Purpose: This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. Results: Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08–0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04–0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. Conclusions: Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

中文翻译：

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放化疗和随后的免疫化疗作为不可切除的局部晚期食管鳞状细胞癌的转化治疗：II 期 NEXUS-1 试验


目的： 本 II 期试验调查了放化疗 （CRT） 后免疫化疗 （iCT） 和手术治疗不可切除的局部晚期食管鳞状细胞癌 （ESCC） 的安全性和有效性。患者和方法： 不可切除的局部晚期 ESCC 患者接受放疗 （50 Gy/25f，5 天/周） 和白蛋白结合型紫杉醇 （100 mg/周第 1 天） 加顺铂 （25 mg/m2 第 1 天/周） 5 周，随后替雷利珠单抗 （200 mg，第 1 天/周期）加化疗 （白蛋白结合型紫杉醇 150 mg/m2 和顺铂 75 mg/m2 第 2 天/周期），持续两个 21 天的周期。转为可切除的患者在 2 至 4 周后接受手术。主要终点是 1 年无进展生存期 （PFS） 率。结果： 30 例患者入组并接受 CRT （中位随访： 21 个月），其中 24 例接受 iCT。20 例 （66.7%） 患者达到可切除性 （R0： 95.2%;病理完全缓解： 65.0%;主要病理反应： 90.0%）。1 年 PFS 和总生存率 （OS） 分别为 79.4% 和 89.6%。R0 切除组表现出更长的 PFS（中位，未达到 vs. 8.4 个月;心率 = 0.28;95% 置信区间，0.08–0.84;P = 0.02）和 OS （中位数，未达到 vs. 19.2 个月;心率 = 0.18;95% 置信区间，0.04–0.73;P < 0.01） 比非手术组。11 例 （11/30， 36.7%） 患者观察到 3 至 4 级不良事件，5 例 （5/24， 20.8%） 患者观察到免疫相关性肺炎。术前 CRT 后微小残留病与不良 PFS 和 OS 相关。结论： 我们的研究达到主要终点。转化 CRT 和随后的 iCT 后手术是不可切除的局部晚期 ESCC 的一种有前途的治疗策略。