|Year : 2022 | Volume
| Issue : 7 | Page : 2041-2048
Computed tomography findings, associated factors, and management of pulmonary nodules in 54,326 healthy individuals
Xinyu Liang1, Yongmei Kong2, Hui Shang3, Mingxin Yang4, Wenjing Lu5, Qingshi Zeng6, Guang Zhang4, Xin Ye7
1 Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, No. 16766, Jingshi Road; Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
2 Shandong Second Provincial General Hospital, Jinan, Shandong Province, China
3 Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province; Department of Radiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, Shandong, China
4 Department of Health Management, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, Shandong Province, China
5 Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, No. 16766, Jingshi Road; Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
6 Department of Radiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, Shandong, China
7 Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, No. 16766, Jingshi Road, Jinan, Shandong Province, China
|Date of Submission||01-Aug-2022|
|Date of Decision||01-Aug-2022|
|Date of Acceptance||28-Oct-2022|
|Date of Web Publication||11-Jan-2023|
Department of Health Management, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, Shandong Province, 250014
Department of Radiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, Shandong Province, 250014
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, No. 16766, Jingshi Road, Jinan, Shandong Province, 250014
Source of Support: None, Conflict of Interest: None
Introduction: To investigate the pulmonary nodules detected by low-dose computed tomography (LDCT), identified factors affecting the size and number of pulmonary nodules (single or multiple), and the pulmonary nodules diagnosed and management as lung cancer in healthy individuals.
Methods: A retrospective analysis was conducted on 54,326 healthy individuals who received chest LDCT screening. According to the results of screening, the detection rates of pulmonary nodules, grouped according to the size and number of pulmonary nodules (single or multiple), and the patients' gender, age, history of smoking, hypertension, and diabetes were statistically analyzed to determine the correlation between each factor and the characteristics of the nodules. The pulmonary nodules in healthy individuals diagnosed with lung cancer were managed with differently protocols.
Results: The detection rate of pulmonary nodules was 38.8% (21,055/54,326). The baseline demographic characteristics of patients with pulmonary nodules were: 58% male and 42% female patients, 25.7% smoking and 74.3% nonsmoking individuals, 40–60 years old accounted for 49%, 54.8% multiple nodules, and 45.2% single nodules, and ≤5-mm size accounted for 80.4%, 6–10 mm for 18.2%, and 11–30 mm for 1.4%. Multiple pulmonary nodules were more common in hypertensive patients. Diabetes is not an independent risk factor for several pulmonary nodules. Of all patients with lung nodules, 26 were diagnosed with lung cancer, accounting for 0.1% of all patients with pulmonary nodules, 0.6% with nodules ≥5 mm, and 2.2% with nodules ≥8 mm, respectively. Twenty-six patients with lung cancer were treated with surgical resection (57.7%), microwave ablation (MWA, 38.5%), and follow-up (3.8%).
Conclusions: LDCT was suitable for large-scale pulmonary nodules screening in healthy individuals, which was helpful for the early detection of suspicious lesions in the lung. In addition to surgical resection, MWA is an option for early lung cancer treatment.
Keywords: Low-dose computed tomography, lung cancer, microwave ablation, pulmonary nodules
|How to cite this article:|
Liang X, Kong Y, Shang H, Yang M, Lu W, Zeng Q, Zhang G, Ye X. Computed tomography findings, associated factors, and management of pulmonary nodules in 54,326 healthy individuals. J Can Res Ther 2022;18:2041-8
|How to cite this URL:|
Liang X, Kong Y, Shang H, Yang M, Lu W, Zeng Q, Zhang G, Ye X. Computed tomography findings, associated factors, and management of pulmonary nodules in 54,326 healthy individuals. J Can Res Ther [serial online] 2022 [cited 2023 Jan 27];18:2041-8. Available from: https://www.cancerjournal.net/text.asp?2022/18/7/2041/367465
Authors Xinyu Liang, Yongmei Kong and Hui Shang contributed to the paper equally.
| > Introduction|| |
In 2020, about 2.2 million new lung cancer cases were detected worldwide. It was the leading cause of cancer-related deaths, with an estimated 1.8 million deaths. In China, lung cancer has the highest morbidity and mortality. The pathological and clinical stages of lung cancer are closely related to the patient's survival rate. However, early diagnosis and treatment are essential approaches to reducing mortality. In 2011, the National Lung Screening Trial reported that lung cancer mortality in high-risk populations could be reduced by 20% using low-dose computed tomography (LDCT) screening instead of standard chest X-ray. As LDCT screening programs have been widely carried out in recent years, asymptomatic pulmonary nodules have been detected more frequently. The detection rate of pulmonary nodules in China is 20%–80%.,,, In an article on chest computed tomography (CT) screening for lung cancer, the authors used a comprehensive and systematic analysis of 88,497 patients to show a significant reduction in lung cancer-related mortality and an increase in early-stage tumor diagnosis. Pulmonary nodules are generally regarded as an early manifestation of lung cancer, so they have received much attention. However, more than >97% of the pulmonary nodules found by LDCT screening are benign. Lung cancer has a detection rate of only 0.7%–2.3%., A high detection rate may lead to overdiagnosis, overtreatment, waste of medical resources, and higher levels of anxiety in patients.,,,, This study retrospectively analyzed 54,326 healthy individuals who underwent chest LDCT screening. According to the screening results, the detection rates of pulmonary nodules, associated factors, and the pulmonary nodules diagnosed and management as lung cancer in healthy individuals.
| > Materials and Methods|| |
The relevant information on physical examinations of the healthy individuals, who received LDCT screening in the First Affiliated Hospital of Shandong First Medical University, from January 1, 2020, to December 31, 2020, was analyzed. A total of 54,326 subjects were enrolled and included in the study cohort. The subjects of this investigation were mainly school teachers, government staff, enterprise employees, and some urban residents of Jinan city, Shandong province [Table 1]. Criteria for determination of pulmonary nodules in lung-imaging features are manifested as focal and increased hazy opacities in the lung parenchyma, with preservation of the bronchial structures and vascular margins, clear or unclear boundary, a diameter ≤3 cm (round or quasi-circular shadow), single or multiple pulmonary nodules, and without atelectasis, hilus lymph node enlargement, or pleural effusion. Pulmonary nodules were diagnosed by two radiologists with more than five years of experience in radiology.
|Table 1: Baseline demographic characteristics of 21,055 patients with pulmonary nodules|
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Thoracic computed tomography scans
All participants underwent CT scans (uCT 760, United Imaging Healthcare Co., Ltd.). Sixty-four CT scans were performed with the following parameters; 120 kVp, tube current of 100~120 mA, and scan layer thickness of 5 mm. The scans were performed from the tip of the lung to the costal diaphragmatic angle (including both lungs). Deep breathing exercises preceded them to ensure the clarity of CT images. The mediastinal and pulmonary windows were imaged on this basis to obtain 1.25~1.55 mm thin layer reconstruction. At the same time, thin layers of pulmonary nodules were imaged by maximal density projection to understand their surrounding morphology and boundaries, such as the structure of adjacent blood vessels and trachea. In this study, the positive result of the CT examination was at least one noncalcified nodule with a diameter of less than 30 mm on the lung image. At least two experienced radiologists performed image analyses before their clinical data. Through the correlation analysis of CT images and the evaluation of the images by computer-aided detection software, the diagnosis rate of pulmonary nodules can be improved, and missed diagnoses can be avoided.
According to CT examination results, 21,055 patients with pulmonary nodules were divided into groups, including the number of pulmonary nodules (single and multiple) and the size of pulmonary nodules (micronodules, <5 mm diameter; minor nodule, 5–10 mm diameter; nodule, 11–30 mm diameter). The age, sex, body mass index (BMI), smoking history, alcohol consumption, hypertension history, and diabetes history of patients with pulmonary nodules were statistically analyzed using different grouping methods.
SPSS 20.0 statistical software was used to analyze the data, and the classification data were expressed in composition ratio and frequency. Chi square test was used to compare the two groups, and binary logistic regression was used to analyze the factors affecting the size and number of pulmonary nodules. P < 0.05 was considered statistically significant.
| > Results|| |
This study detected pulmonary nodules in 21,055 of 54,326 healthy individuals, with a total detection rate of 38.8%. Pulmonary nodules were detected in 12,194 men (57.9%) and 8,861 women (42.1%) patients. According to the number of nodules, 21,055 patients with pulmonary nodules were classified, among which 9,519 patients with single pulmonary nodule (SPN) accounted for 45.2%, and 11,536 patients with multiple pulmonary nodules (MPN) accounted for 54.8%. The baseline demographic characteristics of 21,055 patients with pulmonary nodules are shown in [Table 1].
During the screening process, 21,055 patients were detected with pulmonary nodules, of which 26 patients were diagnosed with malignant pulmonary tumors, accounting for 0.1% of all patients with pulmonary nodules, 0.6% of 4127 patients with nodules larger than 5 mm, 2.2% of 1208 patients with nodules ≥8 mm. Among them. Among them, 69.2% were female, and 30.8% male patients. Subsolid nodules accounted for 84.6%, and solid nodules accounted for 15.4%. Among the pathological types of lung cancer, 25 patients with adenocarcinoma accounted for 95.8% [42.3% adenocarcinoma in situ (AIS), 53.8% microinvasive adenocarcinoma (MIA)], and one with nonadenocarcinoma accounted for 3.8%. Smoking patients accounted for about 19.2%, and nonsmokers accounted for about 80.8%. In this screening, about 30.8% of lung cancer patients were younger than 50 years old, about 19.2% were 51–60 years old, about 26.9% were 61–70 years old, and about 23.1% were older than 70 years old. In the selection of treatment methods, 15 (57.7%) patients underwent surgical resection, 10 (38.5%) patients underwent microwave ablation (MWA) [Figure 1], and 1 (3.8%) was followed up. It can be concluded that MWA, as a new treatment method, is entirely feasible in treating lung cancer. The detailed information of 26 patients with lung cancer is shown in [Table 2].
|Figure 1: A 70-year-old man with pure ground-glass opacity (GGO) (the upper lift lobe, with the size of 25 × 16 mm) was diagnosed pathologically as microinvasive lung adenocarcinoma (MIA). (a) A pure GGO of the left upper lobe pre-microwave ablation (MWA). (b) Two microwave ablation antennas punctured into the lesion. (c) Immediate postablation. (d) Forty-eight hours postablation showed a fried egg sign or a reverse halo sign. (e) One-month postablation. (f) Six months postablation. (g) Twelve months postablation. (h) Twenty-four months postablation, the lesion involuted into a fibrous scar|
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|Table 2: Detection rate of lung cancer in patients with pulmonary nodules|
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Statistical analysis of pulmonary nodules showed that among the positive patients screened, more male patients were found than female patients (57.9% vs. 42.1%) and were mainly distributed in the 40–60 age group. Pulmonary nodules were more common in nonsmokers (smokers: 19.7% vs. nonsmokers: 80.3%). Patients with only one pulmonary nodule were defined as SPN patients, and patients with ≥2 pulmonary nodules were defined as MPN patients. Age was an independent risk factor for the number of pulmonary nodules. [Table 3] Patients older than 60 years were more likely to have MPN than patients younger than 60 years (risk factor: 1.556, confidence interval: 1.460–1.659, P < 0.001); hypertension was also an independent risk factor for the number of pulmonary nodules, and MPN was more common in hypertensive patients than in nonhypertensive patients (hazard coefficient: 1.486, confidence interval: 1.336–1.654, P < 0.001); diabetes was not an independent risk factor for the number of pulmonary nodules (hazard factor: 1.172; confidence interval: 0.994–1.382; P = 0.058).
|Table 3: Statistical table of patient's baseline characteristics and single/multiple disease information|
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Of the 21,055 patients with pulmonary nodules, 16,923 (80.4%) had micronodules; 3,827 (18.2%) minor nodules, and 305 (1.4%) nodules. Additional subgroup analysis according to the lung nodule size showed that gender, age, smoking, hypertension, and diabetes had statistically significant effects on lung nodule size [p < 0.05, [Table 4]], while BMI and alcohol consumption had no statistically significant effects on lung nodule size [P > 0.05, [Table 4]].
|Table 4: Statistical table of factors affecting the size of pulmonary nodules in lung cancer patients|
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According to the sample size and combined with previous studies,, we divided the nodule size into two groups, with 8 mm as the boundary value, and then converted it into a dichotomous variable for logistic regression analysis. The number of patients with nodule sizes larger than 8 mm was 1,208 (2.2%). Age and sex were independent risk factors for nodule size. In our study, among the patients with nodule diameter greater than 8 mm, 3.6% were less than 30 years old, 9% were 30–40 years old, 16% were 41–50 years old, 27.5% were 50–60 years old, 22.8% were 60–70 years old, and 14.9% were 70–80 years old. According to the statistical analysis, there were more male than female patients with nodules larger than 8 mm, and the detection rate was highest in patients aged 50–60. Patients over 80 years old accounted for 6.2% of cases. This suggests that nodules larger than 8 mm are more common in older patients over 60 (risk factor: 2.147, confidence interval: 1.900–2.427, P < 0.001). The study also found that men were more likely to have greater nodules than women (risk factor: 1.196, confidence interval: 1.046–1.368, P = 0.009).
| > Discussion|| |
There are multiple similar lung cancer screening programs. However, the detection rate of pulmonary nodules varies significantly with lung cancer screening programs in Europe, the United States, Asia, and China. In the International Early Lung Cancer Action Plan (I-ELCAP), 4,186 patients had pulmonary nodules among the 31,567 participants (13.3%). In another UK Lung Cancer Screening (UK), 1,015 of 1,991 patients developed pulmonary nodules, accounting for about 50% of cases. In one study, of 65,374 baseline screenings, noncalcified nodules were identified in 28,279 patients (43.3%). In 2017, Liu Yuping et al. screened 53,202 asymptomatic patients for pulmonary nodules, and the results showed that 35,808 patients were diagnosed with at least one pulmonary nodule, with a detection rate of 67.31%. In our study, the incidence of pulmonary nodules investigated was 38.8%. Swensen and Diederich, reported that the detection rate of pulmonary nodules was 41%–50% when the minimum threshold of pulmonary nodules was set at 3 mm, which was not much different from the detection rate of pulmonary nodules detected by this study. CT scan layer thickness can also be used to explain the difference in incidence. It has been reported that when CT scan layer thickness is set at 5 mm, the detection rate of pulmonary nodules is 13.3%. In the screening of pulmonary nodules, the initial CT scan thickness was set as 5 mm, the mediastinal window and pulmonary window were used for imaging, and thin layer reconstruction images of 1.25–1.55 mm were obtained. Therefore, the detection rate of pulmonary nodules was higher than 5 mm slice thickness scanning. The setting of relevant parameters during CT scanning and the update of CAD may also lead to different detection rates of pulmonary nodules.,,,, On the other hand, in the 2021 study by Lianzhen Huang et al., there were 1,629 patients aged 40–60 years with pulmonary nodules, accounting for 83.1% of cases. This significantly differed from our study's 5,178 patients (24.6%) with pulmonary nodules aged 40–60 years. The large difference between the two may be due to different inclusion criteria.
Our study divided lung nodules into three types according to their size. Among them, micronodules accounted for about 80.4%, about the same percentage of micronodules screened by Huang and others. At the same time, gender was also an important characteristic. In our study, there were more male than female patients with lung nodules (p < 0.05), which was statistically significant and was consistent with the results of some other domestic studies that lung nodules are more common in males., In our study, hypertension was an independent risk factor affecting the number of pulmonary nodules, and hypertensive patients were more common in MPN, similar to Bao AIhua et al. Among all patients with pulmonary nodules, 174 MPN patients showed a history of hypertension, 319 SPN patients, 103 MPN patients without hypertension, and 314 SPN patients. These results showed that patients with a history of hypertension were more prone to MPN. However, the effect of hypertension on pulmonary nodules still needs further exploration. Smoking history, an important feature of lung nodules, has also attracted attention from researchers. In our study, 4,149 patients with pulmonary nodules had a smoking history, accounting for 19.7% of cases. There were 16,906 patients with pulmonary nodules without a smoking history, accounting for 80.3% of cases. This is consistent with recent reports of a gradually increasing incidence of pulmonary nodules in nonsmoking patients. In 2013, Cho et al. analyzed 218 patients with pulmonary nodules, in which 453 ground-glass nodules or ground-glass opacity (GGN or GGO) were found. Among them, 125 (57%) were nonsmokers. Among the 84 smokers (39%), 9 had missing information at follow-up. Overall, 60% of patients with pulmonary nodules in this study were nonsmokers, somewhat different from our study results. However, both studies confirm that most patients with pulmonary nodules were nonsmokers. However, Gould et al. noted that the incidence of pulmonary nodules was higher in smokers than in nonsmokers and that a smoking history was an independent risk factor for pulmonary nodules. Another study suggests that smoking could affect the process of protein transcription and translation and may cause direct damage to the DNA chain, resulting in the malignant transformation of delicate cells and ultimately leading to the generation of pulmonary nodules. Therefore, further studies must confirm the association between pulmonary nodules and smoking.
In our study, 26 patients with lung cancer were screened out of 21,055 patients with pulmonary nodules. Of the 26 patients diagnosed with lung cancer, 15 underwent video-assisted thoracoscopic surgery (VATS), and 10 underwent MWA. VATS treatment is still the primary therapy for GGO-like lung cancer. As a minimally invasive local therapy, MWA has achieved good results and shown certain advantages in treating GGO-like lung cancer.,,, In one study, the authors argued that MWA was performed with good results for patients at high surgical risk or who refused surgery. We also reviewed a retrospective, multicenter study by Yang et al. in which postoperative follow-up confirmed the value of MWA in treating early lung cancer. However, there are still many challenges to overcome for applying thermal ablation for GGO- like lung cancer. To become the first-line therapy for GGOs, a prospective, multicenter, randomized, and controlled study focusing on the effectiveness of MWA for single and multiple pulmonary subsolid nodules is needed.
In conclusion, LDCT was suitable for large-scale lung cancer screening, which was helpful for the early detection of suspicious lung lesions. More attention should be paid to lung cancer screening for patients with pulmonary nodules in men aged ≥40 and nodules ≥8 mm. In addition to surgical resection, MWA is an option for treating early lung cancer.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Shandong Provincial Key Research and Development Program (No. 2019GGX101044), the Natural Science Foundation of Shandong Province (No. ZR2020MF026) and The Provincial Natural Science Foundation of China (No. ZR2020MH294) supported this study.
National Natural Science Foundation of China (NSFC 81901851, 82072028) supported this study.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]