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      Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients

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          Abstract

          Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.

          Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI–ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.

          We identified 64 (3.5%) out of 1826 cancer patients with ICI–ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7–73.8%).

          ICI–ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.

          Abstract

          Awareness of clinical/radiological presentation of immunotherapy-related pneumonitis is crucial to ensure a diagnosis http://ow.ly/eIMF30bgolf

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          Most cited references22

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          Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

          Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens.
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            PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course.

            Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.
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              Interstitial lung disease induced by drugs and radiation.

              An ever-increasing number of drugs can reproduce variegated patterns of naturally occurring interstitial lung disease (ILD), including most forms of interstitial pneumonias, alveolar involvement and, rarely, vasculitis. Drugs in one therapeutic class may collectively produce the same pattern of involvement. A few drugs can produce more than one pattern of ILD. The diagnosis of drug-induced ILD (DI-ILD) essentially rests on the temporal association between exposure to the drug and the development of pulmonary infiltrates. The histopathological features of DI-ILD are generally consistent, rather than suggestive or specific to the drug etiology. Thus, the diagnosis of DI-ILD is mainly made by the meticulous exclusion of all other possible causes. Drug dechallenge produces measurable improvement in symptoms and imaging in the majority of patients, whereas corticosteroid therapy is indicated if symptoms are present or drug dechallenge is without an effect. Rechallenge is justified in a minority of patients, and is discouraged for diagnostic purposes only. Pneumotox (www.pneumotox.com) provides updated information on drug-induced respiratory disease. Copyright 2004 S. Karger AG, Basel
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                Author and article information

                Journal
                Eur Respir J
                Eur. Respir. J
                ERJ
                erj
                The European Respiratory Journal
                European Respiratory Society
                0903-1936
                1399-3003
                August 2017
                10 August 2017
                : 50
                : 2
                : 1700050
                Affiliations
                [1 ]Service de Pneumologie, Hôpital Larrey, Centre Hospitalier Universitaire, Université Paul Sabatier, Toulouse, France
                [2 ]Service de Pneumologie, APHP Hôpital Tenon and Sorbonne Universités, UPMC Univ Paris 06, Paris, France
                [3 ]Cellule Biostatistique, Bureau des Essais Cliniques, Institut Claudius Regaud, IUCT-O, Toulouse, France
                [4 ]Service de Dermatologie, IUCT, Centre Hospitalier Universitaire, Université Paul Sabatier, Toulouse, France
                [5 ]Service d'Oncologie Thoracique, University Hospital Bichat, APHP, Paris, France
                [6 ]Department of Thoracic Oncology, Centre Hospitalier Universitaire, Grenoble, France
                [7 ]Hematological Malignancies and Drug Development Departments, Gustave Roussy, Cancer Campus Grand Paris, Villejuif, France
                [8 ]Service d'Oncologie Médicale, Institut de Cancérologie de l'Ouest, St Herblain, Inserm U892, Nantes, France
                [9 ]Service de Pneumologie, Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France
                [10 ]Service de Pneumologie, Oncologie Thoracique et Soins Intensifs Respiratoires, Rouen University, Hopital, CIC INSERM 1404, Quant IF-LITIS, Rouen, France
                [11 ]Medical Oncology Department, Gustave Roussy Cancer Center, Villejuif, France
                [12 ]Service de Pneumologie, Hôpital Foch, Suresne, France
                [13 ]Multidisciplinary Oncology and Therapeutic Innovations Dept, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France
                [14 ]Département de Cancérologie Générale, Centre Oscar Lambret, Lille, France
                [15 ]Département de Cancérologie Médicale, Centre Léon Bérard, Lyon, France
                [16 ]Service de Pneumologie, CHRU Tours, Tours, France
                [17 ]Medical Oncology Department, Lucerne Cantonal Hospital, Luzern, Switzerland
                [18 ]Medical Oncology Department, Kantonsspital St Gallen, St Gallen, Switzerland
                [19 ]Département Oncologie Medicale, Centre Georges-Francois Leclerc, Dijon, France
                [20 ]Service de Pneumonologie, Hôpital Saint Musse, Toulon, France
                [21 ]Service de Pneumologie Aiguë Spécialisée et Cancérologie Thoracique, Hospices Civils de Lyon, Université Claude Bernard, Lyon, France
                [22 ]Service de Dermatologie, Hospices Civils de Lyon, Université Claude Bernard, Lyon, France
                [23 ]Service de Dermatologie, CHU de Grenoble site Nord – Hôpital Albert Michallon, Grenoble, France
                [24 ]Service de Radiologie, Centre Hospitalier Universitaire, Université Paul Sabatier, Toulouse, France
                Author notes
                Julien Mazières, Thoracic Oncology Unit, Respiratory Disease Dept, Hôpital Larrey, CHU Toulouse, Chemin de Pouvourville, 31059 Toulouse Cedex, France. E-mail: mazieres.j@ 123456chu-toulouse.fr
                Article
                ERJ-00050-2017
                10.1183/13993003.00050-2017
                5593387
                28798088
                7ab06c3e-9a16-4827-9e36-d1a726ccd6cf
                Copyright ©ERS 2017
                History
                : 10 January 2017
                : 20 April 2017
                Categories
                Original Articles
                Interstitial Lung Diseases
                6
                13

                Respiratory medicine
                Respiratory medicine

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