Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

https://doi.org/10.1016/j.ejrad.2015.01.021Get rights and content

Highlights

  • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients.

  • ILA was more common in older patients with heavier smoking history.

  • ILA was associated with shorter survival after adjusting for smoking and therapy.

  • ILA could be an additional independent marker for survival in advanced NSCLC.

Abstract

Objective

Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated.

Materials and method

The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA.

Results

ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40).

Conclusion

Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

Introduction

Lung cancer continues to be a leading cause of cancer death for both men and women in the United States [1]. Interstitial lung diseases, characterized by lung parenchymal damages due to various patterns of inflammation and fibrosis, were shown to be associated with the development of lung cancer, presumably because inflammation and fibrosis give rise to genetic damage which lead to lung parenchymal carcinogenesis and ultimately to cancer [2], [3], [4], [5], [6]. Interstitial lung diseases are also associated with smoking, which is one of the most clearly established risk factors and continued smoking is associated with shorter survival in patients with lung cancer [3], [4], [7], [8], [9]. Some prior reports have identified the similarities between the pathogenesis of interstitial lung diseases and smoking-related carcinogenesis, in the aspects of oxidative stress, mutagenesis, angiogenesis, and epithelial to mesenchymal transformation [2], [10], [11]. It is also well established that interstitial lung diseases may be exacerbated in lung cancer patients after local or systemic therapy which can adversely impact the clinical outcome [12], [13], [14], [15]. However, the prevalence of interstitial lung diseases at the time of diagnosis and prior to initiation of treatment and the impact on survival among advanced lung cancer patients have not been systematically investigated.

Computed tomography (CT) of the chest has been the primary modality to noninvasively assess the presence and severity of interstitial lung diseases. Washko et al. reported a sequential reading method for effective and efficient scoring of radiographic interstitial lung abnormalities (ILA) on chest CT using a 4-point scale [16], [17], which has been applied to study the frequency of ILA in smokers from the COPDGene study, participants in the Framingham Heart Study, National Lung Screening Trial participants and other clinical cohorts of subjects at risk of lung cancer [17], [18], [19], [20], [21], [22]. The application of the ILA scoring method to a cohort of patients with established diagnosis of advanced lung cancer may contribute to defining the frequency and severity of ILA in these patients and assess the impact of ILA on clinical outcome of patients with advanced lung cancer.

The purpose of the study is to determine the prevalence of interstitial lung abnormalities (ILA) detected on baseline chest CT in advanced NSCLC patients prior to the initiation of anti-cancer therapy, and investigate the association between ILA and survival duration while adjusting for smoking and other clinical characteristics. The study was carried out to determine if advanced NSCLC patients with smoking history have higher ILA scores than those without, and that patients with higher ILA scores have shorter overall survival compared to those with lower ILA scores.

Section snippets

Patients

The study population included 120 patients with treatment-naïve stage IV (AJCC 7th edition) NSCLC who presented to the Dana-Farber Cancer Institute between August 2011 and July 2012, and had a baseline chest CT prior to the initiation of systemic therapy available for review. These 120 patients resulted from the selection of patients who satisfied these eligibility criteria. Clinical record of the demographics including age, gender, and race, clinical characteristics, and survival, as well as

Patient characteristics and ILA scores

ILA was present in 17 patients (14%), with a score of 3 in two patients and a score of 2 in 15 NSCLC patients, while ILA scores were 1 in 52 patients and 0 in 51 patients. The summary of sequential reading in this study population is provided in Fig. 2.

Table 1 summarizes the patient demographics and disease characteristics of the study population, and the ILA scores on baseline chest CT prior at diagnosis. Significant associations were noted between higher ILA scores and older age (p = 0.01), a

Discussion

ILA was present in 14% of stage IV NSCLC patients at the time of diagnosis of lung cancer. The presence of ILA was associated with heavier smoking history and older age as shown before [17], [21], [22]. Patients with ILA at diagnosis had significantly shorter overall survival, which remained significant after adjusting for other factors including the types of first-line systemic therapy for NSCLC and pack year smoking history, indicating that ILA could be an independent marker for survival in

Conflict of interest statement

Stephanie Cardarella, Suzanne E. Dahlberg, Tetsuro Araki, Christine Lydon, Michael S. Rabin: Nothing to disclose. Mizuki Nishino: Consultant: Bristol-Myers Squibb company. Hiroto Hatabu: Grants from Toshiba Medical, AZE Ltd, Canon Inc. David M. Jackman: Consultant: Genentech, Foundation Medicine; Honoraria: Chugai. Bruce E. Johnson: Consultant: AstraZeneca, Genentech, GE Healthcare, Ariad, Novartis, SYnta, Chugai, Teva, Puma, Transgenomic; Stock Ownership: KEW Group; Other: DFCI post marketing

Acknowledgements

The investigators were supported by 1K23CA157631 (NCI) (M.N.), grants 1RO1CA114465-07 (B.E.J.) and 5R21CA11627-02 (H.H.) from the National Institutes of Health, 2P50CA090578-10 (B.E.J.) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc, as well as by the Doris and William Krupp Research Fund in Thoracic Oncology, the Gallup Fund in Thoracic Oncology, and American Society of Clinical Oncology Translational Research

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