Characteristics of the Patients
A total of 125 patients who met the inclusion criteria were included in our study (Table 1). The chemotherapy included platinum-based, Fluorouracil-based or Paclitaxel-based regimens. The majority of patients were male (86.4%), and the median age was 64 years (interquartile range 56–70). Nearly two-thirds of the patients were current smokers or ex-smokers, and approximately half of the patients were frequent alcohol consumers. Remarkably, patients with a high SUVmax-N were more likely to have linear relatives who were diagnosed with malignant tumours than patients with a low SUVmax-N, suggesting a genetic basis for tumour generation. A total of 69.6% of the patients presented with cT3 or cT4 tumours, and 75.2% of the patients were recognized to have clinical regional lymph node metastasis. The characteristics of the patients are summarized in Table 1.
Table 1
Patients’ clinical characteristics in the study cohort
Characteristic
|
All patients
(n = 125)
|
LN PET-Negative(n = 42)
|
SUVmax-N < 11(%)
(n = 66)
|
SUVmax-N ≥ 11(%)
(n = 17)
|
P
|
Gender
|
|
|
|
|
0.179
|
Male
|
108(86.4)
|
39(92.9)
|
55(83.3)
|
14 (82.4)
|
|
Female
|
17(13.6)
|
3(7.1)
|
11(16.7)
|
3(17.6)
|
|
Age
|
|
|
|
|
0.916
|
༜60
|
40(32.0)
|
12(28.6)
|
24(36.4)
|
4(23.5)
|
|
≥ 60
|
85(68.0)
|
30(71.4)
|
42(63.6)
|
13(76.5)
|
|
Tobacco
|
|
|
|
|
0.364
|
Yes
|
81(64.8)
|
17(40.5)
|
22(33.3)
|
5(29.4)
|
|
No
|
44(35.2)
|
25(59.5)
|
44(66.7)
|
12(70.6)
|
|
Alcohol
|
|
|
|
|
0.045
|
Yes
|
62(49.6)
|
26(61.9)
|
31(47.0)
|
6(35.3)
|
|
No
|
63(50.4)
|
16(38.1)
|
35(53.0)
|
11(64.7)
|
|
Family history
|
|
|
|
|
0.002
|
No
|
13(2.4)
|
28(66.7)
|
59(89.4)
|
16(94.1)
|
|
Yes
|
112(89.6)
|
14(33.3)
|
7(10.6)
|
1(5.9)
|
|
cT
|
|
|
|
|
0.084
|
T1
|
2(1.6)
|
2(4.8)
|
0
|
0
|
|
T2
|
36(28.8)
|
14(33.3)
|
19(28.8)
|
3(17.6)
|
|
T3
|
51(40.8)
|
17(40.5)
|
25(37.9)
|
9(52.9)
|
|
T4
|
36(28.8)
|
9(21.4)
|
22(33.3)
|
5(29.4)
|
|
cN
|
|
|
|
|
0.021
|
N0
|
31(24.8)
|
0
|
0
|
0
|
|
N1
|
60(48.0)
|
14(100.0)
|
37(61.7)
|
9(45.0)
|
|
N2
|
32(25.6)
|
0
|
22(36.7)
|
10(55.0)
|
|
N3
|
2(1.6)
|
0
|
1(1.7)
|
1(5)
|
|
PET-positive LN
|
|
|
|
|
0.282
|
1–2
|
-
|
-
|
41
|
8
|
|
≥ 3
|
-
|
-
|
25
|
9
|
|
Site
|
|
|
|
|
0.615
|
Cervical
|
30(24.0)
|
10(23.8)
|
15(22.7)
|
5(29.4)
|
|
Upper
|
27(21.6)
|
12(28.6)
|
10(15.2)
|
5(29.4)
|
|
Middle
|
41(32.8)
|
9(21.4)
|
27(40.9)
|
5(29.4)
|
|
Lower
|
27(21.6)
|
11(26.2)
|
14(21.2)
|
2(11.8)
|
|
Abbreviations: LN: lymph node; SUVmax-N: the maximum standardized uptake value of metastatic lymph node |
Correlation of SUVmax-T and prognosis
The median overall survival (OS) for all patients was 36.4 months with a median survival of 20.6 months (range: 30.3 -101.2 months). The 2-year, 3-year and 5-year overall survival rates in our cohort were 62.4%, 48.3% and 27.1%, respectively. Sixty-six of the total 125 patients had disease progression in the follow-up, of which the most common progressions were distant metastasis (22/66) and recurrence (20/66). The 2-year, 3-year and 5-year progression-free survival rates were 51.4%, 36.8% and 23.7%, respectively.
The gross tumours of all patients presented higher 18F-FDG uptake than normal tissues with a median SUVmax-T of 12.5 and ranged from 2.9 to 32.8. In total, 83 patients had PET-positive lymph nodes (LNs), and the SUVmax-T of these patients was significantly higher than those with PET-negative LNs (mean: 14.2 vs 10.3, P < 0.01). The maximum, mean and median SUVmax-N were 23.7, 8.0 and 7.3 in patients with PET-positive LNs, respectively. As shown in Fig. 1, only a weak correlation was found between SUVmax-N and SUVmax-T (Pearson r = 0.284).
The survival analysis using X-tile revealed that no proper threshold of SUVmax-T could distinguish between groups of patients with different prognoses. Taking the median SUVmax-T (12.5) as the cut-point, there was no significant difference in the OS (median survival time: 41.2 vs 30.7 months, P = 0.902, Fig. 2A) or PFS (median survival time: 23.4 vs 27.6 months, P = 0.972, Fig. 2B) of patients with high SUVmax-T (n = 62) and low SUVmax-T (n = 63).
Correlation of SUVmax-N and prognosis
The number of PET-positive LNs also could not predict prognosis properly. The OS (median survival time: 47.0 vs 26 months, P < 0.01, Fig. 3A) and PFS (median survival time: 37.3 vs 13.9 months, P < 0.01, Fig. 3B) of patients with PET-negative LNs was significantly better than those with PET-positive LNs. However, the OS and PFS of patients with one or two PET-positive LNs were not significantly better than those with more than two PET-positive LNs (OS: median survival time 30.7 vs 25.7 months, P = 0.96, Fig. 3A; PFS: median survival time 13.2 vs 13.0 months, P = 0.70, Fig. 3B).
An SUVmax-N ≥ 11 was set as the definition for a high SUVmax-N according to the X-tile analysis. Patients with high SUVmax-N had a significantly worse OS and PFS than those with low SUVmax-N (OS: median survival time 30.7 vs 15.9 months, P = 0.02, Fig. 3C; PFS: median survival time 19.1 vs 7.2 months, P < 0.01, Fig. 3D), suggesting that SUVmax-N is a valuable prognostic indicator. Meanwhile, no correlation was found between SUVmax-N and the number of PET-positive LNs (Pearson r = 0.12), cT (Pearson r=-0.13) or clinical staging (Pearson r = 0.05). In the univariate analysis, cT staging, positive or negative lymph nodes on the PET-CT image and the SUVmax-N were established as significant prognostic factors for both OS and PFS (Table 2), and the multivariate analysis showed that SUVmax-N remained as an independent predictor for OS and PFS.
Table 2
Univariate analysis of potential factors affecting OS and PFS
|
OS
|
|
|
PFS
|
|
|
Variable
|
Hazard Ratio
|
95% CI
|
P value
|
Hazard Ratio
|
95% CI
|
P value
|
Age
|
|
|
|
|
|
|
༜60
|
1
|
-
|
|
1
|
-
|
|
≥60
|
1.179
|
0.706–1.969
|
0.528
|
1.036
|
0.625–1.717
|
0.892
|
Gender
|
|
|
|
|
|
|
Male
|
1
|
-
|
|
1
|
-
|
|
Female
|
0.886
|
0.419–1.875
|
0.752
|
0.762
|
0.362–1.606
|
0.475
|
Tobacco
|
|
|
|
|
|
|
Yes
|
1
|
-
|
|
1
|
-
|
|
No
|
1.457
|
0.850–2.498
|
0.171
|
1.635
|
0.950–2.814
|
0.076
|
Alcohol
|
|
|
|
|
|
|
Yes
|
1
|
-
|
|
1
|
-
|
|
No
|
1.603
|
0.980–2.623
|
0.060
|
1.573
|
0.965–2.563
|
0.069
|
Family history
|
|
|
|
|
|
|
No
|
1
|
-
|
|
1
|
-
|
|
Yes
|
1.817
|
0.897–3.681
|
0.097
|
1.454
|
0.759–2.784
|
0.259
|
cT
|
1.189
|
1.078–1.810
|
0.049
|
1.087
|
1.013–1.452
|
0.047
|
PET-positive LN
|
|
|
|
|
|
|
No
|
1
|
-
|
|
1
|
-
|
|
Yes
|
2.147
|
1.204–3.830
|
0.010
|
2.621
|
1.416–4.852
|
0.002
|
SUVmax-T
|
1.022
|
0.978–1.068
|
0.337
|
1.020
|
0.976–1.066
|
0.384
|
SUVmax-N
|
1.071
|
1.028–1.115
|
0.001
|
1.089
|
1.048–1.132
|
0.000
|
Abbreviations: OS: overall survival; PFS: progression free survival; LN: lymph node; SUVmax-T: the maximum standardized uptake value of primary tumor; SUVmax-N: the maximum standardized uptake value of metastatic lymph node |
Table 3
Multivariate Cox regression analysis of potential factors affecting OS and PFS
Variable
|
Hazard Ratio
|
95% CI
|
P value
|
OS
|
|
|
|
SUVmax-N
|
1.075
|
1.028–1.124
|
0.001
|
PFS
|
|
|
|
cT
|
|
|
|
T1
|
1
|
|
|
T2
|
-
|
-
|
0.984
|
T3
|
3.447
|
1.050–11.311
|
0.041
|
T4
|
4.650
|
1.655–13.063
|
0.004
|
PET-positive LN
|
|
|
|
No
|
1
|
-
|
|
Yes
|
2.607
|
1.042–6.519
|
0.040
|
SUVmax-N
|
1.092
|
1.049–1.138
|
0.000
|
Abbreviations: OS: overall survival; PFS: progression free survival; LN: lymph node; SUVmax-N: the maximum standardized uptake value of metastatic lymph node |
To provide a clinically useful tool to predict prognosis, we constructed a nomogram that integrated the SUVmax-N and several clinicopathological risk factors associated with progression-free survival. The T stage, number of PET-positive LNs and SUVmax-N were included in the prediction model (Fig. 4). The C-index of the nomogram was 0.644.