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Pure red cell aplasia (PRCA) is a rare paraneoplastic syndrome observed in 2-5 % of thymomas. Literature reports great variability in its management. Based on an illustrative clinical case, we present a systematic literature review whose main objective is to evaluate the therapeutic management of PRCA. The literature search was performed based on the PICO method in the Medline and Scopus databases. The reference clinical case concerns a 51-year-old woman with stage IVa thymoma. After initial response to chemotherapy, a locoregional progression occurred with PRCA development that responded favorably under second line chemotherapy. The patient finally died in a context of bicytopenia with febrile neutropenia. The systematic review covers 135 articles published between 1950 and 2019. Thymectomy alone or in combination with other therapies showed a 31 % complete remission (CR) rate for PRCA of, whereas none was reported with anti-tumor treatments without thymectomy. Among immunomodulatory therapies, cyclosporin gave the highest percentage of CR (74 %). Finally, the combination of thymectomy and immunomodulatory treatments showed a CR rate of 45 %. Thymectomy appeared to be the most effective anti-tumor treatment for PRCA. Immunomodulatory therapies, particularly cyclosporine, are shown effective, but the risk of infectious complications must be considered. The optimal place of anti-tumor and immunomodulatory therapies against PRCA has yet to be determined.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient’s performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres., info:eu-repo/semantics/published

Synchronous oligometastatic non-small cell lung cancer (NSCLC) definition varies from 1 metastasis in 1 organ (tumour-node-metastasis 8 [TNM8]), 1-3 metastases (European Society for Medical Oncology [ESMO]), ≤3 metastases (including mediastinal nodes [MLN]) after systemic treatment to 3-5 metastases in ongoing trials. A single definition is however needed to design/compare trials. To assess oligometastatic NSCLC definitions used by clinical experts in daily practice and its evolution, we redistributed a 2012 case-based survey (Dooms, the World Congress of Lung Cancer 2013)., info:eu-repo/semantics/published

Introduction: Health Care System - The kingdom of Belgium with its capital Brussels is located in Western Europe (Fig. 1) and has a population of 11,492,641 inhabitants (January 2020) for a surface of 30,689 km2. The country is a member of the European Union (EU) and federally organized with a Dutch-speaking majority in the northern Flemish region, a French-speaking region (Wallonia) in the south, and the Brussels capital region. Its population is mainly of Caucasian ethnicity, with 10% immigrants from different non-EU countries, mostly Africa and Middle East. [...]

info:eu-repo/semantics/published

Resume Introduction Le cancer bronchique, souvent diagnostique a un stade tardif, est la premiere cause de mortalite par cancer. Dans l’optique d’une detection precoce et d’un potentiel traitement curatif, plusieurs etudes ont evalue le scanner thoracique a faible dose (LDCT) comme methode de depistage. L’objectif principal de ce travail est de determiner l’impact du depistage par LDCT sur la mortalite globale d’une population tabagique. Methodes Revue systematique des essais controles randomises (RCT) comparant un depistage par LDCT a l’absence de depistage ou a un depistage par radiographie thoracique. Resultats Treize RCT ont ete identifies dont sept presentent des resultats de mortalite. NSLT rapporte une reduction significative de 6,7 % de la mortalite globale et de 20 % de la mortalite par cancer bronchique apres 6,5 ans de suivi. NELSON montre une reduction significative de la mortalite par cancer bronchique chez les hommes de 24 % a 10 ans. LUSI et MILD montrent respectivement une reduction de mortalite par cancer bronchique de 69 % a 8 ans chez les femmes et de 39 % a 10 ans. Conclusions Le depistage du cancer bronchique est une question complexe. Des precisions sont necessaires quant a la selection des individus, la definition d’un resultat positif et l’attitude face a un nodule suspect.

Introduction It has been demonstrated in unselected populations of cancer patients that prognosis in intensive care is essentially dependent on the extent of the acute physiological disturbance caused by the complication precipitating the admission. By contrast, the prognosis after hospital discharge remains dependent on the characteristics of the underlying neoplasm. The aim of our study was to confirm whether this general finding was the case in a specific population of lung cancer patients, since there are no data on this patient group in the literature. Patients and methods We conducted a retrospective study including all patients with lung cancer admitted to our ICU between September 1, 2008 and December 31, 2013. Results During this period, 180 different patients with lung cancer were admitted into ICU. The simplified acute physiology score II (SAPS II) (OR 1.07 ; 95% CI 1.04-1.11), respiratory failure (OR 4.00; 95% CI 1.76-9.07) and the presence of therapeutic limitations were the 3 factors independently affecting hospital mortality in multivariate analysis. Considering only patients discharged alive from the hospital, the presence of metastases (HR 2.30; 95% CI 1.44-3.65) and limitations on therapy (HR 5,89; IC 95% 3,11-11,14) were the two statistically independent prognostic factors for overall survival. Conclusion In this population of lung cancer patients admitted into ICU, independent predictors of hospital mortality are determined by the physiological perturbations induced by the acute presenting complication. After recovery from this, prognosis is again determined by the characteristics of the underlying cancer.

Introduction: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process.Methods: A pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting.Results: It was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography-computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography-computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits.Conclusion: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Resume Introduction L’irradiation cerebrale prophylactique (ICP) est consideree comme le standard therapeutique du traitement des cancers bronchiques a petites cellules (CBPC) sur la base d’anciennes etudes randomisees, grevees de limitations methodologiques, notamment l’absence d’evaluation cerebrale par une imagerie par resonance magnetique. Le but de cette etude est d’evaluer le risque a ne pas administrer d’ICP en cas d’imagerie cerebrale systematique. Methodes Etude retrospective incluant des CBPC non pretraites, sans ICP et beneficiant d’une imagerie cerebrale au diagnostic. La methode de Kaplan–Meier et le test statistique du log-rank ont ete utilises pour evaluer la survie. Resultats Sur 150 patients, 75 auraient pu etre eligibles pour une ICP. Treize patients ont presente une recidive cerebrale comme premier site de progression sans autre localisation metastatique associee et 6 patients ont eu le cerveau pour seul site de recidive durant l’ensemble de leur suivi. Parmi les patients eligibles pour une ICP, il n’y a pas de difference statistiquement significative pour la survie entre les patients ayant progresse au niveau cerebral ou non (p = 0,11). Conclusions L’impact attendu d’une ICP semble faible en termes de survie globale et de prevention de metastases cerebrales isolees pour des patients ayant une imagerie cerebrale systematique lors des bilans d’evaluation d’un CBPC.

Surgery is the ultimate curative treatment for resectable non-small cell lung cancer (NSCLC). However, the prognosis for operated patients remains disappointing. Multiple randomized studies have shown that administering perioperative chemotherapy improves the prognosis and increases the cure rate by around 3–5%. The purpose of this article is to take stock of the role of perioperative treatments for NSCLC, which can be completely resected. Six questions were evaluated: 1) What is the place of (neo) adjuvant chemotherapy in 2020, among others in the early stages (IB)? 2) Can new chemotherapy agents be combined with a platinum derivative? 3) What is the place of radiochemotherapy for resectable NSCLC? 4) Is there a place for postoperative radiotherapy (PORT)? 5) Is there a place for targeted therapies for resectable NSCLC? 6) What is the place of immunotherapies in the perioperative period?, SCOPUS: re.j, info:eu-repo/semantics/published

Background: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR−/ALK−), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1. Methods: ATLANTIC is a phase 2, open-label, single-arm trial at 139 study centres in Asia, Europe, and North America. Eligible patients had advanced NSCLC with disease progression following at least two previous systemic regimens, including platinum-based chemotherapy (and tyrosine kinase inhibitor therapy if indicated); were aged 18 years or older; had a WHO performance status score of 0 or 1; and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key exclusion criteria included mixed small-cell lung cancer and NSCLC histology; previous exposure to any anti-PD-1 or anti-PD-L1 antibody; and any previous grade 3 or worse immune-related adverse event while receiving any immunotherapy agent. Patients in cohort 1 had EGFR+/ALK+ NSCLC with at least 25%, or less than 25%, of tumour cells with PD-L1 expression. Patients in cohorts 2 and 3 had EGFR−/ALK− NSCLC; cohort 2 included patients with at least 25%, or less than 25%, of tumour cells with PD-L1 expression, and cohort 3 included patients with at least 90% of tumour cells with PD-L1 expression. Patients received durvalumab (10 mg/kg) every 2 weeks, via intravenous infusion, for up to 12 months. Retreatment was allowed for patients who benefited but then progressed after completing 12 months. The primary endpoint was the proportion of patients with increased tumour expression of PD-L1 (defined as ≥25% of tumour cells in cohorts 1 and 2, and ≥90% of tumour cells in cohort 3) who achieved an objective response, assessed in patients who were evaluable for response per independent central review according to RECIST version 1.1. Safety was assessed in all patients who received at least one dose of durvalumab and for whom any post-dose data were available. The trial is ongoing, but is no longer open to accrual, and is registered with ClinicalTrials.gov, number NCT02087423. Findings: Between Feb 25, 2014, and Dec 28, 2015, 444 patients were enrolled and received durvalumab: 111 in cohort 1, 265 in cohort 2, and 68 in cohort 3. Among patients with at least 25% of tumour cells expressing PD-L1 who were evaluable for objective response per independent central review, an objective response was achieved in 9 (12·2%, 95% CI 5·7–21·8) of 74 patients in cohort 1 and 24 (16·4%, 10·8–23·5) of 146 patients in cohort 2. In cohort 3, 21 (30·9%, 20·2–43·3) of 68 patients achieved an objective response. Grade 3 or 4 treatment-related adverse events occurred in 40 (9%) of 444 patients overall: six (5%) of 111 patients in cohort 1, 22 (8%) of 265 in cohort 2, and 12 (18%) of 68 in cohort 3. The most common treatment-related grade 3 or 4 adverse events were pneumonitis (four patients [1%]), elevated gamma-glutamyltransferase (four [1%]), diarrhoea (three [1%]), infusion-related reaction (three [1%]), elevated aspartate aminotransferase (two [

Background Major progresses in the systemic treatment of non-small cell lung cancer (NSCLC) were obtained during the last decade, including the use of immunotherapy and tyrosine kinase inhibitors (TKIs), with impressive results in terms of response and survival rates. Moreover, novel imaging and radiotherapy techniques have allowed the development of stereotactic body radiotherapy (SBRT), with high rates of local disease control and minimal toxicity. These factors propelled the use of combined systemic and local treatment strategies in patients with a low burden of metastases-the oligometastatic disease (OMD). Methods We systematically review the evidence from prospective randomized and non-randomized trials on local ablative therapy for OMD NSCLC published until June 2020. In addition, we present a review of the ongoing and/or recruiting trials in the field. Results We included 16 articles, reporting on 14 prospective clinical trials, starting from the pilot trial conducted in the early 2000's to the recent randomized trials that have showed benefits in survival. We found 24 ongoing trials, which combine multiple local ablative regimens with new systemic therapies, such as new generation TKIs and immunotherapy. Discussion Despite these vast current and ongoing prospective research efforts, there are several issues that impair the generalizability of their findings. These include the heterogeneous definition of OMD, trial design, staging, patient selection, tumor mutational status and treatments used, which may limit their applicability in the clinical practice.

Immunotherapy in lung cancer treatment is a long history paved with failures and some successes. During the last decade, the discovery of checkpoints inhibitors led to major advances in treating advanced and metastatic non-small cell lung cancer (NSCLC). Impressive data from early phase I-II studies were subsequently confirmed in large prospective randomized trials and meta-analyses (High-level of evidence). Three anti- programmed death-1 (PD1) (pembrolizumab, nivolumab) or antiPD-ligand(L)1 (atezolizumab) antibodies showed clinically significant improved survival compared to second-line docetaxel. Then, first-line pembrolizumab monotherapy demonstrated its superiority over platinum-doublet in high PD-L1 NSCLC. The addition of pembrolizumab or atezolizumab to chemotherapy derived the same results regardless of the PD-L1 status. On the opposite, antiCTLA4 (Cytotoxic T-Lymphocyte Associated 4) results are currently disappointing in unselected patients while recent development suggest that the combination of antiPD1 and antiCTLA4 (nivolumab-ipilimumab) positively impact on overall survival. Some secondary analyses also showed that immunotherapy has a positive impact on quality of life and that the clinical improvement can be done at an acceptable incremental cost per QALY. A lot of questions remain unresolved: which is the best treatment duration and is it the same for all patients, how to choose the patients that will have the highest benefit of immunotherapy, how to identify the patients who will have rapid progression, how to improve the current data (new targets, new combinations) horizontal ellipsis

Brain metastases remain a major problem in NSCLC. Major improvements in systemic therapies have been observed during the past decade but their impact on brain metastases control as well as their combination with radiation techniques needs further research.http://bit.ly/2Jn4v5a

Immunotherapy is a new approach for the treatment of lung cancer with impressive long-term resultshttp://bit.ly/35GVzAn

Resume La prise en charge des cancers bronchiques est fonction du type histologique, du statut fonctionnel du patient et de l’extension tumorale. La classification internationale TNM, acceptee conjointement par l’UICC et l’AJCC est utilisee en routine pour les cancers bronchiques non a petites cellules et est recommandee pour les cancers a petites cellules meme si pour ces derniers, l’ancienne classification de la Veterans’ Administration est toujours de mise lors des decisions therapeutiques. Le but de cet article est de presenter la 8e classification TNM, son implication en pratique ainsi que les propositions emanant du IASLC Staging Committee concernant certaines situations cliniques particulieres. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Introduction: Synchronous oligometastatic (sOM) disease is an oncological concept characterized by a limited cancer burden. Patients with oligometastasis could potentially benefit from local radical treatments. Despite the fact that the sOM condition is well recognized, a universal definition, including a specific definition for NSCLC, is not yet available. The aim of this systematic review was to summarize the definitions of and staging requirements for use of the term synchronous oligometastatic in the context of NSCLC. Methods: The key issue was formulated in one research question according to the population, intervention, comparator, and outcomes strategy. The question was introduced in MEDLINE (OvidSP). All articles dealing with sOM NSCLC and providing a definition of synchronous oligometastasis in NSCLC were selected and analyzed. Results: A total of 21 eligible articles focusing on sOM NSCLC were retrieved and analyzed. In 17 studies (81%), patients had to be staged with magnetic resonance imaging or computed tomography of the brain, thoracic and abdominal computed tomography, and positron emission tomography. The total number of metastases allowed in the definitions ranged from one to eight, but in 38.1% of studies the maximum number was 5. Most of the publications did not define the number of involved organs or the maximum number of metastases per organ. For mediastinal lymph node involvement, only five articles (27.8%) counted this as a metastatic site. Conclusions: No uniform definition of sOM NSCLC could be retrieved by this systematic review. However, extended staging was mandated in most of the studies. An accepted oncological definition of synchronous oligometastasis is essential for patient selection to define prospective clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In the last decade, systemic therapy for advanced lung cancer has become diverse, complex and personalised. These new therapies (monoclonal antibodies, tyrosine kinase inhibitors (TKIs) and immunotherapy) have a far different toxicity profile compared to chemotherapy. Furthermore, clinical indications and reimbursement criteria can vary across Europe. The aim of the present online survey was to assess the knowledge, views and challenges facing the European respiratory community in this rapidly changing field. A 15-question web survey was sent to all European Respiratory Society members through the Society's monthly electronic communication. A total of 315 questionnaires were completed. Most of the respondents were male (59.1%), were above 40 years of age (52.9%) and were working in university/academic hospitals (74.8%), the majority as pulmonologists (90%). Only 55% of the participants were aware of the legal processes for drug recognition. Except for epidermal growth factor receptor TKI, up to 38% did not know about the specific toxicities of anaplastic lymphoma kinase/ROS proto-oncogene 1 TKIs, monoclonal antibodies and immune checkpoint inhibitors. Of the respondents, 92% showed an interest in an online platform reporting new drugs' toxicities. Despite a large amount of publicity and integration of new drugs into therapeutic algorithms and clinical guidelines, physicians taking care of lung cancer patients have a need for up-to-date information on systemic therapy toxicity management and legal constraints., Physicians have a need for up-to-date information on new drug toxicity management in thoracic oncology http://ow.ly/j3YA30kOtBz

Resume Introduction Les metastases cerebrales sont des complications frequentes du cancer du poumon (CP). Il n’y a pas de consensus pour une recherche systematique de ces lesions lors du bilan initial. Le but de ce travail est d’evaluer l’impact de l’imagerie cerebrale dans le bilan initial sur l’evaluation du stade d’extension des CP. Methodes Analyse retrospective des patients suivis dans la clinique d’oncologie thoracique de l’institut Jules-Bordet entre le 01/09/2008 et le 31/08/2013, naifs de tout traitement, ayant eu un bilan complet incluant une imagerie cerebrale. Resultats Quatre cent soixante-trois patients consecutivement diagnostiques avec un CP ont ete inclus. L’imagerie par resonance magnetique et/ou un scanner cerebral ont permis de mettre en evidence une/des metastases cerebrales chez 101 patients (21,8 %) dont 67 n’avaient pas de symptomes evocateurs d’une atteinte metastatique cerebrale. L’adjonction d’une imagerie cerebrale dans le bilan d’extension a entraine une modification du stade chez 30 patients (6,5 %), essentiellement stadifies IIIA (n = 10) ou IIIB (n = 14) sans imagerie cerebrale. Conclusion L’ajout de l’imagerie cerebrale dans le bilan initial des cancers du poumon permet de mettre en evidence des metastases cerebrales dans 1 cas sur 5, dont 2/3 asymptomatiques et subsequemment une modification de stade, principalement pour des maladies considerees de stade III.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the last of a series of five and deals mainly with onconeural antibodies involved in neurological paraneoplastic syndromes and provides the final discussion.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes associated with lung cancer appears useful. This article is the first of a series of five and deals with the methodology applied for the review and with renal and rheumatic syndromes.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes associated with lung cancer appears useful. This article is the second of a series of five and deals with hematologic, cutaneous and vascular syndromes.

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the third of a series of five and deals mainly with neurological paraneoplastic syndromes involving the central nervous system.

Objectives: The CONVERT trial showed that twice-daily (BD) concurrent chemoradiotherapy should continue to be considered the standard of care in localised LS-SCLC. A survey was conducted to assess the impact of the CONVERT trial in clinical practice and to identify any relevant research questions for future trials in this setting.Methods and materials: An EORTC Group online survey of LS-SCLC practice was distributed to the EORTC LCG and to members of several European thoracic oncology societies between April and December 2018.Results: 198 responses were analysed. The majority of respondents (88%, n = 174) were aware of the CONVERT trial. Radiation oncologists comprised 56% of all respondents. Once-daily (OD) radiotherapy is still the most commonly used regimen, however the use of concurrent BD radiotherapy increased after the publication of CONVERT (n = 59/186, 32% prior to and n = 78/187, 42% after the publication, p = 0.053). The main reasons for not implementing BD after the CONVERT publication were logistical issues (n = 88, 44%), inconvenience for patients (n = 56, 28%), and the absence of a statistical survival difference between the two arms in CONVERT (n = 38, 19%). Brain MRI was used by 28% during staging but more than half (60%) of the respondents did not routinely image the brain during follow-up. The main research questions of interest in LS-SCLC were 1) integrating novel targeted therapies-immunotherapies (n =. 160, 81%), 2) PCI (+/- hippocampal sparing) vs. MRI surveillance (n = 140, 71%) and, 3) biomarker driven trials (n = 92, 46%).Conclusion: Once daily radiotherapy (60-66 Gy in 30-33 fractions) remains the most prescribed radiotherapy fractionation, despite the findings suggested by the CONVERT trial.

Despite new treatment modalities, including targeted therapies and checkpoint inhibitors, cytotoxic chemotherapy remains central in the care of patients with lung tumors. Use of the pulmonary route to deliver chemotherapy has been proved to be feasible and safe in phase I, Ib/IIa and II trials for lung tumors, with the administration of drug doses to the lungs without prior distribution in the organism. The severe systemic toxicities commonly observed with conventional systemic chemotherapy are consequently reduced. However, development has failed in phase II at best. This review first focuses on the causes of failure of inhaled chemotherapy. It then presents new promising technologies able to take up the current challenges. These technologies include the use of a dry powder inhaler or a smart nebulizer with advanced drug formulations such as controlled-release formulations and nanomedicine. Finally, the potential position of inhaled chemotherapy in patient care is discussed and some indications are proposed based on the literature., SCOPUS: re.j, info:eu-repo/semantics/published

Background Synchronous oligometastatic disease (sOM) has been described as a distinct disease entity; however, there is no consensus on OM definition (OM-d) in non–small-cell lung cancer (NSCLC). A consensus group was formed aiming to agree on a common OM-d that could be used in future clinical trials. A European survey was circulated to generate questions and input for the consensus group meeting. Methods A European Organisation for Research and Treatment of Cancer Lung Cancer Group (LCG)/sOM-d consensus group survey was distributed to LCG, sOM-d consensus group, and several European thoracic oncology societies’ members. Results 444 responses were analysed (radiation oncologist: 55% [n = 242], pulmonologist: 15% [n = 66], medical oncologist: 14% [n = 64]). 361 physicians (81%) aimed to cure sOM NSCLC patients and 82% (n = 362) included the possibility of radical intent treatment in their sOM-d. The maximum number of metastases considered in sOM-d varied: 12% replied 1 metastasis, 42% ≤ 3, and 17% ≥ 5 metastases. 79% (n = 353) stated that number of organs involved was important for sOM-d, and most (80%, n = 355) considered that only ≤3 involved organs (excluding primary) should be included. 317 (72%) included mediastinal lymph node involvement in the sOM-d and 22% (n = 70/317) counted mediastinal lymph node as a metastatic site. Most physicians completed sOM staging with brain magnetic resonance imaging (91%, n = 403) and positron emission tomography/computed tomography (98%, n = 437). Pathology proof of metastatic disease was a requirement to define sOM for 315 (71%) physicians. The preferred primary outcome for sOM clinical trials was overall survival (73%, n = 325). Conclusion Although consensual answers were obtained, several issues remain unresolved and will require further research to agree on a sOM-d.

Resume En 2020, le traitement standard des cancers bronchiques non a petites cellules metastatiques sans alteration oncogenique activable consiste en une immunotherapie, seule ou en combinaison avec une chimiotherapie conventionnelle. Un nouveau concept de maladie oligometastatique a emerge ces dernieres annees, suggerant que l’integration d’un traitement local a visee ablative en adjonction a un traitement systemique pourrait modifier significativement le cours de la maladie cancereuse. Les donnees precliniques montrent un effet synergistique entre les immunotherapies (antiPD1/PDL1 ou antiCTLA4) et la radiotherapie, rationnel fort pour considerer la combinaison de ces deux therapeutiques dans le cadre des cancers oligometastatiques. En clinique, les donnees meme si elles sont cliniquement interessantes, restent preliminaires. De nombreux essais prospectifs, randomises ou non, sont en cours et permettront de repondre a la question dans les prochaines annees. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Resume Introduction On manque d’etudes sur la mise en pratique des recommandations de pratique clinique (RPC) en oncologie thoracique. Methodes Les dossiers des 354 patients avec cancer bronchique non encore traite entre janvier 2009 et decembre 2012 ont ete revus. Tout nouveau traitement devrait etre propose en consultation multidisciplinaire (CMD) sur base d’un programme de soins oncologiques (PSO) fonde sur nos RPC. Resultats On a 636 CMD (332, 176, 81 et 47 en 1 re , 2 e , 3 e et suivantes lignes). Le taux de CMD en 1 re ligne a ete de 94 % avec 88 % et 75 % en conformite avec le PSO et les RPC. En 2 e et 3 e lignes, les taux sont de 93 et 92 % (CMD), 90 et 89 % (PSO), 56 et 63 % (RPC). En 1 re ligne, les principales causes de non-application ont ete, pour le PSO, le refus du patient ou un autre choix par le medecin et pour les RPC le manque de recommandations adequates pour des situations specifiques ou l’apparition de nouveaux traitements. Conclusion La plupart des patients fait l’objet d’une CMD avec bonne application du PSO. Les RPC doivent etre rapidement mises a jour pour incorporer les nouveaux traitements.

Resume Le tabac est le principal responsable de l’epidemie de cancers bronchiques. Neanmoins, on estime que 25 % des cancers bronchiques ne sont pas attribuables a un tabagisme actif. Certaines caracteristiques des patients non-fumeurs atteints de cancer bronchique different des fumeurs : predominance feminine, tendance a survenir a un âge plus jeune, preponderance d’adenocarcinomes avec un profil mutationnel different, pronostic meilleur independamment du stade de la maladie. Les carcinogenes impliques dans la survenue de cancers bronchiques chez le non-fumeur sont detailles.

Resume Introduction Dans une etude princeps, nous avons trouve que des signatures composees de trois ARNm (semaphorine 3D [SEMA3D], cytokeratine 16 [KRT16] et UL16 binding protein 2 [ULBP2]) etaient associees a la reponse a la chimiotherapie par cisplatine-vinorelbine et a la survie des cancers bronchiques non a petites cellules avances (CBNPC). Patients et methodes Le but de la presente etude a ete de developper des tests immunohistochimiques pour KRT16, ULBP2 et SEMA3D et de tester l’expression de ces proteines pour la prediction de la reponse et de la survie sur des biopsies provenant des memes patients que ceux inclus dans l’etude du transcriptome. Resultats Nous n’avons pas pu reproduire par l’etude de l’expression proteique en immunohistochimie la signature de reponse a une chimiotherapie de CBNPC avances, signature que nous avions identifiee sur le transcriptome par des techniques de biologie moleculaire a haut debit dans la premiere phase de notre etude. Conclusion Nous mettons en evidence les difficultes de la recherche translationnelle en oncologie thoracique en soulignant la complexite d’obtention de prelevements tissulaires adequats et les difficultes de realisation et transposition en routine des techniques d’analyse transcriptomiques a haut debit.

18F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64 years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I–II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22–1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I–III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27–1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I–III NSCLC, for squamous cell carcinoma and for adenocarcinoma.

Resume Un facteur pronostique est une variable correlee a un critere d’evaluation utilise pour predire le futur du patient (survie, survie sans progression), independamment du traitement applique. Les facteurs pronostiques sont frequemment utilises comme criteres de selection et de stratification lors de l'inclusion dans des essais cliniques, pour comparer des groupes de patients ou eventuellement pour adapter l'intensite d'un traitement. Leur capacite de prediction ne leur permet pas d’etre utilises pour un pronostic individuel. Les principaux facteurs pronostiques reconnus dans les cancers bronchiques sont le stade d'extension de la neoplasie et l'indice de performance; l’âge, le sexe et le type histologique etant aussi reconnus. Ce travail a pour but de presenter un apercu critique des donnees relatives aux facteurs pronostiques des cancers bronchiques (facteurs pronostiques conventionnels, biologiques et metaboliques), et de presenter les principales limites de cette abondante litterature.

Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS). Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid. 64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5-3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7-7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3-4 neutropenia and thrombopenia, respectively. Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum-etoposide., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives Currently there are many uncertainties in the optimal treatment of malignant pleural mesothelioma (MPM), this is reflected in discrepancies between current guidelines. Our aim was to evaluate the current status of prospective interventional clinical trials within the ClinicalTrials.gov registry in MPM in order to predict a potential impact on MPM management in the next years. Material and Methods The records of 263.832 clinical trials registered were searched in December 2017. Trials starting between 2005 and 2017 (n = 262) were selected for further manual review. Trials including other tumour entities or mesothelioma originating outside the pleura (n = 94) were excluded, as well as trials where the primary endpoint has already been published (n = 22). Results In total, 91 clinical trials were identified and selected for further analysis. Most trials had a single arm design, were in phase I, and were non-randomized. Academic centres were recorded as primary sponsors in the majority of trials (56%), followed by industry in 21%. Most studies investigated targeted (n = 42) or cytotoxic therapies (n = 39). Ten studies investigated different genetic therapies. In 67% of the trials (n = 61) targeted and/or cytotoxic therapies were involved. Treatments involving surgery were investigated in 12 trials (13%), radiotherapy in 10 trials (11%). Only five studies (6%) were phase 3 studies and one was a phase 2/3 study. Four of these five phase 3 trials investigated targeted therapies, while one trial investigated prophylactic radiotherapy of operative tracts. Conclusions Currently running trials in MPM are mostly in early phases and dominated by systemic therapies. Very few trials evaluate loco-regional therapeutic approaches. The current controversy surrounding the use of surgery and radiotherapy within multimodal therapy strategies will not be answered by these trials in the coming years.

Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with advanced stage or relapsing tumours, which require administration of chemotherapy. While cisplatin-adriamycin-cyclophosphamide combination is regularly prescribed, other drugs have been assessed in the literature. Our aim is to evaluate the effectiveness (response rate) of systemic treatments, whatever the therapeutic line, including chemotherapy, targeted therapies and immunotherapies, in thymoma and thymic carcinoma, using the principles of evidence-based medicine. A systematic review was designed using the PICO system, by an experienced librarian and clinicians' experts in thoracic oncology, through the Ovid Medline system. Only phase II-IV trials and retrospective studies including at least 14 patients treated with the same regimen were considered. Articles were independently selected by at least two investigators. Fifty-five eligible articles were retrieved. Sixty% were dealing with platinum-based regimens, mainly cisplatin, and showed overall similar activity (mostly response rate above 50%) independently of the line of treatment or histological type (thymoma versus thymic carcinoma). Non-platinum based regimens included octreotide-prednisone and capecitabine-gemcitabine. Promising data of immunotherapy with antiPDL1 antibody (pembrolizumab) requires confirmation. Based on available data, the most popular and active regimens are cisplatin-anthracycline (CAP or ADOC) or cisplatin-etoposide combinations that should be recommended when considering first-line chemotherapy in thymoma or thymic carcinoma.

Publisher’s Note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations., Background: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. Methods: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. Results: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, BosniaHerzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. Conclusion: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a welldesigned dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research., No research funding was received.

In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled “Immunotherapy, a new standard of care in thoracic malignancies?” was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events. The need for biological selection, currently based on immunohistochemistry testing to identify the tumour expression of programmed death ligand (PD-L)1, was stressed, as well as the need to harmonise PD-L1 testing and techniques. Finally, sessions were dedicated to the combination of ICIs and radiotherapy and the place of ICIs in nonsmall cell lung cancer with oncogenic addictions. Finally, an important presentation was dedicated to the future of antitumour vaccination and of all ongoing trials in thoracic oncology.

Comorbidities are frequent in patients with lung cancer, who are often treated with systemic anticancer therapy. The purpose of the present review is to report the adaptations recommended for the various drugs used in lung cancer treatment, in the context of a specific comorbidity. The literature was reviewed for neurologic, endocrine, hepatic, renal, digestive, cardiovascular, pulmonary, blood and systemic diseases. The comorbidities impact on the systemic anticancer treatment is poorly assessed. There are no good data with a high level of evidence and literature is often limited to experts' opinion and to case reports. We need to improve our knowledge about those patients by adequate multicentric and prospective studies and registries in order to offer them better care in term of evidence-based medicine.

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI.To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.

The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10–15 years but has raised some issues related to their justification and methodology. The present systematic review aimed to assess trial characteristics and methodological aspects.All randomised clinical trials with a hypothesis of noninferiority/equivalence, published in English, were identified. Several readers extracted a priori defined methodological information. A qualitative analysis was then performed.We identified 20 randomised clinical trials (three phase II and 17 phase III), 11 of them being conducted in strong collaboration with industry. We highlighted some deficiencies in the reports like the lack of justification for both the noninferiority assumption and the definition of the noninferiority margin, as well as inconsistencies between the results and the authors' conclusions. CONSORT guidelines were better followed for general items than for specific items (pImprovement in the reporting of the meth"odology of noninferiority/equivalence trials is needed to avoid misleading interpretation and to allow readers to be fully aware of the assumptions underlying the trial designs. They should be restricted to limited specific situations with a strong justification why a noninferiority hypothesis is acceptable.

We report the case of a woman with an ALK positive lung adenocarcinoma, who developed bilateral complex renal cysts 17 months after the introduction of treatment with crizotinib. Clinical investigation led to the conclusion that the cysts were due to anticancer drug. Regression of the renal cysts was observed one month after cessation of the crizotinib. This case illustrates that specific and little known toxicities can occur with these novel molecules which have entered use for the management of lung cancer.

Introduction: In a literature meta-analysis, we showed survival benefits for regimens including cisplatin [hazard ratio (HR) 0.61; 95% confidence interval (CI), 0.57-0.66] and for those including etoposide (HR 0.65; 0.61-0.69). That benefit was mainly observed when etoposide alone or in combination with cisplatin was included in the chemotherapy regimens. Our objective was to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide. Methods: Extensive small-cell lung cancer patients were randomized between cisplatin-etoposide (CE) and ifosfamide + etoposide + epirubicin regimen (IVE) between 2000 and 2013. Results: 176 and 170 eligible patients were allocated to CE and IVE (315 deaths were required before analysis), respectively. Objective response rates were not significantly different: 60% with CE and 59% with IVE. No statistically significant difference in median survival and 1-year and 2-year was observed with rates of 9.6 months, 31 and 5% for CE and 10 months, 39 and 9% for IVE, respectively. HR was 0.84 (95% CI 0.68-1.05, p = 0.16). Only two prognostic factors for survival were retained in multivariate analysis: sex with HR = 0.69 (95% CI 0.49-0.97, p = 0.03) and performance status with HR = 0.53 (95% CI 0.49-0.97, p < 0.0001). After adjustment for these prognostic factors, HR for survival was 0.83 (95% CI 0.65-1.08, p = 0.17). There was more thrombopenia in the CE regimen and more leukopenia with IVE. Conclusion: Combination of CE failed to improve survival in comparison to an etoposide-containing regimen without cisplatin. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00658580?term=ELCWP+01994&rank=1, identifier NCT00658580., SCOPUS: ar.j, info:eu-repo/semantics/published

The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the fourth of a series of five and deals mainly with neurological paraneoplastic syndromes involving the peripheral nervous system and the neuromuscular junction and muscles.

The AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients (APPLE) trial is a randomized, open-label, multicenter, 3-arm, phase II study in advanced, epidermal growth factor receptor (EGFR)-mutant and EGFR tyrosine kinase inhibitor (TKI)-naive non-small-cell lung cancer (NSCLC) patients, to evaluate the best strategy for sequencing gefitinib and osimertinib treatment. Advanced EGFR-mutant NSCLC patients, with World Health Organization performance status 0-2 who are EGFR TKI treatment-naive and eligible to receive first-line treatment with EGFR TKI will be randomized to: In all arms, a plasmatic ctDNA T790M test will be performed by a central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decisions only in arm B. The primary objective is to evaluate the best strategy for sequencing of treatment with gefitinib and osimertinib in advanced NSCLC patients with common EGFR mutations, and to understand the value of liquid biopsy for the decision-making process. The progression-free survival rate at 18 months is the primary end point of the trial. The activity of osimertinib versus gefitinib to prevent brain metastases will be evaluated., SCOPUS: ar.j, info:eu-repo/semantics/published