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新辅助程序性死亡-1阻断联合化疗治疗局部晚期食管鳞状细胞癌

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma.

作者信息

Yang Guozhen, Su Xiaodong, Yang Hong, Luo Guangyu, Gao Chan, Zheng Yating, Xie Wenzhuan, Huang Mengli, Bei Ting, Bai Yuezong, Wang Zhiqiang, Cai Peiqiang, He Haoqiang, Xiang Jin, Cai Muyan, Zhang Yijun, Qu Chunhua, Fu Jianhua, Liu Qianwen, Hu Yi, Zhong Jiudi, Huang Yuanheng, Guo Qiyu, Zhang Xu

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Guangdong Esophageal Cancer Institute, Guangzhou, China.

出版信息

Ann Transl Med. 2021 Aug;9(15):1254. doi: 10.21037/atm-21-3352.

Abstract

BACKGROUND

Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.

METHODS

Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.

RESULTS

Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).

CONCLUSIONS

Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.

摘要

背景

免疫疗法在治疗不可切除的食管鳞状细胞癌(ESCC)方面有效,但对其在术前治疗中的作用知之甚少。本研究旨在评估卡瑞利珠单抗联合化疗在局部晚期ESCC新辅助治疗中的安全性、可行性和疗效。

方法

回顾性纳入2019年11月至2020年6月在中山大学肿瘤防治中心接受新辅助卡瑞利珠单抗联合白蛋白结合型紫杉醇及S-1胶囊治疗后行根治性食管切除术的局部晚期ESCC患者。主要终点为安全性和可行性。此外,还研究了病理反应以及肿瘤免疫微环境(TIME)/肿瘤突变负荷(TMB)与治疗反应之间的关系。

结果

纳入12例患者,均接受了3个疗程的卡瑞利珠单抗联合白蛋白结合型紫杉醇/S-1术前治疗。未发生3级或更高等级的毒性反应。未报告手术延迟或围手术期死亡。9例患者(75%)对治疗有反应,4例达到完全病理缓解(pCR),5例达到主要病理缓解(MPR)。程序性死亡配体1(PD-L1)表达和TMB均与治疗反应无关。TIME分析显示CD56dim自然杀伤细胞丰度较高与原发肿瘤更好的病理反应相关,而M2肿瘤相关巨噬细胞密度较低与淋巴结(LN)更好的病理反应相关。

结论

新辅助卡瑞利珠单抗联合白蛋白结合型紫杉醇及S-1在局部晚期ESCC中安全、可行且有效,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d0/8421958/bb39f72163bd/atm-09-15-1254-f1.jpg

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