Research Letter
Concomitant lung cancer and interstitial lung disease: A challenge in clinical practice
R. Linhas, , D. Machado, S. Campainha, S. Neves, A. Barroso
Pulmonology Department, Centro Hospitalar Vila Nova de Gaia/Espinho, Rua Conceição Fernandes, S/N, 4434-502 Vila Nova de Gaia, Portugal
Dear Editor,

Lung cancer (LC) risk is increased in patients with interstitial lung disease (ILD) and sometimes both occur concomitantly.1 LC incidence is increased 4.96-fold in patients with idiopathic pulmonary fibrosis (IPF) compared with the general population even after adjusting for age, gender and smoking habit.2 Idiopathic interstitial pneumonias are also associated with increased LC risk and connective tissue disease-associated ILD (CT-ILD) may be a predisposing factor for pulmonary malignancy.2

A retrospective analysis of ILD patients diagnosed with LC at our centre in the past 5 years was performed. Characteristics of this cohort were described and outcomes were also reported.

Eleven patients were included [median age 68 (range 36 to 78) years; mostly men (n=9; 81.8%)]. Almost all patients had smoking history (81.8%; ex-smokers n=7; active smokers n=2). The ILDs identified were CT-ILD (n=5; 45.5%), combined pulmonary fibrosis and emphysema (CPFE) (n=2; 18.1%), IPF (n=1; 9.1%), sarcoidosis (n=1; 9.1%), cryptogenic organising pneumonia (n=1; 9.1%) and silicosis (n=1; 9.1%). The most prevalent LC histological type was adenocarcinoma (n=5; 45.5%), followed by squamous cell carcinoma (n=2; 18.1%) and small cell carcinoma (n=2; 18.1%). Most patients were diagnosed at advanced stages (IIIB and IV) (n=7; 63.6%), mainly during clinical and radiological follow-up for the ILD. The tumours were predominantly in the peripheral lung fields, in relation to fibrotic areas. Median time from the onset of ILD to the onset of LC was 4 (range 0.3 to 249.7) months. Surgical resection was performed in 3 patients (27.3%) with stage IIA and IIIA LC; chemotherapy and/or radiotherapy were given to 6 patients (54.5%) with advanced disease (stage III and IV). One patient was refused for radiotherapy due to concern about the adverse effects and prognosis. Three patients (27.3%) had acute exacerbations of the ILD after LC treatment: 1 patient with CPFE and another with sarcoidosis presented acute exacerbation after radiotherapy and 1 patient with IPF presented acute exacerbation after chemotherapy with pemetrexed. Two of these patients died due to respiratory failure. Median survival time from the diagnosis of LC was 6.6 months (range 1.2 to 55.6). Three patients died due to progression of LC.

In our sample the majority of patients had a smoking history. Cigarette smoking is a recognised risk factor for the development of ILD1 but the pathogenesis of LC in patients with ILD is still unclear. IPF has been considered a neoproliferative lung disorder since both IPF and cancer share similar pathogenic hallmarks such as genetic alterations, uncontrolled mesenchymal cell proliferation and tissue invasion behaviour, and dysregulated intracellular signalling pathways.3

The treatment choice for ILD patients presenting LC is a challenge to the physicians. In our sample some patients benefited from LC treatment but the pre-existence of ILD also influenced negatively the prognosis. Voltolini et al. showed that major lung resection in patients with early stage non-small cell LC and ILD was associated with increased postoperative morbidity and mortality, mainly in patients presenting lower preoperative FVC% and DLCO%. There was a higher postoperative mortality for pneumonectomy and lobectomy. No patients died after sublobar resection. Thus, anatomic surgical resections can be an option in appropriately selected LC-ILD patients.4 When planning radiotherapy, it is important to determinate the radiation pneumonitis risk. A recent study showed that fatal radiation pneumonitis tended to be more common in patients with subclinical ILD and that the presence of extensive fibrosis on CT may be a contraindication for thoracic radiotherapy.5 Stereotactic body radiation therapy (SBRT) could also be an option in LC-ILD patients because of its less invasive nature, nevertheless there is an increasing body of evidence suggesting that even SBRT can induce acute exacerbation of ILD. None of our patients were submitted to SBRT.

Chemotherapy plays an irreplaceable role against LC, but LC-ILD patients receiving chemotherapy may face risks of chemotherapy-related acute exacerbation of ILD. The question arises as to whether chemotherapy regimens are efficacious and safe for the co-morbidity population. So far, no consensus has been reached nor has enough evidence been presented to support an optimal treatment strategy for LC–ILD patients – these patients are usually excluded by most clinical trials and the relevant studies are largely single-armed. A previous meta-analysis performed to evaluate the safety and efficacy of chemotherapy in non-small cell LC–ILD patients suggested that chemotherapy might be an effective therapy for these patients, but it also might be associated with higher incidence of acute exacerbations of ILD.6 Recently, the role of anti-fibrotic drugs in LC treatment was studied and the results were promising, opening new perspectives on therapeutic options for these complex patients.7

In conclusion, LC treatment should be considered in patients presenting both LC and ILD, but interdisciplinary evaluation of therapeutic options is mandatory and the patient opinion should also be considered for the final decision. Prospective studies about LC treatment in ILD patients are urgently needed.

Authorship

This paper has 5 authors, because all of them had contributed to this study: Rita Linhas, Sérgio Campainha, Sofia Neves and Ana Barroso participated in study conception and drafting of the manuscript. Daniela Machado collected the data. All authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interest to declare.

References
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Interstitial lung diseases in a lung cancer screening trial
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H. Dai,J. Liu,L. Liang,C. Ban,J. Jiang,Y. Liu
Increased lung cancer risk in patients with interstitial lung disease and elevated CEA and CA125 serum tumour markers
Respirology, 19 (2014), pp. 707-713 http://dx.doi.org/10.1111/resp.12317
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C. Vancheri,M. Failla,N. Crimi,G. Raghu
Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology
Eur Respir J, 35 (2010), pp. 496-504 http://dx.doi.org/10.1183/09031936.00077309
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L. Voltolini,S. Bongiolatti,L. Luzzi,E. Bargagli,A. Fossi,C. Ghiribelli
Impact of interstitial lung disease on short-term and long-term survival of patients undergoing surgery for non-small-cell lung cancer: analysis of risk factors
Eur J Cardiothorac Surg, 43 (2013), pp. e17-e23 http://dx.doi.org/10.1093/ejcts/ezs560
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S. Yamaguchi,T. Ohguri,Y. Matsuki,K. Yahara,H. Oki,H. Imada
Radiotherapy for thoracic tumours: association between subclinical interstitial lung disease and fatal radiation pneumonitis
Int J Clin Oncol, 20 (2015), pp. 45-52 http://dx.doi.org/10.1007/s10147-014-0679-1
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Y.J. Chen,L.X. Chen,M.X. Han,T.S. Zhang,Z.R. Zhou,D.S. Zhong
The efficacy and safety of chemotherapy in patients with nonsmall cell lung cancer and interstitial lung disease: a PRISMA-compliant Bayesian meta-analysis and systematic review
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M. Reck,R. Kaiser,A. Mellemgaard,J.Y. Douillard,S. Orlov,M. Krzakowski,LUME-Lung 1 Study Group
Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial
Lancet Oncol, 15 (2014), pp. 143-155 http://dx.doi.org/10.1016/S1470-2045(13)70586-2
Corresponding author.
Copyright © 2016. Sociedade Portuguesa de Pneumologia

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  • 5-years Impact Factor: 0,841
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