Study on the predictive value of pretreatment peripheral blood inflammatory markers regarding immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma

Abstract

Objective

To explore the effects of pretreatment peripheral blood panimmune-inflammation value (PIV), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the efficacy and prognostic value of immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma (ESCC).

Methods

Clinical data of 107 inoperable advanced or locally advanced ESCC patients were retrospectively analysed between May 2019 and August 2023, the receiver operating characteristic curves (ROCs) of PIV, SII, NLR, and PLR in patients prior to immunotherapy were plotted, and their optimal cutoff values were determined. The risk factors were determined by univariate and multivariate analyses in groups based on the optimal cut-off values.

Results

Peripheral blood PIV, SII and PLR before immunotherapy had predictive value for the optimal efficacy of immunotherapy in patients with inoperable advanced or locally advanced ESCC; patients with PIV ≥415.885, SII ≥834.295 and NLR ≥3.740 had a low objective response rate (ORR), disease control rate (DCR), a short progression-free survival (PFS) and overall survival (OS) after immunotherapy (p < 0.05). Patient tumour stage, distant lymph node metastasis, lung metastasis, liver metastasis, PIV, SII, and NLR were risk factors affecting PFS and OS (p < 0.05). Tumour stage and SII were independent risk factors affecting PFS and OS (p < 0.05).

Conclusion

In patients with inoperable advanced or locally advanced ESCC, peripheral blood PIV, SII, and NLR have predictive value for immunotherapy outcome, SII is an independent risk factor affecting the survival prognosis, and SII ≥834.295 suggests a poor prognosis from immunotherapy.

Keywords:

• Oesophageal squamous cell carcinoma (ESCC)
• peripheral blood inflammatory markers
• immunotherapy
• prognosis

Introduction

Oesophageal cancer (EC) is currently the seventh most commonly diagnosed malignancy and the sixth leading cause of cancer death worldwide [1]. Squamous cell carcinoma (SCC) is the most common histological type of EC, accounting for more than 90% of cases in Asia, represented by China [2, 3]. Oesophageal squamous cell carcinoma (ESCC) has an insidious onset, and the majority of patients are already in advanced stages at the time of diagnosis [4]. Patients with advanced ESCC have a 5-year survival rate of less than 10% and a median survival of approximately 10 months [5, 6]. Immunotherapy combined with chemotherapy prolongs the overall survival in patients with advanced ESCC and has become the standard care written into clinical guidelines [7–11].

However, immunotherapy varies widely in patients with advanced ESCC, and there is a lack of effective predictors of efficacy and prognosis [12]. Predictors such as programmed cell death ligand 1 (PD-L1), tumour mutational burden (TMB) and mismatch repair (MMR) proteins rely on histopathology and have disadvantages such as difficulty of access, long detection period, relatively subjective judgement methods, and limited access to materials that are not representative of the overall state [13, 14] that limit their clinical application and predictive value.

The tumour immune microenvironment (TIM) interacts with immune cells and affects the effect of tumour immunotherapy [15]. Neutrophils, lymphocytes, monocytes and platelets are important components of the TIM and participate in tumour-associated inflammatory responses [16]. Peripheral blood inflammatory markers (NLR, PLR, PIV and SII, etc.) are comprehensive indicators based on inflammatory cells, and they have advantages such as being easy to obtain clinically, having low testing costs, being less affected by tumour heterogeneity and having predictive value for tumour immunotherapy [17]. They have been shown to be associated with the poor prognosis in many tumours, including ESCC [18–22]. However, relevant studies on the predictive value of peripheral blood inflammatory markers regarding the immunotherapeutic efficacy and prognosis of unresectable advanced or locally advanced ESCC have not yet been reported, and the differences in the predictive value of different peripheral blood inflammatory markers are also unclear. Therefore, the above questions urgently need to be answered by clinical studies.

To address these questions, we conducted a retrospective study to explore the predictive role of pretreatment peripheral blood inflammatory markers PIV, SII, NLR and PLR in immunotherapy in patients with unresectable advanced or locally advanced ESCC with an emphasis on efficacy and prognosis. We compared the above indices and screened the risk factors affecting prognosis by unifactorial and multifactorial survival analysis to discover the factors with the best predictive value regarding the efficacy and prognosis of immunotherapy in patients with ESCC. We will explore new indicators for predicting the efficacy and prognosis of immunotherapy in ESCC patients.

Materials and methods

Clinical materials

Clinical data of inoperable advanced or locally advanced ESCC patients who received immunotherapy in Department of Integrated Chinese and Western Medicine and Department of Medical Oncology, Zhongshan Hospital (Xiamen), Fudan University between May 2019 and August 2023 were retrospectively analysed. The patients in this study were refined with cervicothoracic, abdominopelvic and pelvic enhancement computed tomography (CT), cranial enhancement magnetic resonance imaging (MRI) and/or whole-body bone scanning as needed. The clinical staging of patients was based on the American Joint Committee on Cancer (AJCC) 8^th edition. The inclusion criteria were as follows: 1) age greater than 18 years and complete medical records; 2) pathology of ESCC; 3) advanced or locally advanced patients (clinical stage III or IV) who were inoperable at the time of immunotherapy; and 4) completion of at least 2 cycles of immunotherapy. The exclusion criteria were as follows: 1) combination of other malignant tumours; 2) combination of infectious diseases, haematologic diseases, autoimmune diseases, and other conditions that could affect inflammatory indices within 2 weeks prior to immunotherapy; 3) recent or undergoing anti-inflammatory or immunosuppressive treatments; and 4) severe cardiac, hepatic, and renal insufficiency diseases. A total of 196 patients met the inclusion criteria. According to the above inclusion and exclusion criteria, a total of 107 patients were included in this study.

Research methods

Data Collection Basic data, clinical information, pathological and imaging data, and laboratory examinations of enrolled patients were collected through the electronic medical record system. The collected information included sex, age of onset, primary tumour location, pathological grade, local lymph node metastasis, distant metastasis, stage, HER-2 (human epidermal growth factor receptor 2) expression, PD-L1 expression, MMR, TMB, time of first use of immunotherapy, treatment line, specific drugs, treatment effect, time of progression after immunotherapy, time of death after immunotherapy, time of the last follow-up, patient status at the time of the last follow-up, and haematocrit value within 1 week before the first immunotherapy. The PIV, SII, NLR, and PLR were calculated from the haematocrit values of enrolled patients within 1 week before immunotherapy: 1) PIV = neutrophil count × platelet count × monocyte count/lymphocyte count; 2) SII = platelet count × neutrophil count/lymphocyte count; 3) NLR = neutrophil count/lymphocyte count; and 4) PLR = platelet count/lymphocyte count.

Follow-up Observation A combination of electronic medical records, telephone, internet hospital and outpatient review were used to establish the patient’s diagnosis and treatment, laboratory and imaging tests and patient survival. The follow-up period is up to September 30, 2023.

Treatment Enrolled patients received at least 2 cycles of immunotherapy (alone, in combination with chemotherapy, or in combination with targeted therapy) with programmed death-1 (PD-1) inhibitors (including pembrolizumab, nivolumab, tislelizumab, camrelizumab, sintilimab, toripalimab, etc.). The dosage was as recommended by the instruction manual and was to be administered every 3 weeks. Before each immunotherapy session, routine blood test, routine urine test, myocardial markers, electrolytes of liver and kidney function, inflammatory indices, adrenocortical function, thyroid function, tumour markers and electrocardiogram were checked, and enhanced CT scan of cervical, thoracic and abdominal area were checked every 2 cycles of treatment to evaluate the efficacy of the treatment (if the patient cannot tolerate enhanced CT, CT with scanning was performed instead). Observational indicator efficacy assessment was performed according to response evaluation criteria in solid tumours (RECIST) 1.1, and details of each efficacy assessment, optimal efficacy status after immunotherapy, PFS time after immunotherapy, and OS time after immunotherapy were recorded. PFS time was the time from the beginning of immunotherapy to the time of disease progression or death due to any cause, and OS time was the time from the start of immunotherapy to death due to any cause.

The flow chart of this study is detailed in Figure 1.

Figure 1. The flowchart of the study on the predictive value of pretreatment peripheral blood inflammatory markers regarding immunotherapy in patients with inoperable advanced or locally advanced ESCC.

Statistical analysis

Statistical analysis was performed using SPSS 23.0, and statistical tests were performed using two-sided tests, with p < 0.05 being considered statistically significant. Mean ± standard deviation was used to statistically describe the measurement data that conformed to normality and chi-square; median and quartiles were used to statistically describe the measurement data that did not conform to normality and chi-square; frequency or constitutive ratio was used to statistically describe the count data. For measurements that met normality and the Chi-square test, a two independent samples t test was used for between-group comparisons, and analysis of variance (ANOVA) was used for pretreatment and post-treatment comparisons between groups. Two independent samples Wilcoxon rank-sum test was used for between-group comparisons of rank information or measures that did not satisfy normal distribution or chi-square. The Chi-square test was used for component ratios.

The ROC curves of PIV, SII, NLR, and PLR were plotted according to whether the best efficacy was effective or not as the ending index, the maximum value of Youden index was calculated from the ROC curves, and the value corresponding to the maximum value of Youden index was the optimal truncation value (Youden index = sensitivity + specificity-1), with which the indices had the best sensitivity and specificity. According to the best cut-off value, the patients were categorized into groups: higher than the best cut-off value defined the high group, and lower than the best cut-off value defined the low group. Survival curves were plotted by the Kaplan–Meier method, and one-way analyses were performed using the log-rank method; multifactorial analyses were performed using the Cox proportional risk regression model.

Results

Baseline characteristics

A total of 107 patients with inoperable advanced or locally advanced ESCC were included in this study, and the baseline characteristics of the patients are shown in Table 1.

Table 1. Baseline characteristics of patients with inoperable advanced or locally advanced ESCC.

Classification		Number of cases (percentage)
Sex	Male	91 (85.0%)
	Female	16 (15.0%)
Age (years)		62.87 ± 8.61
	<65	58 (54.2%)
	≥65	49 (45.8%)
PS score	0–1	99 (92.5%)
	2	8 (7.5%)
Tumour location	Upper section	22 (20.1%)
	Middle section	35 (32.7%)
	Lower section	50 (46.7%)
Degree of differentiation	Low polarization	47 (43.9%)
	Middle polarization	50 (46.7%)
	High differentiation	10 (9.4%)
Tumour staging	III	48 (44.9%)
	IV	59 (55.1%)
Relocation site	Regional lymph nodes	98 (91.6%)
	Distant lymph nodes	42 (39.3%)
	Liver	14 (13.1%)
	Lung	21 (19.6%)
Radiotherapy	Yes	45 (42.1%)
	No	62 (57.9%)
Number of lines at immunotherapy	Front line	92 (86.0%)
	Second line and above	15 (14.0%)

Optimal cut-off values for PIV, SII, NLR, and PLR

ROC curves were plotted according to whether the parameter was effective (including CR, PR and SD) as an outcome indicator (Figure 2).

Figure 2. ROC curves for peripheral blood inflammatory markers PIV, SII, NLR and PLR in patients with inoperable advanced or locally advanced ESCC prior to immunotherapy: The areas under the curve (AUC) for PIV, SII, NLR, and PLR were 0.833, 0.813, 0.810 and 0.535, the optimal cut-off values for PIV, SII, NLR, and PLR were 415.885, 834.295, 3.740 and 151.250.

The optimal cutoff value in each group was determined by calculating the maximum value of the Youden index (Table 2). Based on the ROC curves and area under the curve of each group, it was suggested that PIV, SII and NLR had good predictive value regarding efficacy.

Table 2. Optimal cut-off values of PIV, SII, NLR, and PLR.

Classification	Optimal cutoff value	Area under the curve(95% CI)	Sensitivity	Specificity
PIV	415.885	0.833(0.735–0.932)	90.9%	67.7%
SII	834.295	0.813(0.702–0.925)	90.9%	76.0%
NLR	3.740	0.810(0.700–0.919)	81.8%	76.0%
PLR	151.250	0.535(0.365–0.705)	81.8%	35.4%

Effect of PIV, SII, NLR, and PLR on ORR and DCR of immunotherapy in patients with inoperable advanced or locally advanced ESCC

Grouped according to the optimal cutoff value, patients with higher values than the optimal cut-off value were defined as constituting the high group, and patients with lower values than the optimal cutoff value were defined as constituting the low group. The effects of PIV, SII, NLR, and PLR on the ORR and DCR of immunotherapy for inoperable advanced or locally advanced ESCC patients were evaluated by using the Chi-square test (Table 3). For inoperable advanced or locally advanced ESCC patients receiving immunotherapy, the SII and NLR low group had higher ORR, and the PIV, SII and NLR low group had higher DCR, and the difference was statistically significant.

Table 3. Effect of PIV, SII, NLR, and PLR on ORR and DCR of immunotherapy in patients with inoperable advanced or locally advanced ESCC.

Classification	Therapeutic effects				N(%)	ORR(%)	P	DCR(%)	P
	CR	PR	SD	PD
PIV							0.071		<0.001*
Low	0	36	29	1	66 (61.7)	54.5		98.5
High	0	15	16	10	41 (38.3)	45.5		75.6
SII							0.016*		<0.001*
Low	0	41	32	1	74 (69.2)	55.4		98.6
High	0	10	13	10	33 (30.8)	30.3		69.7
NLR							0.047*		<0.001*
Low	0	40	32	2	74 (69.2)	54.1		97.3
High	0	11	13	9	33 (30.8)	33.3		72.7
PLR							0.170		0.184
Low	0	22	15	2	39 (36.4)	56.4		94.9
High	0	29	30	9	68 (63.6)	42.6		86.8

1. Complete remission (CR), partial response (PR), stable disease (SD), disease progression (PD).

2. ORR = (CR + PR)/(CR + PR + SD + PD) × 100%, DCR = (CR + PR + SD)/(CR + PR + SD + PD) × 100%.

3. *p < 0.05, the difference is statistically significant.

Relationship between PIV, SII, NLR, and PLR and the prognosis of immunotherapy in patients with inoperable advanced or locally advanced ESCC

Based on the optimal cutoff values, PIV, SII, NLR, and PLR were categorized into high and low groups, and the survival analysis curves were plotted according to OS time and status at the last follow-up (Figure 3). The patients in the low PIV, SII, and NLR groups had longer median OS times, with statistically significant differences (p < 0.01), and the patients in the high and low PLR groups had a similar median OS time, with no statistically significant differences (p = 0.83).

Figure 3. Kaplan–Meier estimates of overall survival (OS) according to PIV (A), SII (B), NLR (C) and PLR (D).

Univariate analysis using the log-rank method suggested that tumour stage, distant lymph node metastasis, lung metastasis, liver metastasis, PIV, SII, and NLR were risk factors affecting PFS and OS in immunotherapy of inoperable advanced or locally advanced ESCC (Table 4). The analysis of the above indicators in the multivariate Cox proportional risk model suggested that tumour stage and SII (best cutoff value 834.295) were independent risk factors for PFS and OS in immunotherapy of inoperable advanced or locally advanced ESCC (Table 5).

Table 4. Univariate analysis of factors affecting PFS and OS in immunotherapy for inoperable advanced or locally advanced ESCC.

Factor	Median PFS (months)	95% CI	P	Median OS (months)	95% CI	P
Sex			0.924			0.919
Male	9.8	6.8–12.8		15.2	11.6–18.8
Female	8.0	5.4–10.6		19.8	4.9–34.7
Age (year)			0.489			0.827
<65	8.6	6.0–11.2		15.2	11.5–18.9
≥65	10.0	3.9–16.1		18.2	7.7–28.7
PS score			0.148			0.337
0–1	10.0	6.2–13.8		17.7	12.9–22.5
2	6.9	0.2–13.6		8.9	6.8–11.0
Tumour location			0.849			0.923
Upper	10.5	7.8–13.2		14.7	10.6–18.8
Middle	8.8	3.6–14.0		19.8	16.1–23.5
Lower	8.6	3.9–13.3		14.4	10.5–18.3
Degree of differentiation			0.932			0.865
Low polarization	8.0	6.1–9.9		14.4	8.1–20.7
Middle polarization	11.1	5.5–16.7		17.7	11.7–23.7
High differentiation	9.8	8.4–11.2		12.0	11.7–12.3
Tumour staging			0.001*			0.020*
III	18.3	9.4–27.2		24.0	NA
IV	8.0	6.4–9.6		14.3	11.3–17.3
Regional lymph node metastasis			0.514			0.926
No	10.5	7.9–13.1		14.3	0.6–28.0
Yes	9.3	6.1–12.5		17.3	12.6–22.0
Distant lymph node metastasis			0.032*			0.039*
No	12.6	6.0–19.2		20.4	12.2–28.6
Yes	8.6	6.8–10.4		14.3	13.1–15.6
Lung metastasis			0.030*			0.035*
No	11.9	7.0–16.8		18.2	11.5–24.9
Yes	8.4	7.2–9.6		15.2	13.4–17.0
Liver metastasis			<0.001*			0.002*
No	11.9	8.3–15.5		17.7	12.0–23.4
Yes	4.3	1.9–6.7		8.7	7.9–9.5
Radiotherapy			0.901			0.956
No	8.5	6.1–10.9		14.3	10.6–18.0
Yes	11.6	7.7–15.5		18.2	13.0–23.4
Number of lines at immunotherapy			0.207			0.507
Front line	9.8	7.1–12.5		15.2	11.6–18.8
Second line and above	7.7	0.0–18.7		17.9	4.4–31.4
PIV			<0.001*			<0.001*
Low	14.1	11.4–16.8		21.2	17.8–24.6
High	6.9	3.3–10.5		8.9	4.8–13.0
SII			<0.001*			<0.001*
Low	13.0	9.2–16.8		20.4	16.8–24.0
High	5.2	1.9–8.5		8.5	7.7–9.3
NLR			<0.001*			<0.001*
Low	13.0	9.3–16.7		19.4	15.6–23.2
High	6.9	3.6–10.2		8.4	6.9–9.9
PLR			0.889			0.827
Low	8.2	5.3–11.1		15.2	9.1–21.3
High	10.0	6.9–13.2		15.2	9.2–21.2

* p < 0.05, statistically significant difference.

Table 5. Multifactorial analysis of factors affecting PFS and OS in immunotherapy of inoperable advanced or locally advanced ESCC.

Factor	PFS		OS
	HR(95% CI)	P	HR(95% CI)	P
Tumour staging(IV vs. III)	2.0 (1.2–3.4)	0.010*	2.4 (1.4–4.1)	0.002*
Liver metastasis(Yes vs. No)	2.5 (1.3–5.0)	0.009*	/	/
SII(High vs. Low)	2.6 (1.5–4.4)	<0.001*	3.2 (1.9–5.4)	<0.001*

* p < 0.05, statistically significant difference.

Discussion

Immunotherapy varies widely in patients with advanced ESCC, and clear predictors of efficacy and prognosis are lacking [12]. Inflammatory response is involved in immunotherapy of tumours, and studies have confirmed that systemic inflammatory response is associated with poor prognosis of tumours [16]. In this study, we retrospectively analysed the clinical data of 107 patients with unresectable advanced or locally advanced ESCC undergoing immunotherapy to reveal for the first time the efficacy and prognostic predictive value of peripheral blood inflammatory markers and to screen for independent risk factors affecting prognosis by survival analysis. The study results indicated that peripheral blood inflammatory markers PIV, SII and NLR had efficacy and prognostic value in immunotherapy for patients with unresectable advanced or locally advanced ESCC, while PLR did not; according to the area under the ROC curve, the predictive value regarding the efficacy of immunotherapy was ranked as follows: PIV, SII, and NLR exhibited areas under the curve of 0.833, 0.813 and 0.813, respectively; peripheral blood inflammatory markers were classified into low and high groups according to the optimal cutoff value determined by the ROC curve; subgroup analysis indicated that low PIV, SII and NLR suggested that patients with unresectable advanced or locally advanced ESCC would have a longer PFS and OS after immunotherapy; univariate analysis suggested that tumour stage, distant lymph node metastasis, lung metastasis, liver metastasis, PIV, SII, and NLR were risk factors affecting PFS and OS in patients receiving immunotherapy for unresectable advanced or locally advanced ESCC, and multivariate Cox proportional risk model analysis suggested that tumour stage and SII (optimal cut-off value of 834.295) were independent risk factors.

TIM plays an important role in tumorigenesis and progression and is a potential marker of tumour immunotherapy response [23, 24]. Inflammatory cells and inflammatory mediators are important components of TIM [25, 26], and neutrophils, lymphocytes, monocytes, and platelets are involved in tumour-associated inflammatory responses and play an important role in tumorigenesis and progression [16]. Neutrophils are involved in the inflammatory response and thus tissue destruction to promote cancer development; lymphocytes are involved in the regulation of the immune system and thus influence cancer development and progression [27]; and platelets act as a source of transforming growth factor β and thus regulate the complex interplay of effector immune cell activation, extravasation, and systemic inflammation to play a pleiotropic role in tumour progression and immune escape [28]. The NLR and PLR, based on the ratio of neutrophils, platelets to lymphocytes, became the first peripheral blood inflammatory markers to be investigated, and have been shown to correlate with the prognosis of a variety of tumours, including lung, gastric, and colorectal cancers [25, 26]. The ORIENT-2 study explored the predictive value of NLR regarding efficacy of combining immuno-chemotherapy in the treatment of advanced or metastatic ESCC and demonstrated that an NLR of ≥3 was associated with poor survival prognosis [15]; patients with NLR ≥3.74 had significantly lower ORR and DCR than those with NLR <3.74, patients in the high NLR group had significantly lower median PFS and OS after immunotherapy than those in the low NLR group, and NLR ≥3.740 was one of the risk factors affecting the prognosis of patients with inoperable advanced or locally advanced ESCC treated with immunotherapy in the univariate analysis, further confirming the value of NLR in predicting the efficacy of immunotherapy for ESCC. PLR ≥133 was confirmed to be associated with an independent risk factor for poor prognosis in postoperative chemotherapy-treated patients with nonmetastatic ESCC [29]. However, the results of the present study showed that PLR was not significantly correlated with the prognosis of immunotherapy in patients with unresectable advanced or locally advanced ESCC and did not have value in predicting the efficacy and prognosis. This suggests that PLR may have different values according to differences in stage of treatment and therapeutic approach in ESCC patients, and the possible reasons deserve further study. As emerging peripheral blood inflammatory markers in recent years, PIV and SII reflect inflammatory protumorigenic cells (i.e., neutrophils, platelets, and monocytes) and anticancer cells (i.e., lymphocytes), and a high value of PIV and SII reflects a state of systemic immunosuppression, with a greater likelihood of tumour progression and metastasis. Therefore, PIV and SII reflect host inflammation and the immune response more comprehensively than NLR and PLR [30, 31]. Studies on the efficacy and prognosis of PIV and SII in the treatment of ESCC patients have focused on surgery, preoperative neoadjuvant chemotherapy, and postoperative adjuvant chemotherapy and radiotherapy [32, 33], but no studies have been conducted to determine the efficacy and prognosis of immunotherapy in ESCC patients who are not operable. The present study confirmed that PIV and SII had efficacy and prognostic value in immunotherapy for patients with unresectable advanced or locally advanced ESCC and were superior to NLR and PLR; unifactorial and multifactorial regression staging further confirmed that a high SII (SII ≥834.295) was an independent risk factor for the duration of PFS and OS in immunotherapy.

In the present study, we explored the predictive value of peripheral blood inflammatory markers regarding the efficacy and prognosis of immunotherapy in patients with unresectable advanced or locally advanced ESCC, compared and screened the best predictive indicators and determined the indicator cutoff values for future use in immunotherapy. However, there are some shortcomings in this study. First, this study is a single-centre retrospective analysis, which may have sample selection bias and experimental error, and prospective studies need to be carried out in the later stages regarding the above predictive indices to further confirm their clinical value. Second, the optimal truncation values of PIV, SII, NLR, and PLR reported by a number of studies, including the present one, do not agree with each other, which is troubling in terms of clinical application, and the clinical application of these indices needs to be further explored in later stages. The follow-up study can further explore the relatively certain reference value range for clinical use. Finally, this study only explored the efficacy and prognosis of immunotherapy from the perspective of inflammatory response and TIM and did not incorporate related factors such as immune cells and even tumour cells, so the predictive value is relatively limited. Future studies can be considered for the establishment of a multidimensional comprehensive efficacy and prognosis prediction system that incorporates peripheral blood inflammatory markers along with PD-L1, TMB and MMR for greater comprehensiveness and accuracy.

Conclusions

Peripheral blood PIV, SII, and NLR before immunotherapy had predictive value regarding immunotherapy outcome in patients with inoperable advanced or locally advanced ESCC, and SII was an independent risk factor affecting the survival prognosis of patients, with SII ≥834.295 suggesting a poor prognosis.

Ethical approval

This study was approved by Ethics Committee of Zhongshan Hospital, Fudan University (Xiamen Branch) (No. B2023-137).

Abbreviations
PIV	=	panimmune-inflammation value
SII	=	systemic immune-inflammation index
NLR	=	neutrophil-to-lymphocyte ratio
PLR	=	platelet-to-lymphocyte ratio
ESCC	=	oesophageal squamous cell carcinoma
ROCs	=	receiver operating characteristic curves
ORR	=	objective response rate
DCR	=	disease control rate
PFS	=	progression-free survival
OS	=	overall survival
PS	=	performance status
EC	=	oesophageal cancer
SCC	=	squamous cell carcinoma
PD-L1	=	programmed cell death ligand 1
TMB	=	tumour mutational burden
MMR	=	mismatch repair
TIM	=	tumour immune microenvironment
CT	=	computed tomography
MRI	=	magnetic resonance imaging
RECIST	=	response evaluation criteria in solid tumours
AJCC	=	American Joint Committee on Cancer

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding author XP Z upon reasonable request.

Additional information

Funding

This work was supported by the Fujian Provincial Health Technology Project under Grant 2021QNB020; and Xiamen Medical and Health Guidance Project under Grant 3502Z20214ZD1075