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Zhang Y, Chen J, Yu F, Zhang W, Zhong Y. Neoadjuvant chemotherapy with or without PD-1/PD-L1 inhibitors in resectable esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials. BMC Gastroenterol 2025; 25:416. [PMID: 40442612 PMCID: PMC12123838 DOI: 10.1186/s12876-025-04030-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Accepted: 05/23/2025] [Indexed: 06/02/2025] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NC) is a cornerstone in the management of resectable esophageal squamous cell carcinoma (ESCC). The integration of PD-1/PD-L1 inhibitors into NC (NIC) regimens has shown promise; however, its efficacy and safety remain uncertain. This meta-analysis aims to compare the potential risks and clinical benefits of NIC versus NC in patients with resectable ESCC based on randomized controlled trials (RCTs). METHODS A thorough search of six databases was performed to identify RCTs evaluating NIC and NC in resectable ESCC. Key outcomes analyzed included the pathological complete response (pCR) rate and the major pathological response (MPR) rate. Other outcomes analyzed included overall survival (OS), event-free survival (EFS), surgery rate, R0 resection rate, and adverse events (AEs). RESULTS Four RCTs encompassing 605 patients were included. NIC significantly improved pCR rate (risk ratio [RR]: 2.66 [1.63, 4.34], P < 0.0001) and MPR rate (RR: 1.74 [1.02, 2.95], P = 0.04) compared to the NC group. Only one phase III RCT reported survival outcomes, showing that the NIC group demonstrated improved OS (HR: 0.48 [0.24, 0.96], P = 0.04) and EFS (HR: 0.62 [0.39, 0.99], P = 0.05). Additionally, surgery rate (RR: 1.11 [1.03, 1.20], P = 0.008) and the number of resected lymph nodes (mean difference [MD]: 3.91 [0.60, 7.21], P = 0.02) were also higher in the NIC group. The R0 resection rate, duration of surgery, and intraoperative blood loss were comparable between the groups. However, the rate of immune-related AEs (irAEs) (RR: 40.80 [5.67, 293.37], P = 0.0002) was significantly higher in the NIC group. Similar surgical complications were observed between the two groups. CONCLUSIONS NIC demonstrates superior efficacy in improving pCR and MPR in resectable ESCC compared to NC alone, and may potentially provide survival benefits, although it is associated with a higher risk of irAEs.
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Affiliation(s)
- Ye Zhang
- Department of Thoracic Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 92 Aiguo Road, Donghu District, Nanchang, 330000, China
| | - Jie Chen
- Department of Thoracic Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 92 Aiguo Road, Donghu District, Nanchang, 330000, China
| | - Fenglian Yu
- Department of Thoracic Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 92 Aiguo Road, Donghu District, Nanchang, 330000, China
| | - Wenxiong Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Yingmei Zhong
- Department of Thoracic Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 92 Aiguo Road, Donghu District, Nanchang, 330000, China.
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Sun X, Li X, Zhao S, Li C, Lin Y, Shen Q, Ding J, Li T, Yin Y, Tao K. Which surrogate endpoint best predict survival in locally advanced gastric cancer patients undergoing neoadjuvant chemoimmunotherapy followed by surgery? A multicenter retrospective study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109517. [PMID: 39662107 DOI: 10.1016/j.ejso.2024.109517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/18/2024] [Accepted: 12/04/2024] [Indexed: 12/13/2024]
Abstract
INTRODUCTION Recent clinical researches have reported that neoadjuvant chemoimmunotherapy (NCIT) significantly improve the pathological complete response (pCR) and major pathological response (MPR) rates. However, surrogate endpoints for survival remains controversy for locally advanced gastric cancer (LAGC) after NCIT. METHODS A retrospective analysis was performed on 84 patients with LAGC who had undergone NCIT following radical resection in three medical centers in China, between July 2020 and September 2023. Survival curves for event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival outcomes. Univariate and multivariate analyses for prognostic factors were based on Cox regression analysis. RESULTS The rates of ypN0, pCR and MPR were 60.7 % (51/84), 26.2 % (22/84) and 39.3 %(33/84),respectively. Patients with ypN0 had better EFS and OS than those with ypN+ (all p < 0.05). Survival was equivalent between pCR and non-pCR group (all p > 0.05). while patients with MPR had better EFS than those with non-MPR (p = 0.028). Furthermore, a multivariate analysis revealed that the lymph nodes(LNs) status was an independent prognostic factor for the EFS (hazard ratio [HR] 5.533, 95 % confidence interval [CI] 1.186-25.804, p = 0.029) and OS (HR 5.116, 95 % CI 1.357-19.281, p = 0.016), but not pCR and MPR (all p > 0.05). Based on the status of pathologic LNs, ypN0 group showed lower depth of tumor invasion, and lower rate of perineural and vascular invasion (all p < 0.05). CONCLUSION These findings demonstrated that ypN0 may be important as a surrogate of favorable clinical outcome in LAGC patients who received NCIT plus curative surgery.
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Affiliation(s)
- Xiong Sun
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuanfei Li
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shijun Zhao
- Department of General Surgery, The Second Hospital of Shandong University, Jinan, China
| | - Chengguo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yao Lin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qian Shen
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianing Ding
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tianhao Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuping Yin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Qi Y, Hu Y, Lin C, Song G, Shi L, Zhu H. A preoperative predictive model based on multi-modal features to predict pathological complete response after neoadjuvant chemoimmunotherapy in esophageal cancer patients. Front Immunol 2025; 16:1530279. [PMID: 39958355 PMCID: PMC11827421 DOI: 10.3389/fimmu.2025.1530279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 01/07/2025] [Indexed: 02/18/2025] Open
Abstract
Background This study aimed to develop a multi-modality model by incorporating pretreatment computed tomography (CT) radiomics and pathomics features along with clinical variables to predict pathologic complete response (pCR) to neoadjuvant chemoimmunotherapy in patients with locally advanced esophageal cancer (EC). Method A total of 223 EC patients who underwent neoadjuvant chemoimmunotherapy followed by surgical intervention between August 2021 and December 2023 were included in this study. Radiomics features were extracted from contrast-enhanced CT images using PyrRadiomics, while pathomics features were derived from whole-slide images (WSIs) of pathological specimens using a fine-tuned deep learning model (ResNet-50). After feature selection, three single-modality prediction models and a combined multi-modality model integrating two radiomics features, 11 pathomics features, and two clinicopathological features were constructed using the support vector machine (SVM) algorithm. The performance of the models were evaluated using receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA). Shapley values were also utilized to explain the prediction model. Results The predictive capability of the multi-modality model in predicting pCR yielded an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.75-1.00), outperforming the radiomics model (AUC 0.70 [95% CI 0.54-0.85]), pathomics model (AUC 0.77 [95% CI 0.53-1.00]), and clinical model (AUC 0.63 [95% CI 0.46-0.80]). Additionally, both the calibration plot and DCA curves support the clinical utility of the integrated multi-modality model. Conclusions The combined multi-modality model we propose can better predict the pCR status of esophageal cancer and help inform clinical treatment decisions.
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Affiliation(s)
- Yana Qi
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yanran Hu
- Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Chengting Lin
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Ge Song
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Liting Shi
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Hui Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
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Yang X, Yin H, Zhang S, Jiang T, Gu J, Jiao H, Wang H, Liang F, Xu S, Fan H, Ding J, Ge D, Wang Q, Yin J, Tan L. Perioperative outcomes and survival after neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 2025; 169:289-300.e6. [PMID: 38944271 DOI: 10.1016/j.jtcvs.2024.06.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/22/2024] [Accepted: 06/10/2024] [Indexed: 07/01/2024]
Abstract
OBJECTIVE This study aimed to compare the difference in perioperative outcomes and prognosis between neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. METHODS The patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy were identified from a prospectively maintained database at Zhongshan Hospital of Fudan University between January 2018 and March 2022. Propensity score matching was performed to balance the 2 groups. RESULTS A total of 124 patient pairs were enrolled in the final analysis. The complete pathological response rate (20.2% vs 29.0%, P = .140) was similar in the 2 groups, whereas the lower major pathological response rate (44.4% vs 61.3%, P = .011) was observed in the neoadjuvant immunochemotherapy group. Neoadjuvant immunochemotherapy was associated with a lower rate of adverse events (42.7% vs 55.6%, P = .047) without additional postoperative complications (38.7% vs 35.5%, P = .693). The neoadjuvant immunochemotherapy group had lower distant metastasis (6.5% vs 16.1%, P = .027) and overall recurrence (11.3% vs 23.4%, P = .019) in the postoperative 1 year. Also, neoadjuvant immunochemotherapy was associated with better progression-free survival (hazard ratio, 0.50; 95% CI, 0.32-0.77; P = .002). Cox proportional hazard analysis showed that neoadjuvant immunochemotherapy (univariable: hazard ratio, 0.55; 95% CI, 0.37-0.82; P = .003; multivariable: hazard ratio, 0.44; 95% CI, 0.29-0.65; P < .001) was one of the independent prognostic factors for progression-free survival. The 2 groups had similar overall survival (hazard ratio, 0.62; 95% CI, 0.36-1.09; P = .094) at the latest follow-up. CONCLUSIONS This retrospective study showed that neoadjuvant immunochemotherapy was safe and effective for patients with locally advanced esophageal squamous cell carcinoma. Further verification is needed in randomized controlled trials.
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Affiliation(s)
- Xinyu Yang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Yin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shaoyuan Zhang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tian Jiang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianmin Gu
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Heng Jiao
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fei Liang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Clinical Statistics Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Songtao Xu
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Thoracic Surgery, Shanghai Geriatric Medical Center, Shanghai, China
| | - Hong Fan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Thoracic Surgery, Xiamen Branch, Zhongshan Hospital, Fudan University, Fujian, China
| | - Jianyong Ding
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Di Ge
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qun Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jun Yin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Qiu Z, Li Z, Liu X, Zhang R, Li Y, Gao C, Mao X, Bao Y, Zhang M, Guo C. From tumor microenvironment to emerging biomarkers: the reshaping of the esophageal squamous cell carcinoma tumor microenvironment by neoadjuvant chemotherapy combined with immunotherapy. Front Immunol 2024; 15:1478922. [PMID: 39703499 PMCID: PMC11655454 DOI: 10.3389/fimmu.2024.1478922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 11/15/2024] [Indexed: 12/21/2024] Open
Abstract
Esophageal squamous cell carcinoma is a cancer with high morbidity and mortality. The advent of immune checkpoint inhibitors has significantly increased complete response rates and postoperative R0 resection rates after neoadjuvant therapy. These drugs can largely reverse the suppression of the immune system caused by the tumor microenvironment, allowing the reactivation of anti-tumor immune infiltrating cells, significantly improving the patient's tumor microenvironment, and thus preventing tumor development. However, there are still some patients who respond poorly to neoadjuvant combined immunotherapy and cannot achieve the expected results. It is now found that exploring changes in the tumor microenvironment not only elucidates patient responsiveness to immunotherapy and identifies more reliable biomarkers, but also addresses the limitations of prediction with imaging examination such as CT and the instability of existing biomarkers. In light of these considerations, this review aims to delve into the alterations within the tumor microenvironment and identify potential predictive biomarkers ensuing from neoadjuvant immunotherapy in the context of esophageal squamous cell carcinoma.
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Affiliation(s)
- Zhengzhou Qiu
- Jiangxi Medical College, Nanchang University, NanChang, China
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
- Jiangxi Key Laboratory of Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
| | - Zhao Li
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
| | - Xingfei Liu
- Jiangxi Medical College, Nanchang University, NanChang, China
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
| | - Ruilin Zhang
- Jiangxi Medical College, Nanchang University, NanChang, China
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
| | - Yongxuan Li
- Jiangxi Medical College, Nanchang University, NanChang, China
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
| | - Chenggen Gao
- Jiangxi Medical College, Nanchang University, NanChang, China
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
- Jiangxi Key Laboratory of Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
| | - Xiaoling Mao
- Jiangxi Key Laboratory of Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
- Medical College, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Yin Bao
- Jiangxi Key Laboratory of Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
- Medical College, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Mingyue Zhang
- Jiangxi Key Laboratory of Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
- Medical College, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Changying Guo
- Department of Thoracic Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Nanchang, China
- Zhejiang-Jiangxi Joint Thoracic Oncology Research Laboratory, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
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Huang YH, Yang GZ, Chen HG, Li XJ, Wu YH, Zhang K, Xu JN, Zhang J. Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma. World J Gastrointest Oncol 2024; 16:3887-3897. [PMID: 39350993 PMCID: PMC11438776 DOI: 10.4251/wjgo.v16.i9.3887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/31/2024] [Accepted: 08/12/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. RESULTS From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.
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Affiliation(s)
- Yuan-Heng Huang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, Guangdong Province, China
- Guangdong Esophageal Cancer Institute, Guangzhou 510060, Guangdong Province, China
| | - Guo-Zhen Yang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, Guangdong Province, China
- Guangdong Esophageal Cancer Institute, Guangzhou 510060, Guangdong Province, China
| | - Hui-Guo Chen
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Xiao-Jun Li
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Yong-Hui Wu
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Kai Zhang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Jian-Nan Xu
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Jian Zhang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
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Lv H, Zhang F, Huang C, Xu S, Li J, Sun B, Gai C, Liu Z, Wang M, Li Z, Tian Z. Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2024; 150:260. [PMID: 38760614 PMCID: PMC11101546 DOI: 10.1007/s00432-024-05793-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/08/2024] [Indexed: 05/19/2024]
Abstract
PURPOSE Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.
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Affiliation(s)
- Huilai Lv
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Fan Zhang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Chao Huang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Shi Xu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Jiachen Li
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Bokang Sun
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Chunyue Gai
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Zhao Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Mingbo Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Zhenhua Li
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Ziqiang Tian
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China.
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China.
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Xin G, Song N, Jiang K. Esophageal squamous cell carcinoma transformed into neuroendocrine carcinoma after neoadjuvant immunochemotherapy: A case report. Oncol Lett 2024; 27:184. [PMID: 38476207 PMCID: PMC10928968 DOI: 10.3892/ol.2024.14317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 02/13/2024] [Indexed: 03/14/2024] Open
Abstract
Immunotherapy provides durable responses for locally advanced esophageal carcinoma clinical therapy in numerous patients. However, the mechanisms of resistance to immunotherapy have not been elucidated. The phenomenon of the histological transformation of non-small cell lung cancer to small cell lung cancer resulting in resistance to immune checkpoint inhibitors (ICIs) has been reported. It remains unclear whether ICIs or chemotherapy could cause a similar transformation from esophageal squamous cell carcinoma (ESCC) to esophageal neuroendocrine carcinoma (ENEC). The present study report the case of a patient initially diagnosed with stage II ESCC who underwent radical surgery after three cycles of neoadjuvant therapy with cisplatin, albumin bound paclitaxel and ICIs. Immunohistochemical staining confirmed the absence of the SCC component and the presence of the NEC component, with negativity for CK5/6 and tumor protein p40, but positive expression of tumor protein p53, pan-cytokeratin, synaptophysin and CD56. The patient was followed up for 5 months with no treatment or postoperative complications. In conclusion, histological transformation to ENEC is a potential mechanism of acquired resistance to ICIs in ESCC. Prospective larger studies are warranted to further characterize ESCC-to-NEC transformation on use of ICIs.
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Affiliation(s)
- Gaojie Xin
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Naicheng Song
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Ke Jiang
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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Song XY, Liu J, Li HX, Cai XW, Li ZG, Su YC, Li Y, Dong XH, Yu W, Fu XL. Enhancing Prediction for Tumor Pathologic Response to Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Cancer by Dynamic Parameters from Clinical Assessments. Cancers (Basel) 2023; 15:4377. [PMID: 37686655 PMCID: PMC10486879 DOI: 10.3390/cancers15174377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/25/2023] [Accepted: 08/30/2023] [Indexed: 09/10/2023] Open
Abstract
To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy.
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Affiliation(s)
- Xin-Yun Song
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
- School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
| | - Jun Liu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Hong-Xuan Li
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Xu-Wei Cai
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Zhi-Gang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Yu-Chen Su
- Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Yue Li
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Xiao-Huan Dong
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Wen Yu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Xiao-Long Fu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
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Jiang H, Li Q, Chen B, Xi M, Makelike K, Liu S, Hu Y, Zhu Y. Phase I study of cisplatin and nanoparticle albumin-bound-paclitaxel combined with concurrent radiotherapy in locally advanced esophageal squamous cell carcinoma. Cancer Med 2023; 12:15187-15198. [PMID: 37334881 PMCID: PMC10417080 DOI: 10.1002/cam4.6205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 05/04/2023] [Accepted: 05/23/2023] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND This phase I study aimed to assess the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin-bound (nab)-paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab-paclitaxel (60 mg/m2 , 75 mg/m2 , and 90 mg/m2 ) and cisplatin (25 mg/m2 ) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50-64 Gy. The primary endpoint was the safety of chemotherapy. RESULTS The study enrolled 12 patients across three dose levels. No treatment-related deaths occurred. One patient in the 60 mg/m2 dose level occurred dose-limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m2 dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m2 based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1-2 of 66.7% and Grade 3-4 of 33.3%), neutropenia (Grade 1-2 of 91.7% and Grade 3-4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%. CONCLUSIONS Weekly schedule of cisplatin and nab-paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab-paclitaxel for further studies is 75 mg/m2 .
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Affiliation(s)
- Hui Jiang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Qiaoqiao Li
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Baoqing Chen
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Mian Xi
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Kanjiebubi Makelike
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Shiliang Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Yonghong Hu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
| | - Yujia Zhu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Sun Yat‐Sen University Cancer CenterGuangzhouPeople's Republic of China
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