Thin-section computed tomography-determined usual interstitial pneumonia pattern affects the decision-making process for resection in newly diagnosed lung cancer patients: a retrospective study

Patients with newly diagnosed lung cancer who underwent bronchoscopy at Nagoya University Hospital from January 2010 and December 2014 were the subjects of this retrospective study. The study was approved by the Institutional Review Board of Nagoya University Graduate School of Medicine (No 2014–0052-2).

Information about patient characteristics, pathological diagnosis of lung cancers, and clinical staging of lung cancers, was obtained from hospital records as previously reported. Spirometry screening assessment was routinely performed when patients admitted to hospital for bronchoscopy [6]. Diffusing capacity of the lung for carbon monoxide (DLCO) was measured using the single breath-holding method and the Burrows’ equation was utilized for DLCO [2]. Subjects were assigned to the COPD group, if they had airflow obstruction as determined by an FEV1/FVC ratio below 0.70 [6]. Severity of airflow limitation in COPD was determined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade [6, 19]. Clinical staging of lung cancer was based on the tumor, node, and metastasis (TNM) staging using the standards of the Union International Contre le Cancer (UICC), 7th edition [20]. Histological type of adenocarcinoma, squamous cell carcinoma (Sq), large cell carcinoma (Large), small cell lung carcinoma (SCLC), and non-small cell lung carcinoma (NSCLC), and carcinoid, were determined according to the World Health Organization’s classification [21].

Involvement of emphysema and fibrosis was evaluated by TSCT as previously reported [14]. Axial TSCT images of the whole lung with a slice thickness of 0.5–1.0-mm were reconstructed at the same increment by using a high-spatial frequency algorithm. After the initial interpretation by at least two radiologists, the evaluation was performed by a chest radiologist (SI) who had 20 years of experiences in reading thoracic CTs. For the present study, emphysema and fibrosis on chest TSCT were evaluated in accordance with the definition described by Cottin et al. [14, 22]. The severity of emphysema was also evaluated visually according to the Goddard classification as previously reported [14, 23]. The severity of fibrosis was classified visually into three categories as follows: 0, normal; 1, possible usual interstitial pneumonia (UIP) pattern and 2, UIP pattern [13, 14].

All data were checked for completeness, and the analyzed variables were tested for normality of distribution by the Shapiro-Wilk test. One-way analysis of variance (ANOVA) was used to compare normally distributed variables among the groups, and Kruskal-Wallis test was used to compare non-normally distributed variables. The t-test was used to compare normally distributed variables between the surgery and the non-surgery group subjects, and Mann-Whitney test was used to compare non-normally distributed variables. Comparisons of proportions among the groups were made using the χ² test or Fisher exact test. Multivariable logistic regression models were prepared to estimate the decision-making factors for proposing thoracic surgery. Inclusion of variables in the models was based on existing knowledge of the factors for proposing thoracic surgery, including age, histology, severity of airflow obstruction, clinical stage, and severity of fibrosis [6]. Statistical analyses were performed with PASW Statistics version 24.0 software (SPSS Inc., Chicago, IL), and a two-sided P value less than 0.05 was considered statistically significant.

Data from 596 patients with lung cancer who were sequentially registered and underwent bronchoscopy from August 2010 to July 2014 were obtained from hospital records. The study population excluded 72 patients who had not undergone pulmonary assessment by spirometry. Twenty-five patients (not evaluated by TSCT for the presence of emphysema and/or fibrosis, or who had received repetitive bronchoscopy) were also excluded from the study population. As a result, the study cohort comprised 499 patients (83.7%). In total, 135 (27.1%) patients showed emphysema without fibrosis. Overall, 74 (14.8%) patients had a finding of fibrosis, and 64 (86.5%) of these patients also had emphysema. The remaining 290 (58.1%) subjects showed evidence of neither emphysema nor fibrosis in their chest CT examinations. Although CPFE might be considered by some as an entity that is distinct from either emphysema or fibrosis [24], patients with fibrosis and CPFE were combined into a fibrosis group for further analysis in this study. The characteristics of the 499 study patients are presented in Table 1. The mean age was 70.0 years. Overall, 348 patients were male and 375 had a history of smoking. Compared with the normal group, the emphysema and fibrosis groups were predominantly male and with a higher smoking history. Although more than 65% of the emphysema group had airflow obstruction (determined by an FEV1/FVC ratio below 0.7), less than 40% of the fibrosis group including patients with CPFE had significant airflow obstruction. The severity of emphysema in the fibrosis group was similar to that in the emphysema group and the proportion of emphysema grade 1 was significantly higher than those with emphysema grade 2 or 3. More than 45% of the fibrosis group had grade 2 disease (UIP pattern).

Overall, 211 patients had pathological stage I disease, 75 patients had stage II disease, and 182 patients had stage III or IV disease. The prevalence of adenocarcinoma, squamous cell carcinoma, and other type of histology were 58.1, 25.7, and 16.2%, respectively. To evaluate the association of TSCT-determined emphysema and/or fibrosis with characteristics of lung cancer, pathological stage and histology were compared among the groups (Table 2). The proportion of patients with stage I disease was significantly higher in the normal group and lower in the emphysema and fibrosis groups. Although determining the clinical stage should be essential before proposing the therapeutic options for lung cancer, uncompleted clinical staging did not differ among the groups. Regarding the tumor histology, the prevalence of adenocarcinoma was significantly higher in the normal group, whereas squamous cell carcinoma was significantly higher in the emphysema and fibrosis groups.

To explore whether the severity of TSCT-determined fibrosis might affect the decision to propose thoracic surgery with curative intent, patients at stage IIIB and IV were excluded from the analysis because they were not eligible for thoracic surgery. In addition, the patients with incomplete clinical staging or SCLC were also excluded. Overall, we evaluated data from 343 patients with lung cancer at stage IA to IIIA who underwent TSCT examination, spirometry, and bronchoscopy. These patients were subdivided according to whether they received thoracic surgery (273 cases) or not (70 cases). The characteristics, spirometric variables, and TSCT data for the patients with or without thoracic surgery are summarized in Table 3. The existence of comorbidities including ischemic disease did not differ among the group. Although measurement of DLCO was performed in more than 97% of patients with thoracic surgery, only 58% of patients without thoracic surgery had DLCO measurement. Even among these surgical candidates, the number of surgeries performed was significantly lower in the fibrosis group (60.8%, 28/46 cases) than in the normal and emphysema groups (84.7%, 177/209 cases; 77.3%, 68/88 cases, respectively). More than 70% of patients with each emphysema grade received thoracic surgery (emphysema grade 1, 61/85 cases; grade 2, 25/34 cases; grade 3, 7/10 cases, respectively) (Table 3 and Fig. 1a). As a consequence, the proportion of each emphysema grade did not differ between surgical candidates and patients with resected lung cancer (Fig. 1a). Although more than 70% of patients with fibrosis grade 1 received thoracic surgery (17/24 cases), only 50% of patients with fibrosis grade 2 received it (11/22 cases) (Table 3 and Fig. 1b). Therefore, among patients with fibrosis and resected lung cancer, those with fibrosis grade 2 were decreased by 8.5%, compared to the surgical candidates (Fig. 1b). Less than 50% of patients with stage III disease received thoracic surgery. More than 80% of patients with adenocarcinoma received thoracic surgery, but more than 30% of patients with squamous cell carcinoma did not. We evaluated the decision-making factors for proposing thoracic surgery (Table 4). Although there were no significant relative odds ratios (ORs) for the comparison between the patients with fibrosis grade 0 and grade 1, the relative ORs for the comparison between the patients with fibrosis grade 0 and grade 2 showed significant confidence intervals (CIs). When the relative ORs for the comparison between the patients with fibrosis grade 0 and grade 2 were adjusted for age, histology, clinical stage, and airflow obstruction, multivariate analysis showed a significant relative OR value of 0.266 (95% CI: 0.087–0.812) (Table 4). Age, GOLD grade 3 airflow obstruction, and clinical stage III-but not squamous cell carcinoma- remained to be independent decision-making factors for thoracic surgery after the adjustment (Table 4).