Abstract
Objectives
Although several studies have highlighted the potential prognostic value of computed tomography-measured pulmonary artery enlargement in various respiratory diseases, the long-term outcomes following lung cancer surgery remain unexplored. This study aimed to assess the predictive value of pulmonary artery enlargement for overall survival in patients with completely resected non–small cell lung cancer.
Methods
We retrospectively identified patients with pathological Tis-1cN0M0 non–small cell lung cancer who underwent complete resection between 2013 and 2018 in our hospital. We reviewed the routine preoperative computed tomography images and measured the pulmonary artery diameter at the bifurcation (PA) and the ascending aorta diameter (A) to calculate the PA/A ratio. Based on a PA/A threshold of 0.8, patients were categorized into high- and low-ratio groups, and their overall survival and cumulative incidence of cause-specific deaths were compared after propensity score matching.
Results
Of the 319 included patients, 116 were categorized into the high-ratio group and 203 into the low-ratio group. After propensity score matching, overall survival was significantly worse in the high-ratio group than in the low-ratio group (5-year overall survival: 89.4% vs 96.2%; P = .006). The high-ratio group had a significantly higher incidence of death not related to lung cancer than the low-ratio group (P = .01).
Conclusions
In patients with resected early-stage non–small cell lung cancer, those with preoperatively pulmonary artery enlargement had a poorer overall survival than those without, possibly attributed to a higher non-lung cancer-related death incidence. Measuring the preoperative PA/A ratio might be a useful tool for risk stratification, and selecting sublobar resection for these patients could improve the long-term prognosis.
Key Words: non–small cell lung cancer, surgery, pulmonary artery, pulmonary hypertension, computed tomography, prognosis
Graphical Abstract
Measurement of the ratio of pulmonary artery diameter to ascending aorta diameter.
Central Message.
CT-measured pulmonary artery enlargement may become a prognostic factor for postoperative patients with early-stage NSCLC, especially influencing death that is not related to lung cancer.
Perspective.
This novel, easy method for measuring pulmonary arteries on preoperative CT scans may improve surgical risk assessment before lung resection by identifying pulmonary hypertension underestimated by conventional methods, such as echocardiography. If independently validated, it might enable postoperative risk stratification of non-lung cancer disease and allow choosing the appropriate surgical procedure.
Complete surgical resection is the standard treatment for early-stage non–small cell lung cancer (NSCLC).1 However, most patients with lung cancer who undergo pulmonary resection have many risk factors, such as older age, smoking, and multiple comorbidities.2 Preoperative assessments, especially cardiopulmonary function tests, are important in this patient population.3
Pulmonary hypertension (PH) is generally known as a prognostic factor for outcomes of non-cardiac surgery, and patients with PH have a higher risk of postoperative complications.4 Although right-sided heart catheterization is the gold standard for diagnosing PH, it is too invasive for routine preoperative assessment. Several studies have reported a relationship between the pulmonary artery (PA) diameter measured on computed tomography (CT) images and mean PA pressure.5,6
Regarding the relationship between PA enlargement and the prognosis of patients with NSCLC, several studies found that PA enlargement is a predictor of postoperative complications.7,8 Eul and colleagues9 reported that a ratio of PA diameter to ascending aorta diameter (PA/A) >1 is associated with reduced progression-free survival and overall survival (OS). However, the studies about postoperative complications assessed only short-term prognosis, and the one reported by Eul and colleagues9 included all-stage NSCLC, which is greatly affected by lung cancer-related death. Few studies have reported the association between PA enlargement and long-term postoperative prognosis. We hypothesized that the preoperative PA/A ratio could be used to determine the long-term prognosis in patients with resected early-stage NSCLC. In this study, we retrospectively investigated the relationship between the PA/A ratio and OS or competing causes of death in patients with completely resected pathologic stage 0-IA3 NSCLC.
Patients and Methods
Ethical Statement
The study protocol complied with the Declaration of Helsinki and was approved on March 25, 2024, by the Clinical Research Area Ethics Committee of the Hyogo Cancer Center (registration No. G-396). Because this was an observational study, the need for written informed consent was waived by the institutional review board. The trial was registered in the UMIN Clinical Trials Registry (UMIN000054414).
Study Design and Patient Selection
The records of patients who underwent complete resection for pathological Tis-1cN0M0 NSCLC between January 2013 and December 2018 at Hyogo Cancer Center were reviewed. Patients receiving induction therapy, those with previous lung resection, those with simultaneous or metachronous cancers within 5 years, and those having aortic aneurysms were excluded. The required sample size was estimated based on a 5-year OS of 80% in the control group and a 10% to 15% lower OS in the group with high PA/A ratios, 80% power, and an alpha value of 0.05 (2-sided). Ultimately, the target sample size of the group with the lower number had to be at least 100 patients because we planned to perform 1:1 propensity score matching.
Surgical Procedure
Pulmonary resection was performed using video-assisted thoracic surgery (VATS) or thoracotomy. Standard complete VATS was conducted using 4 port incisions, with a maximum size of 3.0 to 4.0 cm. Hybrid VATS was performed with one camera port in the eighth or ninth intercostal space and an access minithoracotomy incision in the fourth or fifth intercostal space without cutting any ribs. Cases in which the incision was longer than 8.0 cm or where rib resection was performed were defined as thoracotomies.
Patient Characterization
Clinical and laboratory data were collected from medical records at Hyogo Cancer Center. All patients underwent chest CT scans. The presence of interstitial changes was defined on preoperative CT images as a usual interstitial pneumonia pattern or a possible usual interstitial pneumonia pattern. PH was assessed by transthoracic echocardiography in limited patients. It was defined as a peak tricuspid regurgitation (TR) velocity >2.8 m/second in echocardiography.10 Charlson Comorbidity Index score was used to assess comorbidities. Cardiovascular diseases include coronary heart, cerebrovascular, peripheral arterial, and aortic arterial diseases. Pathological tumor stages were classified according to the Union for International Cancer Control (UICC) classification, eighth edition. Complications within 30 days were recorded if they required treatment (grades II-V in the Clavien-Dindo classification). OS was defined as the period from the date of surgery to death from any cause. To assess tumor recurrence and determine survival, observational follow-up was continued for at least 5 years. During the first 2 years after the surgical intervention, systemic and local examinations were performed every 6 months. From 3 to 5 years postoperatively, these examinations were performed annually.
Measurement of the PA/A Ratio
The primary PA diameter at the PA bifurcation level was measured using the preoperative axial CT scans. Next, the diameter of the ascending aorta was measured at the same slice level as that of the PA measurements. According to the results of a previous report,11 the primary PA and ascending A diameters were measured at the bifurcation of the PA because this level is obvious on axial CT images in most patients and has a small error margin for diameter measurements (Figure 1). After calculating the ratio of the 2 diameters (PA/A), patients were categorized into high- and low-ratio groups with a cutoff value, which is described below.
Figure 1.
Measurements of pulmonary artery (PA) and aorta (A) diameters. On axial chest computed tomography (CT) images, the main PA was measured at the level of the PA bifurcation, and the ascending aorta diameter was measured in the same CT slice. Red arrowheads indicate the branching points of the right and left PAs from the main PA, and black arrows indicate the PA and A diameters for the calculation of the ratio of PA diameter to ascending A diameter.
Statistical Analysis
Baseline data were expressed as medians and percentages for continuous and categorical variables, respectively. Continuous variables were compared using the 2-sided Wilcoxon rank sum test, and categorical variables were analyzed using the χ2 test.
A multivariable-adjusted Cox proportional hazards modeling was used to describe the OS. These models included 4 relevant variables (age, sex, pathologic stage, and PA/A ratio). To determine the appropriate cutoff value of the PA/A ratio, we depicted the restricted cubic spline of the adjusted relative hazard.
Propensity score matching was used to create 2 well-balanced groups of patients with high and low PA/A ratios. Propensity scores were calculated using logistic regression analysis. The covariates included in this model were age, sex, pathological stage, type of surgery (lobar or sublobar), operative approach (open or VATS), forced expiratory volume in 1 second, and the presence of interstitial changes. Matching was performed in a 1:1 ratio with a caliper distance of 0.1. Balance was assessed after matching using standardized differences with a threshold of 0.1.
Kaplan-Meier analyses were then performed on the propensity-matched data to assess the 5-year survival rates in both groups. The cumulative incidences of lung cancer-related deaths and competing causes of death were compared between the 2 groups using the Gray method. Furthermore, the associated hazard ratios and 95% CI were estimated using the Fine-Gray subdistribution hazard model. All statistical analyses were performed using the R software (R Foundation for Statistical Computing).
Results
In total, 600 patients underwent complete resection of pathological Tis-1cN0M0 NSCLC between January 2013 and December 2018. An additional 22 patients were excluded because the pathologic tumor sizes were not classified according to the UICC staging system, eighth edition. Among the 600 patients, 319 were eligible, after excluding those with simultaneous or metachronous cancers and those with a history of thoracic surgery (Figure E1). The number of patients who underwent echocardiography as a preoperative assessment was 155.
Figure E1.
Flowchart of the study cohort selection. aNumbers do not add up because patients have a history of lung resection due to lung cancer. NSCLC, Non–small cell lung cancer; PA/A, ratio of pulmonary artery diameter to ascending aorta diameter; FEV1, forced expiratory volume in 1 second.
The result of the multivariable analysis is shown in Figure 2. PA/A ratio (hazard ratio, 63.8; 95% CI, 6.0-676.0; P < .001) was the independent predictor of OS, as well as age and sex. Figure E2 represents the restricted cubic spline of the adjusted relative hazard. The trend of this curve slightly changed from 0.7 to 0.8, meaning an increase in relative hazard. Therefore, we set the PA/A cutoff value at 0.8.
Figure 2.
Forest plot for multivariable analysis of overall survival. HR, Hazard ratio; PA/A ratio, ratio of pulmonary artery diameter to ascending aorta diameter; pStage, pathologic stage.
Figure E2.
Restricted cubic spline of the adjusted relative hazard. PA/A, Ratio of pulmonary artery diameter to ascending aorta diameter.
We categorized the patients into high- and low-ratio groups using this cutoff value of 0.8. Of the 319 patients, 116 were categorized into the high-ratio group (PA/A >0.8) and 203 into the low-ratio group (PA/A ≤0.8) (Figure E1). Table 1 summarizes the clinical characteristics of patients before and after propensity score matching. Propensity score matching created 2 matched groups of 106 patients each. All relevant variables except for the pathological stage (standardized mean difference = 0.12) were confirmed to be well matched. In the propensity score-matched cohort, the median follow-up period was 68.0 months in the high-ratio group and 71.4 months in the low-ratio group (P = .76). OS was significantly worse in the high-ratio group than in the low-ratio group (5-year OS: 89.4% vs 96.2%; P = .006) (Figure 3). Sensitivity analyses of OS in unmatched cohorts resulted in similar findings (Figure E3).
Table 1.
Clinicopathological characteristics before and after propensity score matching
| Characteristic | Before propensity score matching |
After propensity score matching |
||||||
|---|---|---|---|---|---|---|---|---|
| PA/A ≤0.8 (n = 203) | PA/A >0.8 (n = 116) | P value | SMD | PA/A ≤0.8 (n = 106) | PA/A >0.8 (n = 106) | P value | SMD | |
| Median age (y) | 68.0 (63.0, 74.0) | 68.0 (62.0, 73.3) | .51 | 0.11 | 68.0 (62.0, 73.8) | 68.0 (62.0, 73.0) | .92 | 0.02 |
| Sex | .92 | 0.02 | .78 | 0.06 | ||||
| Male | 104 (51.2) | 58 (50.0) | 48 (45.3) | 51 (48.1) | ||||
| Female | 99 (48.8) | 58 (50.0) | 58 (54.7) | 55 (51.9) | ||||
| Pathologic stage | .23 | 0.24 | .86 | 0.12 | ||||
| 0 | 21 (10.3) | 8 (6.9) | 5 (4.7) | 8 (7.5) | ||||
| IA1 | 48 (23.6) | 31 (26.7) | 31 (29.2) | 29 (27.4) | ||||
| IA2 | 86 (42.4) | 40 (34.5) | 40 (37.7) | 39 (36.8) | ||||
| IA3 | 48 (23.6) | 37 (31.9) | 30 (28.3) | 30 (28.3) | ||||
| Type of surgery | .43 | 0.11 | >.99 | 0.02 | ||||
| Lobar resection | 148 (72.9) | 79 (68.1) | 75 (70.8) | 74 (69.8) | ||||
| Sublobar resection | 55 (27.1) | 37 (31.9) | 31 (29.2) | 32 (30.2) | ||||
| Operative approach | .68 | 0.07 | >.99 | 0.02 | ||||
| Thoracotomy | 42 (20.7) | 21 (18.1) | 18 (17.0) | 19 (17.9) | ||||
| VATS | 161 (79.3) | 95 (81.9) | 88 (83.0) | 87 (82.1) | ||||
| FEV1 | 2.2 (1.9-2.6) | 2.2 (1.8-2.5) | .43 | 0.09 | 2.2 (1.8-2.6) | 2.2 (1.8-2.5) | .81 | 0.03 |
| Presence of interstitial changes | .01 | 0.30 | >.99 | <0.01 | ||||
| Yes | 0 (0.0) | 5 (4.3) | 0 (0.0) | 0 (0.0) | ||||
| No | 203 (100.0) | 111 (95.7) | 106 (100.0) | 106 (100.0) | ||||
| Charlson Comorbidity Index score | .79 | 0.12 | ||||||
| 0 | 154 (75.9) | 83 (71.6) | ||||||
| 1 | 38 (18.7) | 24 (20.7) | ||||||
| 2 | 9 (4.4) | 7 (6.0) | ||||||
| 3 | 2 (1.0) | 2 (1.7) | ||||||
| Cardiovascular diseases | .91 | 0.03 | ||||||
| Yes | 42 (20.7) | 15 (12.9) | ||||||
| No | 161 (79.3) | 101 (87.1) | ||||||
| PH detected by echocardiography | NA | NA | ||||||
| Yes | 1 (0.5) | 2 (1.7) | ||||||
| No | 89 (43.8) | 63 (54.3) | ||||||
| Did not undergo echocardiography | 113 (55.7) | 51 (44.0) | ||||||
| %DLCO | NA | NA | ||||||
| ≤35% | 0 (0.0) | 1 (0.9) | ||||||
| >35%, ≤55% | 1 (0.5) | 1 (0.9) | ||||||
| >55% | 5 (2.5) | 1 (0.9) | ||||||
| Did not measure DLCO | 197 (97.0) | 113 (97.4) | ||||||
| BMI | 22.3 (20.5-24.8) | 23.2 (21.0-25.9) | .02 | 0.31 | ||||
| SAS | .74 | 0.14 | ||||||
| Yes | 2 (1.0) | 0 (0) | ||||||
| No | 201 (99.0) | 116 (100.0) | ||||||
Values are presented as n (%) or median (interquartile range). PA/A, Ratio of pulmonary artery diameter to ascending aorta diameter; SMD, standardized mean difference; VATS, video-assisted thoracic surgery; FEV1, forced expiratory volume in 1 second; PH, pulmonary hypertension; NA, not applicable; DLCO, diffusion capacity of lung for carbon monoxide; BMI, body mass index; SAS, sleep apnea syndrome.
Figure 3.
Overall survival (OS) in patients with complete tumor resection. Propensity score-matched analysis of patients with a ratio of pulmonary artery diameter to ascending aorta diameter (PA/A ratio) >0.8 versus those with a PA/A ≤0.8.
Figure E3.
Overall survival (OS) in patients with complete tumor resection. Unmatched cohorts of patients with a PA/A > 0.8 versus those with a PA/A ≤ 0.8. PA/A, Ratio of pulmonary artery diameter to ascending aorta diameter.
In the high-ratio group, 6 lung cancer-related deaths and 14 other causes of death were recorded, whereas in the low-ratio group, 3 lung cancer-related deaths and 3 other causes of death occurred. Although the cumulative incidence of lung cancer did not differ between the 2 study groups (P = .3), the incidence of competing causes of death was significantly higher in the high-ratio group than in the low-ratio group (P = .01) (Figure 4). The detailed causes of death are listed in Table 2. Although 5 patients with interstitial changes were in the unmatched overall cohort, all were categorized into the PA/A high-ratio group. Therefore, they were excluded from the matched cohort analysis. All 5 patients died within the observational period: 2 from lung cancer, 2 from acute exacerbation of interstitial pneumonia, and 1 from unknown cause.
Figure 4.
Cumulative incidence rates of deaths from lung cancer and those from competing causes. Propensity score-matched analysis of patients with a ratio of pulmonary artery diameter to ascending aorta diameter (PA/A ratio) >0.8 versus those with a PA/A ≤0.8. HR, Hazard ratio; nDeaths, number of deaths; PA/A, ratio of pulmonary artery diameter to ascending aorta diameter.
Table 2.
Detailed causes of non-lung cancer-related deaths
| Postoperative complication | PA/A ≤0.8 (n = 106) | PA/A >0.8 (n = 106) | P value |
|---|---|---|---|
| Non-lung cancer-related deaths | 3 (2.8) | 14 (13.2) | .01 |
| Pneumonia | 0 | 5 | |
| Metachronous cancers | 1 | 2 | |
| Cardiovascular events | 1 | 2 | |
| Cerebral stroke | 0 | 2 | |
| Sudden death | 0 | 2 | |
| Hepatic failure | 0 | 1 | |
| Unknown | 1 | 0 |
Values are presented as n (%) or n. PA/A, Ratio of pulmonary artery diameter to ascending aorta diameter.
Regarding treatments after tumor recurrence, 24 patients experienced lung cancer recurrence (12 in each high- and low-ratio group) in the overall cohort. The proportion of patients who underwent treatment, except for palliative radiation therapy, was not significantly different between the high- and low-ratio groups (66.7% vs 83.3%, respectively; P = .64). Additionally, the incidence of postoperative complications was not significantly different between the 2 groups (9.5% vs 9.9%, respectively; P > .99) (Table 3). The 30- and 90-day mortality rates were 0% in both groups.
Table 3.
Incidence of postoperative complications
| Postoperative complication | PA/A ≤0.8 (n = 203) | PA/A >0.8(n = 116) | P value |
|---|---|---|---|
| Any complications∗ | 20 (9.9)† | 11 (9.5)† | >.99 |
| Cardiopulmonary complications‡ | 7 (3.4) | 8 (6.9) | .26 |
| Air leakage requiring intervention | 10 | 3 | |
| Pneumonia | 4 | 3 | |
| Hypoxemia requiring home oxygen therapy | 2 | 2 | |
| Empyema | 2 | 1 | |
| Arrhythmia | 1 | 2 | |
| Recurrent laryngeal nerve palsy | 2 | 0 | |
| Chylothorax | 1 | 1 | |
| Postoperative bleeding | 1 | 1 | |
| Anaphylaxis | 1 | 0 | |
| Atelectasis | 1 | 0 | |
| Surgical site infection | 0 | 1 |
Values are presented as n or n (%). PA/A, Ratio of pulmonary artery diameter to ascending aorta diameter.
Clavien-Dindo grades II through V.
Numbers do not add up because patients can have more than 1 complication.
Cardiopulmonary complications include 1 or more of the following: pneumonia, empyema, atelectasis requiring bronchoscopic intervention, hypoxemia requiring home oxygen therapy, and arrhythmia requiring medication. Complications related to surgical techniques were excluded.
Of the 155 patients who underwent echocardiography as a preoperative assessment, 3 were identified as having PH. We reviewed the transthoracic echocardiography and reassessed other findings suggesting PH in these patients. The results are shown in Table E1. One of the 3 patients was categorized as having a PA/A ≤0.8 regardless of peak TR velocity >2.8 m/second, and the patient did not represent right atrial area enlargement in contrast to other patients with a PA/A >0.8.
Discussion
In this study, we demonstrated that OS was significantly shorter in patients with a PA/A >0.8 than in those with a PA/A ≤0.8. Likewise, the cumulative incidence of nonlung cancer-related deaths was higher in patients with a PA/A >0.8 than in those with a PA/A ≤0.8 after propensity score matching. See Figure 5 for a graphical abstract of the study.
Figure 5.
NSCLC, Non-small cell lung cancer; PA/A, ratio of pulmonary artery diameter to ascending aorta diameter; CT, computed tomography; OS, overall survival; nDeaths, number of deaths; HR, hazard ratio.
This study shows that PA enlargement on CT images was associated with poorer long-term outcomes in postoperative patients with early-stage NSCLC. Several reports have demonstrated a relationship between a high PA/A ratio and poor prognosis of various respiratory diseases. A higher PA/A ratio is associated with more severe exacerbation of chronic obstructive pulmonary disease,11 higher 90-day mortality from fibrotic interstitial lung disease,12 and higher rates of postoperative cardiopulmonary complications.7,8 Regarding the long-term prognosis of lung cancer, Eul and colleagues9 showed that a PA/A ratio >1 predicts poor OS and progression-free survival. Although their study has been conducted in heterogeneous populations and included patients with stage IV diseases or small cell lung cancer, we observed poor prognosis in patients with early-stage postoperative NSCLC. Although previous reports have demonstrated that PA enlargement is associated with postoperative complications and short-term mortality,7,8 our results showed no significant differences in postoperative complications. The reason for these contradictory short-term outcomes is unclear; however, the long-term influence of the PA/A ratio may be more significant than the short-term influence.
Regarding the cumulative incidence of cause-specific deaths, non-lung cancer-related deaths were significantly more frequent in patients with a PA/A >0.8 than in those with a PA/A ≤0.8 in the current study. Moreover, many of the events occurred after 5 years. This study included only patients with stage 0 to IA3 NSCLC, which certainly resulted in a small effect on lung cancer-related deaths. In general, the estimated 5-year overall mortality of patients with stage IA NSCLC is reportedly only 17% after curative-intent R0 resection.13 Furthermore, non-lung cancer-specific mortality is a significant competing event for lung cancer-specific mortality in patients with stage I NSCLC.14 Most studies assess the 5-year OS as a primary outcome and we tend to be concerned with the 5-year prognosis to determine the best treatment for each patient. However, considering these facts, we must assess the long-term effects on the patient's residual life as well as NSCLC curability. The randomized controlled trial JCOG0802 showed long OS with segmentectomy despite short relapse-free survival in patients with small-sized peripheral NSCLC.15 Pulmonary resection causes a loss of the PA bed, and several studies have reported the deterioration of both right ventricular pump performance and PA pressure after major pulmonary resection.16,17 Although no report has compared the right ventricular dysfunction between lobectomy and segmentectomy, it is more pronounced in pneumonectomy than in lobectomy.18 Therefore, selecting sublobar resection for patients with a high PA/A ratio could reduce non-lung cancer-specific deaths and improve the long-term prognosis for those with early-stage NSCLC.
In this study, we set the cutoff value for the PA/A ratio at 0.8. Previous studies defined PA enlargement as a PA/A ratio >1 based on a report by Ng and colleagues.19 demonstrating a linear correlation between PA/A ratio and mean PA pressure. Truong and colleagues20 proposed a 4-tier classification suggesting underlying PH with a cutoff value of 0.9, 1.0, and 1.1, which were determined by calculating the sensitivity and specificity to diagnose PH. However, in their study, the mean PA pressure of 25 mm Hg was used for the PH definition. The definition of PH has changed from 25 mm Hg to 20 mm Hg,21 and a mean PA pressure of 20 mm Hg corresponded to a PA/A ratio of 0.8 in a linear regression reported by Iyer and colleagues.5 Regarding the previous reports demonstrating the relationship between various respiratory diseases and their prognosis, a cutoff value of 1 was used to categorize the high-risk patients.5,9,12 In our study cohort, only a few patients with PA/A >1 (16 patients [5.0%]) were available, similar to the other studies on surgical patients.7,8 As we mentioned above, the right ventricular burden would deteriorate after lung resection; therefore, we believe that setting a more severe cutoff point than non-surgical studies would be reasonable.
It is widely recognized that right ventricular enlargement is observed in patients with PH, and it is believed to be due to vascular remodeling. Although the mechanism of the remodeling process is under investigation, various signaling pathways to proliferate the PA smooth muscle and endothelial cells are advocated.22 We assume the increase in the PA/A ratio reflects the enlargement of the right ventricle caused by chronic PH. In our surgical patients’ study cohort, most patients with clinically suspected PH were probably excluded; only 3 patients had signs indicative of PH. This suggests that our estimated criterion of a PA/A ratio >0.8 facilitates detecting an underlying PH, which is underestimated by conventional preoperative assessments such as echocardiography-measured TR velocity. Of the three patients with peak TR velocity >2.8 m/second, 2 had a PA/A >0.8 and 1 had a PA/A ≤0.8. Furthermore, the 1 patient with a PA/A ≤0.8 did not represent right atrial area enlargement compared with other patients with a PA/A >0.8. This supports our hypothesis that the PA enlargement reflects right ventricle enlargement.
This study has some limitations. First, because it was a retrospective study, we could not consider unknown confounding factors. Second, we could not analyze the relationship between the PA/A ratio and PA pressure because right-sided heart catheterization was not performed on any patient in this study. Third, although we evaluated PH using echocardiography, echocardiography was undergone only in a limited subpopulation of patients. Moreover, we only measured TR velocity as a PH parameter. Finally, the PA/A ratio data are not robust because slight measurement errors may occur among investigators. Further investigations on the PA/A ratio in large-scale prospective studies are needed to validate these results and clarify which patients should or should not undergo lobar resection in the context of surgery risk management.
Conclusions
We demonstrated that OS was significantly shorter in patients with a PA/A ratio >0.8 than in those with a PA/A ratio ≤0.8, possibly due to a higher non-lung cancer-related death incidence. Measuring the preoperative PA/A ratio might be a useful tool for risk stratification of nonlung cancer disease. Therefore, selecting sublobar resection for patients with a high PA/A ratio could reduce non-lung cancer-specific deaths and improve the long-term prognosis for those with early-stage NSCLC.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflict of interest.
Footnotes
Institutional Review Board Approval: The study protocol complied with the Declaration of Helsinki and was approved on March 25, 2024, by the Clinical Research Area Ethics Committee of the Hyogo Cancer Center (registration No.: G-396).
Informed consent statement: As this was an observational study, the need for written informed consent was waived by the Institutional Review Board.
Appendix E1
Table E1.
Detailed transthoracic echocardiography findings in three patients with peak TR velocity of >2.8 m/s
| Case | Age (y)/sex | PA/A | Peak TR velocity (m/s)∗ | Enlarged RV | D-shaped LV | Estimated systolic RA pressure (mm Hg) | Right ventricular fractional area change (%)† | Right atrial area (cm2)‡ | Presence of pericardial effusion |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 80 F | 0.76 | 3.0 | No | No | 3 | 38.9 | 13.5 | No |
| 2 | 75 M | 1.09 | 3.3 | No | No | 3 | 51.8 | 19.1 | No |
| 3 | 72 F | 0.83 | 2.9 | No | No | 3 | Retained | Enlarged | No |
PA/A, Ratio of pulmonary artery diameter to ascending aorta diameter; TR, tricuspid regurgitation; RV, right ventricle; LV, left ventricle; RA, right atrium; F, female; M, male.
>2.8 m/second is considered to be increased.
<35% is considered to be reduced.
>18 cm2 is considered to be enlarged.
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