The clinicopathological characteristics are summarized in Table 1. All cohorts comprised 39 men (87%) and 6 women, with a median age of 70 years (40–79). The median tumor size was 35 mm (9–106 mm), and the clinical T factor was mainly T1–T2 (73%). The primary histology was adenocarcinoma in 18 patients (40%), squamous cell carcinoma in 18 patients (40%), and others including adenosquamous cell carcinoma or large cell carcinoma and neuroendocrine tumors in 9 patients (20%). In the present study, lobectomy with LN dissection was mainly performed (76%).
Table 1
Characteristics
|
n = 45 (%)
|
Age, median (range)
|
70 (40–79)
|
Sex, male
|
39 (87)
|
Tumor location
RUL
RML
RLL
LUL
LLL
RMLL
|
16 (36)
1 (2)
12 (27)
11 (24)
3 (7)
2 (4)
|
Tumor size, mm, median (range)
|
35 (9-106)
|
Clinical T factor
T1
T2
T3
T4
|
16 (35)
17 (38)
8 (18)
4 (9)
|
Histology
Adenocarcinoma
Squamous cell carcinoma
Others *
|
18 (40)
18 (40)
9 (20)
|
Procedure of operation
Lobectomy
Bi-lobectomy
Pneumonectomy
No resection (only lymph node sampling)
|
34 (76)
7 (16)
2 (4)
2 (4)
|
RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe; RMLL, right middle and lower lobe |
* Including adenosquamous cell carcinoma, large cell carcinoma and neuroendocrine tumors |
Of the 84 hilar or mediastinal LNs clinically diagnosed as positive, 63 were pathologically proven as positive (75%), whereas 21 were pathologically proven as negative (25%). The FDG-PET/CT parameters for negative and positive LNs are presented in Table 2. The SUVmax, MTV, TLG, and LPR of metastatic LNs were higher than those of benign nodes. No significant difference was observed in the primary tumor SUVmax. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640–0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626–0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607–0.885) (Fig. 3a). MTV had the lowest AUC value compared with the above parameters (not shown in Fig. 3A). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1%, 66.7%, 88.3%, 58.3%, and 79.8%, respectively. On the contrary, the LN SUVmax (cutoff value, 4.15) and LN TLG3.5 (cutoff value, 1.26) showed sensitivity values of 79.4% and 81.0%, specificity values of 76.2% and 76.2%, positive predictive values of 90.9% and 91.1%, negative predictive values of 55.2% and 57.1%, and accuracies of 78.6% and 79.8%, respectively. The results of the multivariate analysis of predictors associated with LN metastasis by logistic regression are shown in Table 3. LPR was the independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785–23.301; P = 0.004).
Table 2
FDG-PET/CT parameters for negative and positive LNs
Characteristics
|
Negative LNs
( n = 21)
|
Positive LNs
( n = 63)
|
P value
|
LN station
|
|
|
|
#2R
#3p
#4R
#4L
#5-#6
#7
#8-#9
#10
#11
#12
|
2
1
6
0
0
4
0
2
4
2
|
0
1
14
3
10
15
2
3
8
7
|
|
Primary tumor SUVmax
|
10.66 (2.55–17.91)
|
9.04 (1.66–18.67)
|
0.09
|
LN SUVmax
|
3.54 (2.52–11.20)
|
5.77 (2.81–15.54)
|
0.001
|
LN MTV3.5
|
0.01 (0-13.36)
|
1.44 (0-22.68)
|
0.001
|
LN TLG3.5
|
0.05 (0-71.25)
|
6.34 (0-162.78)
|
0.001
|
LPR
|
0.37 (0.15–1.76)
|
0.81 (0.26–2.26)
|
< 0.001
|
FDG-PET/CT, fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography; LN, lymph node; SUVmax, maximum standardized uptake value; MTV, metabolic tumor volume; TLG, total legion glycolysis; LPR, lymph node-to-primary tumor ratio of SUVmax |
Table 3
Multivariate analysis of predictors associated with LN metastasis by logistic regression
Characteristics
|
OR
|
95%CI
|
P value
|
LN SUVmax
|
1.037
|
0.053–20.207
|
0.98
|
LN TLG3.5
|
8.727
|
0.459–166.02
|
0.15
|
LPR
|
6.450
|
1.785–23.301
|
0.004
|
LN, lymph node; SUVmax, maximum standardized uptake value; TLG, total legion glycolysis; LPR, lymph node-to-primary tumor ratio of SUVmax; OR, odds ratio; CI, confidence interval |
A subgroup analysis based on the histology of primary tumor was performed. In the subgroup analysis of patients with adenocarcinoma (n = 18; 32 LNs), the SUVmax, MTV, TLG, and LPR of metastatic LNs were higher than those of benign nodes, but there was no significant difference in primary tumor SUVmax. In the subgroup analysis of patients with squamous cell carcinoma (n = 18; 34 LNs), the SUVmax and LPR of metastatic LNs were higher than those of benign nodes, but there were no significant differences in primary tumor SUVmax, MTV and TLG of LNs (Supplementary data). In the ROC analysis based on adenocarcinoma, TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639–0.985) than LPR (AUC, 0.792; 95% CI, 0.599–0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625–0.959) (Fig. 3b). Using the optimal TLG3.5 cutoff value of 1.26, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71.4%, 90.9%, 93.8%, 62.5%, and 78.1%, respectively. In the ROC analysis based on squamous cell carcinoma, LPR was a better predictor (AUC, 0.831; 95% CI, 0.642–1.000) than LN SUVmax (AUC, 0.804; 95% CI, 0.593–1.000) or TLG3.5 (AUC, 0.701; 95% CI, 0.436–0.966). On the other hand, there was no predictor in other histological group.