Radiographic features of pneumonitis in patients treated with immunotherapy compared to traditional chemotherapy for non-small cell lung cancer


      • Here we present the first analysis of radiographic findings of IRAE pneumonitis versus pneumonitis caused by chemotherapy
      • Immunotherapy was associated pulmonary nodules and the number of immunotherapy agents correlated with incidence of pulmonary nodules
      • Features of IRAE pneumonitis improved over time while those of chemotherapy pneumonitis worsened



      Pneumonitis has been described as a side effect of immunotherapy as well as traditional chemotherapy. Although immune-related adverse event (IRAE) pneumonitis has been extensively characterized, the relationship between IRAE pneumonitis and pneumonitis secondary to chemotherapy is less clear. Here, we present the first analysis of radiographic features of pneumonitis secondary to immunotherapy compared to chemotherapy.


      Using our radiology records system, we searched chest computed tomography (CT) reports for the term “pneumonitis”. We evaluated medical records to establish chronicity of pneumonitis occurring after medication administration and excluded cases where radiation therapy appeared to be the cause of pneumonitis. We also obtained information regarding demographic, clinical, and treatment characteristics for comparison.


      Patients treated with immunotherapy demonstrated more specific features of pneumonitis including consolidation, ground glass opacities, septal thickening, traction bronchiectasis, and pulmonary nodules compared to those treated with chemotherapy. Immunotherapy treatment correlated with the development of pulmonary nodules (p = 0.048), and administration of more than one immunotherapy agent correlated with a greater incidence of development of nodules (p = 0.050). Radiographic features in patients treated with immunotherapy all decreased over time. Conversely, in patients treated with chemotherapy the incidence of ground glass opacities, traction bronchiectasis, pulmonary nodules, and mediastinal/hilar adenopathy increased over time.


      IRAE-pneumonitis has distinct features and a distinct clinical course compared to pneumonitis secondary to chemotherapy. Importantly, IRAE-pneumonitis features decreased over time, suggesting that careful consideration of the benefit-risk ratio may allow for continuation of immunotherapy in some patients who develop pneumonitis.


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        • National Lung Screening Trial Research T
        Lung cancer incidence and mortality with extended follow-up in the national lung screening trial.
        J Thorac Oncol. 2019; 14: 1732-1742
        • Navada S.
        • Lai P.
        • Schwartz A.G.
        • Kalemkerian G.P.
        Temporal trends in small cell lung cancer: analysis of the national Surveillance, Epidemiology, and End-Results (SEER) database.
        J Clin Oncol. 2006; 24 (7082–7082)
        • Ost D.E.
        • Jim Yeung S.C.
        • Tanoue L.T.
        • Gould M.K.
        Clinical and organizational factors in the initial evaluation of patients with lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2013; 143: e121S-e141S
        • Silvestri G.A.
        • Gonzalez A.V.
        • Jantz M.A.
        • et al.
        Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2013; 143: e211S-e250S
        • Dimou A.
        • Sherman C.
        • Wrangle J.
        Imaging in advanced non-small cell lung cancer: a medical oncology perspective.
        J Thorac Imaging. 2016; 31: 238-242
        • Colt H.G.
        • Murgu S.D.
        • Korst R.J.
        • Slatore C.G.
        • Unger M.
        • Quadrelli S.
        Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2013; 143: e437S-e454S
        • Borghaei H.
        • Paz-Ares L.
        • Horn L.
        • et al.
        Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer.
        New EnglJMed. 2015; 373: 1627-1639
        • Brahmer J.
        • Reckamp K.L.
        • Baas P.
        Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer.
        New Engl J Med. 2015; 373: 123-135
        • Yang C.Y.
        • Yang J.C.
        • Yang P.C.
        Precision management of advanced non-small cell lung cancer.
        Annu Rev Med. 2020; 71: 117-136
        • Horn L.
        • Spigel D.R.
        • Vokes E.E.
        • et al.
        Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057).
        J Clin Oncol. 2017; 35: 3924-3933
        • Kim E.S.
        • Hirsh V.
        • Mok T.
        • et al.
        Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial.
        Lancet. 2008; 372: 1809-1818
        • Herbst R.S.
        • Prager D.
        • Hermann R.
        • et al.
        TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non–small-cell lung cancer.
        J Clin Oncol. 2005; 23: 5892-5899
        • Soria J.-C.
        • Ohe Y.
        • Vansteenkiste J.
        • et al.
        Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer.
        New EnglJMed. 2017; 378: 113-125
        • Mok T.
        • Kim D.-W.
        • Wu Y.-L.
        • et al.
        First-line crizotinib versus pemetrexed–cisplatin or pemetrexed–carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014).
        J Clin Oncol. 2014; 32 (8002–8002)
        • Baxi S.
        • Yang A.
        • Gennarelli R.L.
        • et al.
        Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis.
        BMJ. 2018; 360k793
        • Reuss J.E.
        • Suresh K.
        • Naidoo J.
        Checkpoint inhibitor pneumonitis: mechanisms, characteristics, management strategies, and beyond.
        Curr Oncol Rep. 2020; 22: 56
        • Jain A.
        • Shannon V.R.
        • Sheshadri A.
        Immune-related adverse events: pneumonitis.
        Adv Exp Med Biol. 2018; 995: 131-149
        • Bronstein Y.
        • Ng C.S.
        • Hwu P.
        • Hwu W.J.
        Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy.
        Am J Roentgenol. 2011; 197: W992-W1000
        • Wu J.
        • Hong D.
        • Zhang X.
        • Lu X.
        • Miao J.
        PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis.
        Sci Rep. 2017; 7: 44173
        • Cui P.
        • Huang D.
        • Wu Z.
        • et al.
        Association of immune-related pneumonitis with the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer.
        Ther Adv Med Oncol. 2020; 121758835920922033
        • Kalisz K.R.
        • Ramaiya N.H.
        • Laukamp K.R.
        • Gupta A.
        Immune checkpoint inhibitor therapy–related pneumonitis: patterns and management.
        Radiographics. 2019; 39: 1923-1937
        • Porcu M.
        • De Silva P.
        • Solinas C.
        • et al.
        Immunotherapy associated pulmonary toxicity:biology behind clinical and radiological features.
        Cancers (Basel). 2019; 11
        • Tirumani S.H.
        • Ramaiya N.H.
        • Keraliya A.
        • et al.
        Radiographic profiling of immune-related adverse events in advanced melanoma patients treated with ipilimumab.
        Cancer Immunol Res. 2015; 3: 1185-1192
        • Nishino M.
        • Ramaiya N.H.
        • Awad M.M.
        • et al.
        PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course.
        Clin Cancer Res. 2016; 22: 6051-6060
        • Berthod G.
        • Lazor R.
        • Letovanec I.
        • et al.
        Pulmonary sarcoid-like granulomatosis induced by ipilimumab.
        J Clin Oncol. 2012; 30: e156-e159
        • Limper A.H.
        Chemotherapy-induced lung disease.
        Clin Chest Med. 2004; 25: 53-64
        • Bielopolski D.
        • Evron E.
        • Moreh-Rahav O.
        • Landes M.
        • Stemmer S.M.
        • Salamon F.
        Paclitaxel-induced pneumonitis in patients with breast cancer: case series and review of the literature.
        J Chemother. 2017; 29: 113-117
        • Nagata S.
        • Ueda N.
        • Yoshida Y.
        • Matsuda H.
        • Maehara Y.
        Severe interstitial pneumonitis associated with the administration of taxanes.
        J Infect Chemother. 2010; 16: 340-344
        • Shukuya T.
        • Ishiwata T.
        • Hara M.
        • et al.
        Carboplatin plus weekly paclitaxel treatment in non-small cell lung cancer patients with interstitial lung disease.
        Anticancer Res. 2010; 30: 4357-4361
        • Wang G.S.
        • Yang K.Y.
        • Perng R.P.
        Life-threatening hypersensitivity pneumonitis induced by docetaxel (taxotere).
        Br J Cancer. 2001; 85: 1247-1250
      1. Chi-square test calculator.
        2021 (ORfhwsctcda)
        • Laskin J.J.
        • Sandler A.B.
        First-line treatment for advanced non-small-cell lung cancer.
        Oncology (Williston Park). 2005; 19 (discussion 1678–1680): 1671-1676
        • Khunger M.
        • Rakshit S.
        • Pasupuleti V.
        • et al.
        Incidence of pneumonitis with use of programmed death 1 and programmed death-ligand 1 inhibitors in non-small cell lung cancer: a systematic review and meta-analysis of trials.
        Chest. 2017; 152: 271-281
        • Naidoo J.
        • Wang X.
        • Woo K.M.
        • et al.
        Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy.
        J Clin Oncol. 2017; 35: 709-717
        • Pradere P.
        • Boutros C.
        • Scoazec J.Y.
        • et al.
        Pulmonary nodules and immunotherapy: disease progression or toxicity of anti-PD1/anti-PDL1 checkpoint inhibitors?.
        Eur J Cancer. 2018; 93: 144-146
        • Rashdan S.
        • Minna J.D.
        • Gerber D.E.
        Diagnosis and management of pulmonary toxicity associated with cancer immunotherapy.
        Lancet Respir Med. 2018; 6: 472-478