2024_08_21_1008f06ea14b91a8f94ag

Neoadjuvant chemotherapy with or without camrelizumab in resectableesophageal squamouscell carcinoma: the randomized phase3ESCORT-NEO/NCCES01 trial
新辅助化疗联合或不联合 camrelizumab 治疗可切除食管鳞状细胞癌：随机 3 期 ESCORT-NEO/NCCES01 试验

Received: 29 March 2024 收到日期：2024 年 3 月 29 日
Accepted: 13 May 2024
接受日期：2024 年 5 月 13 日
Published online: 02 July 2024
在线发布：2024 年 7 月 2 日
Check for updates 检查更新

Abstract 摘要

A list of authors and their affiliations appears at the end of the paper Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3NOMO) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; ); camrelizumab, paclitaxel and cisplatin (Cam+TPgroup; ); and paclitaxel with cisplatin (TP group; ), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response ( pCR ), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of and , respectively, compared to in the TP group (Cam+nab-TP versus TP: difference confidence interval (CI) 15.1-32.0, ; Cam+TP versus TP: difference 10.9%, 95% CI3.7-18.1, ). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade treatment-related adverse events during neoadjuvant treatment was for the Cam+nab-TP group, 29.2% for the Cam+TP group and for the TP group; the postoperative complication rates were and , respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior PCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034.
一份作者及其所属机构的名单出现在论文末尾。最近涉及新辅助 camrelizumab（PD-1 抑制剂）加化疗治疗可切除局部晚期食管鳞状细胞癌（LA-ESCC）的单臂研究显示出良好的结果。本多中心、随机、开放标签的 3 期试验旨在进一步评估新辅助 camrelizumab 加化疗后再加用辅助 camrelizumab 的疗效和安全性，与单独的新辅助化疗进行比较。共 391 名可切除的胸部 LA-ESCC 患者（T1b-3N1-3M0 或 T3NOMO）按临床分期（I/II、III 或 IVA）分层，并以 1:1:1 的比例随机分配接受两周期的新辅助治疗。治疗方案包括 camrelizumab、白蛋白结合的紫杉醇和顺铂（Cam+nab-TP 组；）；camrelizumab、紫杉醇和顺铂（Cam+TP 组；）；以及紫杉醇与顺铂（TP 组；），随后进行外科切除。Cam+nab-TP 组和 Cam+TP 组均接受了辅助 camrelizumab 治疗。双主要终点是由盲法独立评审委员会评估的病理完全缓解率（pCR）和由研究者评估的无事件生存期（EFS）。本研究报告了 pCR 率的最终分析。在意向治疗人群中，Cam+nab-TP 组和 Cam+TP 组的 pCR 率分别显著高于 TP 组的，为和（Cam+nab-TP 与 TP：差异，置信区间（CI）15.1-32.0，；Cam+TP 与 TP：差异 10.9%，95% CI 3.7-18.1，）。该研究达到了其 pCR 的主要终点；然而，EFS 尚未成熟。在新辅助治疗期间，Cam+nab-TP 组的治疗相关不良事件发生率为，Cam+TP 组为 29.2%，TP 组为；术后并发症发生率分别为和。新辅助 camrelizumab 加化疗相比单独化疗对局部晚期食管鳞状细胞癌（LA-ESCC）显示出更高的 pCR 率，并具有可耐受的安全性。中国临床试验注册中心标识符：ChiCTR2000040034。

Fig. 1|CONSORT diagram. A total of 411 patients were screened for this study, of whom 391 were successfully enrolled between April 28, 2021, and August 7, 2023.
图 1|CONSORT 图。共有 411 名患者参与了本研究，其中 391 名患者在 2021 年 4 月 28 日至 2023 年 8 月 7 日期间成功入组。

Esophageal cancer is a significant global health issue, ranking seventh in incidence and sixth in mortality among all cancers

, with over half of the global esophageal squamous cell carcinoma (ESCC) cases in China

. In East Asia, neoadjuvant chemotherapy or chemoradiotherapy is standard for resectable locally advanced ESCC (LA-ESCC), with chemotherapy more prevalent

. Studies such as CROSS and NEOCRTEC5010 highlight neoadjuvant chemoradiotherapy's survival benefits over surgery alone

, whereas theJCOG 9907 trial shows neoadjuvant chemotherapy improves overall survival (OS) compared to adjuvant therapy

. Recent phase 3 trials, including CMISG1701 and JCOG1109 (refs. 8,9), along with a network meta-analysis of randomized controlled trials

, have not demonstrated a significant OS advantage when comparing neoadjuvant chemoradiotherapy to chemotherapy for LA-ESCC, leaving the optimal neoadjuvant treatment strategy in question.
食管癌是一个重大的全球健康问题，在所有癌症中发病率排名第七，死亡率排名第六

，全球超过一半的食管鳞状细胞癌（ESCC）病例发生在中国

。在东亚，针对可切除的局部晚期 ESCC（LA-ESCC），新辅助化疗或化放疗是标准治疗，其中化疗更为普遍

。如 CROSS 和 NEOCRTEC5010 等研究强调新辅助化放疗相较于单纯手术的生存益处

，而 JCOG 9907 试验显示新辅助化疗相比于辅助治疗改善了总体生存率（OS）

。最近的三期试验，包括 CMISG1701 和 JCOG1109（参考文献 8,9），以及一项随机对照试验的网络荟萃分析

，在比较新辅助化放疗与 LA-ESCC 的化疗时未显示出显著的 OS 优势，这使得最佳的新辅助治疗策略仍然存在疑问。

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of ESCC. Camrelizumab, a PD-1 inhibitor, has demonstrated promising efficacy and safety in advanced ESCC, including both chemotherapy-refractory and treatment-naive cases, as evidenced by the ESCORT and ESCORT-1st studies

. Following these results, China has approved camrelizumab as a second-line monotherapy for advanced or metastatic ESCC, and in combination with chemotherapy (paclitaxel and cisplatin, TP) as a first-line treatment. Several phase 1b and 2 trials assessing neoadjuvant immunotherapy with camrelizumab and chemotherapy for LA-ESCC report high pathological complete response (pCR) rates of

(refs. 13-18). Our latest retrospective analysis suggests that neoadjuvant chemotherapy plus immunotherapy showed better 3-year OS rates (

versus

) and 3-year disease-free survival (DFS) rates (

versus

) compared to neoadjuvant chemoradiotherapy

. Despite these promising results, there remains a lack of phase 3 confirmatory studies to further validate these findings.
免疫检查点抑制剂（ICIs）彻底改变了食管鳞状细胞癌（ESCC）的治疗。Camrelizumab，一种 PD-1 抑制剂，在晚期 ESCC 中显示出良好的疗效和安全性，包括化疗耐药和治疗初始病例，ESCORT 和 ESCORT-1st 研究对此提供了证据

。在这些结果之后，中国已批准 camrelizumab 作为晚期或转移性 ESCC 的二线单药治疗，并与化疗（紫杉醇和顺铂，TP）联合使用作为一线治疗。几项评估 camrelizumab 与化疗联合的术前免疫治疗的 1b 期和 2 期试验报告了高病理完全缓解（pCR）率，范围为

到

（参考文献 13-18）。我们最新的回顾性分析表明，术前化疗加免疫治疗的 3 年总生存率（OS）为

对比

，3 年无病生存率（DFS）为

对比

，优于术前化疗放疗

。尽管这些结果令人鼓舞，但仍缺乏 3 期确认性研究来进一步验证这些发现。

Beyond selecting the optimal combination of treatment modalities, refining the chemotherapy regimen is crucial for enhancing neoadjuvant treatment outcomes in ESCC. The TP regimen is commonly used, yet nab-paclitaxel, an innovative albumin-bound formulation of paclitaxel, has shown a superior therapeutic profile compared to traditional paclitaxel. This preference for nab-paclitaxel, especially when combined with immunotherapy in LA-ESCC, is supported by several phase 2 studies

. Our retrospective analysis further substantiates this, revealing that neoadjuvant immunotherapy with nab-paclitaxel and cisplatin (nab-TP) achieves higher pCR rates than the combination of immunotherapy with TP regimen

. Against this backdrop, we initiated the ESCORT-NEO/NCCESO1 study, a phase 3, open-label, randomized trial aimed at assessing the efficacy and safety of neoadjuvant camrelizumab plus either TP or nab-TP, as compared to TP alone, in patients with resectable LA-ESCC.
在选择最佳治疗方式组合的基础上，优化化疗方案对于提高食管鳞状细胞癌（ESCC）新辅助治疗的效果至关重要。TP 方案是常用的治疗方案，但纳米白蛋白结合紫杉醇（nab-paclitaxel）作为一种创新的白蛋白结合紫杉醇制剂，其治疗效果优于传统紫杉醇。尤其是在局部晚期食管鳞状细胞癌（LA-ESCC）中，nab-paclitaxel 与免疫治疗联合使用的偏好得到了几项二期研究的支持

。我们的回顾性分析进一步证实了这一点，显示与 TP 方案联合的免疫治疗相比，nab-paclitaxel 与顺铂（nab-TP）的新辅助免疫治疗实现了更高的完全病理缓解率（pCR）

。在此背景下，我们启动了 ESCORT-NEO/NCCESO1 研究，这是一个三期、开放标签、随机试验，旨在评估新辅助 camrelizumab 联合 TP 或 nab-TP 的疗效和安全性，与单独 TP 相比，针对可切除的 LA-ESCC 患者。

Results 结果

Patient disposition 患者处置

A total of 411 patients were screened for this study, of whom 391 were successfully enrolled between April 28, 2021, and August 7, 2023. In the Cam+nab-TP, Cam+TP and TP groups, 132,130 and 125 patients, respectively, were allocated and received neoadjuvant therapy; although the TP group initially had 129 before 4 withdrew consent. Consequently, the intention-to-treat (ITT) populations were 132, 130 and 129, with safety set (SS) populations of 132, 130 and 125, respectively (Fig. 1). As of the data cutoff on October 8, 2023, the median follow-up duration was 8.2 months (interquartile range (IQR), 3.5-15.6 months). The median age of all patients was 63 years (range,

), with

being male. Among these patients,

were in clinical stage I (all cT1N1),

were stage II,

were stage III and

were stage IVA. Tumors were located in the upper, middle and lower thoracic esophagus for

and

patients, respectively. Baseline characteristics were essentially balanced across all three groups (Table 1).
共有 411 名患者参与了本研究，其中 391 名患者在 2021 年 4 月 28 日至 2023 年 8 月 7 日期间成功入组。在 Cam+nab-TP、Cam+TP 和 TP 组中，分别有 132、130 和 125 名患者被分配并接受了新辅助治疗；尽管 TP 组最初有 129 名患者，但有 4 名患者撤回了同意。因此，意向治疗（ITT）人群分别为 132、130 和 129，安全性集（SS）人群分别为 132、130 和 125（图 1）。截至 2023 年 10 月 8 日的数据截止日期，中位随访时间为 8.2 个月（四分位数范围（IQR），3.5-15.6 个月）。所有患者的中位年龄为 63 岁（范围，

），其中

为男性。在这些患者中，

处于临床 I 期（均为 cT1N1），

为 II 期，

为 III 期，

为 IVA 期。肿瘤分别位于上、中和下胸食管的

和

名患者中。基线特征在所有三个组之间基本平衡（表 1）。

Neoadjuvant treatment and surgery summary
新辅助治疗和手术总结

Within the ITT population,132,130 and 125 patients in the Cam + nab-TP, Cam+TP and TP groups, respectively, received neoadjuvant therapy. Of these, 3 in the Cam+nab-TP group, 5 in the Cam+TP group and 3 in the TP group did not complete two cycles of neoadjuvant therapy for several reasons; in the Cam+nab-TP group, two patients discontinued due to
在 ITT 人群中，分别有 132、130 和 125 名患者在 Cam + nab-TP、Cam + TP 和 TP 组接受了新辅助治疗。其中，Cam + nab-TP 组有 3 名、Cam + TP 组有 5 名、TP 组有 3 名患者因多种原因未完成两周期的新辅助治疗；在 Cam + nab-TP 组中，有两名患者因中断治疗。

Table 1 | Baseline characteristics of patients in the ITT population
表 1 | ITT 人群患者的基线特征

Variables 变量

Cam+nab-TP

Cam+TP

Age (years) 年龄（岁）

74 (56.1)

79 (60.8)

63 (48.8)

58 (43.9)

51 (39.2)

66 (51.2)

Median (range) 中位数（范围）

63 (44-75)

65 (44-75)

Sex, n (%) 性别, n (%)

Male 男性

116 (87.9)

112 (86.2)

Female 女性

16 (12.1)

18 (13.8)

25 (19.4)

ECOG PS, n (%)

105 (79.5)

106 (81.5)

104 (80.6)

27 (20.5)

24 (18.5)

25 (19.4)

Tumor location,

(%)
肿瘤位置，

(%)

Upper 上部

12 (9.2)

19 (14.7)

Middle 中间

69 (52.3)

75 (57.7)

57 (44.2)

Lower 下部

53 (40.2)

43 (33.1)

53 (41.1)

T stage,

(%) T 阶段，

(%)

T1b

3 (2.3)

1 (0.8)

2 (1.6)

15 (11.4)

13 (10.0)

19 (14.7)

114 (86.4)

116 (89.2)

108 (83.7)

N stage,

(%) N 阶段，

(%)

20 (15.2)

24 (18.5)

20 (15.5)

71 (53.8)

71 (54.6)

73 (56.6)

38 (28.8)

33 (25.4)

35 (27.1)

3 (2.3)

2 (1.5)

1 (0.8)

Clinical stage,

(%)
临床阶段，

(%)

3 (2.3)

1 (0.8)

2 (1.6)

31 (23.5)

34 (26.2)

35 (27.1)

III

95 (72.0)

93 (71.5)

91 (70.5)

IVA

3 (2.3)

2 (1.5)

1 (0.8)

PD-L1 TPS,

(%) PD-L1 TPS，

（%）

43 (32.6)

59 (45.4)

49 (38.0)

78 (59.1)

61 (46.9)

62 (48.1)

99 (75.0)

98 (75.4)

97 (75.2)

22 (16.7)

22 (16.9)

14 (10.9)

Unknown 未知

11 (8.3)

10 (7.7)

18 (14.0)

PD-L1 CPS,

(%) PD-L1 CPS，

(%)

14 (10.6)

18 (13.8)

15 (11.6)

109 (82.6)

102 (78.5)

96 (74.4)

68 (51.5)

80 (61.5)

72 (55.8)

55 (41.7)

40 (30.8)

39 (30.2)

Unknown 未知

9 (6.8)

10 (7.7)

18 (14.0)

ECOG PS, Eastern Cooperative Oncology Group performance status; TPS, tumor proportion score; CPS, combined positive score.
ECOG PS，东部合作肿瘤学组表现状态；TPS，肿瘤比例评分；CPS，联合阳性评分。
adverse events (AEs) and one due to patient refusal; in the Cam + TP group, four patients discontinued due to AEs and one due to death; and in the TP group, discontinuations were due to one AE and two instances of patient refusal. A total of 114 (86.4%), 116 (89.2%) and 103 (79.8%) underwent esophagectomy. Reasons for cancellation of esophagectomy included refusal of surgery

, surgery intolerability

, disease progression

, exploratory operation

, unresectability

, preoperative death

and loss to follow-up

. Among the exploratory operations, one case in the TP group revealed peritoneal metastasis, while the remaining four cases involved tumors deemed unresectable due to extensive invasion. The median time from the last neoadjuvant treatment to surgery across the Cam+nab-TP, Cam+TP, and TP groups were 5.9 (IQR, 5.0-7.1), 5.7 (IQR, 5.0-7.4) and 5.4 (IQR, 4.9-6.3) weeks, respectively. In terms of types of surgery, the McKeown procedure was the most common, accounting for

in the Cam+nab-TP group,

in the Cam+TP group and

in the TP group. The median number of lymph nodes harvested was 34 (IQR, 24-50), 37 (IQR, 27-48) and 32 (IQR, 27-45), respectively. The median duration of surgery for the Cam+nab-TP, Cam+TP and TP groups was 4.3 hours (range, 2.6-8.9), 4.2 hours (range, 2.8-7.2) and 4.2 hours (range, 2.9-10.8), respectively (Table 2).
不良事件（AEs）和一起因患者拒绝而导致的事件；在 Cam + TP 组中，四名患者因 AEs 而中止治疗，一名因死亡而中止；在 TP 组中，中止治疗的原因包括一起 AE 和两起患者拒绝。共有 114 例（86.4%）、116 例（89.2%）和 103 例（79.8%）接受了食管切除术。取消食管切除术的原因包括拒绝手术

、手术耐受性差

、疾病进展

、探查手术

、不可切除性

、术前死亡

和失访

。在探查手术中，TP 组有一起病例发现腹膜转移，其余四例因广泛浸润被认为不可切除。Cam+nab-TP、Cam+TP 和 TP 组从最后一次新辅助治疗到手术的中位时间分别为 5.9（IQR，5.0-7.1）、5.7（IQR，5.0-7.4）和 5.4（IQR，4.9-6.3）周。在手术类型方面，McKeown 手术是最常见的，分别占 Cam+nab-TP 组的

、Cam+TP 组的

和 TP 组的

。收集的淋巴结中位数为 34 个（四分位数范围，24-50），37 个（四分位数范围，27-48）和 32 个（四分位数范围，27-45），分别。Cam+nab-TP、Cam+TP 和 TP 组的手术中位持续时间分别为 4.3 小时（范围，2.6-8.9），4.2 小时（范围，2.8-7.2）和 4.2 小时（范围，2.9-10.8）（表 2）。

Primary outcome 主要结果

Within the ITT population, the pCR rate was

in the Cam+nab-TP group, markedly higher than the TP group's 4.7% (difference 23.5%,

confidence interval (CI), 15.1-32.0; odds ratio (OR), 8.11;

). The Cam+TPgroup's pCR rate was also significantly greater at

, compared to the TP group (difference 10.9%, 95%

; OR,

) (Table 3). Post hoc subgroup analyses of pCR rates for the Cam+nab-TP group versus TP group and

TP group versus TP group are presented in Extended Data Figs. 1 and 2. Event-free survival (EFS) data have not matured.
在 ITT 人群中，Cam+nab-TP 组的 pCR 率为

，明显高于 TP 组的 4.7%（差异 23.5%，

置信区间（CI），15.1-32.0；优势比（OR），8.11；

，

）。Cam+TP 组的 pCR 率也显著高于 TP 组，为

（差异 10.9%，95%

；OR，

）（表 3）。Cam+nab-TP 组与 TP 组以及

TP 组与 TP 组的 pCR 率的事后亚组分析结果见扩展数据图 1 和图 2。事件无生存期（EFS）数据尚未成熟。

Secondary outcomes 次要结果

Within the ITT population, the major pathological response (MPR) rates in the Cam+nab-TP,Cam+TP, and TP groups were

and

, respectively (Table 3). The R0 resection rates were

(113/114),

and

for the Cam+nab-TP, Cam+TP and TP groups, respectively (Table 2). For the post-neoadjuvant pathological staging (ypTNM) staging, 58 patients (

) achieved stage I in the Cam+nab-TP group, 46 (39.7%) in the Cam+TP group and 27 (26.2%) in the TP group (Supplementary Table 1). The median residual viable tumor cells were

(IQR,

(IQR, 1-70) and

(IQR, 8-80) for Cam+nab-TP, Cam+TP and TPgroups, respectively (Extended Data Fig.3). DFS and OS are not yet mature.
在 ITT 人群中，Cam+nab-TP、Cam+TP 和 TP 组的主要病理反应（MPR）率分别为

和

（表 3）。R0 切除率分别为 Cam+nab-TP 组

（113/114）、Cam+TP 组

和 TP 组

（表 2）。在新辅助治疗后的病理分期（ypTNM）中，Cam+nab-TP 组有 58 名患者（

）达到了 I 期，Cam+TP 组 46 名（39.7%），TP 组 27 名（26.2%）（补充表 1）。Cam+nab-TP、Cam+TP 和 TP 组的中位残余活性肿瘤细胞分别为

（IQR，

）、

（IQR，1-70）和

（IQR，8-80）（扩展数据图 3）。无病生存期（DFS）和总生存期（OS）尚未成熟。

Safety 安全

In the Cam+nab-TP, Cam+TP and TP groups, the rates of surgical complications of any grade were

and

(33/103), respectively. Among these, the proportions of Clavien-Dindo (CD) grade 3 or higher complications were

(7/114), 12.1% (14/116) and

, respectively. Pneumonia and recurrent laryngeal nerve injury were the most common postoperative complications (Table 4 and Supplementary Table 2). One patient (

) in the Cam+TP group and one patient (

) in the TP group required reoperation due to adhesive intestinal obstruction and an anastomotic leak, respectively. The 30 -day postoperative mortality rates were

in the Cam+nab-TP group (one case of sudden death, cause unknown),

in the Cam+TP group (two cases of septic shock) and

in the TP group (one case of myocardial infarction). There was one additional death within 90 days postoperatively in the Cam+nab-TP group, due to severe pneumonia (Table 2).
在 Cam+nab-TP、Cam+TP 和 TP 组中，任何等级的手术并发症发生率分别为

和

（33/103）。其中，Clavien-Dindo（CD）3 级或更高级别并发症的比例分别为

（7/114）、12.1%（14/116）和

。肺炎和喉返神经损伤是最常见的术后并发症（表 4 和补充表 2）。在 Cam+TP 组中有一名患者（

）和在 TP 组中有一名患者（

）因粘连性肠梗阻和吻合口漏分别需要再次手术。30 天术后死亡率在 Cam+nab-TP 组为

（一例突发死亡，原因不明）、在 Cam+TP 组为

（两例脓毒性休克）和在 TP 组为

（一例心肌梗死）。在 Cam+nab-TP 组中术后 90 天内还有一例因重度肺炎死亡（表 2）。

Regarding treatment-related AEs (TRAEs), the incidence rates were

in the Cam+nab-TP group,

(108/130) in the Cam+TP group and

in the TP group. Grade 3 or higher TRAEs occurred in

of the Cam+nab-TP group,

of the Cam+TP group and

of the TP group (Supplementary Table3). The most prevalent grade 3 or higher TRAEs were neutrophil count decreased and white blood cell count decreased (Table 5 and Supplementary Table 4). The rates of TRAEs leading to chemotherapy discontinuation were

for Cam+nab-TP,
关于治疗相关的不良事件（TRAEs），Cam+nab-TP 组的发生率为

，Cam+TP 组为

（108/130），TP 组为

。Cam+nab-TP 组发生 3 级或更高的 TRAEs 为

，Cam+TP 组为

，TP 组为

（补充表 3）。最常见的 3 级或更高的 TRAEs 为中性粒细胞计数减少和白细胞计数减少（表 5 和补充表 4）。导致化疗中断的 TRAEs 发生率为 Cam+nab-TP 组

，

Table 2 | Surgery summary
表 2 | 手术总结

Variables 变量

Cam+nab-TP

Cam+TP

Esophagectomy rate (%)

食管切除率 (%)

Types of surgical procedures, n (%)
手术类型，n (%)

McKeown 麦基翁

107 (93.9)

106 (91.4)

95 (92.2)

Ivor-Lewis 艾沃-刘易斯

6 (5.3)

10 (8.6)

7 (6.8)

Sweet 甜

Other 其他

Margin status,

(%) 边缘状态，

(%)

113 (99.1)

111 (95.7)

95 (92.2)

4 (3.4)

6 (5.8)

1 (0.9)

2 (1.9)

Number of lymph nodes harvested
切除的淋巴结数量

Median (IQR) 中位数（四分位数间距）

37 (27-48)

Time from last neoadjuvant treatment to surgery (weeks)
从最后一次新辅助治疗到手术的时间（周）

Median (IQR) 中位数（四分位间距）

5.9 (5.0-7.1)

Duration of surgery (hours)
手术持续时间（小时）

Median (range) 中位数（范围）

Reoperations,

(%)

再手术，

(%)

1 (0.9)

1 (1.0)

30 天内死亡率，

Mortality within 30 days,

1 (0.9)

2 (1.7)

1 (1.0)

90 天内死亡率，

Mortality within 90 days,

Based on ITT population.

Two patients underwent reoperation for adhesive intestina obstruction (Cam+TP group) or anastomotic leak (TP group).

Mortality within 30 days included sudden postoperative death, cause unknown (Cam+nab-TP group), septic shock (Cam+TP group) and myocardial infarction (TP group).

Mortality within 90 days included mortality within 30 days, with one more death in Cam+nab-TP group (severe pneumonia).

基于意向治疗人群。

两名患者因粘连性肠梗阻（Cam+TP 组）或吻合口漏（TP 组）接受了再手术。

30 天内的死亡包括术后突然死亡，原因不明（Cam+nab-TP 组）、脓毒性休克（Cam+TP 组）和心肌梗死（TP 组）。

90 天内的死亡包括 30 天内的死亡，Cam+nab-TP 组中还有一例死亡（重症肺炎）。
3.8% for Cam+TP and

for the TP group. The rates of discontinuing camrelizumab due to TRAEs were

for both the Cam+nab-TP and Cam+TP groups. Immune-related AEs (irAEs) were only reported in treatment groups that included camrelizumab, with incidences of

in the Cam+nab-TP group and

in the Cam+TP group. Grade 3 or higher irAEs were observed in 4.5% (6/132) of the Cam+nab-TP group and

of the Cam+TP group. The most common irAE was reactive cutaneous capillary endothelial proliferation, which was grade 1-2 in all cases (Supplementary Table 5).
Cam+TP 组的比例为 3.8%，TP 组为

。因治疗相关不良事件（TRAEs）而停止使用 camrelizumab 的比例在 Cam+nab-TP 组和 Cam+TP 组均为

。免疫相关不良事件（irAEs）仅在包含 camrelizumab 的治疗组中报告，Cam+nab-TP 组的发生率为

，Cam+TP 组为

。在 Cam+nab-TP 组中观察到 3 级或更高的 irAEs 发生率为 4.5%（6/132），Cam+TP 组为

。最常见的 irAE 是反应性皮肤毛细血管内皮增生，所有病例均为 1-2 级（补充表 5）。

Discussion 讨论

To the best of our knowledge, the ESCORT-NEO/NCCES01 study represents the first phase 3 trial to assess the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy versus chemotherapy in LA-ESCC. Our findings demonstrate that the addition of camrelizumab to chemotherapy substantially enhances pCR rates in the ITT population. Specifically, the PCR rate for the Cam+nab-TP group and the TP group was

versus

(difference:

, 95% CI, 15.1-32.0; OR: 8.11, 95% CI, 3.28-20.06); for Cam+TP and TP:

versus

(difference:

; OR:

). Our pCR outcomes exceed those of traditional neoadjuvant chemotherapy, which was

, and are numerically comparable to neoadjuvant chemoradiotherapy's

(

CI,

) for LA-ESCC in a meta-analysis

. These results underscore the substantial potential of combining neoadjuvant immunotherapy with chemotherapy in the treatment of LA-ESCC.
根据我们的了解，ESCORT-NEO/NCCES01 研究代表了第一个评估新辅助免疫治疗联合化疗与化疗在局部晚期食管鳞状细胞癌（LA-ESCC）中疗效和安全性的三期试验。我们的研究结果表明，卡瑞利珠单抗与化疗联合使用显著提高了意向治疗（ITT）人群中的完全病理缓解（pCR）率。具体而言，Cam+nab-TP 组和 TP 组的 pCR 率为

对比

（差异：

，95% CI，15.1-32.0；OR：8.11，95% CI，3.28-20.06）；对于 Cam+TP 和 TP 组：

对比

（差异：

；OR：

，

）。我们的 pCR 结果超过了传统新辅助化疗的

，并在数量上与新辅助化疗放疗的

（

CI，

）在一项荟萃分析中的结果相当

。这些结果强调了将新辅助免疫治疗与化疗结合在治疗 LA-ESCC 中的巨大潜力。

Achieving a pCR in patients with locally advanced esophageal cancer after neoadjuvant chemoradiotherapy is associated with improved OS, yet distant recurrence remains prevalent

, highlighting the necessity for more effective systemic treatment, rather than
在接受新辅助化疗放疗的局部晚期食管癌患者中，获得完全病理缓解（pCR）与改善总生存期（OS）相关，但远处复发仍然普遍

，这突显了需要更有效的全身治疗，而不是
Table 3 | Pathological outcomes according to blinded independent pathological review in the ITT population
表 3 | 在 ITT 人群中根据盲法独立病理评审的病理结果

Variables 变量

Cam+nab-TP

Cam+TP

pCR

Rate, % (95%CI) 比率，%（95%置信区间）

差异（与 TP 组相比），%（95%CI）

Difference (vs TP

group), % (95%CI)

OR（与 TP 组相比）

CI）

OR (vs TP group)

CI)

value (vs TP group)

值（与 TP 组相比）

0.0034

MPR

Rate, % (95%CI)

比率，%（95%CI）

差异（与 TP 组相比），%（95%CI）

Difference (vs TP

group), % (95%CI)

OR（与 TP 组相比）

OR (vs. TP group)

因素调整的比率差异是使用 Mantel-Haenszel 方法得出的。' Cochran-Mantel-Haenszel 检验按临床分期（I/II 与 III/IVA）分层，用于比较组间差异。MPR，主要病理反应。

factor-adjusted rate differences were derived using the Mantel-Haenszel method. ' The

Cochran-Mantel-Haenszel test, stratified by clinical stage (I/II versus III/IVA), was used to

compare between groups. MPR, major pathological response.

locoregional treatment, to enhance survival outcomes. The impact of PCR varies across different neoadjuvant regimens. An international cohort study comparing neoadjuvant chemotherapy with chemoradiotherapy in surgically treated esophageal adenocarcinoma revealed a notable decrease in 5-year relapse-free survival for patients achieving

with chemoradiotherapy compared to chemotherapy (

), with chemoradiotherapy associated with a higher incidence of 5-year distant recurrence(OR, 2.50;95% CI1.25-4.99)

. Furthermore, the JCOG1109 trial indicated that neoadjuvant CF (cisplatin and fluorouracil) plus radiotherapy did not significantly enhance survival compared to CF alone (hazard ratio (HR), 0.84;

) despite higher PCR rate, whereas neoadjuvant DCF (docetaxel, cisplatin and fluorouracil) demonstrated both higher PCR rate (

versus

), and long-term survival benefits (HR, 0.68 ;

. Neoadjuvant immunotherapy aims to boost systemic immune responses to tumor antigens, potentially eradicating micro metastatic tumor deposits that could lead to relapse after surgery

. In this study, neoadjuvant immunotherapy plus chemotherapy showed higher pCR rates, which may offer long-term survival benefits. However, the confirmation of these advantages awaits the maturation of our long-term survival data.
局部区域治疗，以提高生存结果。PCR 的影响在不同的新辅助方案中有所不同。一项国际队列研究比较了手术治疗的食管腺癌中新辅助化疗与化学放疗，结果显示接受化学放疗的患者在达到

时，5 年无复发生存率显著低于接受化疗的患者（

对比

），化学放疗与 5 年远处复发发生率更高相关（OR，2.50；95% CI 1.25-4.99）

。此外，JCOG1109 试验表明，与单独 CF（顺铂和氟尿嘧啶）相比，新辅助 CF 加放疗并未显著提高生存率（风险比（HR），0.84；

），尽管 PCR 率更高，而新辅助 DCF（多西他赛、顺铂和氟尿嘧啶）则显示出更高的 PCR 率（

对比

）和长期生存益处（HR，0.68；

）。新辅助免疫治疗旨在增强对肿瘤抗原的全身免疫反应，可能消除微小转移性肿瘤沉积，从而防止手术后复发

。在这项研究中，术前免疫治疗加化疗显示出更高的 pCR 率，这可能提供长期生存益处。然而，这些优势的确认仍需等待我们长期生存数据的成熟。

Recently, several studies have investigated the role of neoadjuvant immunotherapy in upper gastrointestinal malignancies. The KEYNOTE-585 trial represents a phase 3 study investigating neoadjuvant pembrolizumab combined with chemotherapy in gastric and gastroesophagealjunction cancers. Although it did not meet its predefined endpoint for EFS, the treatment group exhibited a median EFS of 44.4 months, compared to 25.3 months in the control group, with a HR of

. The subgroup analysis suggests a trend of benefit, particularly in patients with higher combined positive scores (CPS), echoing results from other phase 3 studies like KEYNOTE-859 (ref. 26) and Checkmate-649 (ref. 27), which highlighted significant survival benefits in advanced gastric cancer treated with immunotherapy combined with chemotherapy. Similarly, the MATTERHORN

and DANTE/FLOT8 trials

, which focused on gastric adenocarcinoma and gastroesophageal junction adenocarcinoma, demonstrated promising pCR rates, further supporting the efficacy of neoadjuvant immunotherapy regimens. However, these trials largely involved gastric cancer patients, which may show different prognoses from those with esophageal cancer, likely due to the potent chemotherapy regimens and tumor heterogeneity.
最近，几项研究调查了新辅助免疫治疗在上消化道恶性肿瘤中的作用。KEYNOTE-585 试验代表了一项 III 期研究，研究新辅助帕博利珠单抗与化疗联合在胃癌和胃食管交界癌中的应用。尽管未达到预设的无事件生存期（EFS）终点，治疗组的中位 EFS 为 44.4 个月，而对照组为 25.3 个月，风险比（HR）为

。亚组分析表明，特别是在合并阳性评分（CPS）较高的患者中，存在获益趋势，这与其他 III 期研究的结果相呼应，如 KEYNOTE-859（参考文献 26）和 Checkmate-649（参考文献 27），这些研究强调了在接受免疫治疗与化疗联合治疗的晚期胃癌患者中显著的生存获益。同样，MATTERHORN

和 DANTE/FLOT8 试验

，专注于胃腺癌和胃食管交界腺癌，显示出令人鼓舞的病理完全缓解（pCR）率，进一步支持了新辅助免疫治疗方案的有效性。然而，这些试验主要涉及胃癌患者，这可能与食管癌患者的预后不同，这可能是由于强效化疗方案和肿瘤异质性所致。

Table 4 | Surgical complications according to CD classification in at least two patients in all groups
表 4 | 所有组中至少两名患者的 CD 分类下的手术并发症

Table

Preoperative TRAE in at least 5% of patients in any group
表

在任何组中至少 5%的患者中发生的术前 TRAE

In the realm of esophageal cancer, a systematic review and meta-analysis that included 27 phase 2 trials encompassing 815 patients underscores the promising clinical and safety outcomes of neoadjuvant immunotherapy combined with chemotherapy in patients with resectable esophageal cancer

. Moreover, the ongoing phase

在食管癌领域，一项包含 27 个二期试验和 815 名患者的系统评价和荟萃分析强调了新辅助免疫治疗与化疗联合在可切除食管癌患者中具有良好的临床和安全性结果

。此外，正在进行的阶段

ECOG-ACRIN EA2174 trial

, which explores a combination of neoadjuvant carboplatin and paclitaxel with concurrent radiation, either with or without nivolumab, followed by adjuvant nivolumab with or without ipilimumab, is poised to further our understanding of perioperative immunotherapy in locoregional esophageal and gastroesophagealjunction
ECOG-ACRIN EA2174 试验

探索了新辅助卡铂和紫杉醇与同步放疗的组合，伴随或不伴随 nivolumab，随后进行辅助 nivolumab 伴随或不伴随 ipilimumab，旨在进一步加深我们对局部区域食管和胃食管交界处围手术期免疫治疗的理解
adenocarcinoma. Distinguishing between ESCC and adenocarcinoma is crucial, as these subtypes vary significantly in pathogenesis, epidemiology, and prognosis

. Notably, the phase 3ESCORT-NEO/NCCESO1study fills a crucial gap in our understanding and provides critical evidence for the efficacy of neoadjuvant immunotherapy plus chemotherapy in ESCC, demonstrating more significant improvements in pCR rates than neoadjuvant chemotherapy alone. In addition to ESCORT-NEO/ NCCES01, several other ongoing phase 3 studies are exploring the role of neoadjuvant immunotherapy in ESCC. These include NCT04848753, which compares neoadjuvant immunochemotherapy to chemotherapy alone; and the KEYSTONE-002 study

, which assesses neoadjuvant immunochemotherapy versus chemoradiotherapy. We anticipate the outcomes from these studies will further elucidate the role of neoadjuvant immunotherapy in the management of ESCC.
腺癌。区分食管鳞状细胞癌（ESCC）和腺癌至关重要，因为这两种亚型在发病机制、流行病学和预后方面存在显著差异

。值得注意的是，3 期 ESCORT-NEO/NCCESO1 研究填补了我们理解中的一个关键空白，并为新辅助免疫治疗加化疗在 ESCC 中的疗效提供了重要证据，显示出 pCR 率的显著改善，优于单独的新辅助化疗。除了 ESCORT-NEO/NCCES01，其他几个正在进行的 3 期研究也在探索新辅助免疫治疗在 ESCC 中的作用。这些研究包括 NCT04848753，该研究比较新辅助免疫化疗与单独化疗；以及 KEYSTONE-002 研究

，该研究评估新辅助免疫化疗与化疗放疗的效果。我们预计这些研究的结果将进一步阐明新辅助免疫治疗在 ESCC 管理中的作用。

In our study, the pCR rate in the Cam+nab-TP group was numerically higher than in the Cam+TP group, which might be attributable to prophylactic corticosteroid for paclitaxel before neoadjuvant therapy

. Corticosteroid use before ICI therapy could influence efficacy, potentially by inhibiting the proliferation of CD8-positive

cells required for an ICI response

. Additionally, the administered frequency and total dose of nab-paclitaxel seemed higher than that of paclitaxel in this study; nab-paclitaxel was administered at

on days 1 and 8 of each cycle, while paclitaxel was given at

only on day 1 of each cycle. A more intensive chemotherapy regimen may further contribute to improved efficacy. However, beyond the administered frequency and total dose, it is important to note that differential clinical activity between nab-paclitaxel and paclitaxel has been observed, possibly due to better drug delivery and reduced toxicities

. Our retrospective study observed that the pCR rate for immunotherapy combined with nab-paclitaxel and platinum-based chemotherapy was

, exceeding the

when combined with paclitaxel and platinum-based chemotherapy for LA-ESCC

. This observation aligns with studies in other cancers, such as lung squamous carcinoma and triple-negative breast cancer, where immunotherapy with nab-paclitaxel demonstrated survival benefits

. Furthermore, meta-analyses showed that nab-paclitaxel can improve pCR rates and survival outcomes when compared with solvent-based paclitaxe

, suggesting that the observed differences in pCR rates may also stem from the inherent properties of the two drugs. Although our study highlights potential benefits of combining ICIs with nab-paclitaxel in LA-ESCC, the lack of a prespecified hypothesis for comparing the Cam+nab-TP and Cam+TP groups necessitates cautious interpretation of these results. Future research should include direct comparative phase 3 randomized controlled trials to elucidate the efficacy and safety of ICI in combination with different taxane-based chemotherapies in treating ESCC.
在我们的研究中，Cam+nab-TP 组的 pCR 率在数值上高于 Cam+TP 组，这可能归因于在新辅助治疗前对紫杉醇的预防性皮质类固醇使用

。在 ICI 治疗前使用皮质类固醇可能会影响疗效，可能是通过抑制对 ICI 反应所需的 CD8 阳性细胞的增殖

。此外，在本研究中，纳米紫杉醇的给药频率和总剂量似乎高于紫杉醇；纳米紫杉醇在每个周期的第 1 天和第 8 天以

给药，而紫杉醇仅在每个周期的第 1 天以

给药。更强烈的化疗方案可能进一步有助于提高疗效。然而，除了给药频率和总剂量外，值得注意的是，已经观察到纳米紫杉醇和紫杉醇之间的临床活性差异，这可能是由于更好的药物递送和减少的毒性

。我们的回顾性研究观察到，免疫治疗与纳米紫杉醇和铂类化疗联合的 pCR 率为

，超过了与紫杉醇和铂类化疗联合时的

，针对 LA-ESCC

。这一观察与其他癌症的研究一致，例如肺鳞状癌和三阴性乳腺癌，其中纳米紫杉醇的免疫治疗显示出生存益处

。此外，荟萃分析显示，与溶剂型紫杉醇相比，纳米紫杉醇可以提高 pCR 率和生存结果

，这表明观察到的 pCR 率差异可能也源于这两种药物的固有特性。尽管我们的研究强调了在 LA-ESCC 中将 ICI 与纳米紫杉醇结合的潜在益处，但缺乏预先指定的假设来比较 Cam+nab-TP 和 Cam+TP 组，因此需要谨慎解读这些结果。未来的研究应包括直接比较的第三阶段随机对照试验，以阐明 ICI 与不同紫杉烷类化疗药物联合治疗 ESCC 的疗效和安全性。

PD-L1 expression, a key biomarker for immunotherapy in ESCC, plays a significant role in guiding treatment decisions. High PD-L1 levels (

) are linked to improved survival with ICI monotherapy

. The ESCORT study revealed that camrelizumab offers clinical benefits across all PD-L1 levels, with greater advantages for those with higher expression

. Nevertheless, PD-L1's role as a biomarker is less clear when immunotherapy is combined with chemotherapy, as studies suggest even patients with low PD-L1 expression can benefit from this treatment

. For instance, the ESCORT-1st study showed enhanced OS for patients with PD-L1 expression

, though without statistical significance

. In our study, approximately half of the patients (

) exhibited PD-L1 positivity (tumor proportion score [TPS]

), aligning with the findings from both the ESCORT (42.6%) and ESCORT-1st studies (55.2%). Our analysis also highlighted a pronounced PCR advantage in patients with higher PD-L1 expression receiving combined treatment. Ultimately, while PD-L1 expression aids in assessing the potential of neoadjuvant immunotherapy with chemotherapy in ESCC, its accuracy requires further validation.
PD-L1 表达是食管鳞状细胞癌（ESCC）免疫治疗的关键生物标志物，在指导治疗决策中发挥着重要作用。高 PD-L1 水平（

）与 ICI 单药治疗的生存改善相关

。ESCORT 研究显示，卡瑞利珠单抗在所有 PD-L1 水平中均提供临床益处，且对高表达患者的优势更大

。然而，当免疫治疗与化疗联合时，PD-L1 作为生物标志物的作用不太明确，因为研究表明即使是低 PD-L1 表达的患者也能从这种治疗中受益

。例如，ESCORT-1st 研究显示 PD-L1 表达的患者的总生存期（OS）有所改善

，尽管没有统计学意义

。在我们的研究中，约一半的患者（

）表现出 PD-L1 阳性（肿瘤比例评分[TPS]

），与 ESCORT（42.6%）和 ESCORT-1st 研究（55.2%）的结果一致。我们的分析还强调了在接受联合治疗的高 PD-L1 表达患者中，PCR 优势明显。最终，虽然 PD-L1 表达有助于评估化疗联合新辅助免疫治疗在食管鳞状细胞癌中的潜力，但其准确性仍需进一步验证。

In the three groups, resection rates were

and

, respectively, indicating that neoadjuvant therapy did not notably affect the execution of surgery. Notably, the median duration of surgery was comparable across all groups, suggesting that adding neoadjuvant immunotherapy to chemotherapy may not complicate surgical procedures. The risks of postoperative morbidity and mortality were similar among the groups, indicating manageable safety for surgery after combined neoadjuvant therapy. These extended dissections resulted in a median of over 30 lymph nodes harvested, surpassing the minimum count necessary for precise staging and management.
在三个组中，切除率分别为

和

，表明新辅助治疗对手术的执行没有显著影响。值得注意的是，手术的中位持续时间在所有组中相当，表明将新辅助免疫治疗添加到化疗中可能不会使手术程序复杂化。术后发病率和死亡率的风险在各组之间相似，表明在联合新辅助治疗后手术的安全性可控。这些扩展的切除导致中位收获超过 30 个淋巴结，超过了精确分期和管理所需的最小数量。

Toxicity associated with neoadjuvant camrelizumab combined with chemotherapy aligned with previous studies, without new safety concerns. The most common severe TRAEs included neutrophil count decreased and white blood cell count decreased, which are recognized AEs of camrelizumab with chemotherapy

. The Cam+nab-TP group exhibited numerically higher rates of total TRAEs at

and grade

TRAEs at

,compared to

and

in the Cam+TP group, and

and

in the TP group. The primary increased TRAEs in the Cam+nab-TP group were manageable and included conditions such as white blood cell count decreased, neutrophil count decreased, anemia, lymphocyte count decreased, platelet count decreased and vomiting. These TRAEs were effectively managed with established clinical protocols, and there were no new or uncontrollable safety signals observed. Additionally, the rates of TRAEs leading to chemotherapy discontinuation were low and comparable across all groups, at

for Cam+nab-TP,

for

, and

for the TP group. Similarly, the rates of discontinuation of camrelizumab due to TRAEs were also low, at

for both the Cam+nab-TP and Cam+TP groups. Therefore, despite the numerically higher incidence of TRAEs in the Cam +nab-TPgroup, these were not associated with an increased risk of serious adverse effects, suggesting that the increased TRAEs may not represent a significant safety concern. Notably, the incidence of grade 3 or higher TRAEs in our study's camrelizumab with chemotherapy group was numerically lower than that reported in the ESCORT-1st study

, potentially attributable to fewer treatment cycles. This observation raises the question of whether the occurrence of AEs might accumulate with an increasing number of treatment cycles, meriting further exploration. The most frequent irAE was reactive cutaneous capillary endothelial proliferation, all instances of which were grade 1 or 2 . A grade 5 TRAE occurred in the Cam+TP group, where a patient experienced acute liver failure on the first day of neoadjuvant therapy, potentially linked to camrelizumab, paclitaxel or cisplatin. This case highlights the necessity of vigilant patient monitoring during combined immunotherapy.
与之前的研究一致，联合化疗的辅助治疗 camrelizumab 相关的毒性没有新的安全性问题。最常见的严重治疗相关不良事件（TRAEs）包括中性粒细胞计数减少和白细胞计数减少，这些是 camrelizumab 与化疗联合使用时公认的不良事件

。Cam+nab-TP 组的总 TRAEs 发生率在

和等级

TRAEs 在

方面的数值高于 Cam+TP 组的

和

，以及 TP 组的

和

。Cam+nab-TP 组主要增加的 TRAEs 是可管理的，包括白细胞计数减少、中性粒细胞计数减少、贫血、淋巴细胞计数减少、血小板计数减少和呕吐。这些 TRAEs 通过既定的临床方案得到了有效管理，并且没有观察到新的或无法控制的安全信号。此外，导致化疗中断的 TRAEs 发生率较低，并且在所有组之间相似，Cam+nab-TP 组为

，

为

，TP 组为

。同样，由于治疗相关不良事件（TRAEs），camrelizumab 的停药率也很低，在 Cam+nab-TP 组和 Cam+TP 组均为

。因此，尽管 Cam+nab-TP 组的 TRAEs 发生率在数字上较高，但这些并未与严重不良事件的风险增加相关，表明 TRAEs 的增加可能并不代表显著的安全隐患。值得注意的是，我们研究中 camrelizumab 与化疗联合使用组的 3 级或更高级别 TRAEs 发生率在数字上低于 ESCORT-1st 研究中报告的

，这可能归因于治疗周期较少。这个观察引发了一个问题，即不良事件的发生是否会随着治疗周期的增加而累积，值得进一步探讨。最常见的免疫相关不良事件（irAE）是反应性皮肤毛细血管内皮增生，所有病例均为 1 级或 2 级。在 Cam+TP 组中发生了一例 5 级 TRAEs，一名患者在新辅助治疗的第一天出现急性肝衰竭，可能与 camrelizumab、紫杉醇或顺铂有关。这个案例强调了在联合免疫治疗期间对患者进行严格监测的必要性。

This study has several limitations. First, this study did not directly compare the two neoadjuvant chemotherapy regimens combined with camrelizumab that were tested. Furthermore, although neoadjuvant chemoradiotherapy is a standard treatment for LA-ESCC, our study did not directly compare neoadjuvant immunochemotherapy with chemoradiotherapy. Previous studies have indicated that patients with ESCC in East Asia respond less to neoadjuvant chemoradiotherapy compared to their Caucasian counterparts

.Moreover, neoadjuvant chemotherapy is currently more widely accepted in East Asia. Second, another dual primary endpoint of this study, EFS, has not yet matured. Although prior studies have indicated that pathological response is correlated with long-term survival

, suggesting it could act as a surrogate endpoint for neoadjuvant immunotherapy, survival outcomes remain the gold standard in phase 3 studies. Another limitation of this study is that it was conducted exclusively in China, which may restrict the generalizability of the findings to populations in other regions. Moreover, the non-blinded design of this study could introduce some degree of bias. Besides, the current study is limited by the absence of comprehensive biomarker data, including a relatively high number of patients with unknown PD-L1 status. It should be noted that biomarker and patient-reported outcomes data are currently being collected as exploratory endpoints to enhance the understanding of treatment effects.
本研究有几个局限性。首先，本研究没有直接比较测试的两种联合 camrelizumab 的辅助化疗方案。此外，尽管新辅助化疗放疗是局部晚期食管鳞状细胞癌（LA-ESCC）的标准治疗，但我们的研究没有直接比较新辅助免疫化疗与化疗放疗。先前的研究表明，东亚的食管鳞状细胞癌（ESCC）患者对新辅助化疗放疗的反应较白人患者差

。此外，目前新辅助化疗在东亚更为广泛接受。其次，本研究的另一个双主要终点 EFS 尚未成熟。尽管先前的研究表明病理反应与长期生存相关

，这表明它可以作为新辅助免疫治疗的替代终点，但生存结果仍然是三期研究中的金标准。本研究的另一个局限性是仅在中国进行，这可能限制了研究结果在其他地区人群中的普遍适用性。此外，本研究的非盲法设计可能引入一定程度的偏倚。此外，目前的研究受到缺乏全面生物标志物数据的限制，包括相对较高数量的未知 PD-L1 状态患者。需要注意的是，生物标志物和患者报告的结果数据目前正在作为探索性终点进行收集，以增强对治疗效果的理解。

In conclusion, this study demonstrated that camrelizumab combined with chemotherapy significantly increased the PCR in the ITT
总之，本研究表明，卡瑞利珠单抗联合化疗显著提高了 ITT 中的 PCR
population. The combined treatment regimen was found to be safe, with no unexpected increase in toxicity. This study contributes new evidence supporting neoadjuvant treatment in LA-ESCC and lays the foundation for developing and optimizing future treatment strategies. We anticipate further confirmation of our findings as survival data continue to mature.
人群。联合治疗方案被发现是安全的，没有意外的毒性增加。这项研究提供了支持局部晚期食管鳞状细胞癌（LA-ESCC）新辅助治疗的新证据，并为未来治疗策略的开发和优化奠定了基础。我们期待随着生存数据的不断成熟，进一步确认我们的发现。

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References 参考文献

Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 71, 209-249 (2021).
Sung, H. 等. 2020 年全球癌症统计数据：GLOBOCAN 对 185 个国家 36 种癌症的发病率和死亡率估计. CA 癌症杂志. 临床. 71, 209-249 (2021).
Han, B. et al. Cancer incidence and mortality in China, 2022. J. Natl Cancer Center 4, 47-53 (2024).
韩, B. 等. 2022 年中国癌症发生率和死亡率. 国家癌症中心杂志 4, 47-53 (2024).
Chinese National Cancer Center; Chinese Association of Thoracic Surgeons; Chinese Society for Thoracic and Cardiovascular Surgery; Chinese Society for Diseases of the Esophagus. [Chinese Guidelines on Perioperative Management of Resectable Esophageal Cancer (2023 edition)]. Zhonghua Yi Xue Za Zhi 103, 2552-2570 (2023).
中国国家癌症中心；中国胸外科医师协会；中国胸心血管外科学会；中国食管疾病学会。[《可切除食管癌围手术期管理中国指南（2023 年版）》]。中华医学杂志 103, 2552-2570 (2023)。
Kitagawa, Y. et al. Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus 20 (2023).
北川裕等. 2022 年日本食道学会编辑的食道癌实践指南：第一部分. 食道 20 (2023).
van Hagen, P. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N. Engl. J. Med. 366, 2074-2084 (2012).
van Hagen, P. 等. 食管或交界癌的术前化放疗. 新英格兰医学杂志 366, 2074-2084 (2012).
Yang, H. et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the Esophagus (NEOCRTEC5O10): A phase III multicenter, randomized, open-label clinical trial. J. Clin. Oncol. 36, 2796-2803 (2018).
杨, H. 等. 新辅助化疗放疗加手术与单纯手术治疗局部晚期食管鳞状细胞癌（NEOCRTEC5O10）：一项 III 期多中心、随机、开放标签临床试验。临床肿瘤学杂志 36, 2796-2803 (2018)。
Ando, N. et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5 -fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann. Surg. Oncol. 19, 68-74 (2012).
安藤，N. 等。随机试验比较术后辅助化疗（顺铂和 5-氟尿嘧啶）与局部晚期食管鳞状细胞癌的术前化疗（JCOG9907）。外科肿瘤学年鉴 19, 68-74 (2012)。
Tang, H. et al. Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial. Ann. Oncol. 34, 163-172 (2023).
唐, H. 等. 新辅助化疗放疗与新辅助化疗后微创食管切除术治疗局部晚期食管鳞状细胞癌的前瞻性多中心随机临床试验. 《肿瘤年鉴》34, 163-172 (2023).
Kato, K. et al. A randomized controlled phase III trial comparing two chemotherapy regimen and chemoradiotherapy regimen as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study. J. Clin. Oncol. 40, 238-238 (2022).
加藤, K. 等. 一项随机对照的 III 期试验，比较两种化疗方案和化放疗方案作为局部晚期食管癌的新辅助治疗，JCOG1109 NExT 研究. 临床肿瘤学杂志. 40, 238-238 (2022).
Faron, M. et al. Individual participant data network meta-analysis of neoadjuvant chemotherapy or chemoradiotherapy in esophageal or gastroesophageal junction carcinoma. J. Clin. Oncol. 41, 4535-4547 (2023).
Faron, M. 等. 食管或胃食管交界癌新辅助化疗或化学放疗的个体参与者数据网络荟萃分析. J. Clin. Oncol. 41, 4535-4547 (2023).
Huang, J. et al. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 21, 832-842 (2020).
黄, J. 等. 卡瑞利珠单抗与研究者选择的化疗作为晚期或转移性食管鳞状细胞癌的二线治疗（ESCORT）：一项多中心、随机、开放标签、第三阶段研究. 柳叶刀肿瘤学. 21, 832-842 (2020).
Luo, H. et al. Effect of Camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st randomized clinical trial. JAMA 326, (2021).
罗, H. 等. Camrelizumab 与安慰剂联合化疗对晚期或转移性食管鳞状细胞癌患者生存率和无进展生存期的影响：ESCORT-1st 随机临床试验. JAMA 326, (2021).
Yang, Y. et al. Neoadjuvant camrelizumab combined with paclitaxel and nedaplatin for locally advanced esophageal squamous cell carcinoma: a single-arm phase 2 study (cohort study). Int. J. Surg. 110, 1430-1440 (2024).
杨, Y. 等. 新辅助卡瑞利珠单抗联合紫杉醇和耐铂治疗局部晚期食管鳞状细胞癌：一项单臂二期研究（队列研究）。国际外科杂志 110, 1430-1440 (2024)。
Liu, J. et al. Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2O19): a multicenter, phase 2 study. Int. J. Cancer 151, 128-137 (2022).
刘, J. 等. 新辅助卡瑞利珠单抗联合化疗治疗可切除的局部晚期食管鳞状细胞癌 (NIC-ESCC2O19): 一项多中心、第二阶段研究. 国际癌症杂志 151, 128-137 (2022).
Liu, J. et al. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J. Immunother. Cancer 10, e004291 (2022).
刘, J. 等. 多中心、单臂、II 期试验，评估卡瑞利珠单抗与化疗作为局部晚期食管鳞状细胞癌的新辅助治疗. J. Immunother. Cancer 10, e004291 (2022).
Yang, W. et al. Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma. J. Immunother. Cancer 10, e003497 (2022).
杨, W. 等. 新辅助程序性细胞死亡 1 阻断联合化疗治疗可切除食管鳞状细胞癌. J. Immunother. Cancer 10, e003497 (2022).
Wang, Z. et al. Phase Ib trial of camrelizumab combined with chemotherapy and apatinib for neoadjuvant treatment of locally advanced thoracic esophageal squamous cell carcinoma. J. Natl Cancer Cent. 2, 98-105 (2022).
王, Z. 等. Camrelizumab 联合化疗和阿帕替尼用于局部晚期胸部食管鳞状细胞癌的新辅助治疗的 I 期试验. J. Natl Cancer Cent. 2, 98-105 (2022).
Gong, L. et al. Camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC): A single-arm, phase II trial. J. Clin. Oncol. 41, 4048-4048 (2023).
龚, L. 等. Camrelizumab 和化疗作为局部晚期食管鳞状细胞癌 (ESCC) 的新辅助治疗：一项单臂、II 期试验。J. Clin. Oncol. 41, 4048-4048 (2023)。
Yu, Y. K. et al. Neoadjuvant chemotherapy combined with immunotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. J. Thorac. Cardiovasc. Surg. 2024, S00225223(24)00008-4 (2024).
余, Y. K. 等. 新辅助化疗联合免疫治疗与新辅助化疗放疗在局部晚期食管鳞状细胞癌患者中的比较. 胸心外科杂志. 2024, S00225223(24)00008-4 (2024).
Yang, Y. et al. Comparison of neoadjuvant nab-paclitaxel plus immunotherapy versus paclitaxel plus immunotherapy for esophageal squamous cell carcinoma. Thorac. Cancer 14, (2023).
杨, Y. 等. 新辅助纳米紫杉醇联合免疫治疗与紫杉醇联合免疫治疗在食管鳞状细胞癌中的比较. 胸部癌症 14, (2023).
Gaber, C. E. et al. Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: a systematic review and meta-analysis. Cancer Med. 13, e7076 (2024).
Gaber, C. E. 等. 接受新辅助化疗或化疗放疗的食管癌患者的病理完全缓解：一项系统评价和荟萃分析。癌症医学. 13, e7076 (2024).
Oppedijk, V. et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J. Clin. Oncol. 32, 385-391 (2014).
Oppedijk, V. 等. 在 CROSS 试验中，仅手术与术前化放疗加手术后的复发模式. J. Clin. Oncol. 32, 385-391 (2014).
Cools-Lartigue, J. et al. An international cohort study of prognosis associated with pathologically complete response following neoadjuvant chemotherapy versus chemoradiotherapy of surgical treated esophageal adenocarcinoma. Ann. Surg. 276, (2022).
Cools-Lartigue, J. 等. 一项国际队列研究，探讨新辅助化疗与化放疗后病理完全缓解相关的预后，针对手术治疗的食管腺癌。外科年鉴 276, (2022)。
Topalian, S. L., Taube, J. M. & Pardoll, D. M. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science 367, eaax0182 (2020).
Topalian, S. L., Taube, J. M. & Pardoll, D. M. 癌症免疫治疗的辅助性检查点阻断。科学 367, eaax0182 (2020)。
Shitara, K. et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 25, 212-224 (2024).
Shitara, K. 等. 局部晚期胃癌或胃食管癌的新辅助和辅助治疗：帕博利珠单抗联合化疗（KEYNOTE-585）：多中心、双盲、随机的 3 期研究的中期分析。柳叶刀肿瘤学. 25, 212-224 (2024).
Rha, S. Y. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 24, 1181-1195 (2023).
Rha, S. Y. 等. 帕博利珠单抗联合化疗与安慰剂联合化疗在 HER2 阴性晚期胃癌中的比较（KEYNOTE-859）：一项多中心、随机、双盲、第三阶段试验。柳叶刀肿瘤学. 24, 1181-1195 (2023)。
Janjigian, Y. Y. et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 398, 27-40 (2021).
Janjigian, Y. Y. 等. 一线 nivolumab 联合化疗与单独化疗治疗晚期胃癌、胃食管交界癌和食管腺癌（CheckMate 649）：一项随机、开放标签、第三阶段试验。柳叶刀 398, 27-40 (2021)。
Janjigian, Y. Y. et al. LBA73 Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study. Ann. Oncol. 34, S1315-S1316 (2023).
Janjigian, Y. Y. 等. LBA73 可切除胃癌和胃食管交界癌（GC/GEJC）对 durvalumab 联合 5-氟尿嘧啶、亚叶酸钙、奥沙利铂和多西他赛（FLOT）的病理完全反应（pCR）：全球 III 期 MATTERHORN 研究的中期结果。肿瘤学年鉴 34, S1315-S1316 (2023)。
Lorenzen, S. et al. Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: interim results from the randomized, multicenter, phase II/III DANTE/IKF-s633 Trial. J. Clin. Oncol. 42, (2024).
Lorenzen, S. 等. 可切除食管胃癌的围手术期阿特珠单抗联合氟尿嘧啶、亚叶酸钙、奥沙利铂和多西他赛：随机、多中心、II/III 期 DANTE/IKF-s633 试验的中期结果。J. Clin. Oncol. 42, (2024)。
Ge, F. et al. Evaluation of clinical and safety outcomes of neoadjuvant immunotherapy combined with chemotherapy for patients with resectable esophageal cancer: a systematic review and meta-analysis. JAMA Netw. Open 5, e2239778 (2022).
Ge, F. 等. 新辅助免疫治疗联合化疗对可切除食管癌患者的临床和安全性结果评估：一项系统评价和荟萃分析。JAMA Netw. Open 5, e2239778 (2022)。
Eads, J. R. et al. A phase II/III study of perioperative nivolumab and ipilimumab in patients (pts) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: a trial of the ECOG-ACRIN Cancer Research Group (EA2174). J. Clin. Oncol. 38, TPS4651-TPS4651 (2020).
Eads, J. R. 等. 一项关于局部区域食管（E）和胃食管交界（GEJ）腺癌患者（pts）围手术期使用 nivolumab 和 ipilimumab 的 II/III 期研究：ECOG-ACRIN 癌症研究组的试验（EA2174）。J. Clin. Oncol. 38, TPS4651-TPS4651 (2020)。
Cancer Genome Atlas Research, N. et al. Integrated genomic characterization of oesophageal carcinoma. Nature 541, 169-175 (2017).
癌症基因组图谱研究，N. 等。食管癌的综合基因组特征分析。自然 541, 169-175 (2017)。
Shang, X. et al. Pembrolizumab combined with neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy followed by surgery for locally advanced oesophageal squamous cell carcinoma: protocol for a multicentre, prospective, randomized-controlled, phase III clinical study (Keystone-002). Front Oncol. 12, 831345 (2022).
Shang, X. 等. 帕博利珠单抗联合新辅助化疗与新辅助放化疗后手术治疗局部晚期食管鳞状细胞癌的比较：一项多中心、前瞻性、随机对照的 III 期临床研究方案（Keystone-002）。肿瘤前沿. 12, 831345 (2022)。
Arbour, K. C. et al. Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small-cell lung cancer. J. Clin. Oncol. 36, 2872-2878 (2018).
阿伯，K. C. 等. 基线类固醇对非小细胞肺癌患者程序性细胞死亡-1 和程序性死亡配体-1 阻断疗效的影响. 临床肿瘤学杂志 36, 2872-2878 (2018).
Im, S. J. et al. Defining cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417-421 (2016).
Im, S. J. 等. 确定在 PD-1 治疗后提供增殖爆发的细胞. 自然 537, 417-421 (2016).
Untch, M. et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 17, 345-356 (2016).
Untch, M. 等. 纳米紫杉醇与溶剂型紫杉醇在早期乳腺癌新辅助化疗中的比较（GeparSepto-GBG 69）：一项随机、第三阶段试验。柳叶刀肿瘤学. 17, 345-356 (2016)。
Franzoi, M. A. & de Azambuja, E. Atezolizumab in metastatic triple-negative breast cancer: IMpassion130 and 131 trials - how to explain different results? ESMO Open 5, e001112 (2020).
Franzoi, M. A. & de Azambuja, E. Atezolizumab 在转移性三阴性乳腺癌中的应用：IMpassion130 和 131 试验 - 如何解释不同的结果？ESMO Open 5, e001112 (2020)。
Paz-Ares, L. et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med. 379, 2040-2051 (2018).
Paz-Ares, L. 等. 帕博利珠单抗联合化疗治疗鳞状非小细胞肺癌. 新英格兰医学杂志 379, 2040-2051 (2018).
Zong, Y., Wu, J. & Shen, K. Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: a systematic review and meta-analysis. Oncotarget 8, 17360-17372 (2017).
宗, Y., 吴, J. & 沈, K. 纳米颗粒白蛋白结合的紫杉醇作为乳腺癌的新辅助化疗：系统评价和荟萃分析。肿瘤靶向 8, 17360-17372 (2017)。
Liu, M., Liu, S., Yang, L. & Wang, S. Comparison between nab-paclitaxel and solvent-based taxanes as neoadjuvant therapy in breast cancer: a systematic review and meta-analysis. BMC Cancer 21, 118 (2021).
刘, M., 刘, S., 杨, L. & 王, S. 纳米白蛋白结合紫杉醇与溶剂基础紫杉烷作为乳腺癌新辅助治疗的比较：一项系统评价和荟萃分析。BMC 癌症 21, 118 (2021)。
Kojima, T. et al. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J. Clin. Oncol. 38, 4138-4148 (2020).
小岛, T. 等. 随机三期 KEYNOTE-181 研究，比较 pembrolizumab 与化疗在晚期食管癌中的疗效. J. Clin. Oncol. 38, 4138-4148 (2020).
Sun, J. M. et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 398, 759-771 (2021).
孙, J. M. 等. 帕博利珠单抗联合化疗与单独化疗在晚期食管癌一线治疗中的比较（KEYNOTE-590）：一项随机、安慰剂对照的三期研究. 柳叶刀 398, 759-771 (2021).
Wu, H. X. et al. Clinical benefit of first-line programmed death-1 antibody plus chemotherapy in low programmed cell death ligand 1 -expressing esophageal squamous cell carcinoma: a post hoc analysis of JUPITER-06 and meta-analysis. J. Clin. Oncol. 41, (2023).
吴, H. X. 等. 低程序性细胞死亡配体 1 表达的食管鳞状细胞癌中一线程序性死亡-1 抗体加化疗的临床益处：JUPITER-06 的事后分析和荟萃分析. J. Clin. Oncol. 41, (2023).
Eyck, B. M. et al. Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma: multicentre East Asian and Dutch database comparison. Br. J. Surg. 109, 1312-1318 (2022).
Eyck, B. M. 等. 食管鳞状细胞癌新辅助化疗放疗的病理反应：东亚和荷兰多中心数据库比较。英国外科杂志 109, 1312-1318 (2022)。
Chen, Y. et al. Does major pathological response after neoadjuvant Immunotherapy in resectable nonsmall-cell lung cancers predict prognosis? A systematic review and meta-analysis. Int. J. Surg. 109, 2794-2807 (2023).
陈, Y. 等. 新辅助免疫治疗后可切除非小细胞肺癌的主要病理反应是否预测预后？一项系统评价和荟萃分析。国际外科杂志 109, 2794-2807 (2023)。

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(c) The Author(s) 2024
（c）作者 2024

Abstract 摘要

Jianjun Qin , Liyan Xue , Anlin Hao , Xiaofeng Guo (1) , Tao Jiang , Yunfeng Ni , Shuoyan Liu , Yujie Chen , Hongjing Jiang , Chen Zhang , Mingqiang Kang , Jihong Lin , Hecheng Li , Chengqiang Li , Hui Tian , Lin Li , Junke , Yong Zhang ，Jianqun Ma ，Xiaoyuan Wang ，Maoyong Fu ，Hao Yang ，Zhaoyang Yang ，Yongtao Han ，Longqi Chen ， Lijie Tan (1) , Tianyang Dai , Yongde Liao , Weiguo Zhang , Bin Li , Qixun Chen , Shiping Guo , Yu Qi , Li Wei , Zhigang Li (1) , Ziqiang Tian , Xiaozheng Kang , Ruixiang Zhang , Yong Li , Zhen Wang , Xiankai Chen , Zhiguo Hou , Rongrong Zheng , Wenqing Zhu , Jie He &in Li (D)
秦建军 , 薛丽燕 , 郝安林 , 郭晓峰 (1) , 姜涛 , 倪云峰 , 刘硕言 , 陈宇杰 , 姜洪静 , 张晨 , 康明强 , 林继红 , 李和成 , 李成强 , 田辉 , 李林 , 军科 , 张勇 , 马建群 , 王小园 , 傅毛勇 , 杨浩 , 杨朝阳 , 韩永涛 , 陈龙奇 , 谭丽杰 (1) , 戴天阳 , 廖永德 , 张伟国 , 李斌 , 陈启勋 , 郭世平 , 齐宇 , 韦丽 , 李志刚 (1) , 田自强 , 康晓政 , 张瑞祥 , 李勇 , 王震 , 陈先凯 , 侯志国 , 郑荣荣 , 朱文清 , 何杰 & 李 (D)

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Thoracic Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Surgery of Esophageal Cancer, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.

Department of Thoracic Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.

Department of Thoracic Surgery, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.

Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, China.

Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Thoracic Surgery, Henan Provincial People's Hospital, Zhengzhou, China.

Department of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Medical Affairs, Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China.

These authors contributed equally: Jianjun Qin, Liyan Xue. e-mail: hejie@cicams.ac.cn; liyin@cicams.ac.cn

中国上海复旦大学中山医院胸外科。

中国泸州西南医科大学附属医院胸外科。

中国武汉华中科技大学同济医学院联合医院胸外科。

中国洛阳河南科技大学第一附属医院食管癌外科。

中国兰州兰州大学第二医院及临床医学院胸外科。

中国杭州中国科学院大学癌症医院浙江癌症医院胸外科。

中国太原山西省癌症医院胸外科。

中国郑州郑州大学第一附属医院胸外科。

中国郑州河南省人民医院胸外科。

中国上海上海交通大学医学院上海胸科医院食管外科。

河北医科大学第四医院胸外科，石家庄，中国。

江苏恒瑞医药股份有限公司医务部，上海，中国。

这些作者贡献相同：秦建军，薛丽妍。电子邮件：hejie@cicams.ac.cn；liyin@cicams.ac。cn

Methods 方法

Study design and patients
研究设计和患者

The ESCORT-NEO/NCCES01 study is a multicenter, randomized, open-label, phase 3 trial conducted across 24 centers in China, which enrolled patients with LA-ESCC. The inclusion criteria were: 1) provision of a written informed consent form and voluntary participation in the study;2) histopathological or cytological confirmation of ESCC;3) Thoracic esophageal cancer confirmed by computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), clinically staged as T1b-3N1-3MO or T3NOMO according to the 8th edition of the American Joint Committee on Cancer staging system;4) expectation to achieve a R 0 resection;5) age between 18 and 75 years, applicable to both male and female patients; 6) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1;7) no prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy or surgery;8) scheduled for surgery following the completion of neoadjuvant therapy; 9) no contraindications to undergoing surgery;10) normal function of major organs, including a) hematology (no administration of blood components, cell growth factors, leukocyte-elevating drugs, platelet-elevating drugs, or anemia-correcting drugs within 14 days before the first administration of the study drug) (neutrophil count

liter

, platelet count

liter

, hemoglobin

liter

); b) blood biochemistry (total bilirubin

upper limit of normal (ULN), alanine aminotransferase

, aspartate aminotransferase

ULN, serum creatinine

ULN or creatinine
ESCORT-NEO/NCCES01 研究是一项多中心、随机、开放标签的第三阶段试验，在中国的 24 个中心进行，招募了患有局部晚期食管鳞状细胞癌（LA-ESCC）的患者。纳入标准为：1）提供书面知情同意书并自愿参与研究；2）组织病理学或细胞学确认食管鳞状细胞癌（ESCC）；3）通过计算机断层扫描（CT）、磁共振成像（MRI）、内镜超声（EUS）确认的胸部食管癌，临床分期为 T1b-3N1-3MO 或 T3NOMO，依据美国癌症联合委员会第八版分期系统；4）期望实现 R0 切除；5）年龄在 18 至 75 岁之间，适用于男性和女性患者；6）东部肿瘤合作组表现状态（ECOG PS）为 0-1；7）无食管癌的先前抗肿瘤治疗，包括放疗、化疗或手术；8）在完成新辅助治疗后计划进行手术；9）无进行手术的禁忌症；10）主要器官功能正常，包括 a）血液学（在首次给药前 14 天内未使用血液成分、细胞生长因子、白细胞升高药物、血小板升高药物或纠正贫血药物）（中性粒细胞计数

升

，血小板计数

升

，血红蛋白bin

升

); b) 血液生化 (总胆红素

正常上限 (ULN)，丙氨酸氨基转移酶

，天冬氨酸氨基转移酶

ULN，血清肌酐

ULN 或肌酐

lation function: international normalized ratio

ULN, activated partial thromboplastin time

ULN;11) female participants of childbearing potential must have a negative serum pregnancy test result within 72 h before the first dose of the study drug and agree to use effective contraception (for example, intrauterine devices, hormonal contraceptives or condoms) during the study period and for at least 3 months following the last dose, and male participants with partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 3 months after the last dose; and 12) participants must demonstrate good compliance and cooperation with follow-up requirements throughout the study.
翻译功能：国际标准化比率

ULN，活化部分凝血酶时间

ULN；11）具有生育潜力的女性参与者在首次服用研究药物前 72 小时内必须有阴性的血清妊娠测试结果，并同意在研究期间及最后一次服药后至少 3 个月内使用有效的避孕措施（例如，宫内节育器、激素避孕药或安全套）；具有生育潜力的男性参与者必须是外科绝育或同意在研究期间及最后一次服药后 3 个月内使用有效的避孕措施；12）参与者必须在整个研究期间表现出良好的依从性和配合随访要求。

Patients with any of the following conditions were excluded from participating in this study:1) Presence of a tumor with obvious invasion into adjacent organs of the esophageal lesion, such as major arteries or the trachea. 2) Metastases to supraclavicular lymph nodes. 3) Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage.4) Poor nutritional status, defined as a body mass index less than

; however, patients whose nutritional status improved after symptomatic support and who were subsequently reassessed and approved by the principal investigator were considered for enrollment. 5) History of allergy to monoclonal antibodies, any component of camrelizumab, paclitaxel, cisplatin or other platinum-based drugs. 6) Prior or ongoing treatment that included: a) any form of radiotherapy, chemotherapy or other anti-tumor drugs; b) use of immunosuppressive drugs or systemic corticosteroid therapy for immunosuppressive purposes (doses exceeding

prednisone or its equivalent) within 2 weeks before the first dose of the study drug (inhaled or topical steroids, as well as adrenal corticosteroid replacement therapy exceeding doses of

prednisone or equivalent, were allowed, provided there was no active autoimmune disease); c) receipt of a live attenuated vaccine within 4 weeks before the first dose of the study drug; or d) undergoing major surgery or experiencing serious trauma within 4 weeks before the first dose of the study drug. 7) History of any active or past autoimmune disease, including, but not limited to, interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism and hypothyroidism (even if under hormone replacement therapy). Exceptions may be made for patients with historical psoriasis or childhood asthma/ allergy that resolved without intervention in adulthood; however, patients requiring ongoing medical intervention with bronchodilators were excluded. 8) History of immunodeficiency, including those testing positive for human immunodeficiency virus, other acquired or congenital immune deficiencies, or a history of organ transplantation or allogeneic bone marrow transplantation. 9) Presence of clinically uncontrolled cardiac symptoms or diseases, including but not limited to: New York Heart Association class II or above heart failure, unstable angina pectoris, myocardial infarction within the past year or clinically notable supraventricular or ventricular arrhythmias that were either untreated or uncontrolled with treatment.10) Any serious infection (National Cancer Institute Common Terminology Criteria for Adverse Events > grade 2) within 4 weeks before the first dose of the study drug, including severe pneumonia, bacteremia or infection complications requiring hospitalization; active pulmonary inflammation evident on baseline chest

-ray; or symptoms and signs of infection requiring oral or intravenous antibiotic therapy within 14 days before the first dose of the study drug, excluding prophylactic use of antibiotics.11) Patients with an active tuberculosis infection based on medical history or CT test, those who have had an active tuberculosis infection within the past year, or those with a history of tuberculosis beyond one year without proper treatment. 12) Presence of active hepatitis B virus, defined as hepatitis B virus DNA levels

copies

or active hepatitis C virus, indicated by positive hepatitis C antibody and hepatitis

virus RNA levels above the lower limit of detection of the assay. 13) Any other malignancies diagnosed within the past 5 years before the first dose of the study drug, with the exception of malignancies with a low risk of metastasis or death (5-year survival rate

), such as adequately treated basal cell carcinoma of the skin, squamous cell skin cancer or carcinoma in situ of the cervix.14) Pregnant or lactating women. 15) Presence of other factors that, in the investigator's judgment, may necessitate forced withdrawal from the study. These factors included other serious diseases (including psychiatric disorders) that required concomitant therapy, alcoholism, drug abuse or family or social factors that may compromise the safety or compliance of the subjects.
在本研究中，以下任何情况的患者被排除在外：1）肿瘤明显侵入食管病变邻近器官，如主要动脉或气管。2）转移至锁骨上淋巴结。3）无法控制的胸腔积液、心包积液或需要反复引流的腹水。4）营养状态差，定义为体重指数低于

；然而，经过对症支持后营养状态改善并经主要研究者重新评估和批准的患者可考虑入组。5）对单克隆抗体、camrelizumab、紫杉醇、顺铂或其他铂类药物的过敏史。 6) 先前或正在进行的治疗包括：a) 任何形式的放疗、化疗或其他抗肿瘤药物；b) 在研究药物首次给药前 2 周内使用免疫抑制药物或系统性皮质类固醇治疗以免疫抑制为目的（剂量超过

的泼尼松或其等效物），（允许使用吸入或局部类固醇，以及超过

的泼尼松或等效物的肾上腺皮质激素替代治疗，前提是没有活动性自身免疫疾病）；c) 在研究药物首次给药前 4 周内接种活减毒疫苗；或 d) 在研究药物首次给药前 4 周内接受重大手术或经历严重创伤。7) 任何活动性或过去的自身免疫疾病病史，包括但不限于间质性肺炎、肠炎、肝炎、垂体炎、血管炎、肾炎、甲亢和甲减（即使在激素替代治疗下）。对于有历史银屑病或儿童哮喘/过敏且在成年后自行缓解的患者，可以做出例外；然而，需持续使用支气管扩张剂进行医疗干预的患者被排除在外。8) 免疫缺陷病史，包括人类免疫缺陷病毒阳性、其他获得性或先天性免疫缺陷，或器官移植或异体骨髓移植的历史。9) 存在临床上无法控制的心脏症状或疾病，包括但不限于：纽约心脏协会 II 级或以上的心力衰竭、不稳定型心绞痛、过去一年内的心肌梗死或临床上显著的室上性或室性心律失常，且未接受治疗或治疗无效。10) 在首次服用研究药物前的 4 周内，任何严重感染（国家癌症研究所不良事件通用术语标准 > 2 级），包括重度肺炎、菌血症或需要住院的感染并发症；基线胸部

-射线显示的活动性肺部炎症；或在首次服用研究药物前 14 天内需要口服或静脉抗生素治疗的感染症状和体征，不包括抗生素的预防性使用。11) 根据病史或 CT 检查有活动性结核感染的患者，过去一年内有活动性结核感染的患者，或有超过一年未接受适当治疗的结核病史的患者。12) 存在活动性乙型肝炎病毒，定义为乙型肝炎病毒 DNA 水平

或

拷贝

，或活动性丙型肝炎病毒，表现为丙型肝炎抗体阳性和丙型肝炎

病毒 RNA 水平高于检测限。 13) 在研究药物首次给药前 5 年内诊断出的任何其他恶性肿瘤，除低转移或死亡风险的恶性肿瘤（5 年生存率

）外，例如经过适当治疗的皮肤基底细胞癌、鳞状细胞皮肤癌或宫颈原位癌。14) 孕妇或哺乳期女性。15) 研究者判断可能需要强制退出研究的其他因素。这些因素包括需要同时治疗的其他严重疾病（包括精神疾病）、酗酒、药物滥用或可能影响受试者安全性或依从性的家庭或社会因素。

The study protocol was approved by the Ethics Committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Anyang Cancer Hospital; Tangdu Hospital, Air Force Military Medical University; Fujian Provincial Cancer Hospital; Tianjin Medical University Cancer Institute and Hospital; Fujian Medical University Union Hospital; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Qilu Hospital of Shandong University; The First Affiliated Hospital of Xi'an Jiaotong University; Harbin Medical University Cancer Hospital; Affiliated Hospital of North Sichuan Medical College;Sichuan Cancer Hospital; West China Hospital, Sichuan University; Zhongshan Hospital, Fudan University; The Affiliated Hospital of Southwest Medical University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; The First Affiliated Hospital of Henan University of Science and Technology; The Second Hospital & Clinical Medical School, Lanzhou University; Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital; Shanxi Provincial Cancer Hospital; First Affiliated Hospital of Zhengzhou University; Henan Provincial People's Hospital;Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine; The Fourth Hospital of Hebei Medical University. All enrolled patients provided written informed consent. The study was registered before patient enrollment (ChiCTR2000040034). An independent data monitoring committee was established to ensure ongoing participant safety and data integrity throughout the trial.
研究方案已获得中国医学科学院肿瘤医院/北京协和医学院国家癌症中心/国家临床肿瘤研究中心；安阳癌症医院；空军军医大学唐都医院；福建省肿瘤医院；天津医科大学肿瘤研究所及医院；福建医科大学附属医院；上海交通大学医学院瑞金医院；山东大学齐鲁医院；西安交通大学第一附属医院；哈尔滨医科大学肿瘤医院；北川医学院附属医院；四川省肿瘤医院；四川大学华西医院；复旦大学中山医院；西南医科大学附属医院；华中科技大学同济医学院协和医院；河南科技大学第一附属医院；兰州大学第二医院及临床医学院；中国科学院大学肿瘤医院，浙江省肿瘤医院；山西省肿瘤医院的伦理委员会批准医院；郑州大学第一附属医院；河南省人民医院；上海交通大学医学院上海胸科医院；河北医科大学第四医院。所有入组患者均提供了书面知情同意。该研究在患者入组前进行了注册（ChiCTR2000040034）。成立了独立的数据监测委员会，以确保在整个试验过程中参与者的安全和数据的完整性。

The sex of participants was collected according to the identity information provided by the patients. Gender, as shaped by social and cultural circumstances, was not specifically assessed or reported in the study design. Both male and female patients were eligible.
参与者的性别是根据患者提供的身份信息收集的。性别作为社会和文化环境塑造的结果，在研究设计中并未特别评估或报告。男性和女性患者均符合资格。

Post hoc subgroup analysis of pCR was performed based on sex (male versus female). Patients were provided with the study treatment for free (including camrelizumab, paclitaxel, albumin-bound paclitaxel and cisplatin) and also received a transportation reimbursement.
对 pCR 的事后亚组分析是基于性别（男性与女性）进行的。患者免费提供研究治疗（包括 camrelizumab、紫杉醇、白蛋白结合紫杉醇和顺铂），并且还获得了交通补贴。

Procedure 程序

Eligible patients were randomly assigned in a 1:1:1 ratio to either the Cam+nab-TP group, the Cam+TP group, or the TP group using the randomized trial management system. Randomization was stratified according to clinical stage into I/II, III, and IVA. All patients underwent two 3-week cycles of neoadjuvant therapy. The Cam+nab-TP group received camrelizumab ( 200 mg on day 1 ), albumin-bound paclitaxel (

on days 1 and 8 ), and cisplatin (

on day 1 ). The Cam+TP group was administered camrelizumab ( 200 mg on day 1), paclitaxel (

on day 1 ), and cisplatin (

on day 1 ), while the TP group was given paclitaxel (

on day 1 ) and cisplatin (

on day 1 ). Currently, there is no recommended dose of nab-paclitaxel for patients with ESCC, and the dose of nab-paclitaxel used in our study was derived from existing literature on other cancer types and corroborated by our own preliminary findings

. For paclitaxel administration, patients received prophylactic agents including dexamethasone, diphenhydramine and H 2 receptor antagonists (cimetidine or ranitidine) to prevent hypersensitivity reactions. Cisplatin was administered after dilution in a similar solution, with adequate hydration and diuresis implemented to prevent renal toxicity; no prophylactic antiemetic corticosteroids were used. In this study, the camrelizumab dose was fixed, but chemotherapy doses could be adjusted in response to AEs as detailed in the protocol. Following the completion of neoadjuvant therapy, participants were reassessed for surgery eligibility, which was scheduled to occur within

weeks later. The surgical procedure involved esophagectomy and lymph node dissection, with the McKeown approach and a total two-field lymphadenectomy being recommended

. Both minimally invasive and open esophagectomy were deemed acceptable. For those in the Cam+nab-TP and Cam+TP groups, postoperative adjuvant therapy with camrelizumab ( 200 mg every 3 weeks) was prescribed for up to 15 cycles.
符合条件的患者通过随机试验管理系统以 1:1:1 的比例随机分配到 Cam+nab-TP 组、Cam+TP 组或 TP 组。随机分配根据临床分期分层为 I/II、III 和 IVA。所有患者接受了两个为期 3 周的辅助治疗周期。Cam+nab-TP 组接受了 camrelizumab（第 1 天 200 mg）、白蛋白结合型紫杉醇（第 1 天和第 8 天

）和顺铂（第 1 天

）。Cam+TP 组接受了 camrelizumab（第 1 天 200 mg）、紫杉醇（第 1 天

）和顺铂（第 1 天

），而 TP 组则接受了紫杉醇（第 1 天

）和顺铂（第 1 天

）。目前，对于食管鳞状细胞癌（ESCC）患者尚无推荐的 nab-紫杉醇剂量，我们研究中使用的 nab-紫杉醇剂量来源于其他癌症类型的现有文献，并得到了我们自己初步发现的证实

。在紫杉醇给药时，患者接受了包括地塞米松、苯海拉明和 H2 受体拮抗剂（西咪替丁或雷尼替丁）在内的预防性药物，以防止过敏反应。顺铂在稀释后以类似溶液给药，并实施了充分的水合和利尿以防止肾毒性；未使用预防性抗呕吐类固醇。在本研究中，camrelizumab 的剂量是固定的，但化疗剂量可以根据不良事件进行调整，如方案中详细说明的。在新辅助治疗完成后，参与者将重新评估手术资格，手术计划在

周内进行。手术程序包括食管切除术和淋巴结清扫，推荐使用 McKeown 方法和总两区淋巴结清扫

。微创和开放式食管切除术均被认为是可接受的。对于 Cam+nab-TP 和 Cam+TP 组的患者，术后辅助治疗使用 camrelizumab（每 3 周 200 毫克），最多可进行 15 个周期。

In this study, all pathological samples were reviewed by a blind independent review committee (BIRC), with the tumor regression grade evaluated according to the Mandard criteria, which involves comparing the proportion of viable tumor to fibrosis confirmed microscopically

. The study documented all AEs, postoperative complications and postoperative mortality at 30 and 90 days. AEs were graded and recorded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Postoperative complications were classified as per the standards of the Esophageal Complications Consensus Group

, and the severity was graded according to the

classification

.
在本研究中，所有病理样本均由盲法独立审查委员会（BIRC）进行审查，肿瘤退缩等级根据 Mandard 标准进行评估，该标准涉及比较显微镜下确认的存活肿瘤与纤维化的比例

。研究记录了所有不良事件（AEs）、术后并发症和术后 30 天及 90 天的死亡率。AEs 的分级和记录遵循国家癌症研究所不良事件通用术语标准第 5.0 版。术后并发症根据食管并发症共识小组的标准进行分类

，严重程度根据

分类

进行分级。

Furthermore, before treatment initiation, formalin-fixed paraffin-embedded tissue sections acquired through endoscopic biopsy were used to determine PD-L1 expression levels at a central laboratory via immunohistochemistry (PD-L1 IHC 22C3 pharmDx kit, Dako). The assessment of PD-L1 expression involved both CPS and TPS. The CPS is defined as the number of PD-L1 staining cells divided by the total number of viable tumor cells, multiplied by 100; the TPS represents the percentage of viable tumor cells exhibiting membrane staining, assessed in a sample of at least 100 viable tumor cells.
此外，在治疗开始之前，通过内窥镜活检获得的福尔马林固定石蜡包埋组织切片被用于在中心实验室通过免疫组化（PD-L1 IHC 22C3 pharmDx 试剂盒，Dako）确定 PD-L1 表达水平。PD-L1 表达的评估涉及 CPS 和 TPS。CPS 定义为 PD-L1 染色细胞的数量除以总的存活肿瘤细胞数量，再乘以 100；TPS 表示表现出膜染色的存活肿瘤细胞的百分比，评估样本至少包含 100 个存活肿瘤细胞。

Endpoints 终点

The study's dual primary endpoints included the pCR rate, assessed by the BIRC, and EFS, evaluated by the investigators. PCR is defined as the absence of residual tumor at the primary tumor site (tumor regression grade 1) and negative lymph nodes. Secondary endpoints included the MPR rate (defined as less than

residual viable tumor cells in the primary tumor) assessed by BIRC,RO resection rate,ypTNM staging according to the 8 th edition of the American Joint Committee on Cancer, OS, DFS, AEs and surgical complications.
该研究的双主要终点包括由 BIRC 评估的 pCR 率和由研究者评估的 EFS。pCR 定义为原发肿瘤部位无残余肿瘤（肿瘤退缩等级 1）和淋巴结阴性。次要终点包括由 BIRC 评估的 MPR 率（定义为原发肿瘤中残余活性肿瘤细胞少于

），RO 切除率，按照美国癌症联合委员会第 8 版的 ypTNM 分期，OS，DFS，AE 和手术并发症。

Statistical analysis 统计分析

This study was designed to demonstrate the superiority of the Cam+nab-TP and Cam+TP groups over the TP group, focusing on the dual primary endpoints of pCR and EFS. The overall type I error rate

for the dual primary endpoints was controlled at 0.025 (one-sided) using the graphical approach by Maurer and Bretz, with 0.005 allocated to the PCR hypothesis and 0.02 to the EFS hypothesis tests initially. The comparisons of pCR between the Cam+nab-TP versus TP group, as well as the Cam+TP versus TP group, were sequentially tested at the 0.005 level. If pCR was shown to be superior in the Cam+nab-TP group compared to the TP group, the pCR comparison between the Cam+TP and TP groups would subsequently be tested. Similarly, for EFS comparisons, the following will be tested hierarchically:Cam+nab-TP + Cam+TP versus TP, Cam+nab-TP versus TP, and Cam+TP versus TP. If both

rates in the Cam+nab-TP and Cam+TP groups are significantly higher compared with the TP group, the EFS hypotheses will be tested at the 0.025 level; otherwise, they will be tested at the 0.02 level. This report focuses on the final analysis of pCR rates.
本研究旨在证明 Cam+nab-TP 组和 Cam+TP 组在 pCR 和 EFS 这两个主要终点上优于 TP 组。通过 Maurer 和 Bretz 的图形方法，将这两个主要终点的总体 I 型错误率控制在 0.025（单侧），其中 0.005 分配给 PCR 假设，0.02 分配给 EFS 假设测试。Cam+nab-TP 组与 TP 组之间的 pCR 比较，以及 Cam+TP 组与 TP 组之间的比较，均在 0.005 水平上进行顺序测试。如果 Cam+nab-TP 组的 pCR 显示优于 TP 组，则随后将测试 Cam+TP 组与 TP 组之间的 pCR 比较。同样，对于 EFS 比较，将按层次测试：Cam+nab-TP + Cam+TP 与 TP，Cam+nab-TP 与 TP，以及 Cam+TP 与 TP。如果 Cam+nab-TP 组和 Cam+TP 组的

率显著高于 TP 组，则 EFS 假设将在 0.025 水平上进行测试；否则，将在 0.02 水平上进行测试。本报告重点关注 pCR 率的最终分析。

The sample size was calculated using NCSS&PASS version 15.0. Assuming pCR rates of 30% for the Cam+nab-TP group, 25% for the Cam+TP group and

for the TP group, and using a 1:1:1 randomization ratio with an

level set at 0.005 (one-sided), it was calculated that 111 patients per group would provide at least

power to establish the superiority of the Cam+nab-TP group over the TP group, and at least 75% power to demonstrate that the Cam+TP group surpasses the TP group. To accommodate a potential dropout rate of

, the study planned to enroll 130 participants in each group. We assumed the median EFS in the TP group to be 30 months. The expected HR for the Cam+nab-TP and Cam+TP groups (combined test groups) compared to the TP group was 0.67 . With an initial

set at a one-sided level of 0.02 and with a randomization ratio of 2:1 (Cam+nab-TP and Cam+TP groups versus TP group), a total of 228 events ( 141 in the combined test groups and 87 in the TP group) are necessary to achieve at least

power to detect the superiority of the test groups. Based on an enrollment period of 36 months, a total study duration of 84 months, and an anticipated dropout rate of

, approximately 390 patients were required across the three groups. The final analysis of pCR was performed as prespecified when all randomized patients had the opportunity to undergo surgery.
样本量使用 NCSS&PASS 版本 15.0 进行计算。假设 Cam+nab-TP 组的 pCR 率为 30%，Cam+TP 组为 25%，TP 组为

，并使用 1:1:1 的随机化比例，设定

水平为 0.005（单侧），计算得出每组需要 111 名患者，以提供至少

的统计功效来证明 Cam+nab-TP 组优于 TP 组，并且至少 75%的功效来证明 Cam+TP 组优于 TP 组。为了适应潜在的

脱落率，研究计划在每组招募 130 名参与者。我们假设 TP 组的中位 EFS 为 30 个月。与 TP 组相比，Cam+nab-TP 和 Cam+TP 组（联合测试组）的预期 HR 为 0.67。初始

设定为单侧水平 0.02，随机化比例为 2:1（Cam+nab-TP 和 Cam+TP 组对 TP 组），总共需要 228 个事件（联合测试组 141 个，TP 组 87 个），以达到至少

的功效来检测测试组的优越性。根据 36 个月的入组期，总研究持续时间为 84 个月，预计的脱落率为

，大约需要 390 名患者分布在三个组中。当所有随机分配的患者都有机会接受手术时，最终的 pCR 分析按预先规定进行。

Efficacy analysis adhered to the ITT principle, including all randomized participants. The SS comprised individuals who received at least one dose of the study drug. The

CIs for PCR and MPR rates were computed using the Clopper-Pearson method. Adjusted differences in PCR rates and ORs, along with their 95% CIs between the Cam+nab-TP and TP groups, as well as between the Cam+TP and TP groups, were calculated using the Mantel-Haenszel method, stratified by clinical stage (I/II versus III/IVA). The pCR between Cam+nab-TP and TP groups as well as between Cam+TP and TP groups were compared by using stratified Cochran-Mantel-Haenszel test with the same stratification factor. Post hoc subgroup analyses of pCR , based on baseline characteristics, were performed, with rate differences estimated and presented in an unadjusted forest plot for each subgroup comparison. All statistical analyses were conducted using SAS software version 9.4. Data collection was performed using Bioknow electronic data capture system.
疗效分析遵循意向治疗（ITT）原则，包括所有随机参与者。SS 包括至少接受过一次研究药物剂量的个体。PCR 和 MPR 率的

置信区间（CIs）使用 Clopper-Pearson 方法计算。Cam+nab-TP 组与 TP 组之间，以及 Cam+TP 组与 TP 组之间的 PCR 率的调整差异和比值比（ORs），连同它们的 95%置信区间，使用 Mantel-Haenszel 方法计算，按临床阶段（I/II 与 III/IVA）分层。Cam+nab-TP 组与 TP 组之间，以及 Cam+TP 组与 TP 组之间的 pCR 比较使用相同分层因素的分层 Cochran-Mantel-Haenszel 检验进行。基于基线特征的 pCR 事后亚组分析被执行，估计并在每个亚组比较中以未调整的森林图呈现率差异。所有统计分析均使用 SAS 软件版本 9.4 进行。数据收集使用 Bioknow 电子数据采集系统进行。

Reporting summary 报告摘要

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.
有关研究设计的更多信息，请参阅与本文相关的《自然》系列报告摘要。

Data availability 数据可用性

Due to intellectual property and confidentiality obligations, individual deidentified participant data that underlie the results reported in this
由于知识产权和保密义务，个别去标识化参与者数据是报告结果的基础
article can be requested 24 months after study completion. Qualified researchers must submit a proposal to the corresponding author at liyin@cicams.ac.cn, outlining the reasons for requesting the data. The leading clinical site and sponsor will review the request to ensure compliance with intellectual property and confidentiality obligations and will respond within two weeks. A signed data access agreement with the sponsor is required before any data can be shared. The study protocol and statistical analysis plan are available alongside the published article.
文章可以在研究完成后 24 个月内请求。合格的研究人员必须向通讯作者提交提案，电子邮件地址为 liyin@cicams.ac.cn，说明请求数据的理由。主要临床地点和赞助商将审查请求，以确保遵守知识产权和保密义务，并将在两周内作出回应。在共享任何数据之前，需要与赞助商签署数据访问协议。研究方案和统计分析计划与已发布的文章一起提供。

Code availability 代码可用性

No custom code was used for data analysis in this study.
本研究中未使用自定义代码进行数据分析。

References 参考文献

Gianni, L. et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann. Oncol. 33, (2022).
Gianni, L. 等. 三阴性、早期高风险和局部晚期乳腺癌新辅助治疗中有或没有阿特珠单抗的病理完全反应（pCR）：NeoTRIP Michelangelo 随机研究。肿瘤学年鉴 33, (2022)。
Wang, H. Y. et al. Weekly nanoparticle albumin-bound paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma. Onco Targets Ther. 9, 5663-5669 (2016).
王, H. Y. 等. 每周纳米颗粒白蛋白结合的紫杉醇联合顺铂与每周溶剂基础的紫杉醇加顺铂作为中国晚期食管鳞状细胞癌患者的一线治疗. 肿瘤靶向治疗. 9, 5663-5669 (2016).
Kang, X. et al. NCC/CATS/CSTCVS/STM expert consensus on perioperative immunotherapy for esophageal cancer. Ann. Esophagus 4, AOE6504 (2021).
康, X. 等. NCC/CATS/CSTCVS/STM 关于食管癌围手术期免疫治疗的专家共识. 食管年鉴 4, AOE6504 (2021).
Mandard, A. M. et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 73, 2680-2686 (1994).
Mandard, A. M. 等. 食管癌术前化疗放疗后肿瘤退缩的病理评估。临床病理相关性。癌症 73, 2680-2686 (1994)。
Low, D. E. et al. International consensus on standardization of data collection for complications associated with esophagectomy: esophagectomy complications consensus group (ECCG). Ann. Surg. 262, 286-294 (2015).
低，D. E. 等。关于食管切除术相关并发症数据收集标准化的国际共识：食管切除术并发症共识小组（ECCG）。外科年鉴 262, 286-294 (2015)。
Dindo, D., Demartines, N. & Clavien, P. A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann. Surg. 240, (2004).
Dindo, D., Demartines, N. & Clavien, P. A. 外科并发症分类：在 6336 名患者队列中的新提案及调查结果。外科年鉴 240, (2004).

Acknowledgements 致谢

This study was funded by Jiangsu Hengrui Pharmaceuticals. The sponsor was involved in the collection, analysis and interpretation of data, as well as in the preparation of the manuscript. We extend our gratitude to all patients who participated in this trial and their families, as well as the researchers and staff at each study center for their invaluable contributions. We thank Chi Ma, Feng Zhao, Jin Yan, Aichun Chen (Department of Medical Affairs, Jiangsu Hengrui Pharmaceuticals) and Chenxuan Liu (former employee of Jiangsu Hengrui Pharmaceuticals) for data interpretation, and Ni Guan (Department of Medical Affairs, Jiangsu Hengrui Pharmaceuticals) for statistical support. Medical writing support was provided by Fangzhou Xia and Zhongjiang Chen (Department of Medical Affairs, Jiangsu Hengrui Pharmaceuticals) according to good publication practice guidelines.
本研究由江苏恒瑞医药资助。赞助方参与了数据的收集、分析和解释，以及手稿的准备。我们对所有参与本试验的患者及其家属，以及各研究中心的研究人员和工作人员表示感谢，感谢他们的宝贵贡献。我们感谢马驰、赵峰、闫金、陈爱春（江苏恒瑞医药医疗事务部）和刘晨轩（江苏恒瑞医药前员工）对数据的解释，以及关妮（江苏恒瑞医药医疗事务部）提供的统计支持。医学写作支持由夏方舟和陈中江（江苏恒瑞医药医疗事务部）根据良好的出版实践指南提供。

Author contributions 作者贡献

J.Q. and L.X. contributed equally to this work. Yin Li, J.H., J.Q., Z.H., and R. Zheng were responsible for the conception and design of the study. Yin Li, J.Q., L.X., A.H., X.G., T.J., Y.N., S.L., Y.C., H.J., C.Z., M.K., J.L., H.L., C.L., H.T., L.L., J.F., Y.Z., J.M., X.W., M.F., H.Y., Z.Y., Y.H., L.C., L.T., T.D., Y. Liao, W.Z., B.L., Q.C., S.G., Y.Q., L.W., Z.L., Z.T., X.K., R. Zhang, Yong Li, Z.W., and X.C. contributed to data collection. W.Z. directed the statistical analysis. All authors were involved in data interpretation, manuscript writing, review, and approved the final manuscript for submission.
J.Q. 和 L.X. 对本研究贡献相同。Yin Li, J.H., J.Q., Z.H. 和 R. Zheng 负责研究的构思和设计。Yin Li, J.Q., L.X., A.H., X.G., T.J., Y.N., S.L., Y.C., H.J., C.Z., M.K., J.L., H.L., C.L., H.T., L.L., J.F., Y.Z., J.M., X.W., M.F., H.Y., Z.Y., Y.H., L.C., L.T., T.D., Y. Liao, W.Z., B.L., Q.C., S.G., Y.Q., L.W., Z.L., Z.T., X.K., R. Zhang, Yong Li, Z.W. 和 X.C. 参与了数据收集。W.Z. 负责统计分析。所有作者均参与了数据解释、手稿撰写、审阅，并批准最终手稿提交。

Competing interests 竞争利益

Z.H., R. Zheng and W.Z. are employees of Jiangsu Hengrui Pharmaceuticals. The other authors declare no competing interests.
Z.H.、R. Zheng 和 W.Z. 是江苏恒瑞医药的员工。其他作者声明没有竞争利益。

Additional information 附加信息

Extended data is available for this paper at
该论文的扩展数据可在此处获得
https://doi.org/10.1038/s41591-024-03064-w.
Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41591-024-03064-w.
补充信息在线版本包含可在 https://doi.org/10.1038/s41591-024-03064-w 获取的补充材料。

Correspondence and requests for materials should be addressed to Jie He or Yin Li.
请将信件和材料请求发送给何杰或李尹。

Peer review information Nature Medicine thanks Ken Kato, Nataliya Uboha and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Saheli Sadanand, in collaboration with the Nature Medicine team.
同行评审信息《自然医学》感谢 Ken Kato、Nataliya Uboha 及其他匿名审稿人对本工作的同行评审所做的贡献。主要处理编辑：Saheli Sadanand，与《自然医学》团队合作。

Reprints and permissions information is available at www.nature.com/reprints.
转载和许可信息可在 www.nature.com/reprints 获取。

Extended Data Fig.

Post hoc subgroup analysis of pCR between Cam+TP group and TP group. The central points on each bar represent the mean difference in PCR rates between the two groups, while the bars indicate the
扩展数据图

Cam+TP 组与 TP 组之间 pCR 的事后亚组分析。每个条形图上的中心点代表两组之间 PCR 率的平均差异，而条形图则表示
95% CI. pCR, pathological complete response;ECOG PS, Eastern Cooperative Oncology Group performance status; TPS, tumor proportion score;CPS, combined positive score; CI , confidence interval.
95% CI。pCR，病理完全反应；ECOG PS，东部合作肿瘤学组表现状态；TPS，肿瘤比例评分；CPS，联合阳性评分；CI，置信区间。
a

Extended Data Fig. 3 |Depth of pathological regression in primary tumor. (a) Cam+nab-TP group, (b) Cam+TPgroup and (c) TPgroup. RVT, residual viable tumor cells; IQR, interquartile range.
扩展数据图 3 | 原发肿瘤的病理退化深度。 (a) Cam+nab-TP 组，(b) Cam+TP 组和 (c) TP 组。RVT，残余活性肿瘤细胞；IQR，四分位数范围。

Reporting Summary 报告摘要

Nature Portfolio wishes to improve the reproducibility of the work that we publish. This form provides structure for consistency and transparency in reporting. For further information on Nature Portfolio policies, see our Editorial Policies and the Editorial Policy Checklist.
自然出版集团希望提高我们发布工作的可重复性。此表格为报告提供了一致性和透明度的结构。有关自然出版集团政策的更多信息，请参阅我们的编辑政策和编辑政策检查表。

Statistics 统计数据

For all statistical analyses, confirm that the following items are present in the figure legend, table legend, main text, or Methods section.
对于所有统计分析，请确认以下项目在图例、表格说明、正文或方法部分中存在。
n/a

Confirmed n/a

确认
The exact sample size

for each experimental group/condition, given as a discrete number and unit of measurement
每个实验组/条件的确切样本大小

，以离散数字和计量单位表示
A statement on whether measurements were taken from distinct samples or whether the same sample was measured repeatedly
关于测量是来自不同样本还是同一样本重复测量的声明
The statistical test(s) used AND whether they are one- or two-sided
所使用的统计检验及其是单侧还是双侧
Only common tests should be described solely by name; describe more complex techniques in the Methods section.
仅应仅通过名称描述常见测试；在方法部分描述更复杂的技术。
A description of all covariates tested
所有测试的协变量描述
A description of any assumptions or corrections, such as tests of normality and adjustment for multiple comparisons
对任何假设或修正的描述，例如正态性检验和多重比较的调整
A full description of the statistical parameters including central tendency (e.g. means) or other basic estimates (e.g. regression coefficient) AND variation (e.g. standard deviation) or associated estimates of uncertainty (e.g. confidence intervals)
统计参数的完整描述，包括集中趋势（例如均值）或其他基本估计（例如回归系数）以及变异（例如标准差）或相关的不确定性估计（例如置信区间）

For null hypothesis testing, the test statistic (e.g.

) with confidence intervals, effect sizes, degrees of freedom and

value noted Give

values as exact values whenever suitable.
对于零假设检验，检验统计量（例如

）与置信区间、效应大小、自由度和

值一起记录。根据需要提供

值作为精确值。

For Bayesian analysis, information on the choice of priors and Markov chain Monte Carlo settings
对于贝叶斯分析，关于先验选择和马尔可夫链蒙特卡洛设置的信息

For hierarchical and complex designs, identification of the appropriate level for tests and full reporting of outcomes

对于层次性和复杂的设计，识别适当的测试级别和全面报告结果

Estimates of effect sizes (e.g. Cohen's

, Pearson's

), indicating how they were calculated
效应大小的估计（例如，Cohen's

，Pearson's

），指示它们是如何计算的
Our web collection on statistics for biologists contains articles on many of the points above.
我们关于生物学家的统计数据的网络收藏包含了上述许多要点的文章。

Software and code 软件和代码

Policy information about availability of computer code
关于计算机代码可用性的政策信息
Data collection 数据收集
Data collection was performed using Bioknow EDC.
数据收集使用了 Bioknow EDC。
Data analysis 数据分析

For manuscripts utilizing custom algorithms or software that are central to the research but not yet described in published literature, software must be made available to editors and
对于使用自定义算法或软件的手稿，这些算法或软件对研究至关重要但尚未在已发表文献中描述，必须向编辑提供软件

Data 数据

Policy information about availability of data
关于数据可用性的政策信息
All manuscripts must include a data availability statement. This statement should provide the following information, where applicable:
所有手稿必须包含数据可用性声明。该声明应提供以下信息（如适用）：

Accession codes, unique identifiers, or web links for publicly available datasets
获取代码、唯一标识符或公开可用数据集的网页链接
A description of any restrictions on data availability
数据可用性限制的描述
For clinical datasets or third party data, please ensure that the statement adheres to our policy
对于临床数据集或第三方数据，请确保该声明符合我们的政策

Reporting on sex and gender
关于性别和性别报告

Population characteristics
人口特征

Recruitment 招聘

Ethics oversight 伦理监督
We used sex to report the biological factors for male

and female

patients. Gender, as shaped by social and cultural circumstances, was not specifically assessed or reported in the study design. Sex or gender was not considered in the study design. Both male and female patients were eligible. The sex was summarized as part of demographic characteristics in Table 1. The sex of participants was collected according to the identity information provided by the patients. No individuallevel data were reported. No prior analysis was sex-based. Subgroup analysis of pCR was performed based on sex (male vs female).
我们使用性别来报告男性

和女性

患者的生物因素。性别作为社会和文化环境塑造的结果，在研究设计中没有特别评估或报告。研究设计中没有考虑性别或性别。男性和女性患者均符合资格。性别作为人口特征的一部分在表 1 中进行了总结。参与者的性别是根据患者提供的身份信息收集的。没有报告个体层面的数据。之前的分析没有基于性别。根据性别（男性与女性）进行了 pCR 的亚组分析。

The median age of all patients was 63 years (range:

), with

being male. Of the patients, 6 (1.5%) were in clinical stages I (all cT1N1),

in stage II,

in stage III, and

in stage IVA. Tumors were located in the upper, middle, and lower thoracic esophagus for 41 (10.5%), 201 (51.4%), and 149 (38.1%) patients, respectively.
所有患者的中位年龄为 63 岁（范围：

），其中

为男性。在患者中，6 例（1.5%）处于临床 I 期（均为 cT1N1），

处于 II 期，

处于 III 期，

处于 IVA 期。肿瘤分别位于上、中、下胸食管，41 例（10.5%）、201 例（51.4%）和 149 例（38.1%）。

Patients with LA-ESCC were recruited from 24 centers in China using eligibility criteria pre-specified in the study protocol and randomized to the three treatment arms. Key inclusion criteria were histologically confirmed ESCC located in the thoracic esophagus, staged as T1b-3N1-3M0 or T3NOMO according to American Joint Committee on Cancer (AJCC) Staging 8th edition; candidates deemed suitable for RO resection; ages between 18 and 75 years; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1; treatment naïve; and adequate organ function. Major exclusion criteria included synchronous or metachronous double malignancies within 5 years, history of autoimmune disease, and the use of immunosuppressive drugs or systemic steroids within 2 weeks prior to enrollment. The detailed inclusion and exclusion criteria are provided in the study protocol.
来自中国 24 个中心的 LA-ESCC 患者根据研究方案中预先规定的资格标准招募，并随机分配到三个治疗组。主要纳入标准为：经组织学确认的位于胸食管的 ESCC，按照美国癌症联合委员会（AJCC）第 8 版分期为 T1b-3N1-3M0 或 T3NOMO；被认为适合进行 RO 切除的候选者；年龄在 18 至 75 岁之间；东部合作肿瘤学组（ECOG PS）表现状态为 0-1；未接受过治疗；以及器官功能良好。主要排除标准包括在 5 年内有同步或异时双重恶性肿瘤、 autoimmune 疾病史，以及在入组前 2 周内使用免疫抑制药物或全身类固醇。详细的纳入和排除标准在研究方案中提供。

The study protocol was approved by the Ethics Committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Anyang Cancer Hospital; Tangdu Hospital, Air Force Military Medical University; Fujian Provincial Cancer Hospital; Tianjin Medical University Cancer Institute and Hospital; Fujian Medical University Union Hospital; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Qilu Hospital of Shandong University; The First Affiliated Hospital of Xi'an Jiaotong University; Harbin Medical University Cancer Hospital; Affiliated Hospital of North Sichuan Medical College; Sichuan Cancer Hospital; West China Hospital, Sichuan University; Zhongshan Hospital, Fudan University; The Affiliated Hospital of Southwest Medical University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; The First Affiliated Hospital of Henan University of Science and Technology; The Second Hospital & Clinical Medical School, Lanzhou University; Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital; Shanxi Provincial Cancer Hospital; First Affiliated Hospital of Zhengzhou University; Henan Provincial People's Hospital; Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine; The Fourth Hospital of Hebei Medical University. All enrolled patients provided written informed consent.
研究方案已获得中国医学科学院肿瘤医院/北京协和医学院国家癌症中心/国家临床肿瘤研究中心；安阳癌症医院；空军军医大学唐都医院；福建省肿瘤医院；天津医科大学肿瘤研究所及医院；福建医科大学附属医院；上海交通大学医学院瑞金医院；山东大学齐鲁医院；西安交通大学第一附属医院；哈尔滨医科大学肿瘤医院；北四川医学院附属医院；四川省肿瘤医院；四川大学华西医院；复旦大学中山医院；西南医科大学附属医院；华中科技大学同济医学院协和医院；河南科技大学第一附属医院；兰州大学第二医院及临床医学院；中国科学院大学肿瘤医院，浙江省肿瘤医院；山西省肿瘤医院的伦理委员会批准医院；郑州大学第一附属医院；河南省人民医院；上海交通大学医学院上海胸科医院；河北医科大学第四医院。所有入组患者均提供了书面知情同意。

Note that full information on the approval of the study protocol must also be provided in the manuscript.
请注意，手稿中还必须提供关于研究方案批准的完整信息。

Field-specific reporting
领域特定报告

Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.
请从下面选择最适合您研究的选项。如果您不确定，请在做出选择之前阅读相关部分。

Life sciences

Behavioural & social sciences

Ecological, evolutionary & environmental sciences

生命科学

行为与社会科学

生态、进化与环境科学
For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf
有关包含所有部分的文档参考副本，请参见 nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design
生命科学研究设计

All studies must disclose on these points even when the disclosure is negative.
所有研究必须在这些方面进行披露，即使披露是负面的。

Data exclusions Efficacy results were performed in the ITT population and surgical population. Safety analyses were performed in patients who received study treatment. No data were excluded from the analyses
数据排除效能结果是在意向治疗（ITT）人群和手术人群中进行的。安全性分析是在接受研究治疗的患者中进行的。分析中没有排除任何数据。

We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.
我们需要作者提供关于许多研究中使用的某些类型材料、实验系统和方法的信息。在这里，请指明所列的每种材料、系统或方法是否与您的研究相关。如果您不确定列表中的某项是否适用于您的研究，请在选择回应之前阅读相关部分。

Materials & experimental systems 材料与实验系统			Methods 方法
n/a 不适用	Involv 参与	olved in the study 参与研究	n/a 不适用	Involved in the study 参与研究
】		Antibodies 抗体	】	ChIP-seq
め		Eukaryotic cell lines 真核细胞系	X	Flow cytometry 流式细胞术
め		Palaeontology and archaeology 古生物学和考古学		MRI-based neuroimaging 基于 MRI 的神经影像学
Х		Animals and other organisms 动物和其他生物
	X	Clinical data 临床数据
】		Dual use research of concern 双重使用的关注研究

Clinical data 临床数据

Policy information about clinical studies
临床研究的政策信息
All manuscripts should comply with the ICMJE guidelines for publication of clinical research and a completed CONSORT checklist must be included with all submissions.
所有手稿应遵循 ICMJE 关于临床研究发表的指南，并且所有提交的稿件必须附上完整的 CONSORT 检查表。
Clinical trial registration
临床试验注册

Study protocol 研究方案
Data collection 数据收集
The study was registered prior to patient enrollment (ChiCTR2000040034).
该研究在患者入组之前注册（ChiCTR2000040034）。

Submitted with manuscript
提交的手稿

391 patients were enrolled from 24 hospitals in China between April 28, 2021, and August 7, 2023. Data cutoff date of this analysis was October 8, 2023. All efficacy and safety data were collected at the participating clinical centers, including National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Anyang Cancer Hospital; Tangdu Hospital, Air Force Military Medical University; Fujian Provincial Cancer Hospital; Tianjin Medical University Cancer Institute and Hospital; Fujian Medical University Union Hospital; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Qilu Hospital of Shandong University; The First Affiliated Hospital of Xi'an Jiaotong University; Harbin Medical University Cancer Hospital; Affiliated Hospital of North Sichuan Medical College; Sichuan Cancer Hospital; West China Hospital, Sichuan University; Zhongshan Hospital, Fudan University; The Affiliated Hospital of Southwest Medical University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; The First Affiliated Hospital of Henan University of Science and Technology; The Second Hospital & Clinical Medical School, Lanzhou University; Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital; Shanxi Provincial Cancer Hospital; First Affiliated Hospital of Zhengzhou University Henan Provincial People's Hospital; Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine; The Fourth Hospital of Hebei Medical University.
391 名患者于 2021 年 4 月 28 日至 2023 年 8 月 7 日期间从中国的 24 家医院招募。此次分析的数据截止日期为 2023 年 10 月 8 日。所有疗效和安全性数据均在参与的临床中心收集，包括国家癌症中心/国家临床癌症研究中心/中国医学科学院肿瘤医院；安阳癌症医院；空军军医大学唐都医院；福建省肿瘤医院；天津医科大学肿瘤研究所及医院；福建医科大学联合医院；上海交通大学医学院瑞金医院；山东大学齐鲁医院；西安交通大学第一附属医院；哈尔滨医科大学肿瘤医院；北四川医学院附属医院；四川省肿瘤医院；四川大学华西医院；复旦大学中山医院；西南医科大学附属医院；华中科技大学同济医学院联合医院；河南科技大学第一附属医院；兰州大学第二医院及临床医学院；中国科学院大学肿瘤医院，浙江省肿瘤医院意大利；山西省癌症医院；郑州大学第一附属医院河南省人民医院；上海胸科医院，上海交通大学医学院；河北医科大学第四医院。

Outcomes 结果
The study's dual primary endpoints included the pCR rate, assessed by the BIRC, and event-free survival (EFS), evaluated by the investigators. PCR is defined as the absence of residual tumor at the primary tumor site (TRG grade 1) and negative lymph nodes. Secondary endpoints include the major pathological response (MPR) rate (defined as less than 10% residual viable tumor cells in the primary tumor) assessed by BIRC, RO resection rate, post-neoadjuvant pathological staging (ypTNM) according to the AJCC 8th edition, OS, DFS, AEs, and surgical complications.
该研究的双主要终点包括由 BIRC 评估的 pCR 率和由研究者评估的无事件生存期（EFS）。pCR 定义为原发肿瘤部位无残余肿瘤（TRG 等级 1）和淋巴结阴性。次要终点包括由 BIRC 评估的主要病理反应（MPR）率（定义为原发肿瘤中残余活肿瘤细胞少于 10%）、RO 切除率、根据 AJCC 第 8 版的术后新辅助病理分期（ypTNM）、总生存期（OS）、无病生存期（DFS）、不良事件（AEs）和手术并发症。

Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Department of Thoracic Surgery, Anyang Cancer Hospital, Anyang, China. Department of Thoracic Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, China. Department of Thoracic Surgery, Fujian Provincial Cancer Hospital, Fuzhou, China. Department of Esophageal Minimal Invasive Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, China. Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. "Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China. Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. Department of Thoracic Surgery, Sichuan Cancer Hospital, Chengdu, China. Department of Thoracic Surgery, West China Hospital Sichuan University, Chengdu, China.
中国医学科学院北京协和医学院国家癌症中心/国家临床癌症研究中心/癌症医院胸外科食管和纵隔肿瘤学科，北京，中国。中国医学科学院北京协和医学院国家癌症中心/国家临床癌症研究中心/癌症医院病理学科，北京，中国。中国安阳癌症医院胸外科，安阳，中国。西安空军军医大学唐都医院胸外科，西安，中国。福建省癌症医院胸外科，福州，中国。天津医科大学肿瘤研究院及医院食管微创外科，天津，中国。福建医科大学附属医院胸外科，福州，中国。上海交通大学医学院瑞金医院胸外科，上海，中国。山东大学齐鲁医院胸外科，济南，中国。西安交通大学第一附属医院胸外科，中国西安。 "哈尔滨医科大学肿瘤医院胸外科，中国哈尔滨。南充北四川医科大学附属医院胸外科，中国南充。四川省肿瘤医院胸外科，中国成都。四川大学华西医院胸外科，中国成都。

Neoadjuvant chemotherapy with or without camrelizumab in resectableesophageal squamouscell carcinoma: the randomized phase3ESCORT-NEO/NCCES01 trial 新辅助化疗联合或不联合 camrelizumab 治疗可切除食管鳞状细胞癌：随机 3 期 ESCORT-NEO/NCCES01 试验

Abstract 摘要

Results 结果

Patient disposition 患者处置

Neoadjuvant treatment and surgery summary新辅助治疗和手术总结

Table 1 | Baseline characteristics of patients in the ITT population表 1 | ITT 人群患者的基线特征

Primary outcome 主要结果

Secondary outcomes 次要结果

Safety 安全

Table 2 | Surgery summary表 2 | 手术总结

Discussion 讨论

Table 4 | Surgical complications according to CD classification in at least two patients in all groups表 4 | 所有组中至少两名患者的 CD 分类下的手术并发症

Online content 在线内容

References 参考文献

Abstract 摘要

Methods 方法

Study design and patients研究设计和患者

Procedure 程序

Endpoints 终点

Statistical analysis 统计分析

Reporting summary 报告摘要

Data availability 数据可用性

Code availability 代码可用性

References 参考文献

Acknowledgements 致谢

Author contributions 作者贡献

Competing interests 竞争利益

Additional information 附加信息

Reporting Summary 报告摘要

Statistics 统计数据

Software and code 软件和代码

Data 数据

Field-specific reporting领域特定报告

Life sciences study design生命科学研究设计

All studies must disclose on these points even when the disclosure is negative.所有研究必须在这些方面进行披露，即使披露是负面的。

Clinical data 临床数据

Submitted with manuscript提交的手稿

Neoadjuvant chemotherapy with or without camrelizumab in resectableesophageal squamouscell carcinoma: the randomized phase3ESCORT-NEO/NCCES01 trial
新辅助化疗联合或不联合 camrelizumab 治疗可切除食管鳞状细胞癌：随机 3 期 ESCORT-NEO/NCCES01 试验

Neoadjuvant treatment and surgery summary
新辅助治疗和手术总结

Table 1 | Baseline characteristics of patients in the ITT population
表 1 | ITT 人群患者的基线特征

Table 2 | Surgery summary
表 2 | 手术总结

Table 4 | Surgical complications according to CD classification in at least two patients in all groups
表 4 | 所有组中至少两名患者的 CD 分类下的手术并发症

Study design and patients
研究设计和患者

Field-specific reporting
领域特定报告

Life sciences study design
生命科学研究设计

All studies must disclose on these points even when the disclosure is negative.
所有研究必须在这些方面进行披露，即使披露是负面的。

Submitted with manuscript
提交的手稿