Data Sheet 1_Analysis of the safety and efficacy of PD-1/PD-L1 inhibitors combined with chemotherapy in the treatment of locally advanced resectable esophageal squamous cell carcinoma: a systematic review and meta-analysis based on four randomized controlled trials.docx

BackgroundEsophageal cancer is a leading type of cancer globally. Most patients diagnosed with esophageal cancer present at a locally advanced stage, for which the standard treatment paradigm involves a multimodal approach combining neoadjuvant therapy with surgical resection. However, even under this regimen, 30%–40% of patients develop distant metastases postoperatively. This underscores an urgent need to refine existing therapeutic strategies and develop innovative multimodal protocols to address persistent oncological challenges in this high-risk population. In recent years, the advent of immunotherapy has expanded its application from advanced to early-stage settings, with neoadjuvant immunotherapy gaining traction in the management of locally advanced esophageal cancer. However, critical uncertainties persist regarding its preoperative use. This study aims to conduct a meta-analysis comparing the efficacy and safety of neoadjuvant chemoimmunotherapy (nICT) versus conventional neoadjuvant chemotherapy (nCT) in this patient population.
MethodsA comprehensive literature retrieval strategy was implemented across PubMed (NLM), Embase (Elsevier), and the Cochrane Central Register of Controlled Trials, targeting studies published prior to December 2024 that compared novel immunochemotherapy (nICT) with conventional nCT in locoregionally advanced esophageal carcinoma. Pooled statistical analysis of the eligible randomized controlled trials (RCTs) was subsequently conducted to evaluate comparative safety and efficacy profiles.
ResultsThe final analysis incorporated four randomized controlled trials (RCTs) comprising a total cohort of 629 participants. Patients receiving nICT for locoregionally advanced esophageal carcinoma demonstrated significantly prolonged intervals between final preoperative treatment and definitive surgical resection when compared to those undergoing conventional nCT alone [weighted mean difference (WMD): 0.71 weeks; 95% confidence interval (CI) 0.39–1.02; P < 0.0001]. The combined treatment showed significant advantages in pathological complete response (PCR) [odds ratio (OR): 3.44; 95% CI 1.98–5.97; P < 0.0001] and major pathological response (MPR) (OR: 2.56; 95% CI 1.23–5.30; P = 0.01). However, the incidence of anemia as an adverse reaction was higher in the combined treatment group (OR: 1.83; 95% CI 1.08–3.09; P = 0.02).
ConclusionNeoadjuvant chemotherapy combined with immunotherapy for treating locally advanced esophageal cancer is effective and safe. However, due to the absence of long-term follow-up data, additional large-scale, multicenter randomized controlled trials are required to confirm these results.

背景：食管癌是全球范围内高发的恶性肿瘤类型之一。多数确诊食管癌的患者就诊时已处于局部进展期，此类患者的标准治疗范式为新辅助治疗联合手术切除的多模态综合疗法。然而即便采用该治疗方案，仍有30%~40%的患者在术后发生远处转移。这凸显出亟需优化现有治疗策略、开发创新型多模态治疗方案，以解决这一高风险人群持续存在的肿瘤学难题。近年来，免疫治疗的应用范畴已从晚期肿瘤拓展至早期疾病场景，新辅助免疫治疗在局部进展期食管癌的临床管理中逐渐获得认可，但目前其术前应用仍存在诸多关键不确定性。本研究旨在开展一项荟萃分析，对比新辅助化学免疫治疗（neoadjuvant chemoimmunotherapy, nICT）与传统新辅助化疗（conventional neoadjuvant chemotherapy, nCT）在该患者群体中的疗效与安全性。
方法：本研究在PubMed（美国国立医学图书馆，NLM）、Embase（爱思唯尔，Elsevier）及Cochrane对照试验中心注册库中实施了全面的文献检索策略，检索时限截至2024年12月，纳入对比新型免疫化疗方案（nICT）与传统nCT治疗局部区域进展期食管癌的相关研究。随后对符合纳入标准的随机对照试验（randomized controlled trial, RCT）进行汇总统计分析，以评估二者的安全性与疗效对比特征。
结果：最终共纳入4项随机对照试验（RCT），合计629名受试者。与仅接受传统nCT的患者相比，接受nICT治疗的局部区域进展期食管癌患者，其末次术前治疗至确定性手术切除的间隔时间显著延长[加权均数差（weighted mean difference, WMD）：0.71周；95%置信区间（confidence interval, CI）0.39~1.02；P < 0.0001]。联合治疗方案在病理完全缓解（pathological complete response, PCR）[比值比（odds ratio, OR）：3.44；95%CI 1.98~5.97；P < 0.0001]及主要病理缓解（major pathological response, MPR）（OR：2.56；95%CI 1.23~5.30；P = 0.01）方面均展现出显著优势。但联合治疗组的贫血不良反应发生率更高（OR：1.83；95%CI 1.08~3.09；P = 0.02）。
结论：新辅助化疗联合免疫治疗用于局部进展期食管癌的治疗兼具有效性与安全性。但由于缺乏长期随访数据，仍需开展更多大规模多中心随机对照试验以验证本研究结果。