lung cancer. In addition, the phenotypic data contained in the histological images reflects the overall effect of molecular alterations on the behavior of cancer cells and provides a practical visual reading of the aggressiveness of the disease. However, the human evaluation of the histological images is sometimes subjective and may lack reproducibility. Therefore, computational analysis of histological imaging using so-called “artificial intelligence” (AI) approaches has recently received considerable attention to improve this diagnostic accuracy. Thus, computational analysis of lung cancer images has recently been evaluated for the optimization of histological or cytological classification, prognostic prediction or genomic profile of patients with lung cancer. This rapidly growing field constantly demonstrates great power in the field of computing medical imaging by producing highly accurate detection, segmentation or recognition tasks. However, there are still several challenges or issues to be addressed in order to successfully succeed the actual transfer into clinical routine. The objective of this review is to emphasize recent applications of AI in pulmonary cancer pathology, but also to clarify the advantages and limitations of this approach, as well as the perspectives to be implemented for a potential transfer into clinical routine., L’histopathologie est l’outil fondamental utilisé en anatomopathologie depuis plus d’un siècle pour établir le diagnostic final d’un carcinome bronchopulmonaire. L’information phénotypique présente sur les images histologiques reflète l’effet global des altérations moléculaires sur le comportement des cellules cancéreuses et fournit une lecture visuelle pratique de l’agressivité de la maladie. Cependant, l’évaluation humaine de l’image histologique peut être parfois subjective et assez peu reproductible selon les cas. Par conséquent, l’analyse computationnelle de l’imagerie histologique via des approches dites « d’intelligence artificielle » (IA) a récemment reçu une attention considérable afin d’améliorer cette précision diagnostique. Ainsi, l’analyse computationnelle d’images de cancer du poumon a récemment été évaluée pour l’optimisation de la classification histologique ou cytologique, la prédiction du pronostic ou du profil génomique des patients atteints d’un cancer pulmonaire. Ce domaine, en pleine croissance, fait constamment preuve d’une grande puissance dans le domaine de l’informatique d’imagerie médicale en produisant des tâches de détection, de segmentation ou de reconnaissance d’une très grande précision. Cependant, il subsiste plusieurs défis ou enjeux majeurs à relever afin de réussir le transfert réel de cette nouvelle approche en routine clinique. L’objectif de cette revue est de faire le point sur les applications récentes de l’IA en pathologie cancéreuse pulmonaire, mais aussi d’apporter des clarifications sur les avantages et les limites de cette approche, ainsi que les perspectives à mettre en œuvre pour un transfert potentiel dans la pratique quotidienne des pathologistes.

Background Exogenous lipoid pneumonia is a rare disease resulting from intra-alveolar accumulation of lipids of mineral, vegetal, or animal origin, that induce a foreign body type of inflammatory reaction in the lungs. Gastroesophageal reflux disease and other esophageal abnormalities have often been associated with this disease. Case presentation We herein report the case of an 83-year-old patient in whom a follow-up chest computed tomography scan, for a lingular consolidation, showed multifocal ground glass and consolidative opacities with areas of low attenuation, suggestive of exogenous lipid pneumonia. The patient had been on piascledine capsules (avocado/soybean unsaponifiables) for 20 years and had a hiatal hernia with documented gastroesophageal reflux disease. After thorough history taking, no other predisposing factors were found. The diagnosis was confirmed using oil red staining of bronchoalveolar lavage showing lipid-laden macrophages and extracellular lipid droplets. Conclusions To our knowledge, this is the first case of ELP secondary to avocado/soybean unsaponifiables in the literature.

International audience; Early-stage treatment improves prognosis of lung cancer and two large randomized controlled trials have shown that early detection with low-dose computed tomography (LDCT) reduces mortality. Despite this, lung cancer screening (LCS) remains challenging. In the context of a global shortage of radiologists, the high rate of false-positive LDCT results in overloading of existing lung cancer clinics and multidisciplinary teams. Thus, to provide patients with earlier access to life-saving surgical interventions, there is an urgent need to improve LDCT-based LCS and especially to reduce the false-positive rate that plagues the current detection technology. In this context, LCS can be improved in three ways: (1) by refining selection criteria (risk factor assessment), (2) by using Computer Aided Diagnosis (CAD) to make it easier to interpret chest CTs, and (3) by using biological blood signatures for early cancer detection, to both spot the optimal target population and help classify lung nodules. These three main ways of improving LCS are discussed in this review.

Background: Lung cancer (LC) screening with low dose chest computed tomography (LDCT) reduces the mortality of eligible individuals. Biological blood signatures act as a screening tool per se and may refine the selection of patients at risk or may help to classify undetermined nodules detected on LDCT.We previously showed that circulating tumor cells (CTC) could be detected by the isolation by size of epithelial tumor cell technique (ISET) long before the cancer was diagnosed radiologically. So, we tested whether CTC could be used as biomarker for screening lung cancer. Methods: We conducted a prospective, multicenter, cohort study in 21 French university centers. Participants had to be eligible for LC screening and to have chronic obstructive pulmonary disease. They underwent 3 screening rounds at 1-year intervals including LDCT and a matched blood test for CTC detection. Participants and investigators were blinded to the results of CTC detection. Cytopathologists were blinded to clinical and radiological findings. Findings: We enrolled 614 participants, predominantly men (71%), aged 65.1 ± 6.5 years, heavy smokers with 52.7 ± 21.5 pack-years. Nodules were detected on 178 (29%) baseline LDCTs. Nineteen subjects (3.1%) were diagnosed with a prevalent LC and nineteen (2.8 %) with an incident LC. Extra-pulmonary cancers (EPC) were diagnosed in 26 (4.2 %) participants. At baseline, the sensitivity of CTC detection for LC detection was 26.3 %. The ISET test was unable to predict LC or EPC development. Interpretation: The CTC detection-based LC screening using ISET failed to confirm our initial promising results. Trial Registration: ClinicalTrials.gov identifier: NCT02500693. Funding Statement: Conseil Departemental 06, Fondation UNICE, Fondation AVENI, Fondation de France, and Ligue Contre le Cancer - Comite des Alpes-Maritimes and private donators. Declaration of Interests: The authors stated: "None declared." Ethics Approval Statement: National ethic committee approval (CPP Sud Mediterranee V; registration # 15.072) and ANSM (Ministry of Health).

Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by &gt, 6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (R2 = 0.73) and melanoma (R2 = 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35, FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC.

Histopathology is the fundamental tool of pathology used for more than a century to establish the final diagnosis of lung cancer. In addition, the phenotypic data contained in the histological images reflects the overall effect of molecular alterations on the behavior of cancer cells and provides a practical visual reading of the aggressiveness of the disease. However, the human evaluation of the histological images is sometimes subjective and may lack reproducibility. Therefore, computational analysis of histological imaging using so-called "artificial intelligence" (AI) approaches has recently received considerable attention to improve this diagnostic accuracy. Thus, computational analysis of lung cancer images has recently been evaluated for the optimization of histological or cytological classification, prognostic prediction or genomic profile of patients with lung cancer. This rapidly growing field constantly demonstrates great power in the field of computing medical imaging by producing highly accurate detection, segmentation or recognition tasks. However, there are still several challenges or issues to be addressed in order to successfully succeed the actual transfer into clinical routine. The objective of this review is to emphasize recent applications of AI in pulmonary cancer pathology, but also to clarify the advantages and limitations of this approach, as well as the perspectives to be implemented for a potential transfer into clinical routine.

IntroductionLung cancer (LC) is the leading cause of death from cancer. Early diagnosis of LC is of paramount importance in terms of prognosis. The health authorities of most countries do not accept screening programmes based on low-dose chest CT (LDCT), especially in Europe, because they are flawed by a high rate of false-positive results, leading to a large number of invasive diagnostic procedures. These authorities advocated further research, including companion biological tests that could enhance the effectiveness of LC screening. The present project aims to validate early diagnosis of LC by detection and characterisation of circulating tumour cells (CTCs) in a peripheral blood sample taken from a prospective cohort of persons at high-risk of LC.Methods and analysisThe AIR Project is a prospective, multicentre, double-blinded, cohort study conducted by a consortium of 21 French university centres. The primary objective is to determine the operational values of CTCs for the early detection of LC in a cohort of asymptomatic participants at high risk for LC, that is, smokers and ex-smokers (≥30 pack-years, quitted ≤15 years), aged ≥55 years, with chronic obstructive pulmonary disease (COPD). The study participants will undergo yearly screening rounds for 3 years plus a 1-year follow-up. Each round will include LDCT plus peripheral blood sampling for CTC detection. Assuming 5% prevalence of LC in the studied population and a 10% dropout rate, a total of at least 600 volunteers will be enrolled.Ethics and disseminationThe study sponsor is the University Hospital of Nice. The study was approved for France by the ethical committee CPP Sud-Méditerranée V and the ANSM (Ministry of Health) in July 2015. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations.Trial registration numberNCT02500693.

Immunotherapy aims to amplify the anticancer immune response through reactivation of the lymphocytic response raised against several tumor neo-antigens. To obtain an effective immune response, this therapeutic approach requires that a number of immunological checkpoints be passed, such as the activation of excitatory costimulatory signals or the avoidance of coinhibitory molecules. Among the immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1 has received much attention because of remarkable efficacy in numerous clinical trials for various cancer types, including non-small cell lung cancer (NSCLC). However, several limitations exist with these therapeutic agents when used as monotherapy, with objective responses observed in only 30-40% of patients, with the majority of patients demonstrating innate resistance, and approximately 25% of responders later demonstrating disease progression. Recent developments in the understanding of cancer immunology have the potential to identify mechanisms of innate and acquired resistance to immune checkpoint inhibitors through translational research in human samples. This review focuses on the biological basic principles for immunological checkpoint blockade, and highlights the current status and the perspectives of this therapeutic approach in NSCLC patients.

We assessed the relationships between changes in lung compliance, lung volumes and dynamic hyperinflation in patients with emphysema who underwent bronchoscopic treatment with nitinol coils (coil treatment) (n=11) or received usual care (UC) (n=11). Compared with UC, coil treatment resulted in decreased dynamic lung compliance (CLdyn) (p=0.03) and increased endurance time (p=0.010). The change in CLdyn was associated with significant improvement in FEV1 and FVC, with reduction in residual volume and intrinsic positive end-expiratory pressure, and with increased inspiratory capacity at rest/and at exercise. The increase in end-expiratory lung volume (EELV) during exercise (EELVdyn-ch=EELVisotime EELVrest) demonstrated significant attenuation after coil treatment (p=0.02).

Background: The detection of a ROS1 rearrangement in advanced or metastatic lung adenocarcinoma (LUAD) lead to a targeted treatment with tyrosine kinase inhibitors with improved progression free survival (PFS) and overall survival (OS) of the patients. Thus, it is mandatory to screen systematically for the ROS1rearrangement in this patient population. ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH), however ROS1 immunohistochemistry (IHC) can be used as a screening test since is largely available, easy, rapid to perform, and cost-effective. However, some false positive and negative IHC results are observed when using the D4D6 clone leading to confirmatory ROS1 FISH in IHC positive samples. Patients and methods: We evaluated the sensitivity and specificity of anti-ROS1 SP384 (Ventana, Tucson, AZ) and D4D6 (Cell Signaling, Danvers, MA) antibodies in a multicenter population of 336 LUAD cases enriched for ROS1 FISH positive cases (n=51) provided from 6 French molecular pathology platforms. Three senior lung pathologists independently scored the SP384 slides as positive or negative around a cutoff of staining in >30% tumor cells at a ≥2+ intensity level, and for the D4D6 clone around a cutoff of ≥2+ intensity level in any tumor cells. Inter-reader precision between pathologists was assessed. Results were correlated to the PFS and the OS of patients treated with crizotinib. Results: Sensitivity and specificity rates were 100% (95%CI 93.2-100%) and 99.31% (95%CI 97.51-99.92%) for the SP384 clone, and 90.6% (95%CI 79.34-96.87%) and 99.65% (95%CI 98.05-99.99%) for the D4D6 clone, respectively. Inter-reader agreement was 97.5% (95%CI 94.8-99.7) for the SP384 clone and 86.3% (95%CI 91.3-95.6) for the D4D6 clone. Overall, when compared to ROS1 FISH analysis, the SP384 clone had an accuracy of 99.4%, while D4D6 clone of 98.2%. Using log-rank test, we observed that LUAD with positive ROS1 SP384 status had a longer PFS than those characterized by the D4D6 clone (P=0.021). Conclusions: Interpretation above a cutoff of >30% tumor cells with staining at a ≥2+ intensity level, the ROS1 SP384 clone demonstrates superior sensitivity to D4D6 clone, while preserving similar specificity rate for the detection of ROS1 rearrangements. The presented data provide evidence that the SP384 clone may be used for effective stratification prior to confirmation with orthogonal methods. Citation Format: Véronique Hofman, Isabelle Rouquette, Sandra Lassalle, Simon Heeke, Jean-Christophe Sabourin, Nicolas Piton, Julien Mazières, Jean-Michel Vignaud, Clémence Yguel, Anne Laure Lepage, Frédéric Bibeau, Elodie Long-Mira, Katia Zahaf, Hugues Begueret, Jonathan Benzaquen, Michel Poudenx, Charles-Hugo Marquette, Marius Ilie, Paul Hofman. Multicenter study evaluating the ROS1 status in lung adenocarcinoma using the novel SP384 immunohistochemistry clone. Towards a new algorithm for ROS1 status assessment in routine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3127.

Background: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform. Methods: Clinical samples from 90 patients (60 Retrospectively and 30 Prospectively) with lung adenocarcinoma were sequenced with both systems. Mutations were analyzed and EGFR, KRAS, BRAF, NRAS, ALK, PIK3CA and ERBB2 genes were compared and sampling time and suitability for clinical testing were assessed. Results: Both sequencing systems showed perfect concordance for the overlapping genes. Correlation of allele frequency was r2 = 0.93 for the retrospective patients and r2 = 0.81 for the prospective patients. Hands-on time and total run time were shorter using the PGM system, while the GeneReader platform provided good traceability and up-to-date interpretation of the results. Conclusion: We demonstrated the suitability of the GeneReader NGS system in routine practice in a clinical pathology laboratory setting.

International audience; Severe emphysema is a difficult to treat condition with limited efficacy of currently available treatments. Endobronchial coil treatment (ECT) is a minimally invasive endobronchial treatment which consists of placing shape-memory nitinol coils in emphysematous lobes to enhance lung recoil and reduce lung hyperinflation at rest and during exercise [1, 2]. Randomised studies demonstrated an improvement in exercise capacity, lung function and quality of life, and showed an acceptable safety profile at 1 year [3–6]. However, to our best knowledge, longer term safety and effectiveness results beyond 1 year have not been reported thus far.REVOLENS (Réduction volumique endobronchique par spirales) (NCT01822795) is a 1:1 randomised controlled study of 100 patients (50 patients treated with coils and optimal medical management and 50 patients treated with optimal medical management only) in 10 centres across France. Patients treated with optimal medical management only were offered coil treatment after 1 year. The study protocol [7] and 1-year results [5] of the REVOLENS study have been previously described, demonstrating a decrease in lung hyperinflation and improvement in quality of life. In the present study, we analysed efficacy and safety data at 2 years in the 50 patients randomised to the ECT group.