Correlation between the changes in sPD-1 after neoadjuvant therapy in patients with esophageal squamous cell carcinoma and pathological response

doi:10.3760/cma.j.cn371439-20251019-00045

Abstract

Abstract:

Objective To investigate the correlation between dynamic changes in serum soluble programmed death-1 （sPD-1） during neoadjuvant camrelizumab combined with chemotherapy and pathological response in patients with esophageal squamous cell carcinoma （ESCC）， and to evaluate the feasibility of sPD-1 as a predictive indicator of therapeutic efficacy. Methods A total of 125 patients with locally advanced ESCC who received neoadjuvant treatment with camrelizumab combined with albumin paclitaxel and cisplatin at Affiliated Huai′an No.1 People's Hospital of Nanjing Medical University from January 2019 to December 2021 were selected as the research subjects. Serum sPD-1 levels were measured at baseline， after the first cycle， after the second cycle， and before surgery. Patients were divided into the decreasing group （n=45） and non-decreasing group （n=80） based on early sPD-1 reduction （≥30% vs. <30%）. Correlations between sPD-1 dynamic changes and pathological complete response （pCR）， major pathological response （MPR）， and event-free survival （EFS） were analyzed using generalized estimating equation （GEE） models. Logistic regression model was used to identify the influencing factors of patients' pathological response； Kaplan-Meier curves were plotted to assess EFS in patients from the decreasing and non-decreasing groups， and the log-rank test was conducted； the Cox proportional hazards regression model was used to evaluate the influencing factors of patients' EFS. Results All 125 patients completed neoadjuvant therapy and surgery， with an R0 resection rate of 100% and no perioperative deaths. The baseline sPD-1 levels in the decreasing and non-decreasing groups were 5.9 （4.5， 7.3） and 5.7 （4.3， 7.6） ng/ml， respectively， with no statistically significant difference （Z=0.52， P=0.472）. Following the first treatment cycle， sPD-1 levels decreased to 3.1 （2.4， 4.0） ng/ml in the decreasing group and 4.8 （3.7， 6.5） ng/ml in the non-decreasing group， with a statistically significant difference （Z=19.26， P<0.001）. After the second treatment cycle， levels were 2.8 （2.2， 3.7） and 4.5 （3.4， 6.0） ng/ml， respectively， with a statistically significant difference （Z=22.13， P<0.001）. Before surgery， sPD-1 levels were 2.6 （2.0， 3.5） and 4.2 （3.3， 5.7） ng/ml，with a statistically significant difference （Z=21.84， P<0.001）. GEE analysis revealed that both the main effects of time （χ²=112.40， P<0.001） and group （χ²=7.63， P=0.006） were significant， and a significant interaction effect between time and group was observed （χ²=9.18， P=0.027）. After the first treatment cycle， the pCR rate for patients in decreasing group was 42.2% （19/45）， significantly higher than the 19.5% （16/80） in the non-decreasing group （χ²=7.59， P=0.006）. The MPR rate in the decreasing group was 68.9% （31/45）， significantly higher than that in the non-decreasing group， which was 48.1% （38/80）（χ²=5.35， P=0.021）. The survival analysis showed that the median EFS in the decreasing group was 34 months， longer than that of 28 months in the non-decreasing group （χ²=8.33， P=0.004）. Multivariate analysis indicated that an early reduction in sPD-1 of ≥30% （OR=2.34， 95%CI： 1.18-4.63， P=0.015） and baseline sPD-1 levels （OR=0.89， 95%CI： 0.80-0.98， P=0.023） were independent influencing factors of pCR in patients with locally advanced ESCC. Furthermore， early sPD-1 reduction ≥30% （HR=0.44， 95%CI： 0.23-0.85， P=0.014） and baseline sPD-1 （HR=1.09， 95%CI： 1.02-1.18， P=0.021） were identified as independent influencing factors for EFS in patients with locally advanced ESCC. The total incidence of adverse events was 52.0% （65/125）， mainly consisting of bone marrow suppression and mild to moderate immune-related reactions； the incidence of grade ≥3 adverse events was 9.6% （12/125）， with no treatment-related deaths. Conclusions Both baseline sPD-1 levels and early dynamic decline during neoadjuvant camrelizumab plus chemotherapy are significantly associated with pathological response and EFS in patients with locally advanced ESCC. Serum sPD-1， as a simple and dynamically monitorable peripheral blood marker， is expected to become a predictive tool for the efficacy of neoadjuvant immunotherapy.

Key words: Esophageal squamous cell carcinoma, Neoadjuvant chemotherapy, Camrelizumab, Programmed cell death-1, Pathological response

Gu Lei, Han Jihua, Tian Wenze, Zhou Wubi, Xin Yong. Correlation between the changes in sPD-1 after neoadjuvant therapy in patients with esophageal squamous cell carcinoma and pathological response[J]. Journal of International Oncology, 2026, 53(5): 276-282.

Figures/Tables 10

References 18

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项目	下降组（n=45）	非下降组（n=80）	t/χ²值	P值
年龄（岁）^a	68.2±7.1	66.7±7.9	0.33	0.742
性别^b
男	33（73.3）	57（71.3）	0.01	0.971
女	12（26.7）	23（28.7）	0.01	0.971
临床分期^b
Ⅲ期	28（62.2）	48（60.0）	0.06	0.812
Ⅱ期	17（37.8）	32（40.0）	0.06	0.812
吸烟史^b
是	28（62.2）	46（57.5）	0.25	0.623
否	17（37.8）	34（42.5）	0.25	0.623
饮酒史^b
是	24（53.3）	40（50.0）	0.11	0.744
否	21（46.7）	40（50.0）
BMI（kg/m²）^a	22.5±2.5	22.3±2.9	0.36	0.724
血红蛋白（g/L）^a	127.6±14.9	128.2±16.1	0.18	0.862
白蛋白（g/L）^a	39.8±4.7	39.5±4.9	0.32	0.753
LDH（U/L）^b
≥220	12（26.7）	22（27.5）	0.01	0.934
<220	33（73.3）	58（72.5）	0.01	0.934
ECOG体能状态评分（分）^b
1	15（33.3）	29（36.3）	0.09	0.763
0	30（66.7）	51（63.7）	0.09	0.763

时间点	下降组（n=45）	非下降组（n=80）	Z/Wald χ²值	P值
基线	5.9（4.5，7.3）	5.7（4.3，7.6）	0.52	0.472
治疗第1周期后	3.1（2.4，4.0）	4.8（3.7，6.5）	19.26	<0.001
治疗第2周期后	2.8（2.2，3.7）	4.5（3.4，6.0）	22.13	<0.001
术前	2.6（2.0，3.5）	4.2（3.3，5.7）	21.84	<0.001
时间主效应			112.40	<0.001
组别主效应			7.63	0.006
交互作用（时间×组别）			9.18	0.027

时间点	达到MPR组（n=69）	未达到MPR组（n=56）	Z值	P值
基线	5.8（4.6，7.2）	5.9（4.4，7.5）	0.39	0.531
治疗第1周期后	3.0（2.3，3.9）	4.7（3.8，6.4）	19.26	<0.001
治疗第2周期后	2.7（2.1，3.6）	4.4（3.4，5.9）	22.13	<0.001
术前	2.5（2.0，3.3）	4.1（3.2，5.6）	21.84	<0.001

时间点	达到pCR组（n=35）	未达到pCR组（n=90）	Z值	P值
基线	5.7（4.4，7.1）	5.9（4.5，7.6）	0.51	0.478
治疗第1周期后	2.9（2.3，3.8）	4.8（3.7，6.5）	19.26	<0.001
治疗第2周期后	2.6（2.1，3.5）	4.5（3.5，6.0）	22.13	<0.001
术前	2.4（1.9，3.2）	4.2（3.3，5.7）	21.84	<0.001

变量	β值	SE值	OR值	95%CI	P值
早期sPD-1下降≥30%（是/否）	0.96	0.33	2.60	1.33~5.09	0.004
基线sPD-1（ng/ml）	-0.13	0.05	0.88	0.79~0.98	0.020
BMI（kg/m²）	-0.07	0.04	0.93	0.86~1.00	0.061
年龄（岁）	-0.01	0.01	0.99	0.97~1.02	0.384
性别（男/女）	0.08	0.29	1.08	0.61~1.92	0.792
临床分期（Ⅲ期/Ⅱ期）	0.21	0.31	1.23	0.67~2.26	0.498
肿瘤部位（中段/上段或下段）	0.15	0.28	1.16	0.67~2.01	0.594
吸烟史（有/无）	0.19	0.27	1.21	0.70~2.09	0.512
饮酒史（有/无）	0.11	0.26	1.11	0.66~1.88	0.689
血红蛋白（g/L）	-0.01	0.01	0.99	0.97~1.01	0.276
白蛋白（g/L）	-0.02	0.03	0.98	0.92~1.03	0.412
LDH（≥220 U/L/<220 U/L）	0.24	0.29	1.27	0.72~2.25	0.406
ECOG体能状态评分（1分/0分）	0.31	0.35	1.36	0.68~2.74	0.379