Radiation Oncology Key Laboratory of Sichuan Province, Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Immunol. 2022 Dec 16;13:1041233. doi: 10.3389/fimmu.2022.1041233. eCollection 2022.
Neoadjuvant chemoradiotherapy (NCRT) plus radical esophagectomy is currently the standard treatment for resectable esophageal or gastroesophageal junction (GEJ) carcinoma. The aim of this study is to evaluate the efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or GEJ carcinoma. Prospective clinical trials investigating efficacy and/or safety of neoadjuvant immunotherapy with immune checkpoint inhibitors (ICIs) followed by radical esophagectomy in patients with newly diagnosed resectable esophageal or GEJ carcinoma were identified through literature search. Quality assessment was performed by using the Newcastle-Ottawa scale. Preliminary treatment outcomes of pathologically complete response (pCR, ypT0N0) and grade 3-4 adverse effects (AEs) were pooled together and then compared with standard NCRT of the historical control CROSS study by Chi-square (χ) test. A two-sided value < 0.05 was considered statistically significant. A total of 17 eligible non-randomized trials with 455 participants were included into analysis. The most common primary endpoint was pCR (n = 7, 41%), and the median sample size and follow-up period was 23 patients and 7.9 months, respectively. For patients receiving neoadjuvant immunotherapy, the overall pCR, R0 resection, and grade 3-4 AE rates were 33.2%, 95.5%, and 35.1%, respectively. For esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), neoadjuvant immunochemoradiotherapy showed no significant improvement in pCR rate than NCRT (ESCC, 50% vs 48.7%, = 0.9; EAC, 32.6% vs 23.1%, = 0.22). Grade 3-4 AEs were the most common in patients with neoadjuvant immunochemoradiotherapy, significantly higher than immunochemotherapy (46.7% vs 32.8%, = 0.04) and NCRT (46.7% vs 18.1%, < 0.0001). In conclusion, for patients with resectable esophageal or GEJ carcinoma, the addition of ICIs to standard NCRT could not improve pCR rate in both ESCC and EAC, but significantly increased the risk of severe AEs. Large-scale phase 3 randomized trials were urgently needed to further confirm the survival benefit and safety profile of neoadjuvant immunotherapy.
新辅助放化疗（NCRT）加根治性食管切除术目前是可切除食管或胃食管交界处（GEJ）癌的标准治疗方法。本研究旨在评估新辅助免疫疗法在可切除食管或 GEJ 癌中的疗效和安全性。通过文献检索，确定了前瞻性临床试验，以评估新辅助免疫疗法联合免疫检查点抑制剂（ICI）在新诊断为可切除食管或 GEJ 癌患者中的疗效和/或安全性，并进行根治性食管切除术。采用纽卡斯尔-渥太华量表进行质量评估。通过 χ 检验对病理完全缓解（ypT0N0，pCR）和 3-4 级不良事件（AE）的初步治疗结果进行汇总比较，并与历史对照 CROSS 研究的标准 NCRT 进行比较。双侧 值<0.05 被认为具有统计学意义。共纳入 17 项符合条件的非随机试验，共 455 例患者纳入分析。最常见的主要终点是 pCR（n=7，41%），中位样本量和随访时间分别为 23 例和 7.9 个月。接受新辅助免疫治疗的患者，总体 pCR、R0 切除和 3-4 级 AE 发生率分别为 33.2%、95.5%和 35.1%。对于食管鳞癌（ESCC）和腺癌（EAC），新辅助免疫化疗与 NCRT 相比，pCR 率无显著改善（ESCC，50%比 48.7%， = 0.9；EAC，32.6%比 23.1%， = 0.22）。新辅助免疫化疗患者中最常见的 3-4 级 AE 显著高于免疫化疗（46.7%比 32.8%， = 0.04）和 NCRT（46.7%比 18.1%，<0.0001）。总之，对于可切除食管或 GEJ 癌患者，标准 NCRT 联合 ICI 不能提高 ESCC 和 EAC 的 pCR 率，但显著增加严重 AE 的风险。迫切需要进行大规模的 3 期随机试验，以进一步证实新辅助免疫治疗的生存获益和安全性。
