The association of chest computed tomography-defined visual emphysema and prognosis in patients with nonsmall cell lung cancer

Yixiao Zhang, Jiawen Yi, Dan Sun, Yanping Su, Yingting Zuo, Min Zhu, Shu Zhang, Kewu Huang, Xiaojuan Guo, Yuhui Zhang
ERJ Open Research 2023 9: 00195-2023; DOI: 10.1183/23120541.00195-2023

Abstract

Background Although computed tomography (CT)-defined emphysema is considered a predictor of lung cancer risk, it is not fully clear whether CT-defined emphysema is associated with the prognosis of lung cancer. We aimed to assess the clinical impact of CT-defined emphysema on the survival of lung cancer.

Methods In the prospective cohort study of nonsmall cell lung cancer (NSCLC), the correlation between CT-defined emphysema and clinical variables was analysed. A multivariable Cox regression model was built to assess the association between CT-defined emphysema and overall survival (OS) for up to 8.8 years. The differences in survival analyses were derived by Kaplan–Meier analysis and log-rank testing. Low attenuation area (LAA%) was defined as the per cent of voxels below −950 HU.

Results 854 patients were included and CT-defined emphysema was present in 300 (35.1%) at diagnosis. Epidermal growth factor receptor (EGFR) wild-type (OR 1.998; p<0.001) and anaplastic lymphoma kinase (ALK) wild-type (OR 2.277; p=0.004) were associated with CT-defined emphysema. CT-defined emphysema remained a significant predictor of prognosis adjusting for age, sex, smoking history, tumour histology and Eastern Cooperative Oncology Group Performance Status (ECOG PS), whether in I-IIIA stage (adjusted hazard ratio (HR) 1.745; p=0.017) or in IIIB-IV stage (adjusted HR 1.291; p=0.022). Stratified analyses showed that OS rate among the driver oncogene groups with different CT-defined emphysema status differed significantly (log-rank p<0.001). Furthermore, patients with centrilobular emphysema (CLE) with LAA% >17% displayed poorer survival than those with LAA% ≤17% (median 432 versus 670 days; HR 1.564; p=0.020).

Conclusions CT-defined emphysema, especially CLE with LAA%>17%, is an independent predictor of NSCLC prognosis. Moreover, prospective studies are needed to further explore this association.

Tweetable abstract

Computed tomography (CT)-defined emphysema is often considered a predictor of lung cancer risk. This prospective cohort study adds that CT-defined emphysema is significantly associated with worse survival, regardless of oncogene status or tumour stage. https://bit.ly/3Phnwse

Introduction

Lung cancer is the leading cause of cancer-related deaths throughout the world [1], and nonsmall cell lung cancer (NSCLC) is the most frequent histological subtype (∼80–85%) [2]. Numerous studies have demonstrated that computed tomography (CT)-defined emphysema is a predictor for the risk of lung cancer development [3, 4]. We questioned whether CT-defined emphysema affected the prognosis of NSCLC. Some researchers have explored the association between the prognosis of lung cancer and the presence of CT-defined emphysema but have yielded inconsistent results in different tumour stages and races [5–9]. Ueda et al. [10] have suggested that early-stage NSCLC patients with CT-defined emphysema, not airway obstruction, had a poorer prognosis than those without it, while another study [8] did not find any differences in survival of lung cancer related to CT-defined emphysema among African American patients. To date, studies on the importance of CT-defined emphysema in determining the outcomes of patients with NSCLC are scarce. Moreover, molecular testing has become the standard procedure for patients with NSCLC [11, 12]. Previous studies with a comparatively small sample size indicated that the proportion of patients with CT-defined emphysema was lower in patients with epidermal growth factor receptor (EGFR) mutations than in wild-type patients [13–16]. The association between anaplastic lymphoma kinase (ALK) and CT-defined emphysema remains contradictory [14, 15]. Thus, the oncogene status of patients with CT-defined emphysema has not been thoroughly defined.

To address these issues, in this prospective cohort study, we sought to evaluate the oncogene status of NSCLC patients with CT-defined emphysema and investigate the prognostic value of CT-defined emphysema according to oncogene status and tumour stage. Other survival analyses in different stratification groups were also explored. Furthermore, we reported an exploratory analysis to assess the effects of airway obstruction on overall survival (OS).

Methods

Study population

Patients from an observational cohort with newly diagnosed NSCLC at Beijing Chao-Yang Hospital from January 2014 to December 2020 were eligible to enter our study [17, 18]. Enrolled patients were prospectively followed from diagnosis to death, loss to follow-up or censoring date (November 2022), with the median follow-up period being 1738 days (1690–1786 days). Eligibility criteria included histological confirmation of NSCLC diagnosis, detection of EGFR mutation/Kirsten rat sarcoma viral oncogene (KRAS) mutation/ALK rearrangement detection and high-resolution computed tomography (HRCT). Patients were excluded if they had insufficient clinical data available. Permission for data analysis was approved by the Ethics Committee of the Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China (No. 2021-ke-443), and written informed consent was obtained from all patients.

Data collection

Demographic data, comorbidity-related factors, tumour-related factors and treatment-related factors were obtained from Electronic Medical Records. A subset of participants also underwent pre-bronchodilator spirometry at diagnosis, and forced expiratory volume in 1 s per forced vital capacity (FEV1/FVC) ≤70% was defined as airway obstruction. COPD severity was assessed based on pulmonary function test (PFT). Participants with FEV1 >80%, 80% but ≥50% or 50% but ≥30% or ≤30% were classified as mild, moderate, severe and very severe, respectively [19]. The patients involved were staged according to the classification of TNM of the International Association for the Study of Lung Cancer (version 8) [20] and divided into localised stages, including stage I, II and III A, and advanced stages, including stage III B, III C and IV. Detailed methods about genotype evaluation techniques have been provided in our previous publications [17, 21].

Assessment of CT-defined emphysema

CT-defined emphysema was defined as disrupted lung vasculature and parenchyma with low attenuation that occupies any lung zone in HRCT [22]. It was diagnosed by two pulmonologists from HRCT scans of the chest for visual assessment, and discordances were adjudicated by a thoracic radiologist. Patients were dichotomised according to the presence or absence of the CT-defined emphysema. For patients with CT-defined emphysema, visual assessment of CT scans to describe subtypes based on the Fleischner Society guidelines was performed [22]. CT-defined emphysema is classified as centrilobular and paraseptal, while panlobular emphysema was not used in this study because it associates with α1-antitrypsin deficiency [22, 23]. Further, we quantified the severity on the baseline screening CT scan. The Hounsfield unit (HU) threshold for low attenuation area (LAA) in quantitative assessments was defined using −950 HU [24, 25]. Furthermore, subjects with CT-defined emphysema were then divided into those with mild (LAA% ≤9%) and those with moderate–severe (LAA% >9%) emphysema [25].

Imaging of HRCT

All included patients underwent 64-slice spiral CT (Siemens Healthcare, Forchheim, Germany) at the time of diagnosis. HRCT examinations were acquired from a single breath-held scanning at end-inspiration for the scope from the apex of the lung to the diaphragm. Images were displayed at window settings appropriate for viewing the lung parenchyma (lung window setting: level −450 HU; width 1300 HU; and mediastinal window settings: level 40 HU; width 400 HU). Image quantitative assessments were performed on AW 4.7 Server workstation (GE Healthcare, Chicago, IL, USA) using advanced application Thoracic VCAR software.

Statistical analysis

Mean±sd or median (interquartile range) were used to describe continuous variables as appropriate. Categorical variables were described as frequencies and percentages. The association between CT-defined emphysema and patient characteristics was evaluated using logistic regression. And Cox regression was performed to analyse the associations between CT-defined emphysema with OS. The differences in survival between groups were derived by Kaplan–Meier analysis and log-rank testing. Statistical significance was defined as a two-tailed p-value of <0.05 for all tests. Statistical analyses were performed with SPSS version 21.0 and R version 4.1.0. A professional epidemiologist reviewed the study.

Results

Participant characteristics

A total of 869 NSCLC patients were initially enrolled in this study. 15 patients were excluded due to absent HRCT at baseline (n=6) and insufficient clinical records (n=9) (figure 1). Thus, 854 eligible patients were included in this study. The median follow-up for OS was 1738 days. Finally, 29 patients were lost to follow-up, predominantly owing to an inability to contact patients by phone for assessment. 393 patients were alive and censored at last follow-up.

FIGURE 1
FIGURE 1

Study flow diagram. CT: computed tomography; HRCT: high-resolution computed tomography; NSCLC: nonsmall cell lung cancer; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase.

The clinicopathological characteristics of the study participants are summarised in table 1. The median age of all patients was 62 years and 61.9% of the patients were older than 60 years. Male patients (55.4%) and people who never smoke (54.8%) were predominant in this study. Regarding the oncogene status, the respective proportions of identified driver oncogene types for EGFR mutated/KRAS mutated/ALK rearranged were 37.8%/10.7%/9.3%.

View this table:
TABLE 1

Baseline characteristics of patients

CT-defined emphysema was present in 300 (35.1%) patients at diagnosis. 162 patients’ tumours were located in an emphysematous area, and the histological type in 68.5% (111 out of 162) patients was adenocarcinoma. Moreover, 153 (51.0%) had LAA% ≤9% and 147 (49.0%) had LAA% >9%. CT-defined emphysema was predominantly located in upper lobe lung in the mild group (LAA% ≤9%) but was distributed more diffusely in the moderate or severe group (LAA% >9%). Centrilobular emphysema (CLE) was the predominant type in our cohort (67.0%, 201 out of 300). 108 (53.7%) CLE had LAA% ≤9% and 93 (46.3%) had LAA% >9%, respectively. No significant associations were found between tumour location and tumour histology (p=0.740) or molecular markers (all p>0.05) (supplementary e-table 1).

Association between CT-defined emphysema and patient characteristics

Bivariate analyses revealed that EGFR wild-type (odds ratio (OR) 1.998; 95% confidence interval (CI) 1.475–2.707; p<0.001) and ALK wild-type (OR 2.277; 95% CI 1.291–4.018; p=0.004) were significantly associated with the presence of CT-defined emphysema (table 2). 62.3% of the EGFR/ALK wild-type cases were in patients who were currently smoking or used to smoke. Among EGFR or/and ALK wild-type patients, the presence of CT-defined emphysema correlated with smoking status (all p<0.001) (supplementary e-table 2).

View this table:
TABLE 2

The association between patient characteristics and CT-defined emphysema

Association between CT-defined emphysema and OS

The Kaplan–Meier survival analyses showed that patients with CT-defined emphysema had significantly worse survival compared to those without it (median, 585 days versus 1269 days; hazard ratio (HR) 1.512; 95% CI 1.254–1.823; p<0.001) (figure 2a). CT-defined emphysema remained a significant predictor of poorer OS when controlled for age, sex, smoking history, tumour histology and Eastern Cooperative Oncology Group Performance Status (ECOG PS), whether in I-IIIA stage (adjusted HR 1.745; 95% CI 1.102–2.763, p=0.017) or in IIIB-IV stage (adjusted HR 1.291; 95% CI 1.037–1.606, p=0.022) (table 3).

FIGURE 2
FIGURE 2

a) Kaplan–Meier curves showing patients with CT-defined emphysema had worse OS compared with those without CT-defined emphysema. b) Kaplan–Meier curves showing patients with EGFR/ALK wild-type had worse OS compared with those with EGFR mutation/ALK rearrangement. c) Kaplan–Meier curves showing OS rate among the driver oncogene groups with different CT-defined emphysema status differed significantly (log-rank p<0.001). EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase; CT: computed tomography; OS: overall survival.

View this table:
TABLE 3

Multivariable Cox regression analyses of CT-defined emphysema status with overall survival

We evaluated the association between CT-defined emphysema and OS stratified by oncogene status (figure 2). Patients with EGFR mutations/ALK rearrangements compared with wild-type cases experienced remarkably improved survival outcomes (median 1699 versus 479 days; HR 0.444; 95% CI 0.360–0.520; p<0.001) (figure 2b). Kaplan–Meier curves showed OS rate among the driver oncogene groups with different CT-defined emphysema status differed significantly (log-rank p<0.001). More specifically, the presence of CT-defined emphysema was associated with worse OS among the patients with EGFR/ALK wild-type (median 365 versus 623 days; HR 0.779; 95% CI 0.612–0.980; p=0.034) (figure 2c). When the analysis was limited to the patients with EGFR mutations/ALK rearrangement, no relationship between CT-defined emphysema and the OS rate was observed (median 1443 versus 1957 days; HR 0.762; 95% CI 0.523–1.065; p=0.107).

Subsequently, analysis showed that 258 patients who experienced death were staged as IIIB-IV, and their risk of mortality was 3.782-fold higher than that of patients as I-IIIA (figure 3a). In the stratified analysis, there were significant differences in the rate of OS among the tumour stage groups with different CT-defined emphysema status based on the log-rank tests (p<0.001) (figure 3b).

FIGURE 3
FIGURE 3

a) Kaplan–Meier curves showing patients staged as IIIB-IV had worse OS than I-IIIA patients. b) Kaplan–Meier curves showing OS rate among the tumour stage groups with different CT-defined emphysema status differed significantly (log-rank p<0.001). OS: overall survival.

Stratified survival analysis by severity of CT-defined emphysema was analysed. Kaplan–Meier curves showed no significant difference between the mild (LAA% ≤9%) and moderate–severe group (LAA% >9%) (median 590 versus 543 days; HR 1.096; 95% CI 0.822–1.465; p=0.532) (supplementary e-figure 1a). In order to screen out the patients with the worst prognosis, a new cut-off value (17%) to distinguish different severity was calculated using receiver operating characteristic curve. CLE with LAA% >17% displayed poorer survival than those with LAA% ≤17% (median 432 versus 670 days; HR 1.564; 95% CI 1.085–2.518; p=0.020) (supplementary e-figure 1b).

Furthermore, Kaplan–Meier curves showed OS rate among treatment received and year of diagnosis groups with different CT-defined emphysema status differed significantly (both log-rank p<0.001) (supplementary e-figure 2). Male patients had worse OS compared with female, and male patients with CT-defined emphysema displayed poorer survival than those without CT-defined emphysema (supplementary e-figure 3).

Association between airway obstruction and OS

Overall, 57.7% (493 out of 854) of the patients had both spirometry and CT data available. 157 out of 493 patients (31.8%) had airway obstruction on spirometry (supplementary e-table 3). We performed a sensitivity analysis only including those with spirometry. The median survival of the airway obstruction group was significantly shorter than that of the non-airway obstruction group (median 898 versus 1415 days; HR 1.431; 95% CI 1.114–1.956; p=0.301) (figure 4).

FIGURE 4
FIGURE 4

Kaplan–Meier curves showing patients with airway obstruction had worse overall survival (OS) compared with those without airway obstruction.

CT-defined emphysema and spirometry

Among individuals who had both spirometry and CT data available, 38.9% (192 out of 493) had CT-defined emphysema. Roughly 80% of patients are graded as mild and moderate in our study (supplementary e-table 3). 54.7% had CT-defined emphysema but normal spirometry. Additionally, PFT severity score correlates with emphysema severity (Kendall's tau-b=0.311, p=0.003) and emphysema site (Kendall's tau-b=0.207, p=0.048) significantly.

Discussion

To our knowledge, this is the first prospective cohort study to characterise CT-defined emphysema and investigate its potential impact on NSCLC prognosis in the molecular era. We demonstrate that CT-defined emphysema is more common in EGFR and ALK wild-type. We also suggest that NSCLC patients with CT-defined emphysema have a worse OS. Importantly, CLE with LAA% >17% was associated with poorer survival in patients with CT-defined emphysema.

It was reported that the prevalence of emphysema detected on CT in NSCLC patients ranged from 31.2% to 58.0% [10, 26], which was relatively higher than our result (35.1%). Perhaps this study enrolled patients in this cohort who underwent genetic testing and had a relatively high proportion of adenocarcinoma (79.4%), decreasing the prevalence of CT-defined emphysema. There is wide geographic and ethnic variation in the prevalence of CT-defined emphysema. Previous studies have shown that Americans and the British have a much higher incidence [8, 27, 28]. The Genetic Epidemiology of COPD Study confirmed that there are racial differences in the severity of emphysema [29] and pathogenesis for the differences may encompass genetic or epigenetic effects, immune system response and demographic characteristics [30].

Notably, EGFR and ALK wild-type are significantly associated with the presence of CT-defined emphysema in the bivariate analysis, implying a potential association between oncogene status and CT-defined emphysema. Similarly to our findings, prior studies found that the frequency of EGFR mutation was lower in patients with CT-defined emphysema [13–16]. Patients with EGFR mutations who did not smoke were less likely to have CT-defined emphysema, and a plausible reason is that most NSCLC patients with EGFR mutation have a history of non-smoking [13]. Regarding the status of ALK, Rizzo et al. [16] did not find any correlation between ALK wild-type and CT-defined emphysema even in the univariate analysis. However, the correlation and mechanism between underlying lung diseases and oncogene status in NSCLC have not been thoroughly investigated.

In the present study, it appears that CT-defined emphysema has prognostic significance in patients with NSCLC even after accounting for covariables. Our results further support that the presence of CT-defined emphysema, even if patients are asymptomatic and without airway obstruction, represents genuine lung disease [24, 28, 31]. Young et al. [32]found that the risk of dying of lung cancer increased with worsening airway obstruction. However, it is not cost-effective to perform spirometry for all patients because currently there is a paucity of evidence to prove that screening spirometry has net benefit [33, 34]. Lin et al. [35] reviewed randomised controlled trials of any screening method including spirometry, questionnaire or risk assessment followed by spirometry, and concluded that screening for COPD does not improve health-related quality of life or reduce morbidity or mortality. Adams et al. [36] showed that combined screening for lung cancer and COPD using low-dose CT might help to re-evaluate screening benefit in subjects with emphysema and determine the risk of competing causes of death. We contend that it is prudent to identify CT-defined emphysema in pretreatment CT images, rather than focusing on airway obstruction by spirometry, as CT data are more commonly available for lung cancer patients. Overall, an accurate and cost-effective screening approach should be assessed in future.

In the past decades, a few studies have reported correlations between CT-defined emphysema and survival (table 4). The different outcomes recorded in the literature between CT-defined emphysema and survival may be related to the target population, study sample size and different ethnicities. Two retrospective cohort studies in African American patients and Japanese patients have found that CT-defined emphysema was not associated with a worse prognosis [7, 8]. The discrepancy in the results between these studies and ours may be explained by several reasons. Firstly, these studies follow a retrospective cohort design in which relatively small sample sizes are used in the analyses. The Japanese study only enrolled NSCLC patients who underwent complete resection [7], while in our study, the prospective cohort included newly diagnosed NSCLC. Secondly, the proportion of patients with CT-defined emphysema that were included in the studies was 75% in African American patients and 27% in Japanese patients, respectively. Lastly, the method to determine the presence of CT-defined emphysema was evaluated by a semiquantitative method in African American patients and by visual assessment in Japanese patients and ours.

View this table:
TABLE 4

Characteristics of studies that assessed CT-defined emphysema

To date, relatively few studies have investigated the relationships between CT-defined emphysema, oncogene status and prognosis among NSCLC patients. The stratified analysis demonstrated that the group with EGFR mutations/ALK rearrangements who did not have CT-defined emphysema displayed the highest OS rate, whereas the EGFR/ALK wild-type group who had CT-defined emphysema showed the poorest survival. In patients who are driver oncogene positive, tyrosine kinase inhibitor therapy could abrogate the risks of CT-defined emphysema on patient survival [37]. In the EGFR/ALK wild-type subgroup, CT-defined emphysema may contribute predominantly to the prognosis. In view of the fact that TNM classification is the leading predictor of prognosis in NSCLC [20], we further stratify patients by tumour stage and find that CT-defined emphysema is a significant established risk factor regardless of tumour stage. This is congruent with the results in previous studies among patients with surgically resected, localised stage lung cancer [10, 38].

To screen out the patients with the worst prognosis, we adapted a new cut-off value (17%) to distinguish between different severities and found that CLE with LAA% >17% displayed poorer survival. This result was similar to those of Shiraishi et al. [39], which suggested that the moderate or more severe CLE was associated with higher long-term mortality among patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3 or higher. Therefore, we believed that identifying patients with CLE with LAA% >17% could help clinicians prioritise more intensive surveillance and individualised treatment, including optimisation of medication therapy and nonpharmacological approaches, such as pulmonary rehabilitation and education. However, the mechanistic links on how CT-defined emphysema affects survival in NSCLC have not been elaborated [38, 40].

Our study has several limitations. Firstly, considering the high ratio of alive patients at the end of follow-up in our cohort, there was a relatively high proportion of censored data, which may affect the power of this study. But significant differences were detectable in our results. Secondly, not all individuals were tested for spirometry, so the analysis for airway obstruction was limited to small size subgroups of patients. Finally, even though this prospective cohort study enrolled a relatively large sample size, it was a single-centre study and may have potential biases limiting the generalisability of our results.

In conclusion, CT-defined emphysema is an independent predictor for NSCLC prognosis, and CLE (LAA% >17%) displayed poorer survival. Clinicians should pay more attention to the detrimental impact of CT-defined emphysema on NSCLC patients to ensure early interventions and provide precision management. Moreover, prospective studies are needed to further explore this association.

Supplementary material

Supplementary Material

Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

Supplementary material 00195-2023.SUPPLEMENT

Acknowledgements

We would like to thank Xin Liu from Department of Radiology at Beijing Chao-Yang Hospital for her computed tomography-defined emphysema diagnosis assistance and Shiyan Yan, a statistical expert from International Acupuncture and Moxibustion Innovation Institute of Beijing University of Chinese Medicine, for her help in revising the manuscript.

Footnotes

  • Provenance: Submitted article, peer reviewed.

  • Data availability statement: Data are available upon reasonable request, to be made to the corresponding author.

  • Author contributions: Y. Zhang is the guarantor of this article. Y. Zhang, J. Yi, K. Huang, X. Guo and Y. Zhang participated and conceived the study design. Y. Zhang, J. Yi, D. Sun, Y. Su, Z. Ma, M. Zhu and S. Zhang contributed to the data collection, patients recruited, treated and followed-up. X. Guo contributed to visual and quantitative assessments of CT-defined emphysema. Y. Zhang, J. Yi, D. Sun and Y. Zuo analysed the data. Y. Zhang and J. Yi wrote the first manuscript draft. All the authors reviewed the final version of the manuscript.

  • Support statement: This work was supported by grants from Clinical Research Incubation Project, Beijing Chao-Yang Hospital, Capital Medical University (grant number CYFH202212), and the Reform and Development Program of Being Institute of Respiratory Medicine (grant number Ggyfz202322). The sponsors played no role in the design, conduct, data collection, analysis or interpretation of the study. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Ethics approval: Ethical approval was obtained from the Ethics Committee of the Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China (number 2021-ke-443).

  • Conflict of interest: None declared.

  • Received March 27, 2023.
  • Accepted August 25, 2023.
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

References

  1. ↵
    1. Siegel RL,
    2. Miller KD,
    3. Fuchs HE, et al.
    Cancer statistics, 2022. CA Cancer J Clin 2022; 72: 7–33. doi:10.3322/caac.21708
    OpenUrlCrossRefPubMed
  2. ↵
    1. Travis WD,
    2. Brambilla E,
    3. Noguchi M, et al.
    International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6: 244–285. doi:10.1097/JTO.0b013e318206a221
    OpenUrlCrossRefPubMed
  3. ↵
    1. Yong PC,
    2. Sigel K,
    3. de-Torres JP, et al.
    The effect of radiographic emphysema in assessing lung cancer risk. Thorax 2019; 74: 858–864. doi:10.1136/thoraxjnl-2018-212457
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Yang X,
    2. Wisselink HJ,
    3. Vliegenthart R, et al.
    Association between chest CT-defined emphysema and lung cancer: a systematic review and meta-analysis. Radiology 2022; 304: 322–330. doi:10.1148/radiol.212904
    OpenUrl
  5. ↵
    1. Mouronte-Roibás C,
    2. Leiro-Fernández V,
    3. Ruano-Raviña A, et al.
    Chronic obstructive pulmonary disease in lung cancer patients: prevalence, underdiagnosis, and clinical characterization. Respiration 2018; 95: 414–421. doi:10.1159/000487243
    OpenUrlPubMed
    1. Gao YH,
    2. Guan WJ,
    3. Liu Q, et al.
    Impact of COPD and emphysema on survival of patients with lung cancer: a meta-analysis of observational studies. Respirology 2016; 21: 269–279. doi:10.1111/resp.12661
    OpenUrlCrossRef
  7. ↵
    1. Kumagai S,
    2. Marumo S,
    3. Yamanashi K, et al.
    Prognostic significance of combined pulmonary fibrosis and emphysema in patients with resected non-small-cell lung cancer: a retrospective cohort study. Eur J Cardiothorac Surg 2014; 46: e113–e119. doi:10.1093/ejcts/ezu384
    OpenUrlCrossRefPubMed
  8. ↵
    1. Mina N,
    2. Soubani AO,
    3. Cote ML, et al.
    The relationship between chronic obstructive pulmonary disease and lung cancer in African American patients. Clin Lung Cancer 2012; 13: 149–156. doi:10.1016/j.cllc.2011.09.006
    OpenUrlCrossRefPubMed
  9. ↵
    1. Yasuura Y,
    2. Terada Y,
    3. Mizuno K, et al.
    Quantitative severity of emphysema is related to the prognostic outcome of early-stage lung cancer. Eur J Cardiothorac Surg 2022; 62: ezac499. doi:10.1093/ejcts/ezac499
    OpenUrl
  10. ↵
    1. Ueda K,
    2. Jinbo M,
    3. Li TS, et al.
    Computed tomography-diagnosed emphysema, not airway obstruction, is associated with the prognostic outcome of early-stage lung cancer. Clin Cancer Res 2006; 12: 6730–6736. doi:10.1158/1078-0432.CCR-06-1196
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Daly ME,
    2. Singh N,
    3. Ismaila N, et al.
    Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline. J Clin Oncol 2022; 40: 1356–1384. doi:10.1200/JCO.21.02528
    OpenUrlCrossRefPubMed
  12. ↵
    1. Ettinger DS,
    2. Wood DE,
    3. Aisner DL, et al.
    Non-small cell lung cancer, Version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2022; 20: 497–530. doi:10.6004/jnccn.2022.0025
    OpenUrlCrossRefPubMed
  13. ↵
    1. Liu Q,
    2. Huang Q,
    3. Yu Z, et al.
    Clinical characteristics of non-small cell lung cancer patients with EGFR mutations and ALK&ROS1 fusions. Clin Respir J 2022; 16: 216–225. doi:10.1111/crj.13472
    OpenUrl
  14. ↵
    1. Yang X,
    2. Liu M,
    3. Ren Y, et al.
    Using contrast-enhanced CT and non-contrast-enhanced CT to predict EGFR mutation status in NSCLC patients: a radiomics nomogram analysis. Eur Radiol 2022; 32: 2693–2703. doi:10.1007/s00330-021-08366-y
    OpenUrl
  15. ↵
    1. Liu Y,
    2. Kim J,
    3. Qu F, et al.
    CT Features associated with epidermal growth factor receptor mutation status in patients with lung adenocarcinoma. Radiology 2016; 280: 271–280. doi:10.1148/radiol.2016151455
    OpenUrlPubMed
  16. ↵
    1. Rizzo S,
    2. Petrella F,
    3. Buscarino V, et al.
    CT Radiogenomic characterization of EGFR, K-RAS, and ALK mutations in non-small cell lung cancer. Eur Radiol 2016; 26: 32–42. doi:10.1007/s00330-015-3814-0
    OpenUrl
  17. ↵
    1. Dou F,
    2. Zhang Y,
    3. Yi J, et al.
    Association of ALK rearrangement and risk of venous thromboembolism in patients with non-small cell lung cancer: a prospective cohort study. Thromb Res 2020; 186: 36–41. doi:10.1016/j.thromres.2019.12.009
    OpenUrl
  18. ↵
    1. Li J,
    2. Yi J,
    3. Hua L, et al.
    Development and validation of a predictive score for venous thromboembolism in newly diagnosed non-small cell lung cancer. Thromb Res 2021; 208: 45–51. doi:10.1016/j.thromres.2021.10.013
    OpenUrl
  19. ↵
    1. Singh D,
    2. Agusti A,
    3. Anzueto A, et al.
    Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Respir J 2019; 53: 1900164. doi:10.1183/13993003.00164-2019
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Goldstraw P,
    2. Chansky K,
    3. Crowley J, et al.
    The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016; 11: 39–51. doi:10.1016/j.jtho.2015.09.009
    OpenUrlCrossRefPubMed
  21. ↵
    1. Dou F,
    2. Li H,
    3. Zhu M, et al.
    Association between oncogenic status and risk of venous thromboembolism in patients with non-small cell lung cancer. Respir Res 2018; 19: 88.
    OpenUrl
  22. ↵
    1. Lynch DA,
    2. Austin JH,
    3. Hogg JC, et al.
    CT-definable subtypes of chronic obstructive pulmonary disease: a statement of the Fleischner society. Radiology 2015; 277: 192–205. doi:10.1148/radiol.2015141579
    OpenUrlCrossRefPubMed
  23. ↵
    1. Shiraishi Y,
    2. Shimada T,
    3. Tanabe N, et al.
    The prevalence and physiological impacts of centrilobular and paraseptal emphysema on computed tomography in smokers with preserved ratio impaired spirometry. ERJ Open Res 2022; 8: 00063-2022. doi:10.1183/23120541.00063-2022
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Labaki WW,
    2. Xia M,
    3. Murray S, et al.
    Quantitative emphysema on low-dose CT imaging of the chest and risk of lung cancer and airflow obstruction: an analysis of the national lung screening trial. Chest 2021; 159: 1812–1820. doi:10.1016/j.chest.2020.12.004
    OpenUrl
  25. ↵
    1. Mascalchi M,
    2. Romei C,
    3. Marzi C, et al.
    Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial. Eur Radiol 2023; 33: 3115–3123. doi:10.1007/s00330-023-09504-4
    OpenUrl
  26. ↵
    1. Gullón JA,
    2. Suárez I,
    3. Medina A, et al.
    Role of emphysema and airway obstruction in prognosis of lung cancer. Lung Cancer 2011; 71: 182–185. doi:10.1016/j.lungcan.2010.05.018
    OpenUrlCrossRefPubMed
  27. ↵
    1. Bishawi M,
    2. Moore W,
    3. Bilfinger T
    . Severity of emphysema predicts location of lung cancer and 5-y survival of patients with stage I non-small cell lung cancer. J Surg Res 2013; 184: 1–5. doi:10.1016/j.jss.2013.05.081
    OpenUrl
  28. ↵
    1. Lynch DA,
    2. Moore CM,
    3. Wilson C, et al.
    CT-based visual classification of emphysema: association with mortality in the COPDGene study. Radiology 2018; 288: 859–866. doi:10.1148/radiol.2018172294
    OpenUrl
  29. ↵
    1. Hansel NN,
    2. Washko GR,
    3. Foreman MG, et al.
    Racial differences in CT phenotypes in COPD. COPD 2013; 10: 20–27. doi:10.3109/15412555.2012.727921
    OpenUrlCrossRef
  30. ↵
    1. Siegfried JM
    . Sex and gender differences in lung cancer and chronic obstructive lung disease. Endocrinology 2022; 163: bqab254. doi:10.1210/endocr/bqab254
    OpenUrl
  31. ↵
    1. Zulueta JJ,
    2. Wisnivesky JP,
    3. Henschke CI, et al.
    Emphysema scores predict death from COPD and lung cancer. Chest 2012; 141: 1216–1223. doi:10.1378/chest.11-0101
    OpenUrlCrossRefPubMed
  32. ↵
    1. Young RP,
    2. Ward RC,
    3. Scott RJ, et al.
    Airflow limitation and mortality during cancer screening in the National Lung Screening Trial: why quantifying airflow limitation matters. Thorax 2023; 78: 690–697. doi:10.1136/thorax-2022-219334
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Mangione CM,
    2. Barry MJ,
    3. Nicholson WK, et al.
    Screening for chronic obstructive pulmonary disease: US preventive services task force reaffirmation recommendation statement. JAMA 2022; 327: 1806–1811. doi:10.1001/jama.2022.5692
    OpenUrl
  34. ↵
    1. Lei J,
    2. Huang K,
    3. Pan J, et al.
    The national COPD screening programme in China: rationale and design. ERJ Open Res 2023; 9: 00597-2022. doi:10.1183/23120541.00597-2022
    OpenUrlAbstract/FREE Full Text
  35. ↵
    1. Lin JS,
    2. Webber EM,
    3. Thomas RG
    . U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. Screening for Chronic Obstructive Pulmonary Disease: A Targeted Evidence Update for the US Preventive Services Task Force. Rockville, MD, Agency for Healthcare Research and Quality (US), 2022.
  36. ↵
    1. Adams SJ,
    2. Stone E,
    3. Baldwin DR, et al.
    Lung cancer screening. Lancet 2023; 401: 390–408. doi:10.1016/S0140-6736(22)01694-4
    OpenUrl
  37. ↵
    1. Owen DH,
    2. Singh N,
    3. Ismaila N, et al.
    Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.2. J Clin Oncol 2023: 41: e10-e20.
  38. ↵
    1. Murakami J,
    2. Ueda K,
    3. Sano F, et al.
    Pulmonary emphysema and tumor microenvironment in primary lung cancer. J Surg Res 2016; 200: 690–697. doi:10.1016/j.jss.2015.09.004
    OpenUrl
  39. ↵
    1. Shiraishi Y,
    2. Tanabe N,
    3. Shimizu K, et al.
    Stronger associations of centrilobular than paraseptal emphysema with longitudinal changes in diffusing capacity and mortality in COPD. Chest 2023; 164: 327–.
    OpenUrl
  40. ↵
    1. Houghton AM
    . Mechanistic links between COPD and lung cancer. Nat Rev Cancer 2013; 13: 233–245. doi:10.1038/nrc3477
    OpenUrlCrossRefPubMed
Back to top
Email
Print
Citation Tools
The association of chest computed tomography-defined visual emphysema and prognosis in patients with nonsmall cell lung cancer
Yixiao Zhang, Jiawen Yi, Dan Sun, Yanping Su, Yingting Zuo, Min Zhu, Shu Zhang, Kewu Huang, Xiaojuan Guo, Yuhui Zhang
ERJ Open Research Nov 2023, 9 (6) 00195-2023; DOI: 10.1183/23120541.00195-2023
del.icio.us logo Technorati logo Twitter logo Connotea logo Facebook logo Mendeley logo
Full Text (PDF)

Jump To

Subjects