Background

For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC.

Methods

This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM).

Results

A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325–0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236–0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280–0.858], P = 0.011; HR 0.454 [95%CI 0.246–0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis.

Conclusions

Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

中文翻译：

---

局部晚期食管鳞状细胞癌诱导免疫治疗加化疗随后进行根治性放化疗：一项倾向评分匹配研究

背景

对于无法切除的局部晚期食管鳞状细胞癌（ESCC）患者，同步放化疗（CCRT）是目前的标准治疗方法；然而，预后仍然不佳。免疫疗法与化疗相结合已证明可以改善晚期食管鳞癌的生存结果。然而，目前缺乏关于 CCRT 前诱导免疫治疗加化疗对不可切除的局部晚期 ESCC 的作用的报道。因此，本研究旨在评估诱导免疫治疗加化疗随后进行根治性放化疗对不可切除的局部晚期食管鳞癌患者的疗效和安全性。

方法

本研究回顾性收集了2017年至2021年在我机构诊断为局部晚期食管鳞癌并接受根治性CCRT治疗的患者的临床数据。患者被分为两组：诱导免疫治疗加化疗组（诱导IC组）或CCRT组。为了评估无进展生存期（PFS）和总生存期（OS），我们在进行倾向评分匹配（PSM）后采用Kaplan-Meier方法。

结果

本研究共纳入132例不可切除的局部晚期ESCC患者，其中诱导IC组61例（45.26%）患者，CCRT组71例（54.74%）患者。中位随访时间为 37.0 个月，中位 PFS 和 OS 分别为 25.2 个月和 39.2 个月。与 CCRT 组相比，诱导 IC 组患者的 PFS 和 OS 显着改善（中位 PFS：未达到 [NR] 与 15.9 个月，风险比 [HR] 0.526 [95%CI 0.325–0.851] ，P  = 0.0077；中位 OS：NR 与 25.2 个月，HR 0.412 [95%CI 0.236–0.719]，P  = 0.0012）。PSM（50 对）后，诱导 IC 组的 PFS 和 OS 均优于 CCRT 组（HR 0.490 [95%CI 0.280–0.858]，P  = 0.011；HR 0.454 [95%CI 0.246–0.837]，P  = 0.0093），2 年 PFS 率分别为 67.6 和 42.0%，2 年 OS 率分别为 74.6 和 52.0%。多变量分析显示，较低的肿瘤分期、双药同步化疗、CCRT 前诱导免疫治疗加化疗与较好的预后相关。

结论

我们的结果首次表明，对于不可切除的局部晚期 ESCC，诱导免疫疗法加化疗，然后进行 CCRT，可提供生存获益和可控的安全性。应该进行更多前瞻性临床研究。