Impact of interstitial lung disease and simultaneous lung cancer on therapeutic possibilities and survival

Eniko Barczi, Tamas Nagy, Livia Starobinski, Abigel Kolonics-Farkas, Noemi Eszes, Aniko Bohacs, Adam Domonkos Tarnoki, David Laszlo Tarnoki, Veronika Müller, Eniko Barczi, Tamas Nagy, Livia Starobinski, Abigel Kolonics-Farkas, Noemi Eszes, Aniko Bohacs, Adam Domonkos Tarnoki, David Laszlo Tarnoki, Veronika Müller

Abstract

Background: Fibrosing interstitial lung diseases (ILDs) are associated with poor survival and an increased risk of developing lung cancer (LC). Patient and LC characteristics, therapeutic possibilities and survival in this rare patient population are not well established.

Methods: Fibrosing ILD patients treated at the Department of Pulmonology Semmelweis University were reviewed retrospectively between 2012-2018 (N = 160). All patients with concomitant LC (N = 23) underwent detailed pulmonary evaluation. Cancer characteristics including driver mutation data, as well as therapy and survival were analyzed.

Results: ILD-LC patients (56% men, mean age 73 ± 6 years) had mild-moderate lung functional impairment (forced vital capacity [FVC]: 80 ± 24%ref., forced expiratory volume in one second [FEV1]: 76 ± 27%ref.; transfer factor of the lung for carbon monoxide [TLCO]: 62 ± 25% reference). In 56% of cases histology confirmed adenocarcinoma followed by squamous cell carcinoma in 26%. Lobectomy could only be performed in one case; driver mutation was present in one patient. Chemotherapy was most commonly administered; however, 26% could only receive supportive palliative care. Four idiopathic pulmonary fibrosis patients received concomitant nintedanib to their LC treatment. Median survival of ILD-LC patients was only 321 days.

Conclusions: Diagnosis and therapy of ILD-LC is challenging and patients have a very limited survival. A significant proportion of patients could only receive palliative care indicating the need for better management strategies in this special patient population. The evaluation of the effect of cotreatment with antifibrotics needs further study.

Key points: Interstitial lung diseases are often associated with lung cancer Diagnosis is challenging and therapy often limited due to underlying lung disease. Patients received platinum based chemotherapy or only supportive care.

Keywords: Interstitial lung disease; lung cancer; nintedanib; survival; therapy.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Figures

Figure 1
Figure 1
Summary of patients, disease characteristics and therapies of individual patients. () Female; () Male; () Former smoker; () Never smoker; () GAP I; () GAP II; () GAP III; () Nintedanib therapy; () Adenocarcinoma; () Squamous cell carcinoma; () Small cell lung cancer; () Early stage (I, II, IIIA); () Locally advanced/metastatic (IIIB, IV); () ECOG 0–1; () ECOG 2; () ECOG 2–3; () IPF; () CTD‐ILD or NSIP; () Lobectomy; () Platinum doublet therapy +/‐ irradiation; () Mono chemotherapy +/‐ irradiation or only irradiation; () Not receiving/refusing active oncotherapy; ()Progressive lung fibrosis; () Progression of lung cancer.
Figure 2
Figure 2
Survival curve of ILD‐LC patients. The average survival was 321 days from the diagnosis of LC (men: 340 days, women: 288 days; ns) in ILD patients.

References

    1. Travis WD, Costabel U, Hansell DM et al An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188 (6): 733–48.
    1. Ryerson CJ, Kolb M. The increasing mortality of idiopathic pulmonary fibrosis: Fact or fallacy? Eur Respir J 2018; 51 (1): 1702420.
    1. Efficacy and safety of nintedanib in patients with progressive fibrosing interstitial lung disease (PF‐ILD) ‐ Full Text View ‐ . [Cited 19 Dec 2019.] Available from URL: .
    1. Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, Müller V, Kreuter M. The therapy of idiopathic pulmonary fibrosis: What is next? Eur Respir Rev 2019; 28: 190021.
    1. Bogos K, Kiss Z, Gálffy G et al Revising incidence and mortality of lung cancer in central Europe: An epidemiology review from Hungary. Front Oncol 2019; 9: 1051.
    1. Matsushita H, Tanaka S, Saiki Y et al Lung cancer associated with usual interstitial pneumonia. Pathol Int 1995; 45 (12): 925–32.
    1. Karampitsakos T, Tzilas V, Tringidou R. Lung cancer in patients with idiopathic pulmonary fibrosis. Pulm Pharmacol Ther 2017; 45: 1–10.
    1. Ballester B, Milara J, Cortijo J et al Idiopathic pulmonary fibrosis and lung cancer: Mechanisms and molecular targets. Int J Mol Sci 2019; 20 (3): E593.
    1. Nagy A, Müller V, Kolonics‐Farkas AM, Eszes N, Vincze K, Horvath G. Worse lung cancer outcome in patients with lower respiratory tract infection confirmed at time of diagnosis. Thorac Cancer 2019; 10 (9): 1819–26.
    1. Detterbeck FC, Nicholson AG, Franklin WA et al The IASLC lung cancer staging project: Summary of proposals for revisions of the classification of lung cancers with multiple pulmonary sites of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol 2016; 11 (5): 639–50.
    1. Mirsadraee S, Oswal D, Alizadeh Y, Caulo A, van Beek E. The 7th lung cancer TNM classification and staging system: Review of the changes and implications. World J Radiol 2012; 4 (4): 28–34.
    1. Raghu G, Collard HR, Egan JJ. An official ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis: Evidence‐based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183 (6): 788–824.
    1. Demedts M, Costabel U. ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Eur Respir J. 2002; 19 (5): 794–6.
    1. EMPIRE Registry: Homepage . [Online]. [Cited 19 Dec 2019.] Available from URL: .
    1. Tran T, Sterclová M, Mogulkoc N et al The European MultiPartner IPF registry (EMPIRE): Validating long‐term prognostic factors in idiopathic pulmonary fibrosis. Respir Res 2020; 21 (1): 11.
    1. Miller MR, Hankinson J, Brusasco V et al Standardisation of spirometry. Eur Respir J 2005; 26 (2): 319–38.
    1. Salisbury ML, Xia M, Zhou Y et al Idiopathic pulmonary fibrosis: Gender‐age‐physiology index stage for predicting future lung function decline. Chest 2016; 149 (2): 491–8.
    1. Barczi E, Starobinski L, Kolonics‐Farkas A et al Long‐term effects and adverse events of nintedanib therapy in idiopathic pulmonary fibrosis patients with functionally advanced disease. Adv Ther 2019; 36: 1221–32.
    1. Yoon JH, Nouraie M, Chen X et al Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – Analysis of institutional and population data. Respir Res 2018; 19 (1): 195.
    1. Naccache JM, Gibiot Q, Monnet I et al Lung cancer and interstitial lung disease: A literature review. J Thorac Dis 2018; 10 ((6)): 3829–44.
    1. Kawasaki H, Ogura T, Yokose T, Nagai K, Nishiwaki Y, Esumi H. p53 gene alteration in atypical epithelial lesions and carcinoma in patients with idiopathic pulmonary fibrosis. Hum Pathol 2001; 32 (10): 1043–9.
    1. Kishi K, Homma S, Kurosaki A, Motoi N, Yoshimura K. High‐resolution computed tomography findings of lung cancer associated with idiopathic pulmonary fibrosis. J Comput Assist Tomogr 2006; 30 (1): 95–9.
    1. Chung JH, Goldin JG. Interpretation of HRCT scans in the diagnosis of IPF: Improving communication between pulmonologists and radiologists. Lung 2018; 196 (5): 561–7.
    1. Raghu G, Remy‐Jardin M, Myers JL. Diagnosis of idiopathic pulmonary fibrosis an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2018; 198 (5): e44–68.
    1. Cserepes M, Ostoros G, Lohinai Z. Subtype‐specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum‐based chemotherapy. Eur J Cancer 2014; 50: 1819–28.
    1. Kempf E, Rousseau B, Besse B, Paz‐Ares L. KRAS oncogene in lung cancer: Focus on molecularly driven clinical trials. Eur Respir Rev 2016; 25 (139): 71–6.
    1. Honda T, Sakashita H, Masai K. Deleterious pulmonary surfactant system gene mutations in lung adenocarcinomas associated with usual interstitial pneumonia. JCO Precis Oncol 2018; 2: 1–24.
    1. Yamaguchi S, Ohguri T, Matsuki Y et al Radiotherapy for thoracic tumors: Association between subclinical interstitial lung disease and fatal radiation pneumonitis. Int J Clin Oncol 2015; 20 (1): 45–52.
    1. Gandhi L, Rodríguez‐Abreu D, Gadgeel S. Pembrolizumab plus chemotherapy in metastatic non‐small‐cell lung cancer. N Engl J Med 2018; 378 (22): 2078–92.
    1. Reck M, Mok TSK, Nishio M et al Atezolizumab plus bevacizumab and chemotherapy in non‐small‐cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open‐label phase 3 trial. Lancet Respir Med 2019; 7 (5): 387–401.
    1. Richeldi L, Crestani B, Azuma A et al Outcomes following decline in forced vital capacity in patients with idiopathic pulmonary fibrosis: Results from the INPULSIS and INPULSIS‐ON trials of nintedanib. Respir Med 2019; 156: 20–5.
    1. Dhillon S. Nintedanib: A review of its use as second‐line treatment in adults with advanced non‐small cell lung cancer of adenocarcinoma histolog. Target Oncol 2015; 10 (2): 303–10.
    1. Planchard D, Popat S, Kerr K. Metastatic non‐small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow‐up. Ann Oncol 2018; 29: iv192–237.
    1. Raghu G, Rochwerg B, Zhang Y et al An official ATS/ERS/JRS/ALAT clinical practice guideline: Treatment of idiopathic pulmonary fibrosis: An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 2015; 192 ((2)): e3–e19.
    1. Clinical Trials Using Pirfenidone ‐ National Cancer Institute . [Online]. [Cited 08 Jan 2020.] Available from URL: .

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