World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 13, Number 4, August 2022, pages 195-204

Pathological Responses of the Primary Tumor and Locoregional Lymph Nodes After Neoadjuvant Immunochemotherapy in Esophageal Squamous Cell Cancer

Figure 1. Flowchart of patient eligibility for inclusion. Of the 83 patients receiving neoadjuvant immunochemotherapy, 71 patients were evaluated at least once via radiological imaging. Eventually, a total of 51 patients underwent surgery. Based on the response of primary tumor and lymph nodes, patients were categorized into different groups. ESCC: esophageal squamous cell carcinoma.

Figure 2. Tumor and nodal responses in ESCC patients with various clinical stages. (a) Differences in pathological T stage between cT3 and cT4a patients. Various color blocks represent depths of tumor invasion. (b) Differences in pathological lymph node response (represented by different color blocks) among cN0, cN1 and cN2 groups after neoadjuvant immunochemotherapy. ESCC: esophageal squamous cell carcinoma.

Figure 3. Multivariate regression analysis for pretreatment predictors associated with combined tumor and nodal responses. Variables with P values ≤ 0.1 in the univariate analysis were included in this step. The forest plot showed that treatment cycles and pretreatment platelet counts were independent predictors for combined TN responses. Pre-N:L: pretreatment neutrophil to lymphocyte ratio; Pre-platelets: pretreatment platelet count; BMI: body mass index.

Figure 4. Kaplan-Meier curves for overall survival in the surgical cohort. The difference in OS between pathologically good-responders (TN-GRs) and poor-responders (TN-PRs). Significant difference in overall survival between these groups was observed. OS: overall survival.

**Table 1.** Clinicopathological Characteristics of Esophageal Squamous Cell Cancer Patients
Characteristics	N (%)
BMI: body mass index; IQR: interquartile range; pCR: pathological complete response.
Sex
Male	41 (80.4)
Female	10 (19.6)
Age (years)
Median	60
IQR	54 - 65
BMI
Median	22.1
IQR	20.2 - 24.6
History of smoking
Never smoker	20 (39.2)
Previous smoker	31 (60.8)
Pack year in current or previous smokers
Median	40
IQR	22.5 - 50
History of drinking
Never drinker	22 (43.1)
Previous drinker	29 (56.9)
Years of drinking
Median	30
IQR	17 - 35
Daily drinking amount (mL)
Median	225
IQR	100 - 375
Family oncological history
Yes	16 (31.4)
No	35 (68.6)
Tumor location
Thoracic upper portion	6 (11.8)
Thoracic middle portion	23 (45.1)
Thoracic lower portion	21 (41.2)
Esophagogastric junction	1 (2.0)
Clinical T stage
T3	31 (60.8)
T4a	20 (39.2)
Clinical N stage
N0	20 (39.2)
N1	29 (56.9)
N2	2 (3.9)
Clinical TNM stage
II	13 (25.5)
III	18 (35.3)
IVA	20 (39.2)
Preoperative cycles
Two	28 (54.9)
Three	21 (41.2)
Four	2 (3.9)
pCR status
pCR	11 (21.6)
non-pCR	40 (78.4)
Neoadjuvant pathological tumor depth
T0	11 (21.6)
Tis	9 (17.6)
T1a	5 (9.8)
T1b	2 (3.9)
T2	8 (15.7)
T3	15 (29.4)
T4a	1 (2.0)
Neoadjuvant pathological lymph node
N0	34 (66.7)
N1	12 (23.5)
N2	3 (5.9)
N3	2 (3.9)
Neoadjuvant pathological stage
I	27 (52.9)
II	7 (13.7)
IIIA	6 (11.8)
IIIB	9 (17.6)
IVA	2 (3.9)
Lymphovascular invasion
Yes	4 (7.8)
No	47 (92.2)
Perineural invasion
Yes	4 (7.8)
No	47 (92.2)
R0
Yes	5 (9.8)
No	46 (90.2)

Table 1. Clinicopathological Characteristics of Esophageal Squamous Cell Cancer Patients

Characteristics

N (%)

BMI: body mass index; IQR: interquartile range; pCR: pathological complete response.

Sex

Male

41 (80.4)

Female

10 (19.6)

Age (years)

Median

IQR

54 - 65

BMI

Median

22.1

IQR

20.2 - 24.6

History of smoking

Never smoker

20 (39.2)

Previous smoker

31 (60.8)

Pack year in current or previous smokers

Median

IQR

22.5 - 50

History of drinking

Never drinker

22 (43.1)

Previous drinker

29 (56.9)

Years of drinking

Median

IQR

17 - 35

Daily drinking amount (mL)

Median

225

IQR

100 - 375

Family oncological history

Yes

16 (31.4)

35 (68.6)

Tumor location

Thoracic upper portion

6 (11.8)

Thoracic middle portion

23 (45.1)

Thoracic lower portion

21 (41.2)

Esophagogastric junction

1 (2.0)

Clinical T stage

31 (60.8)

T4a

20 (39.2)

Clinical N stage

20 (39.2)

29 (56.9)

2 (3.9)

Clinical TNM stage

13 (25.5)

III

18 (35.3)

IVA

20 (39.2)

Preoperative cycles

Two

28 (54.9)

Three

21 (41.2)

Four

2 (3.9)

pCR status

pCR

11 (21.6)

non-pCR

40 (78.4)

Neoadjuvant pathological tumor depth

11 (21.6)

Tis

9 (17.6)

T1a

5 (9.8)

T1b

2 (3.9)

8 (15.7)

15 (29.4)

T4a

1 (2.0)

Neoadjuvant pathological lymph node

34 (66.7)

12 (23.5)

3 (5.9)

2 (3.9)

Neoadjuvant pathological stage

27 (52.9)

7 (13.7)

IIIA

6 (11.8)

IIIB

9 (17.6)

IVA

2 (3.9)

Lymphovascular invasion

Yes

4 (7.8)

47 (92.2)

Perineural invasion

Yes

4 (7.8)

47 (92.2)

Yes

5 (9.8)

46 (90.2)

**Table 2.** Univariate and Multivariate Binary Logistic Regression of Pretreatment Clinicopathological Factors for Prediction of Tumor and Nodal Responses
Variable	Poor-responder vs. good-responder
CI: confidence interval; BMI: body mass index.
Sex	1.562 (0.389 - 6.269)	0.529
Age (years)	4.0 (1.225 - 13.056)	0.022	1.086 (0.984 - 1.198)	0.102
BMI	1.185 (0.981 - 1.431)	0.078	1.291 (0.994 - 1.678)	0.056
Pretreatment clinical T stage	0.923 (0.294 - 2.898)	0.891
Pretreatment clinical N stage	1.115 (0.407 - 3.052)	0.833
Pretreatment clinical stage	1.335 (0.663 - 2.688)	0.418
Cycles	4.875 (1.428 - 16.641)	0.011	5.271 (1.278 - 21.740)	0.022
Pretreatment neutrophil-to-lymphocyte ratio	1.433 (0.929 - 2.210)	0.039	1.587 (0.860 - 2.930)	0.14
Pretreatment while blood cells (× 10⁹/L)	0.979 (0.745 - 1.288)	0.88
Pretreatment hemoglobin (g/L)	0.990 (0.957 - 1.024)	0.557
Pretreatment red blood cells (× 10¹²/L)	0.477 (0.142 - 1.602)	0.231
Pretreatment platelets (× 10⁹/L)	0.988 (0.976 - 1.000)	0.053	0.979 (0.962 - 0.996)	0.017
Pretreatment neutrophils (× 10⁹/L)	1.095 (0.791 - 1.515)	0.586
Pretreatment lymphocytes (× 10⁹/L)	0.462 (0.166 - 1.290)	0.141
Pretreatment monocytes (× 10⁹/L)	0.346 (0.027 - 4.378)	0.412

Table 2. Univariate and Multivariate Binary Logistic Regression of Pretreatment Clinicopathological Factors for Prediction of Tumor and Nodal Responses

Variable

Poor-responder vs. good-responder

Univariate

Multivariate

Odds ratio (95% CI)

P value

Odds ratio (95% CI)

P value

CI: confidence interval; BMI: body mass index.

Sex

1.562 (0.389 - 6.269)

0.529

Age (years)

4.0 (1.225 - 13.056)

0.022

1.086 (0.984 - 1.198)

0.102

BMI

1.185 (0.981 - 1.431)

0.078

1.291 (0.994 - 1.678)

0.056

Pretreatment clinical T stage

0.923 (0.294 - 2.898)

0.891

Pretreatment clinical N stage

1.115 (0.407 - 3.052)

0.833

Pretreatment clinical stage

1.335 (0.663 - 2.688)

0.418

Cycles

4.875 (1.428 - 16.641)

0.011

5.271 (1.278 - 21.740)

0.022

Pretreatment neutrophil-to-lymphocyte ratio

1.433 (0.929 - 2.210)

0.039

1.587 (0.860 - 2.930)

0.14

Pretreatment while blood cells (× 10⁹/L)

0.979 (0.745 - 1.288)

0.88

Pretreatment hemoglobin (g/L)

0.990 (0.957 - 1.024)

0.557

Pretreatment red blood cells (× 10¹²/L)

0.477 (0.142 - 1.602)

0.231

Pretreatment platelets (× 10⁹/L)

0.988 (0.976 - 1.000)

0.053

0.979 (0.962 - 0.996)

0.017

Pretreatment neutrophils (× 10⁹/L)

1.095 (0.791 - 1.515)

0.586

Pretreatment lymphocytes (× 10⁹/L)

0.462 (0.166 - 1.290)

0.141

Pretreatment monocytes (× 10⁹/L)

0.346 (0.027 - 4.378)

0.412