Patient characteristics
There were 105 patients in GR group and 100 patients in PR group. As shown in Table 1, there was significant difference in histologic grade between two groups. After propensity score matching, 73 patients in each group were enrolled in the study, and the difference in histologic grade was eliminated, suggesting that the data were comparable. Besides, the higher pre-CRT and post-CRT carcinoembryonic antigen (CEA) levels were related to the poor tumor response (p=0.026 and 0.002, respectively).
Table 1 Clinic characteristics of patients
Variables
|
All patients
|
Matched patients
|
GR group
(n=105)
|
PR group
(n=100)
|
P
|
GR group
(n=73)
|
PR group
(n=73)
|
P
|
Gender, n (%)
|
|
|
0.436
|
|
|
0.473
|
Male
|
66(62.9)
|
69(69.0)
|
|
46(63.0)
|
51(69.9)
|
|
Female
|
39(37.1)
|
31(31.8)
|
|
27(37.0)
|
22(30.1)
|
|
Age (years), n (%)
|
|
|
1.000
|
|
|
0.728
|
≥60
|
45(42.9)
|
43(43.0)
|
|
31(42.5)
|
34(46.6)
|
|
<60
|
60(57.1)
|
57(57.0)
|
|
42(57.5)
|
39(53.4)
|
|
BMI (kg/m2)
|
22.10±3.70
|
22.10±3.53
|
0.800
|
22.10±3.70
|
22.10±1.94
|
0.554
|
DTAV (cm), n (%)
|
|
|
0.192
|
|
|
0.838
|
≥6
|
25(23.8)
|
33(33.0)
|
|
24(32.9)
|
26(35.6)
|
|
<6
|
80(76.2)
|
67(67.0)
|
|
49(67.1)
|
47(64.4)
|
|
Pre-CRT CEA (ng/ml), n (%)
|
|
0.022
|
|
|
0.026
|
≥5
|
33(31.4)
|
48(48.0)
|
|
20(27.4)
|
34(46.6)
|
|
<5
|
72(68.6)
|
52(52.0)
|
|
53(72.6)
|
39(53.4)
|
|
Post-CRT CEA (ng/ml), n (%)
|
|
0.005
|
|
|
0.002
|
≥5
|
12(11.4)
|
28(28.0)
|
|
6(8.2)
|
21(28.8)
|
|
<5
|
93(88.6)
|
72(72.0)
|
|
67(91.8)
|
52(71.2)
|
|
Histologic grade, n (%)
|
|
|
0.001
|
|
|
1.000
|
Low
|
1(0.9)
|
13(13.0)
|
|
1(1.4)
|
1(1.4)
|
|
High
|
104(99.1)
|
87(87.0)
|
|
72(98.6)
|
72(98.6)
|
|
Clinical stage, n (%)
|
|
|
0.345
|
|
|
1.000
|
II
|
12(11.4)
|
17(17.0)
|
|
12(16.4)
|
13(17.8)
|
|
III
|
93(88.6)
|
83(83.0)
|
|
61(83.6)
|
60(82.2)
|
|
Operation type, n (%)
|
|
|
0.196
|
|
|
1.000
|
AR
|
92(87.6)
|
80(80.0)
|
|
60(82.2)
|
61(83.6)
|
|
APR
|
13(12.4)
|
20(20.0)
|
|
13(17.8)
|
12(16.4)
|
|
|
|
|
|
|
|
|
|
|
GR: good response; PR: poor response; BMI: Body Mass Index; DTAV: Distance to the anal verge; CRT: chemoradiotherapy; CEA: Carcinoembryonic antigen; AR: Anterior resection; APR: Abdominal-perineal resection.
Hematological characteristics
Before CRT, there were significant differences in lymphocyte count, NLR, PLR and MLR between GR and PR groups (p=0.006, 0.002, 0.008 and 0.043, respectively). After adjusting with propensity score matching, the NLR and PLR in GR group were notably lower than those in PR group (p=0.014 and 0.025, respectively). No significant difference in lymphocyte count and MLR was noticed between the two groups (Table 2). Moreover, after CRT, there was no statistically significant difference in all hematological characteristics between two groups before and after propensity score matching (Table 3).
Table 2 Hematological characteristics before CRT
Variables
|
All patients
|
Matched patients
|
GR group
(n=105)
|
PR group
(n=100)
|
p
|
GR group
(n=73)
|
PR group
(n=73)
|
P
|
Hemoglobin (g/L)
|
145.00±21.00
|
138.50±29.25
|
0.056
|
140.00±21.00
|
141.00±23.00
|
0.574
|
WBC (×109/L)
|
5.38±2.34
|
5.66±2.24
|
0.284
|
5.35±1.36
|
5.66±1.94
|
0.393
|
Neutrophil (×109/L)
|
3.28±1.63
|
3.42±1.88
|
0.265
|
3.24±1.53
|
3.41±1.85
|
0.433
|
Lymphocyte (×109/L)
|
1.58±0.80
|
1.27±0.81
|
0.006
|
1.58±0.68
|
1.43±0.87
|
0.149
|
Monocyte (×109/L)
|
0.40±0.22
|
0.39±0.19
|
0.484
|
0.40±0.21
|
0.38±0.18
|
0.331
|
Platelet (×109/L)
|
236.00±97.00
|
227.00±109.00
|
0.373
|
236.00±94.00
|
225.00±113.00
|
0.367
|
Albumin (g/L)
|
42.80±4.40
|
42.00±5.08
|
0.161
|
42.20±4.60
|
42.70±5.50
|
0.962
|
NLR
|
2.20±1.01
|
2.41±1.97
|
0.002
|
2.20±0.75
|
2.26±1.46
|
0.014
|
PLR
|
146.22±75.08
|
174.22±115.83
|
0.008
|
141.77±73.00
|
159.48±118.41
|
0.025
|
MLR
|
0.27±0.15
|
0.31±0.23
|
0.043
|
0.26±0.14
|
0.25±0.23
|
0.357
|
CRT: chemoradiotherapy; GR: good response; PR: poor response; WBC: White blood cell; NLR: neutrophil-lymphocyte-ratio; MLR: monocyte-lymphocyte-ratio; PLR: platelet-lymphocyte-ratio.
Table 3 Hematological characteristics after CRT
Variables
|
All patients
|
Matched patients
|
GR group
(n=105)
|
PR group
(n=100)
|
P
|
GR group
(n=73)
|
PR group
(n=73)
|
P
|
Hemoglobin (g/L)
|
139.00±19.00
|
134.00±20.00
|
0.487
|
138.00±21.00
|
134.00±19.00
|
0.482
|
WBC (×109/L)
|
3.68±1.90
|
4.20±2.39
|
0.076
|
3.68±1.72
|
4.18±2.46
|
0.113
|
Neutrophil (×109/L)
|
2.20±1.47
|
2.77±2.01
|
0.232
|
2.22±1.38
|
2.74±2.07
|
0.275
|
Lymphocyte (×109/L)
|
0.76±0.46
|
0.79±0.56
|
0.198
|
0.72±0.43
|
0.75±0.55
|
0.666
|
Monocyte (×109/L)
|
0.40±0.22
|
0.44±0.27
|
0.611
|
0.38±0.22
|
0.46±0.25
|
0.093
|
Platelet (×109/L)
|
179.00±77.00
|
183.50±71.25
|
0.226
|
181.00±64.00
|
184.00±55.00
|
0.678
|
Albumin (g/L)
|
42.30±4.80
|
42.10±4.05
|
1.000
|
42.50±4.80
|
42.30±4.30
|
0.760
|
NLR
|
3.17±2.32
|
3.02±3.12
|
0.835
|
3.18±2.42
|
3.49±2.82
|
0.577
|
PLR
|
234.41±154.82
|
216.50±156.02
|
0.480
|
250.00±175.50
|
229.49±159.58
|
0.802
|
MLR
|
0.53±0.37
|
0.51±0.43
|
0.578
|
0.53±0.35
|
0.63±0.40
|
0.097
|
CRT: chemoradiotherapy; GR: good response; PR: poor response; WBC: White blood cell; NLR: neutrophil-lymphocyte-ratio; MLR: monocyte-lymphocyte-ratio; PLR: platelet-lymphocyte-ratio.
Predictive factors for tumor response
After analyzing the ROC curves of pre-CRT NLR, and pre-CRT PLR (Fig. 2), the cutoff values of pre-CRT NLR and pre-CRT PLR were 3.10 and 198.7, respectively (Table 4), and all patients were divided into two groups based on cutoff values. Factors with significant differences between the two groups were analyzed using a multivariate analysis model (Table 5). The results suggested that post-CRT CEA and pre-CRT NLR were the predictors of tumor response (p=0.019 and 0.005, respectively), while pre-CRT PLR was not related with tumor response (p=0.472).
Table 4 Predictive value of prognostic factors
|
AUC
|
95%CI
|
sensitivity
|
specificity
|
pre-CRT NLR
|
0.580
|
0.486-0.674
|
30.1
|
94.5
|
pre-CRT PLR
|
0.578
|
0.485-0.671
|
34.2
|
82.2
|
AUC: area under curve; CI: confidence interval; CRT: chemoradiotherapy; NLR: neutrophil-lymphocyte-ratio; PLR: platelet-lymphocyte-ratio.
Table 5 Multivariate analysis of tumor response
Variables
|
OR
|
95% CI
|
P
|
Post-CRT CEA (≥5 vs <5)
|
1.839
|
1.107-3.055
|
0.019
|
Pre-CRT NLR (≥3.10 vs <3.10)
|
2.047
|
1.241-3.377
|
0.005
|
Pre-CRT PLR (≥198.7 vs <198.7)
|
1.356
|
0.591-3.115
|
0.472
|
OR: odds ratio; CI: confidence interval; CRT: chemoradiotherapy; CEA: Carcinoembryonic antigen; NLR: neutrophil-lymphocyte-ratio; PLR: platelet-lymphocyte-ratio.
The association between the pre-CRT NLR and the TRG
According to the cutoff value, pre-CRT NLR was stratified into low NLR group and high NLR group. The relationship between pre-CRT NLR and TRG was analyzed and we found that 44.2% of patients had a poor TRG (TRG2-4) in low NLR group and 69.2% in high NLR group (Fig. 3), and this difference was statistically significant (p=0.036).