The predictive value of systemic immune-inflammation index in the efficacy of neoadjuvant immunochemotherapy for esophageal cancer and the construction of clinical prediction model_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SONG Min ¹ , KONG Feifei ² , ZHAO Haibo ³ ,  CUI Hongxia ³ ,  CAI Haibo ⁴

1. Jining Medical University, Jining, 272000, Shandong, P. R. China;
2. Department of Hematology and Oncology, Qufu People’s Hospital, Qufu, 273100, Shandong, P. R. China;
3. Department of Oncology, The First People’s Hospital of Jining, Jining, 272000, Shandong, P. R. China;
4. Department of Thoracic Surgery, The First People’s Hospital of Jining, Jining, 272000, Shandong, P. R. China;

Corresponding author：

CUI Hongxia, Email: chxjnyy@163.com; CAI Haibo, Email: 13518670801@163.com

Keywords：

Esophageal cancer; neoadjuvant immunochemotherapy; major pathological response; systemic immune-inflammation index; clinical prediction model

DOI：

10.7507/1007-4848.202412051

Video：

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Objective To explore the predictive value of the pre-treatment systemic immune-inflammation index (SII) for major pathological response (MPR) after neoadjuvant immunochemotherapy (nICT) in esophageal cancer, and to construct a clinical prediction model combined with relevant clinical characteristics. Methods Retrospective collection of clinical data from patients with locally advanced esophageal cancer who received nICT followed by radical surgery at the First People's Hospital of Jining from January 2022 to June 2023. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of pre-treatment SII and neutrophil-lymphocyte ratio (NLR) for the efficacy of nICT in esophageal cancer. The optimal cut-off value was determined based on the maximum Youden index. Further, univariate and multivariate logistic regression analyses were employed to identify predictors for MPR after nICT in esophageal cancer and to construct a nomogram model. The model was evaluated using the area under the ROC curve (AUC), and internal validation was conducted using the Bootstrap method. Results A total of 63 patients were included, with 38 males and 25 females, and a median age of 67 (49-79) years. The ROC curve indicated that the optimal cut-off value for pre-treatment SII was 521.7, with an AUC of 0.701 [95%CI (0.564, 0.838)] for predicting MPR after nICT in esophageal cancer. The ROC curve showed that the optimal cut-off value for pre-treatment NLR was 2.32, with an AUC of 0.681 [95%CI (0.544, 0.818)]. Multivariate logistic regression analysis results revealed cT stage [OR=0.232, 95%CI (0.071, 0.759), P=0.016] and SII [OR=5.477, 95%CI (1.584, 18.939), P<0.001] as independent predictors for MPR after nICT in esophageal cancer. Based on the multivariate logistic regression results, a clinical prediction model was constructed, with an AUC of 0.789 on the ROC curve. The calibration plot showed a good agreement between the prediction curve and the ideal curve. Conclusion Pre-treatment SII can serve as an independent predictive indicator for MPR in patients with esophageal cancer after nICT. The clinical model, established in combination with cT stage, can better predict the efficacy of nICT in esophageal cancer.

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2.	Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: The randomized controlled CROSS trial. J Clin Oncol, 2021, 39(18): 1995-2004.
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11.	林光一, 梁伟成, 唐汉, 等. 免疫炎症指标对食管鳞癌新辅助放化疗疗效的预测价值. 中华消化外科杂志, 2023, 22(3): 363-370.Lin GY, Liang WC, Tang H, et al. The value of immune inflammatory index in predicting the therapeutic efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma. Chin J Dig Surg, 2023, 22(3): 363-370.
12.	Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res, 2014, 20(23): 6212-6222.
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16.	张春艳, 刘明珠, 侯宁, 等. 系统免疫炎症指数对放化疗老年食管癌患者预后的预测作用. 现代消化及介入诊疗, 2021, 26(3): 314-318.Zhang CY, Liu MZ, Hou N, et al. The predictive effect of systemic immune-inflammation index on the prognosis of elderly patients with esophageal cancer with radiotherapy and chemotherapy. Mod Dig Interv, 2021, 26(3): 314-318.
17.	张旺, 曹家兴, 刘九洋, 等. 全身免疫炎症指数对乳腺癌新辅助化疗疗效的预测价值及临床预测模型的构建. 中华乳腺病杂志(电子版), 2023, 17(3): 136-142.Zhang W, Cao JX, Liu JY, et al. Predictive value of systemic immune-inflammation index for neoadjuvant chemotherapy response in breast cancer and establishment of clinical prediction model. Chin J Breast Dis (Electron Version), 2023, 17(3): 136-142.
18.	Yang W, Xing X, Yeung SJ, et al. Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma. J Immunother Cancer, 2022, 10(1): e3497.
19.	Liu J, Li J, Lin W, et al. Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study. Int J Cancer, 2022, 151(1): 128-137.
20.	Wu Z, Zheng Q, Chen H, et al. Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma. J Thorac Dis, 2021, 13(6): 3518-3528.
21.	Han W, Weng K, Zhang P, et al. Predictive value of systemic immune-inflammation index for pathological complete response in patients receiving neoadjuvant immunochemotherapy for locally advanced esophageal cancer. Front Surg, 2023, 9: 1091601.
22.	Zhang X, Gari A, Li M, et al. Combining serum inflammation indexes at baseline and post treatment could predict pathological efficacy to anti-PD-1 combined with neoadjuvant chemotherapy in esophageal squamous cell carcinoma. J Transl Med, 2022, 20(1): 61.

1. He Z, Ke Y. Precision screening for esophageal squamous cell carcinoma in China. Chin J Cancer Res, 2020, 32(6): 673-682.
2. Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: The randomized controlled CROSS trial. J Clin Oncol, 2021, 39(18): 1995-2004.
3. Yang H, Liu H, Chen Y, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phaseⅢmulticenter, randomized, open-label clinical trial. J Clin Oncol, 2018, 36(27): 2796-2803.
4. 冉兴强, 施贵冬, 李洋云, 等. 免疫检查点抑制剂在食管癌新辅助治疗中的研究进展. 中国胸心血管外科临床杂志, 2024, 31(4): 621-630.Ran XQ, Shi GT, Li YY, et al. Progress of immune checkpoint inhibitors in neoadjuvant therapy for esophageal cancer. Chin J Clin Thorac Cardiovasc Surg, 2024, 31(4): 621-630.
5. Lu Z, Wang J, Shu Y, et al. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): Multicentre, randomised, double blind, phase 3 trial. BMJ, 2022: e68714.
6. Kojima T, Hara H, Tsuji A, et al. First-line pembrolizumab+chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus, 2022, 19(4): 683-692.
7. Song Y, Zhang B, Xin D, et al. First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: A randomized, double-blind phase 3 trial. Nat Med, 2023, 29(2): 473-482.
8. Shen L, Kato K, Kim S, et al. Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): A randomized phaseⅢstudy. J Clin Oncol, 2022, 40(26): 3065-3076.
9. Anand S, Bhati G, Gurram R, et al. Does neutrophil-to-lymphocyte ratio (NLR) predict pathologic response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma? J Gastrointest Cancer, 2021, 52(2): 659-665.
10. Wu Y, Chen J, Zhao L, et al. Prediction of pathologic response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma incorporating hematological biomarkers. Cancer Res Treat, 2021, 53(1): 172-183.
11. 林光一, 梁伟成, 唐汉, 等. 免疫炎症指标对食管鳞癌新辅助放化疗疗效的预测价值. 中华消化外科杂志, 2023, 22(3): 363-370.Lin GY, Liang WC, Tang H, et al. The value of immune inflammatory index in predicting the therapeutic efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma. Chin J Dig Surg, 2023, 22(3): 363-370.
12. Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res, 2014, 20(23): 6212-6222.
13. Powell AGMT, Chin C, Coxon AH, et al. Neutrophil to lymphocyte ratio as a predictor of response to neoadjuvant chemotherapy and survival in oesophageal adenocarcinoma. BJS Open, 2020, 4(3): 416-423.
14. Jomrich G, Paireder M, Kristo I, et al. High systemic immune-inflammation index is an adverse prognostic factor for patients with gastroesophageal adenocarcinoma. Ann Surg, 2021, 273(3): 532-541.
15. Feng JF, Chen S, Yang X. Systemic immune-inflammation index (SII) is a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus. Medicine (Baltimore), 2017, 96(4): e5886.
16. 张春艳, 刘明珠, 侯宁, 等. 系统免疫炎症指数对放化疗老年食管癌患者预后的预测作用. 现代消化及介入诊疗, 2021, 26(3): 314-318.Zhang CY, Liu MZ, Hou N, et al. The predictive effect of systemic immune-inflammation index on the prognosis of elderly patients with esophageal cancer with radiotherapy and chemotherapy. Mod Dig Interv, 2021, 26(3): 314-318.
17. 张旺, 曹家兴, 刘九洋, 等. 全身免疫炎症指数对乳腺癌新辅助化疗疗效的预测价值及临床预测模型的构建. 中华乳腺病杂志(电子版), 2023, 17(3): 136-142.Zhang W, Cao JX, Liu JY, et al. Predictive value of systemic immune-inflammation index for neoadjuvant chemotherapy response in breast cancer and establishment of clinical prediction model. Chin J Breast Dis (Electron Version), 2023, 17(3): 136-142.
18. Yang W, Xing X, Yeung SJ, et al. Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma. J Immunother Cancer, 2022, 10(1): e3497.
19. Liu J, Li J, Lin W, et al. Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study. Int J Cancer, 2022, 151(1): 128-137.
20. Wu Z, Zheng Q, Chen H, et al. Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma. J Thorac Dis, 2021, 13(6): 3518-3528.
21. Han W, Weng K, Zhang P, et al. Predictive value of systemic immune-inflammation index for pathological complete response in patients receiving neoadjuvant immunochemotherapy for locally advanced esophageal cancer. Front Surg, 2023, 9: 1091601.
22. Zhang X, Gari A, Li M, et al. Combining serum inflammation indexes at baseline and post treatment could predict pathological efficacy to anti-PD-1 combined with neoadjuvant chemotherapy in esophageal squamous cell carcinoma. J Transl Med, 2022, 20(1): 61.

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