Preoperative neutrophil-to-lymphocyte ratio predicts the prognosis of esophageal squamous cell cancer patients undergoing minimally invasive esophagectomy after neoadjuvant chemotherapy

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Data availability statement

Research data are not shared.

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Figure legend

Figure 1A

A receiver operating characteristic curve was generated to analyze the relationship

between the NLR and overall survival in 174 patients. NLR, neutrophil-to-lymphocyte

ratio. P = 0.0173, AUC = 0.63777

Figure 1B

Kaplan–Meier curves that were generated to analyze the survival differences among the

174 patients divided according to the cutoff value of the NLR are shown. The patients

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with an NLR < 1.9 exhibited a longer overall survival than patients with an NLR ≥ 1.9

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(P = 0.0018).

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Figure 2A

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A receiver operating characteristic curve was generated to analyze the relationship

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between the NLR and overall survival in 121 patients who received NAC.

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P = 0.0127, AUC = 0.63026

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Figure 2B

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Kaplan–Meier curves were generated to analyze the survival differences among 121

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patients treated with NAC who were divided according to the cutoff value of the NLR.

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The 5-year overall survival rate in patients with an NLR < 2.5 (64%) was significantly

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better than that in patients with an NLR ≥ 2.5 (39%) (P = 0.004).

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Figure 3

Kaplan–Meier curves were generated to analyze the survival differences among 121

patients treated with NAC who were divided according to the NLR status. The 5-year

overall survival rate in patients whose NLR decreased during NAC (55%) was not

significantly better than that in patients whose NLR increased during NAC (43%) despite

the fact that there was tendency to better prognosis in NLR decreased group.

Authorship

1) Substantial contributions to the conception or design of the work, or acquisition,

analysis, or interpretation of data for the work: N.Urakawa, M.Yamamoto,

H.Hasegawa, K.Yamashita, and T.Matsuda.

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2)

Drafting the work or revising it critically for important intellectual content:

T.Kato, and T.Oshikiri.

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3) Final approval of the version to be published: Y.Kakeji.

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4) Agreement to be accountable for all aspects of the work in ensuring that questions

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related to the accuracy or integrity of any part of the work are appropriately

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investigated and resolved: G.Takiguchi, S.Kanaji, T.Nakamura, and S.Suzuki.

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Table 1. Characteristics of 174 patients divided according to the cutoff point for the NLR

Total

NLR ≥ 1.9

NLR < 1.9

n = 174

n = 118

n = 56

Gender

Male/Female

0.7758

154 (89%)/20 (11%)

105 (89%)/13 (11%)

49 (87%)/7 (13%)

Age

≥63/<63

0.1684

121 (70%)/53 (30%)

86 (73%)/32 (27%)

35 (63%)/21 (37%)

Tumor location

0.3428

Ut

30 (17%)

21 (18%)

9 (16%)

Mt

86 (50%)

54 (46%)

32 (57%)

Lt

58 (33%)

43 (36%)

15 (27%)

pT Stage (8th)*

0.0111

T1

105 (60%)

62 (53%)

43 (77%)

T2

12 (7%)

10 (8%)

2 (3%)

T3

54 (31%)

43 (36%)

11 (20%)

T4

3 (2%)

3 (3%)

0 (0%)

pN Stage (8th)*

0.1019

N0

88 (51%)

55 (47%)

33 (59%)

N1

57 (33%)

41 (35%)

16 (29%)

N2

21 (12%)

18 (15%)

3 (5%)

N3

8 (4%)

4 (3%)

4 (7%)

Surgical margin

P value

0.9331

Negative/positive

158(91%)/16(9%)

107(91%)/11(9%)

51(91%)/5(9%)

Pneumonia**

+/−

0.0620

50 (29%)/124 (71%)

39 (33%)/79 (67%)

11 (20%)/45 (80%)

Operation time

0.1570

(min)

≥740/<740

56 (32%)/118 (68%)

42 (36%)/76 (64%)

42 (75%)/14 (25%)

Blood loss (mL)

≥415/<415

0.0201

68 (39%)/106 (61%)

53 (45%)/65 (55%)

15 (27%)/41 (73%)

*UICC, Union for International Cancer Control

** Higher

than Clavien–Dindo classification grade II was recognized as a postoperative morbidity.

NLR, neutrophil to lymphocyte ratio

Table 2. Univariate and multivariate analyses using the Cox proportional hazard model in 174 patients to determine independent prognostic

factors for overall survival

Factors

Patients

(n = 174)

Overall Survival

Univariate analysis

Multivariate analysis

HR (95% CI)

154/20

1.049 (0.503–2.188)

0.897

121/53

1.403 (0.833–2.365)

0.202

HR (95% CI)

2.195 (1.103–4.367)

0.025

Gender

Male/Female

Age

≥63/<63

Tumor location

0.528

Ut

30

1.000

Mt

86

1.152 (0.598–2.220)

0.671

Lt

58

1.432 (0.725–2.828)

0.300

118/56

2.447 (1.367–4.382)

0.0026

NLR

≥1.9/<1.9

pT Stage (8th)

<0.0001

<0.0001

T1

105

1.000

1.000

T2

12

2.197 (0.903–5.347)

0.0826

2.031 (0.799–5.157)

0.136

T3

54

5.290 (3.184–8.790)

<0.0001

3.802 (2.169–6.661)

<0.0001

T4

10.784 (3.231–35.993)

0.0001

8.221 (2.204–30.660)

0.0017

pN Stage (8th)

<0.0001

<0.0001

N0

88

1.000

1.000

N1

57

1.490 (0.850–2.613)

0.163

1.071 (0.600–1.909)

0.815

N2

21

5.742 (3.102–10.629)

<0.0001

2.687 (1.342–5.381)

0.053

N3

13.767 (5.833–32.492)

<0.0001

24.120 (8.444–68.897)

<0.0001

50/124

1.497 (0.928–2.416)

0.097

1.682 (1.014–2.791)

0.043

56/118

1.935 (1.221–3.068)

0.0049

1.785 (1.079–2.955)

0.024

68/106

1.895 (1.199–2.995)

0.0062

1.531 (0.935–2.507)

0.090

Pneumonia*

+/−

Operation time(min)

≥740/<740

Blood loss(mL)

≥415/<415

*Higher

than Clavien–Dindo classification grade II was recognized as a postoperative morbidity

HR, hazard ratio; CI, confidence interval; Lt, lower thoracic; Mt, middle thoracic; Ut, upper thoracic

Table 3. Characteristics of 121 patients who were treated with neoadjuvant chemotherapy and who were divided according to the cutoff point

for the NLR

Total

n = 121

n (%)

NLR ≥ 2.5

NLR < 2.5

n = 61

n = 60

n (%)

n (%)

Gender

Male/Female

0.5471

107 (88%)/14 (12%)

55 (90%)/6 (10%)

52 (87%)/8 (13%)

Age

≥63/<63

P value

0.8867

86 (71%)/35 (29%)

43 (70%)/18 (30%)

43 (72%)/17 (28%)

Tumor location

0.0678

Ut

17 (14%)

11 (18%)

6 (10%)

Mt

58 (48%)

23 (38%)

35 (58%)

Lt

46 (38%)

27 (44%)

19 (32%)

pT Stage (8th)*

0.0118

T1

57 (47%)

21 (34%)

36 (60%)

T2

11 (9%)

7 (12%)

4 (7%)

T3

50 (41%)

30 (49%)

20 (33%)

T4

3 (3%)

3 (5%)

0 (0%)

pN Stage (8th)*

0.2446

N0

50 (41%)

25 (41%)

25 (42%)

N1

45 (37%)

21 (35%)

24 (40%)

N2

19 (16%)

13 (21%)

6 (10%)

N3

7 (6%)

2 (3%)

5 (8%)

Surgical margin

Negative/Positive

0.9738

107(88%)/14(12%)

54(89%)/7(11%)

53(88%)/7(12%)

Pneumonia**

+/−

0.4612

36 (30%)/85 (70%)

20 (33%)/41 (67%)

16 (27%)/44 (73%)

Operation time(min)

≥711/<711

0.0013

56 (46%)/65 (54%)

37 (61%)/24 (39%)

19 (32%)/41 (68%)

Blood loss(mL)

≧415/＜415

0.0781

52 (43%)/69 (57%)

31 (51%)/30 (49%)

*UICC, Union for International Cancer Control

**Higher

than Clavien–Dindo classification grade II was recognized as a postoperative morbidity.

21 (35%)/39 (65%)

Table 4. Univariate and multivariate analyses using Cox proportional hazard models to determine independent prognostic factors for overall

survival (121 patients who were treated with neoadjuvant chemotherapy)

Factors

Patients

(n =

Overall Survival

Univariate analysis

Multivariate analysis

121)

HR (95% CI)

107/14

1.012 (0.460–2.226)

0.975

86/35

1.623 (0.894–2.944)

0.111

HR (95% CI)

1.922 (1.050–3.519)

0.034

Gender

Male/Female

Age

≥63/<63

Tumor location

0.904

Ut

17

1.000

Mt

58

1.169 (0.554–2.467)

0.680

Lt

46

1.174 (0.542–2.542)

0.682

61/60

2.112 (1.255–3.556)

0.0049

NLR

≥2.5/<2.5

pT Stage (8th)

<0.0001

0.029

T1

57

1.000

T2

11

1.898 (0.752–4.792)

0.174

1.791 (0.691–4.644)

0.230

T3

50

3.767 (2.106–6.738)

<0.0001

2.430 (1.262–4.677)

0.0078

T4

7.912 (2.305–27.158)

0.001

5.141 (1.305–20.243)

0.0192

pN Stage (8th)

1.000

<0.0001

<0.0001

N0

50

1.000

1.000

N1

45

1.650 (0.865–3.147)

0.128

1.572 (0.809–3.053)

0.181

N2

19

5.829 (2.880–11.797)

<0.0001

3.722 (1.687–8.213)

0.001

N3

38.124 (13.220–

<0.0001

42.940 (12.806–

<0.0001

109.937)

143.984)

Pneumonia*

+/−

36/85

1.680 (0.997–2.830)

0.051

1.687 (0.956–2.976)

0.070

56/65

1.802 (1.089–2.982)

0.0219

1.571 (0.903–2.733)

0.109

52/69

1.946 (0.179–3.213)

0.0092

1.861 (1.084–3.195)

0.024

Operation time (min)

≥711/<711

Blood loss (mL)

≥415/<415

*Higher

than Clavien–Dindo classification grade II was recognized as a postoperative morbidity.

HR, hazard ratio; CI, confidence interval; Lt, lower thoracic; Mt, middle thoracic; Ut, upper thoracic

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