18F-FDG accumulation in less-affected lung area predicts postoperative interstitial lung disease acute exacerbation in lung cancer: A case control study

doi:10.21203/rs.3.rs-19006/v1

Background: Pneumonectomy for lung cancer with interstitial lung disease (ILD) has been shown to cause postoperative acute exacerbation (AE) of the ILD. The accumulation of ¹⁸F-flurodeoxyglucose (FDG) on normal parenchymal or less-affected lung fields in ¹⁸F-FDG-positron emission tomography (PET)/computed tomography (CT) has been reported to be related to ILD disease activity and prognosis. To determine whether ¹⁸F-FDG accumulation in normal parenchymal or less-affected lung fields on ¹⁸F-FDG-PET/CT can predict postoperative AE of ILD in non-small cell lung cancer (NSCLC) patients with ILD.

Methods: This retrospective study included 36 NSCLC patients with ILD, who underwent ¹⁸F-FDG-PET/CT at 2 institutions before pulmonary surgery. A single volume-of-interest (VOI) was placed to measure the mean standardized uptake value (SUV_mean) in normal or less-affected lung fields at 12 areas on the ventral and dorsal locations of both lungs, in each level of the aortic arch, tracheal bifurcation, and the orifice of the right lower pulmonary vein into the left atrium. The region to which the target VOI was set corresponded to no or minimally increased attenuation on high resolution CT. The SUV_mean was defined as the mean SUV of the target VOI, SUV_{tissue fraction (TF)} as the corrected SUV_mean by using TF and mean computed tomography density (CTD_mean) as the mean attenuation of the corresponding target VOI on HRCT. We performed a phantom study to optimize SUV difference among 2 institutions. The corrected SUV_mean (cSUV_mean) and corrected SUV_TF (cSUV_TF) were calculated based on the phantom study result.

Results: Among 36 NSCLC patients with ILD who underwent pulmonary surgery, 8 patients developed postoperative AE of ILD. The cSUV_mean values in the ventral and dorsal locations at the aortic arch level, and in the ventral location at the tracheal bifurcation level in the group with postoperative AE were higher than in the group without postoperative AE. There was no significant difference in the value of cSUV_TF and CTD_mean between the groups with and without postoperative AE.

Conclusion: ¹⁸F-FDG accumulation in the normal or less-affected lung fields can potentially predict postoperative AE of ILD in NSCLC patients with ILD.

Pulmonology

interstitial lung disease

lung cancer

postoperative acute exacerbation of interstitial lung disease

18F-flurodeoxyglucose positron emission tomography/computed tomography

Interstitial lung disease (ILD) results not only from parenchymal lung diseases of known or unknown etiology, but also in lung regions with both inflammation and fibrotic changes (1, 2). ILDs are recognized as a risk factor for lung cancer (3-5). Since therapy of lung cancer, such as surgery, chemotherapy, and chemoradiotherapy sometimes provoke acute exacerbation (AE) of ILD, treatment should be chosen carefully (6-8). Pneumonectomy poses a risk of postoperative AE for patients with lung cancer-associated ILD and has a reported mortality rate between 33.3% and 100% (9-13). In a retrospective study conducted in Japan, the incidence of postoperative AE and the mortality rate in lung-cancer-associated ILD was 9.3% and high as 43.9%, respectively (13). Moreover, a high Krebs von den Lungen-6 (KL-6) value, male sex, history of AE, preoperative steroid use, and the surgical procedure were identified as possible risk factors for postoperative AE (13).

¹⁸F-flurodeoxyglucose (FDG) positron-emission tomography (PET) has been proven to be useful for the detection and follow-up of neoplastic lesions (14). Recently, several reports have stated that ¹⁸F-FDG accumulation may be related to disease activity in patients with ILDs (15-17). Furthermore, increased ¹⁸F-FDG uptake in apparently normal lung parenchyma on high-resolution computed tomography (HRCT) was observed in patients with idiopathic pulmonary fibrosis (IPF), and was related to the prognosis (18-20). These reports suggested that a high uptake of ¹⁸F-FDG in the less-affected lung parenchyma may be an indicator of the disease activity and progression in ILD.

This retrospective study was conducted to investigate whether ¹⁸F-FDG accumulation in the less-affected lung parenchyma on HRCT can predict postoperative AE in non-small cell lung cancer (NSCLC)-associated ILD.

Patient Selection

In the patient selection process, 388 patients with NSCLC who underwent pulmonary surgery in Shiga University of Medical Science between January 2011 and　December 2016 were initially enrolled. Among them, 38 patients with NSCLC complicated with ILD who underwent ¹⁸F-FDG PET/CT before pulmonary surgery in our hospital or Oumikusatsu Tokushukai Hospital were identified. 2 patients with glucose metabolism abnormalities were excluded. Thus, finally, 36 patients with ILD were included.

To investigate the difference in ¹⁸F-FDG accumulation in the apparently normal or less-affected lung area between NSCLC patients with or without ILD, we additionally included 50 consecutive NSCLC patients without ILD who underwent both ¹⁸F-FDG PET/CT before pulmonary surgery and surgery in our hospital between August 2015 and December 2016.

Available patient characteristics, clinical laboratory data, and pulmonary functional tests, including age, sex, smoking status, Eastern Cooperative Oncology Group (ECOG) performance status, histology of NSCLC, surgical procedure, stage of NSCLC, lactate dehydrogenase, C-reactive protein, krebs von den lungen-6 (KL-6), and surfactant protein-D were obtained from medical records. Whether ILD was associated with NSCLC or not was estimated by chest HRCT underwent within 3 months before pulmonary surgery. Based on HRCT image findings the NSCLC patients with ILD were classified into having the usual interstitial pneumonia (UIP) pattern and non-UIP pattern. The UIP pattern was assigned when abnormal shadows, including subpleural basal predominance, reticular abnormalities, and honeycombing with or without traction bronchiectasis were present and features of an inconsistent UIP pattern were absent, according to the International Consensus Statement of IPF(21). Otherwise, patients were diagnosed as having a non-UIP pattern.

This study was approved by our institutional review board (approved number: 29-190, November 2, 2017). The need to obtain informed patient consent was waived because of the retrospective nature of this research.

Criteria for Postoperative Exacerbation of ILD

The diagnosis of postoperative AE of ILD was based on the definition of the International Working Group Report for AE of IPF (22). The diagnostic criteria were as follows: acute worsening or development of dyspnea, typically of < 1 month duration after pulmonary surgery; new bilateral ground-glass opacity and/or consolidation on computed tomography (CT); deterioration not fully explained by cardiac failure or fluid overload (22).

PET/CT Image Data Acquisition

¹⁸F-FDG PET scanning was performed using a combined PET/CT scanner (Discovery PET/CT 710, General Electronics, Fairfield, CT, USA) in our institution, or a Discovery PET/CT ST (General Electronics) in Oumikusatsu Tokushukai Hospital). All patients were instructed to fast for 5 hours or longer before ¹⁸F-FDG administration. Blood glucose level was measured before ¹⁸F-FDG injection to confirm a level of less than 150 mg/dL (23). Since the blood glucose level influenced ¹⁸F-FDG accumulation in brain (24, 25), patients with unknown blood glucose level were excluded if accumulation of ¹⁸F-FDG in their brains was judged to be insufficient. There were no cases whose blood glucose level before ¹⁸F-FDG-PET imaging exceeded 150 mg/dl. However, among 10 patients for whom blood glucose level values were unavailable, 2 patients were excluded from analysis because of faint ¹⁸F-FDG accumulation demonstrated in the brain. Three-dimensional PET data were acquired from the head to the thigh 60 min after the injection of a dose of 185–330 MBq/kg of ¹⁸F-FDG.

High Resolution CT Image Data Acquisition

All patients underwent enhanced or un-enhanced chest HRCT by 64-row helical mode using 320-row multidetector CT scanners (Aquilion ONE, Canon Medical Systems, Otawara, Tochigi, Japan) or 16-row helical scan mode (Sensation Cardiac, Siemens, Munich, Germany) within 3 months after ¹⁸F-FDG PET/CT. Other scanning parameters were as follows: tube voltage = 120 kVp, tube current; 180–320 mA (for 64-row mode) or 340–400 mA (for 16-row mode), slice thickness = 0.5 mm (for 64-row mode) and 0.75 mm (for 16-row mode), rotation time; 0.5 s (for 64-row mode) or 0.375 s (for 16-row mode); helical pitch; 40 (for 64-row mode) and 15 (for 16-row mode). CT images were reconstructed with 1-mm slice thickness, 1-mm interval, and lung kernel.

Image Analysis

PET images were analyzed on a dedicated workstation (Advantage Workstation, version 2.0; General Electronics, Fairfield, CT, USA). On PET/CT images, a single cubic target volume-of-interest (VOI) of approximately 18 cm³ in volume (26 mm × 26 mm × 26 mm) was carefully placed to include normal-appearing regions while avoiding the mediastinum, chest wall, central bronchus, and blood vessels, in 12 areas (Figure 1): the ventral and dorsal locations in both lungs at each of the 3 predefined levels: aortic arch (AA), tracheal bifurcation (TB), and the orifice of the right lower pulmonary vein into the left atrium (RLPV), while referring to non-increased attenuation on HRCT images. Standardized uptake values (SUVs) were defined as follows: SUV_mean was measured in a target VOI. SUV_maxwas measured as the highest SUV in ILD lesion (18, 19). SUV_{tissue fraction (TF)} was analyzed to adjust for metabolic condition, regardless of differences in the degree of region-based aeration (26, 27). Mean CT density (CTD_meanon PET/CT) as well as SUV_mean was simultaneously obtained. CTD_mean on HRCT were measured using Image J (Version 1.51. National Institutes of Health, Bethesda, ML, USA), by placing an identical-sized VOI at essentially the same location where the VOI was set on PET/CT.

SUV_mean, SUV_TF, SUV_max, and CTD_mean on HRCT were independently assessed by 1 chest physician and 1 thoracic radiologist with 15 and 20 years of experience, respectively, to determine interobserver agreement.

Phantom Study for Adjustment of Measured Values between the Institutions The SUV values measured for images obtained at the 2 institutions were adjusted according to a method described in a previous study (28). Phantom experiments were performed with modification of the dedicated guideline issued by the Japan Nuclear Medicine Society, by using the National Electrical Manufacturers Association (NEMA) body phantom. The NEMA body phantom, with spherical containers of 6 different diameters: 10, 13, 17, 22, 28, and 37 mm, filled with ¹⁸F-FDG, for insertion into different body parts, was scanned for 30 minutes in list-mode. The radioactivity levels were 2.65 kBq/mL for spherical containers filled with ¹⁸F-FDG arranged and 0.66 KBq/mL for background parts, over 60 minutes at the time of data acquisition. SUV_max values of the image slice with the most highly integrated radio-isotope and the 2 antero-posterior neighboring image slices were averaged as the actual SUV_max for the spherical containers. The gauged mean SUV in the phantom background was determined as the mean of the SUVs of 12 ROIs of 37-mm diameter in the image slice with the most highly integrated radio-isotope and its 4 anteroposterior neighboring image slices for the 10-mm spherical container. The calibration factor was determined by dividing the actual SUV_max by the gauged mean SUV of the phantom background to reduce inconsistencies between 2 institutes. This adjustment for inter-institutional variability in SUV values shrunk the range from 0.69-0.89 to 0.74-0.97 when the SUV_max ratio was described as the SUV_max of the one institution to the SUV_max of the control institution. The original measured SUV_max values for both institutions were corrected by multiplication with the calibration factors derived from the phantom studies to minimize inter-institutional SUV variability; these values were defined as cSUV.

Statistical Analysis

Univariate analyses were conducted to identify the difference in geographic data, physiological parameters, and laboratory data between patients with NSCLC with ILD and without ILD, and between the NSCLC patients with and without postoperative exacerbation of ILD. All continuous and categorical variables were analyzed with Wilcoxon’s test and the chi-square test. For locations with difference in cSUV_mean, cSUV_TF, and cSUV_max measured values based on PET/CT between NSCLC patients with and without postoperative exacerbation of ILD, receiver operating characteristic (ROC) curve analysis were performed. Two-sided P values of less than 0.05 were considered statistically significant. The normality of SUV_mean, SUV_TF, and CTD_mean on HRCT measured by the 2 observers was evaluated with the Shapiro–Wilk test. Inter-observer variance was evaluated by Spearman’s correlation coefficient for the measured values. All statistical analyzes were performed using JMP 9.0 software (SAS Institute Inc., Cary, NC, USA).

Patient Characteristics

Table E1 shows the characteristics of the NSCLC patients with ILD and those without. The median age was 73.5 years (range: 68–77 years) in NSCLC patients with ILD and 69 years (range: 63.8–72.3 years) in those without. Most NSCLC patients with ILD were men, with good ECOG performance status, and were smokers. The frequencies of adenocarcinoma and squamous cell carcinoma were higher in NSCLC patients with than in those without ILD. There was no significant difference in the surgical procedure used and stage between the 2 groups. The %VC, the %FVC, the %TLC, the DLco, and the %DLco in NCSLC patients were lower in those with than in those without ILD.

Table 1 shows the characteristics of the NSCLC patients with and without postoperative AE. Eight patients developed postoperative AE. The median duration of postoperative AE was 12 days (range: 7–32 days). The median age was 71 years (range: 66–77.3 years) in NSCLC patients with postoperative AE of ILD and 73.5 years (range: 69.3–77 years) in NSCLC patients without ILD. Most patients with postoperative AE were male, with good ECOG performance status and were smokers. There was no significant difference in histology, surgical procedure, and stage between those with and those without postoperative AE. In terms of interstitial pneumonia classification, 4 (50%) and 12 cases (43%) were diagnosed with UIP in the AE group and the non-AE group, respectively. No significant difference was found in terms of pulmonary function test parameters between the 2 groups, except for a slightly larger value of surfactant protein D in patients with postoperative AE.

Inter-observer Agreement

Values measured by the 2 observers were not all normally distributed. Spearman correlation coefficients for inter-observer differences in measured SUV_mean, SUV_TFranged from 0.86 to 0.97, from 0.80 to 0.92, from (Table E2-E4) respectively. The value in SUV_max of patients with ILD (n=36) was 0.874 (P <0.001). Thus, there were small inter-observer variances.

Comparison of Corrected SUV_mean, Corrected SUV_TF, and CTD_mean on HRCT between NSCLC patients with and without ILD

cSUV_mean was higher in NSCLC patients with than in those without ILD, in all locations except for both locations at the AA level, the ventral location at the TB level, and the ventral location at the RLPV level in the left lung (Table E5). cSUV_TF was higher in all locations in NSCLC patients with than in those without ILD (Table E5). CTD_mean on HRCT was similar between NSCLC patients with and those without ILD at all locations (Table E6).

Comparison of Corrected SUV_mean, Corrected SUV_TF, Corrected SUV_max, and CTD_mean on HRCT between NSCLC patients with and those without postoperative ILD exacerbation

In NSCLC patients with postoperative ILD exacerbation, the value of cSUV_mean in the right ventral and dorsal locations at the AA level, and the right ventral location at the TB level were higher than in those without postoperative AE (P = 0.01, P = 0.02, P = 0.02, respectively) (Table 2). Receiver operating characteristic (ROC) curve analysis at the 3 locations with a greater cSUV_mean for NSCLC patients with AE also showed that the area under curve (AUC) for the right ventral location at the AA level in the right lung was greatest (AUC = 0.82), with an optimal cut-off value of 0.46. This cut-off value yielded a sensitivity of 75.0% and a specificity of 56.8% (Figure E1).

The value of cSUV_TF, cSUV_max, and CT_mean on HRCT showed no significant difference between the NSCLC patients with and those without postoperative AE at any of the locations (Tables 2, 3, E7).

We investigated whether SUV in the less-affected lung parenchyma could predict postoperative AE of ILD in patients with NSCLC and ILD. The SUV_mean in NSCLC patients with postoperative AE of ILD was significantly higher than in those without AE, in several regions. ROC analysis showed that the AUC was greatest in the right ventral location at the AA level. Increased ¹⁸F-FDG uptake in the dorsal and lower lung field has been shown to be associated with a gravitational effect and blood flow increase in some previous studies that used ¹⁸F-FDG PET imaging (29, 30). Since respiratory movement in the lower lung field is generally regarded as larger than in the upper lung field, FDG accumulation tended to be overestimated in ¹⁸F-FDG PET imaging in the lower lung field under free-breathing conditions. In an additional visual evaluation on HRCT before pulmonary surgery, with regard to the laterality of the interstitial lung shadow, the interstitial lung shadow in the group with postoperative AE was predominant in the right lung (P = 0.06). Therefore, while taking into account the factors influencing FDG accumulation, we consider that the higher SUV_mean in the ventral region of the upper lung field in those with postoperative AE than in those without AE is meaningful, and that SUV_mean measurement in normal-appearing ventral regions may be useful to predict postoperative AE.

On the other hand, SUV_TF was not significantly different between NSCLC patients with and those without postoperative AE. This may be because the mean CT value of ¹⁸F-FDG-PET/CT in the right upper and middle lung field was higher in individuals with than in those without postoperative AE of ILD (data not shown). In contrast, the mean CT value of HRCT obtained at peak-inspiration was similar between those with and those without postoperative AE of ILD. Since ¹⁸F-FDG-PET/CT image data were obtained under free breathing conditions, the breathing level could not be kept constant. Data acquisition might sometimes have occurred during the expiratory phase on FDG-PET/CT in some patients. Moreover, the average CT value may be affected by the degree of pulmonary regional collapse as well as the increased blood flow. Therefore, SUV might be overcorrected based on regional CT density, due to the predominant focal collapse in NSCLC patients with postoperative AE of ILD, which could have obscured differences in SUV_TF between NSCLC patients with and those without postoperative AE of ILD. These results paradoxically imply that conventional CT obtained at peak-expiration may be useful for differentiating patients at increased risk of postoperative AE from those not at. As SUV_TF needs to be calculated by measuring the CT value of soft tissue and air (26), more time is required for imaging, which should be addressed as a drawback of SUV_TF calculation.

As in previously reports (18, 19), both SUV_mean and SUV_TF in the less-affected lung fields of NSCLC patients with ILD were significantly higher than in those patients without ILD. These results suggest that accumulation of ¹⁸F-FDG in less-affected lung fields may reflect inflammatory conditions in the pulmonary interstitium, which cannot be visually detected with conventional HRCT. However, the mechanism underlying accumulation of ¹⁸F-FDG in less-affected lung fields has remained incompletely understood. Disorders of the alveolar epithelium, migration of inflammatory cells, and release of inflammatory mediators were involved in the process of lung fibrosis in a bleomycin-hamster model (31). ¹⁸F-FDG migrates into cells via glucose transporter 1 (GLUT-1), which was shown to be expressed in fibrocytes, bronchial epithelial cells, and inflammatory cells (32-34). These mechanisms may contribute to accumulation of ¹⁸F-FDG in ILD. Accumulation of ¹⁸F-FDG in less-affected lung fields in cases with ILDs would therefore show disease activity before morphological changes become detectable on HRCT.

There were several limitations in this study. First, this is a retrospective analysis with a small sample size. Therefore, the usefulness of SUV_mean measurement for less-affected regions in ventral upper lung field should be re-assessed in a larger number of cases in future. Second, regions where emphysematous changes exceeded 50% of the area were excluded from the target VOI setting in this study; however, the effect of emphysema could not be excluded completely. In a previous report, accumulation of ¹⁸F-FDG in emphysema was elevated in chronic obstructive pulmonary disease patients as compared to healthy control (35).

In conclusion, the accumulation of ¹⁸F-FDG in the less-affected lung fields may be able to predict postoperative AE of ILD in patients with NSCLC with ILD. If the value of SUV_mean in the less-affected lung field of the ventral region of the upper to middle lung field is high, patients should be monitored for AE of ILD after pulmonary surgery.

ILD: interstitial lung disease; AE: acute exacerbation; FDG: ¹⁸F-flurodeoxyglucose; PET: positron emission tomography; CT: computed tomography; NSCLC: non-small cell lung cancer; VOI: volume-of-interest; SUV_mean: mean standardized uptake value; TF: tissue fraction; CTD_mean: mean computed tomography density; cSUV_mean: corrected SUV_mean; cSUV_TF: corrected SUV_TF; HRCT: high-resolution computed tomography; IPF: idiopathic pulmonary fibrosis; ECOG: Eastern Cooperative Oncology Group; KL-6: krebs von den lungen-6; UIP: usual interstitial pneumonia; AA: aortic arch; TB: tracheal bifurcation; RLPV: right lower pulmonary vein into the left atrium: NEMA: National Electrical Manufacturers Association; ROC: receiver operating characteristic; GLUT-1: glucose transporter 1; PAE: postoperative acute exacerbation; PS: performance status; ADC: adenocarcinoma; SQ: squamous cell carcinoma; AdSQ: adenosquamous cell carcinoma; Large: large cell carcinoma; %pred.: percent predicted; VC: vital capacity; FVC: forced vital capacity; TLC: total lung capacity; DL_CO: diffusing capacity of the lung for carbon monoxide; SP–D: surfactant protein–D; LDH: lactate dehydrogenase; CRP: C-reactive protein; AAV: aortic arch ventral; AAD: aortic arch dorsal; TBV: tracheal bifurcation ventral; TBD: tracheal bifurcation dorsal; RLPVV: right lower pulmonary vein ventral; RLPVD: right lower pulmonary vein dorsal.

Ethics approval and consent to participate

This study was approved by our institutional review board (approved number: 29-190, November 2, 2017). The need to obtain informed patient consent was waived because of the retrospective nature of this research.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files.

Competing interests

The authors declare no competing interests in association with this article.

Funding

None.

Authors’ contributions

KF, YuN, TN, JH, and YaN conceived and designed the study. KF, YN, HN, AN-S, TN, MN, KK, HI, NN, and KM were involved in the analysis and interpretation of the clinical data; KF, YN, and YN were involved in the drafting the manuscript.

Acknowledgment

We would like to thank Editage (www.editage.com) for English language editing.

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Table 1. The characteristics of the non-small cell lung cancer (NSCLC) patients with or without postoperative acute exacerbation of interstitial lung disease.

	PAE (+) n = 8	PAE (–) n = 28	P
Age	71 (66–77.3)	73.5 (69.3–77)	0.54
Sex (M/F)	8/0	25/3	0.21
Smoking (Current + Former/Never)	8/0	27/1	0.47
Pack–year	49 (40.5–73.3)	51 (38.5–76.5)	0.79
ECOG PS (0–1/2)	7/1	28/0	0.08
Histology (ADC/SQ/AdSq/Large)	2/4/1/1	14/13/1/0	0.19
Surgical procedure (Wedge/resection/Segmentectomy/ Lobectomy/Bilobectomy)	0/2/5/1	4/3/21/0	0.11
Stage (Ⅰ/Ⅱ/Ⅲ/Ⅳ）	6/0/1/1	20/4/4/0	0.17
UIP/non-UIP	4/4	12/16	0.72
VC (L)	3.08 (2.58–3.38)	3.03 (2.64–3.60)	0.70
%VC (%)	94.4 (84.0–105.9)	98.3 (82.5–112.2)	0.51
FVC (L)	3.00 (2.55–3.39)	3.04 (2.68–3.62)	0.80
%FVC (%)	94.9 (84.2–104.4)	98.3 (81.8–113.3)	0.48
TLC (L) PAE+ = 7, PAE– = 26	4.81 (4.35–5.07)	4.94 (4.23–5.43)	0.71
%TLC (%) PAE+ = 7, PAE– = 26	87.5 (77.4–94.3)	91.2 (79.8–98.1)	0.41
DLco (ml/min/mmHg) PAE+ = 7, PAE– = 26	11.99 (9.81–15.16)	10.94 (8.88–14.23)	0.39
%DLco (%) PAE+ = 7, PAE– = 26	85.8 (50.1–105.6)	73.4 (61.23–93.18)	0.66
KL–6 PAE+ = 8, PAE– = 23	476.8 (349.0–1287.9)	461.0 (308.8–648)	0.46
SP–D PAE+ = 7, PAE– = 20	185 (105–314)	108 (51.1–147.0)	0.03
LDH	203 (189–267.3)	199.5 (171.5–224)	0.61
CRP	0.28 (0.12–0.32)	0.19 (0.12–0.49)	0.92

Data are presented as the number or median (interquartile range).

Abbreviations: PAE: postoperative acute exacerbation; NSCLC: non–small cell lung cancer; ILD: interstitial lung disease; ECOG: Eastern Cooperative Oncology Group; PS: performance status; ADC: adenocarcinoma; SQ: squamous cell carcinoma; AdSQ: adenosquamous cell carcinoma; Large: large cell carcinoma; %pred.: percent predicted; VC: vital capacity; FVC: forced vital capacity; TLC: total lung capacity; DL_CO: diffusing capacity of the lung for carbon monoxide; KL-6: Krebs von den Lungen–6; SP–D: surfactant protein–D; LDH: lactate dehydrogenase; CRP: C-reactive protein.

Table 2. Comparison of correct SUV_mean and SUV_TF between non-small cell lung cancer (NSCLC) patients with or without postoperative acute exacerbation of interstitial lung disease (ILD).

Correct SUV_mean

Correct SUV_TF

PAE+

median

PAE–

median

P

PAE+

median

PAE–

median

P

Right lung

RAV

PAE+ = 8, PAE– = 22

0.51

(0.43–0.63)

0.40

(0.29–0.44)

0.01

2.56

(2.06–2.77)

2.25

(1.97–2.47)

0.21

RAD

PAE+ = 8, PAE– = 22

0.56

(0.48–0.62)

0.45

(0.36–0.50)

0.02

2.59

(2.35–2.78)

2.20

(1.88–2.62)

0.21

RBV

PAE+ = 8, PAE– = 26

0.50

(0.36–0.58)

0.36

(0.29–0.41)

0.02

2.54

(2.23–2.86)

2.24

(1.90–2.45)

0.11

RBD

PAE+ = 7, PAE– = 22

0.55

(0.48–0.57)

0.45

(0.41–0.53)

0.28

2.40

(2.29–2.76)

2.20

(1.88–2.80)

0.52

RLPVV

PAE+ = 8, PAE– = 27

0.44

(0.37–0.51)

0.35

(0.28–0.45)

0.16

2.50

(2.00–2.81)

2.22

(1.87–2.56)

0.28

RLPVD

PAE+ = 7, PAE– = 26

0.57

(0.47–0.77)

0.53

(0.43–0.62)

0.37

2.37

(2.10–2.57)

2.45

(2.08–2.66)

0.66

Left

lung

LAV

PAE+ = 7, PAE– = 22

0.41

(0.35–0.50)

0.39

(0.32–0.43)

0.49

2.06

(1.86–2.24)

2.33

(1.91–2.65)

0.32

LAD

PAE+ = 7, PAE– = 22

0.49

(0.41–0.56)

0.44

(0.36–0.47)

0.26

2.23

(1.81–2.61)

2.23

(1.97–2.46)

0.98

LBV

PAE+ = 8, PAE– = 26

0.45

(0.37–0.53)

0.38

(0.32–0.41)

0.95

2.41

(2.24–2.74)

2.28

(1.91–2.54)

0.23

LBD

PAE+ = 8, PAE– = 27

0.55

(0.43–0.63)

0.47

(0.39–0.52)

0.15

2.29

(1.86–2.54)

2.28

(1.97–2.56)

0.95

LLPVV

PAE+ = 7, PAE– = 18

0.44

(0.41–0.62)

0.32

(0.36–0.39)

0.06

2.34

(1.75–2.41)

2.16

(1.82–2.50)

0.63

LLPVD

PAE+ = 7, PAE– = 23

0.63

(0.55–0.71)

0.51

(0.42–0.59)

0.11

2.26

(2.17–2.57)

2.18

(1.95–2.44)

0.42

Data are presented as the number or median (interquartile range). Abbreviations: SUV: standardized uptake value; TF: tissue fraction; NSCLC: non–small cell lung cancer; ILD: interstitial lung disease; PAE: postoperative acute exacerbation; AAV: aortic arch ventral; AAD: aortic arch dorsal; TBV: tracheal bifurcation ventral; TBD: tracheal bifurcation dorsal; RLPVV: right lower pulmonary vein ventral; RLPVD: right lower pulmonary vein dorsal.

Table 3. Comparison of mean computed tomography density of target volume-of-interest (VOI) in high-resolution computed tomography (HRCT) between non-small cell lung cancer (NSCLC) patients with and without postoperative acute exacerbation of interstitial lung disease (ILD).

CTD_mean

ILD+

median

ILD–

median

P

Right

lung

AAV

PAE+ = 8, PAE– = 22

–877.0

(–883.2 to –830.2)

–878.6

(–905.2 to –868.0)

0.25

AAD

PAE+ = 8, PAE– = 22

–822.3

(–889.0 to –808.2)

–857.6

(–878.1 to –834.3)

0.13

TBV

PAE+ = 8, PAE– = 26

–878.5

(–894.2 to –867.2)

–884.4

(–912.9 to –866.6)

0.35

TBD

PAE+ = 7, PAE– = 22

–872.2

(–877.1 to –854.7)

–855.2

(–876.1 to –837.6)

0.56

RLPVV

PAE+ = 8, PAE– = 27

–896.6

(–908.1––883.7)

–884.5

(–919.1 to –871.6)

0.95

RLPVD

PAE+ = 7, PAE– = 26

–841.1

(–871.7 to –813.7)

–857.3

(–882.7 to –841.7)

0.23

Left

lung

AAV

PAE+ = 7, PAE– = 22

–866.4

(–903.0 to –819.2)

–882.6

(–911.1 to –862.9)

0.16

AAD

PAE+ = 7, PAE– = 22

–865.4

(–893.8 to –829.0)

–868.6

(–891.3 to –838.4)

0.94

TBV

PAE+ = 8, PAE– = 26

–882.2

(–906.7 to –855.9)

–884.7

(–905.9 to –873.9)

0.53

TBD

PAE+ = 8, PAE– = 27

–866.0

(–887.5 to –838.1)

–871.3

(–898.4 to –847.5)

0.49

RLPVV

PAE+ = 7, PAE– = 18

–880.0

(–895.0 to –870.6)

–882.5

(–898.0 to –853.3)

0.90

RLPVD

PAE+ = 7, PAE– = 23

–846.4

(–886.0 to –837.4)

–852.6

(–874.8 to –812.7)

1.00

Data are presented as the number or median (interquartile range).

Abbreviations: CTD_mean: mean computed tomography density; VOI: volume of interest; HRCT: high-resolution computed tomography; TF: tissue fraction; NSCLC: non–small cell lung cancer; ILD: interstitial lung disease; PAE: postoperative acute exacerbation; RAV: right aortic arch ventral; RAD: right aortic arch dorsal; LAV: left aortic arch ventral; LAD: left aortic arch dorsal, RBV: right bronchial bifurcation ventral; RBD: right bronchial bifurcation dorsal; LBV: left bifurcation ventral; LBD: left bronchial bifurcation dorsal; RLPVV: right lower pulmonary vein ventral; RLPVD: right lower pulmonary vein dorsal; LLPVV: left lower pulmonary vein ventral; LLPVD: left lower pulmonary vein dorsal.

FigureE1.pptx

¹⁸F-FDG accumulation in less-affected lung area predicts postoperative interstitial lung disease acute exacerbation in lung cancer: A case control study

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Abstract

Figures

Background

Methods

Results

Discussion

List Of Abbreviations

Declarations

References

Tables

Supplementary Files

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