Risk Factors and Clinical Characteristics of Lung Cancer in Idiopathic Pulmonary Fibrosis

A Retrospective Cohort Study

Hongseok Yoo; Byeong-Ho Jeong; Myung Jin Chung; Kyung Soo Lee; O. Jung Kwon; Man Pyo Chung

Disclosures

BMC Pulm Med. 2019;19(149) 

In This Article

Results

The baseline characteristics of 938 patients at the time of IPF diagnosis are summarized in Table 1. Mean age at IPF diagnosis was 65.6 years. Most patients were male (79.3%) and current (23.5%) or ex-smokers (49.3%). Mean duration of follow up was 4.5 years. The median interval between pulmonary function tests was 13 (IQR, 12–20) months. Among the 938 patients, lung cancer developed in 135. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years (Figure 1). The incidence density rate was 32.6/1000 person-years.

Figure 1.

Cumulative incidence of lung cancer development in patients with idiopathic pulmonary fibrosis using Kaplan-Meier curve. Cumulative incidences were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years

Patients with lung cancer were more commonly male and current or ex-smokers at IPF diagnosis. In addition, they had better FVC and were more likely to have airflow limitation (Forced expiratory volume in 1 s/FVC < 70%) (Table 1). Univariate Cox regression analysis for proportional risk on baseline characteristics showed male gender, current smoking, better FVC, and airflow limitation at IPF diagnosis were associated with lung cancer development. Although not statistically significant, rapid annual decline in FVC was associated with a tendency toward lung cancer development (Table 2). Multivariate Cox regression analysis showed male gender, current smoking, and rapid decline in FVC were independently associated with lung cancer development (Table 2, Figure 2). When subgroup analysis on current and ex-smokers was performed, pack-year of smoking and rapid decline of FVC were significantly associated with lung cancer development (Additional file 1: Table S1, Additional file 1: Figure S1).

Figure 2.

Cumulative incidence of lung cancer development according to (a) gender (P < 0.001, log-rank test), b smoking status at diagnosis of idiopathic pulmonary fibrosis (P < 0.001, log-rank test), and (c) annual decline of 10% or more in forced vital capacity (P = 0.0563, log-rank test) using Kaplan-Meier curve

Figure S1.

Cumulative incidence of lung cancer development according to pack-years of smoking using Kaplan-Meier curve in current and ex-smokers. (n=684) (P< 0.001, log-rank test)

Detailed characteristics of 135 patients with lung cancer are in Table 3. Mean age at lung cancer diagnosis was 69.0 years. Most patients were male (94.8%) and were current or ex-smokers. Median interval between IPF diagnosis and lung cancer was 38 months (IQR, 20–67). Median FVC was 84% (IQR, 71–93) and DLco was 62% (IQR, 50–77) at lung cancer diagnosis.

For histologic types of lung cancer, squamous cell carcinoma was the most common (32.6%) followed by adenocarcinoma (28.1%). Twenty-seven (20.0%) patients were diagnosed with small cell carcinoma. For 17 (12.6%) of patients who were diagnosed with non-small cell carcinoma, specific cell type could not be determined due to insufficient amount of specimen. Pathology review of one patient showed both squamous and small cells. Details on histopathologic types and stages of lung cancer are available on supplement. (Additional file 1: Table S2, Table S3, and Table S4).

Chest radiographs and CT scans at lung cancer diagnosis were available for review in all patients. (Table 4) Visible lung lesions on chest radiograph were observed in 104 (77.0%) patients. Lung cancer frequently developed in regions abutting fibrosis (29.6%) or within fibrosis (44.4%). Median CT fibrosis score was 25 (IQR, 15–38) and median CT emphysema score was 10 (IQR, 0–20). The time interval from most recent chest CT without lung cancer to chest CT at lung cancer diagnosis was 23 months (IQR, 11–43). The number of patients with chest CT interval of 1 year or less was 35 (26.7%). The stages of lung cancer did not differ between patients whose interval of chest CT scans was 1 year or less and more than 1 year (P for trend = 0.141). (Additional file 1: Table S5) However, the proportion of stage I lung cancer was higher in patients whose interval of chest CT scans was 1 year or less (38.9% vs. 21.2%, P = 0.038).

Survival of patients with and without lung cancer was analyzed. The median survival of patients with lung cancer was 3.4 years compared to 9.8 years in patients without lung cancer. The difference was statistically significant (P < 0.001). (Additional file 1: Figure S2).

Figure S2.

Kaplan-Meier survival analysis comparing IPF patients with and without lung cancer. (PP< 0.001, log-rank test)

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