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Li C, Wang X, Deng L, Wang J, Zhang T, Wang W, Liu W, Lv J, Feng Q, Zhou Z, Chen X, Zhang R, Qin J, Li Y, Bi N. Survival and Perioperative Outcomes After Addition of Immunotherapy to Neoadjuvant Chemoradiotherapy for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma. Thorac Cancer 2025; 16:e70054. [PMID: 40156491 PMCID: PMC11954129 DOI: 10.1111/1759-7714.70054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 03/14/2025] [Accepted: 03/19/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Currently, neoadjuvant chemoradiotherapy combined with immunotherapy (NCRI) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is attracting attention. The purpose of this study was to compare the surgical outcomes and survival between patients receiving NCRI and neoadjuvant chemoradiotherapy (NCRT) followed by surgery. METHODS This study retrospectively included patients with locally advanced ESCC and treated with NCRI or NCRT followed by esophagectomy. Two groups were compared for pathologic complete response (pCR) rate, R0 resection rate, and 3-year recurrence-free survival (RFS). Surgery time, the number of lymph nodes removed, postoperative complications, and 30-day mortality were also compared. Propensity score matching (PSM) was performed to minimize the potential impact of confounding factors. RESULTS After PSM, patients in the NCRI group showed a significantly higher pCR rate compared with those in the NCRT group (54.2% vs. 27.1%, p = 0.046). R0 resection rate (100% vs. 89.6%, p = 0.251), surgery time (p = 0.614), the number of lymph nodes removed (p = 0.526), the incidence of total postoperative complications (46.4% vs. 37.9%, p = 0.564) and 30-day mortality (3.6% vs. 1.1%, p = 0.983) were comparable between the two groups. The NCRI group exhibited a significantly higher 3-year RFS rate compared to the NCRT group (79.2% vs. 62.5%, p = 0.032). CONCLUSION For patients with locally advanced ESCC, NCRI showed a significantly higher pCR rate than conventional NCRT, without increased operative risk. NCRI followed by surgery exhibited a superior RFS compared to NCRT followed by surgery. Prospective studies are needed in the future.
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Affiliation(s)
- Canjun Li
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xin Wang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Lei Deng
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianyang Wang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Tao Zhang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Wenqing Wang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Wenyang Liu
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jima Lv
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Qinfu Feng
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zongmei Zhou
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xiankai Chen
- Department of Thoracic SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Ruixiang Zhang
- Department of Thoracic SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianjun Qin
- Department of Thoracic SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yin Li
- Department of Thoracic SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Nan Bi
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Zhu Y, Zhang Z, Chen S, Bai G, Xu Q, Zhang L, Gao M, Ruan A, Guo L. Prognostic factors in locally advanced oesophageal squamous cell carcinoma: a clinical and radiomic analysis of neoadjuvant immunochemotherapy before surgery. Front Oncol 2025; 15:1508477. [PMID: 40182030 PMCID: PMC11966397 DOI: 10.3389/fonc.2025.1508477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 02/17/2025] [Indexed: 04/05/2025] Open
Abstract
Background The treatment of locally advanced oesophageal squamous cell carcinoma (LAESCC) without distant metastasis remains a subject of debate. Neoadjuvant immunochemotherapy (NIC) combined with surgery is the preferred initial approach for managing LAESCC. However, information on the clinical efficacy and survival of patients with LAESCC treated with NIC followed by surgery is limited. Methods This retrospective analysis aimed to identify predictors NIC treatment effectiveness and on patient survival. We developed a Cox proportional hazards model and Kaplan-Meier curve to estimate progression-free survival (PFS) and overall survival (OS) following NIC treatment and surgery. Results Overall, 225 patients with LAESCC were divided into training (157) and test set (68) (7:3). After a median follow-up of 2.86 years, death was observed as a positive event in 41 patients (26.1%). It is statistically significant to construct a prediction model combining radiomics features pre- and post-NIC with clinical features to predict the PFS and OS of LAESCC. The combined model showed the highest performance in predicting both disease-free survival and OS compared with the clinical or radiomics models. multivariate Cox regression analysis identified smoking (HR = 1.417, 95% confidence interval [CI]: 0.875-2.293, p = 0.156), Ki67(HR = 2.426, 95% confidence interval [CI]: 1.506-3.908, p = 0.000) and postRad-S1 (HR = 1.867, 95% CI: 1.053-3.311, p = 0.033) as significant independent covariates associated with high PFS. While Ki67 and postRad-S2 were prognostic factors significantly associated with OS (HR = 1.521, 95% CI: 0.821-2.818, p = 0.183; HR = 1.912, 95% CI: 1.001-3.654, p = 0.050, respectively). Conclusion For patients with LAESCC treated with NIC followed by surgery, the combined model effectively evaluated the efficacy of NIC and predicted PFS and OS. Additionally, different independent predictors were associated with PFS and OS, providing clues for future studies.
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Affiliation(s)
- Yan Zhu
- Department of Radiology, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
| | - Zhenzhong Zhang
- Department of Thoracic Surgery, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
| | - Shuangqing Chen
- Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Genji Bai
- Department of Radiology, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
| | - Qingqing Xu
- Department of Radiology, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
| | - Lili Zhang
- Department of Pathology, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
| | - Max Gao
- Computer Science and Engineering, University of California, Davis, Davis, United States
| | - Aichao Ruan
- Department of Thoracic Surgery, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
| | - Lili Guo
- Department of Radiology, the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China
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Han D, Dong J, Wang Q, Li B, Liu J, Liu H, Qiu B, Zhang W, Yang H, Shen W, Zhang Y, Zhu X, Wang Y, Wu L, Sun H, Huang W. Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts. BMC Cancer 2024; 24:1086. [PMID: 39223503 PMCID: PMC11367793 DOI: 10.1186/s12885-024-12825-2] [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: 03/27/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. METHODS From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1-6 and the second for cases 7-9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. RESULTS The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76-0.81; mean Hmean = 2.11-3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63-0.64; mean Hmean = 5.66-7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature. CONCLUSIONS We have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.
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Affiliation(s)
- Dan Han
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China
| | - Jinling Dong
- Department of Oncology, Yankuang New Journey General Hospital, Zoucheng, 273500, China
| | - Qifeng Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China
| | - Jun Liu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200050, China
| | - Hui Liu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Bo Qiu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Wencheng Zhang
- Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Hong Yang
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Wenbin Shen
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050017, China
| | - Yaowen Zhang
- Department sixth of Radiotherapy, Anyang Cancer Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, 455001, China
| | - Xiangzhi Zhu
- Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, China
| | - Yi Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Lei Wu
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Hongfu Sun
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China.
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Zhou D, Chen D, Song P, Hu Z, Xu S, Zhu R, Chen Y. Does neoadjuvant therapy contribute to increased risk in anastomotic leakage of esophageal cancer? A network meta-analysis. J Evid Based Med 2024; 17:559-574. [PMID: 39161209 DOI: 10.1111/jebm.12634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 07/15/2024] [Indexed: 08/21/2024]
Abstract
AIM Conflicting results have been reported about the impact of neoadjuvant therapy on anastomotic leakage (AL) after esophagectomy. We aimed to unravel the potential effect of neoadjuvant therapy on AL after esophagectomy through a network meta-analysis. METHODS A Bayesian network meta-analysis was performed by retrieving relevant literature from PubMed, EMbase, The Cochrane Library and Web of Science Core Collection. Randomized clinical trials (RCTs) and retrospective studies (RS) comparing the following treatment modalities were included: neoadjuvant chemoradiation (nCRT), neoadjuvant chemotherapy (nCT), neoadjuvant radiotherapy (nR), neoadjuvant immunochemotherapy (nICT), and surgery alone (SA). Subgroup analyses by radiation dose, examined lymph nodes (ELN), route of reconstruction, site of anastomosis, and surgical approach were also conducted. RESULTS A total of 62 studies with 12,746 patients were included for the present study, among which 17 were RCTs. There were no significantly statistical differences observed among the five treatment modalities in AL for both RCTs (nCRT-nICT: risk ratio 1.51, 95% confidence interval 0.52-4.4; nCT-nICT: 1.71, 0.56-5.08; nICT-nR: 0.79, 0.12-8.02; nICT-SA: 0.59, 0.2-1.84) and RS (nCRT-nICT: odds ratio 1.53, 95% confidence interval 0.84-2.84; nCT-nICT: 1.56, 0.87-2.88; nICT-SA: 0.6, 0.31-1.12; nICT-nR: 1.08, 0.09-36.02). Subgroup analysis revealed that no significant difference in AL was observed among the five treatment modalities except for the impact of nCRT versus nCT (0.21, 0.05-0.73) on AL with a radiation dose ≥41.4 Gy. CONCLUSIONS Neoadjuvant therapy do not significantly increase the incidence of AL after esophagectomy. Administration of irradiation with a moderate dose is not associated with elevated risk in AL. Clinicians can be less apprehensive about prescribing nCRT.
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Affiliation(s)
- Da Zhou
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Donglai Chen
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peidong Song
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Zihao Hu
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Sukai Xu
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Rongying Zhu
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yongbing Chen
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
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Ma Y, Yu J, Ma X, Li Q, Su Q, Cao B. Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy. Asia Pac J Clin Oncol 2024; 20:180-187. [PMID: 37171038 DOI: 10.1111/ajco.13961] [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: 10/24/2022] [Revised: 03/10/2023] [Accepted: 03/29/2023] [Indexed: 05/13/2023]
Abstract
Esophageal cancer (EC) is the seventh most common cancer worldwide. Patients with EC have a generally poor prognosis mainly due to the lack of effective treatments. Cancer immunotherapy is a promising novel treatment option for EC. This literature review investigated the clinical efficacy of immunotherapy either alone or in combination with chemotherapy or targeted therapy. In addition, we analyzed the adverse events associated with immune checkpoint inhibitors (ICIs). In conclusion, ICIs increase the efficacy of EC treatments, thereby improving the outcomes of EC patients. The findings of this study may help enhance the response to immunotherapy, diminish toxicity, and thus eventually improve medical care for patients with EC.
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Affiliation(s)
- Yingjie Ma
- Department of Oncology, Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Junxian Yu
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Xiaoting Ma
- Department of Oncology, Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Qin Li
- Department of Oncology, Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Qiang Su
- Department of Oncology, Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Bangwei Cao
- Department of Oncology, Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
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Yuan MX, Cai QG, Zhang ZY, Zhou JZ, Lan CY, Lin JB. Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer: A meta-analysis. World J Gastrointest Oncol 2024; 16:214-233. [PMID: 38292844 PMCID: PMC10824113 DOI: 10.4251/wjgo.v16.i1.214] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/20/2023] [Accepted: 12/04/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer (EC) treatment is still a subject of debate. AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for locally advanced EC (LAEC). METHODS A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biomedical Literature Database Article. Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected. RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival. The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate (OSR) [odds ratio (OR) = 0.95], complete response rate (OR = 3.15), and R0 clearance rate (CR) (OR = 2.25). However, nCT demonstrated a better 5-year OSR (OR = 1.02) than nCRT. Moreover, when compared to nCRT, nCT showed reduced risks of cardiac complications (OR = 1.15) and pulmonary complications (OR = 1.30). CONCLUSION Overall, both nCRT and nCT were effective in terms of survival outcomes for LAEC. However, nCT exhibited better performance in terms of postoperative complications.
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Affiliation(s)
- Mao-Xiu Yuan
- The Graduate School, Fujian Medical University, Fuzhou 350000, Fujian Province, China
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Qi-Gui Cai
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Zhen-Yang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China
| | - Jian-Zhong Zhou
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Cai-Yun Lan
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Jiang-Bo Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China
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Jiang N, Zhang J, Guo Z, Wu Y, Zhao L, Kong C, Song X, Gu L, Zhao Y, Li S, He X, Ren B, Zhu X, Jiang M. Short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab for locally advanced esophageal squamous cell carcinoma (SCALE-1): a single-arm phase Ib clinical trial. J Immunother Cancer 2024; 12:e008229. [PMID: 38199609 PMCID: PMC10806572 DOI: 10.1136/jitc-2023-008229] [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] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population. METHODS RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m2), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4-6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform. RESULTS Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity. CONCLUSIONS Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients. TRIAL REGISTRATION NUMBER ChiCTR2100045104.
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Affiliation(s)
- Ning Jiang
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jingyuan Zhang
- Department of Pathology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Zhen Guo
- Department of Medical Imaging Center, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yinan Wu
- Department of Pathology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lijun Zhao
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Cheng Kong
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xue Song
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lingling Gu
- Department of Medical Imaging Center, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yang Zhao
- Department of Biostatistics, Nanjing Medical University, Nanjing, China
| | - Si Li
- Medical Department, Jiangsu Simcere Diagnostics Co. Ltd.; Nanjing Simcere Co. Ltd.; The State Key Laboratory of Translational Medicine and Innovative Drug Development, Nanjing, China
| | - Xia He
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Binhui Ren
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiangzhi Zhu
- Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ming Jiang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Wang HC, Huang X, Chen J, Li Y, Cong Y, Qu BL, Feng SQ, Liu F. Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. World J Gastroenterol 2023; 29:5641-5656. [PMID: 38077159 PMCID: PMC10701330 DOI: 10.3748/wjg.v29.i41.5641] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/07/2023] [Accepted: 10/23/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND Pembrolizumab combined with chemotherapy has been proven effective as first-line therapy in patients with advanced esophageal cancer. Few trials have assessed the safety and efficacy of this treatment in patients with locally advanced disease. AIM To analyze long-term outcomes of pembrolizumab in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in the real world. METHODS Patients with advanced ESCC admitted to our center from October 2019 to October 2021 were enrolled in this study. Clinical staging of the patients was based on the 8th edition of the American Joint Committee on Cancer TNM staging system. The patients received different treatments based on clinical stage. In brief, patients with locally advanced and resectable ESCC received neoadjuvant therapy combined with surgery. For those who were not candidates for resection, radical concurrent chemoradiotherapy plus pembrolizumab was more preferable. Patients with metastatic ESCC or who were unsuitable for radiotherapy underwent chemotherapy in combination with pembrolizumab. Long-term survival outcomes such as overall survival (OS), progression-free survival, disease-free survival, long-term adverse effects (AEs), immune maintenance therapy and predictors of immune checkpoint inhibitors (ICIs) efficacy were evaluated. RESULTS A total of 55 patients with advanced ESCC were enrolled in this retrospective, observational study. The median age was 61 years (range 44-74), with 47.3% (26/55) of the patients in stage IV and 45.5% of the patients had the tumor (25/55) located in the middle third of the esophagus. The median OS in all patients was not reached. The 12-mo OS rate among all patients was 78.8% and the 18-mo OS rate was 72.7%. 9 patients died due to tumor progression and 7 patients died due to treatment-related complications. The therapeutic effect evaluated at the interim evaluation was significantly reflected in the long-term outcome. Patients with complete response or partial response in all patients (P = 0.005) and in the chemoradiotherapy plus pembrolizumab group (P = 0.007) obtained a better prognosis than non-responders. A total of 20 patients (20/55, 36%) received immune maintenance therapy. Baseline peripheral blood biomarkers of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil-to-(leukocyte-neutrophil) ratio did not predict the efficacy of ICIs. CONCLUSION Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC, with safe and manageable long-term AEs.
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Affiliation(s)
- Hong-Chi Wang
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang Huang
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Jing Chen
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Ye Li
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Yang Cong
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Bao-Lin Qu
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Sheng-Qiang Feng
- Health Service, The Guard Bureau of Joint Staff Department of Chinese PLA, Beijing 100017, China
| | - Fang Liu
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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9
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Liu Y. Perioperative immunotherapy for esophageal squamous cell carcinoma: Now and future. World J Gastroenterol 2023; 29:5020-5037. [PMID: 37753366 PMCID: PMC10518742 DOI: 10.3748/wjg.v29.i34.5020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/19/2023] [Accepted: 08/15/2023] [Indexed: 09/08/2023] Open
Abstract
Esophageal cancer (EC) ranks among the most prevalent malignant tumors affecting the digestive tract. Esophageal squamous cell carcinoma (ESCC) stands as the prevailing pathological subtype, encompassing approximately 90% of all EC patients. In clinical stage II-IVA locally advanced ESCC cases, the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection. Despite concerted efforts, the long-term outcomes for ESCC patients remain unsatisfactory, with dismal prognoses. However, recent years have witnessed remarkable strides in immunotherapy, particularly in the second- and first-line treatment of advanced or metastatic ESCC, with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies, including ESCC. This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC, focusing specifically on the role of immune checkpoint inhibitors during the perioperative period. Additionally, the review will explore promising biomarkers and offer insights into future prospects.
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Affiliation(s)
- Yong Liu
- Department of Thoracic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430011, Hubei Province, China
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10
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Wong LY, Liou DZ, Backhus LM, Lui NS, Shrager JB, Berry MF. The impact of neoadjuvant immunotherapy on perioperative outcomes and survival after esophagectomy for esophageal cancer. JTCVS OPEN 2023; 14:547-560. [PMID: 37425457 PMCID: PMC10328967 DOI: 10.1016/j.xjon.2023.03.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 03/18/2023] [Accepted: 03/24/2023] [Indexed: 07/11/2023]
Abstract
Objective Immunotherapy for esophageal cancer is relatively novel but increasingly used. This study evaluated the early use of immunotherapy as an adjunct to neoadjuvant chemoradiotherapy before esophagectomy for locally advanced disease. Methods Perioperative morbidity (composite of mortality, hospitalization ≥21 days, or readmission) and survival of patients with locally advanced (cT3N0M0, cT1-3N + M0) distal esophageal cancer in the National Cancer Database from 2013 to 2020 who underwent neoadjuvant immunotherapy plus chemoradiotherapy or chemoradiotherapy alone followed by esophagectomy were evaluated using logistic regression, Kaplan-Meier curves, Cox proportional hazards methods, and propensity-matched analysis. Results Immunotherapy was used in 165 (1.6%) of 10,348 patients. Younger age (odds ratio, 0.66; 95% confidence interval, 0.53-0.81; P < .001) predicted immunotherapy use, which slightly delayed time from diagnosis to surgery versus chemoradiation alone (immunotherapy 148 [interquartile range, 128-177] days vs chemoradiation 138 [interquartile range, 120-162] days, P < .001). There were no statistically significant differences between the immunotherapy and chemoradiation groups for the composite major morbidity index (14.5% [24/165] vs 15.6% [1584/10,183], P = .8). Immunotherapy was associated with a significant improvement in median overall survival (69.1 months vs 56.3 months, P = .005) and 3-year overall survival in univariate analysis (65.6% [95% confidence interval, 57.7-74.5] vs 55.0% [53.9-56.1], P = .005), and independently predicted improved survival in multivariable analysis (hazard ratio 0.68 [95% confidence interval, 0.52-0.89], P = .006). Propensity-matched analysis also showed that immunotherapy use was not associated with increased surgical morbidity (P = .5) but was associated with improved survival (P = .047). Conclusions Neoadjuvant immunotherapy use before esophagectomy for locally advanced esophageal cancer did not lead to worse perioperative outcomes and shows promising results on midterm survival.
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Affiliation(s)
- Lye-Yeng Wong
- Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, Calif
| | - Douglas Z. Liou
- Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, Calif
| | - Leah M. Backhus
- Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, Calif
- VA Palo Alto Health Care System, Palo Alto, Calif
| | - Natalie S. Lui
- Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, Calif
| | - Joseph B. Shrager
- Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, Calif
- VA Palo Alto Health Care System, Palo Alto, Calif
| | - Mark F. Berry
- Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, Calif
- VA Palo Alto Health Care System, Palo Alto, Calif
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11
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Jiang M, Hu Y, Lin G, Chen C, Li H. Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions. Front Immunol 2023; 14:1177085. [PMID: 37325652 PMCID: PMC10261849 DOI: 10.3389/fimmu.2023.1177085] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/22/2023] [Indexed: 06/17/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide and often diagnosed at advanced stages with poor prognosis. Combination of radiotherapy and immunotherapy seems to be a promising approach for treating ESCC. This comprehensive review article summarizes the current state of combination of radiotherapy and immunotherapy in locally advanced/metastatic ESCC, delineates the clinical trials that merit attention, and outlines unresolved issues and future research directions in this field. The clinical trial findings suggest that radio-immunotherapy combination may improve tumor response and overall survival with manageable side effects, highlighting the importance of patient selection and the necessity for further research to optimize treatment strategies. Issues such as irradiation dosage, fractionation regimen, irradiation site and technique of radiotherapy, as well as the timing, sequence and duration of combination therapy will all affect treatment outcomes, justifying further in-depth investigation.
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Affiliation(s)
- Mengjie Jiang
- Department of Radiotherapy, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
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12
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Wang H, Song C, Zhao X, Deng W, Dong J, Shen W. Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis. Front Immunol 2023; 14:1170569. [PMID: 37251393 PMCID: PMC10213267 DOI: 10.3389/fimmu.2023.1170569] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/02/2023] [Indexed: 05/31/2023] Open
Abstract
Objective This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.
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Affiliation(s)
| | | | | | | | | | - Wenbin Shen
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
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13
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Zhou RQ, Luo J, Li LJ, Du M, Wu QC. Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study. BMC Surg 2023; 23:114. [PMID: 37161374 PMCID: PMC10170768 DOI: 10.1186/s12893-023-02023-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 04/30/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Neoadjuvant therapy is recommended to improve the prognosis of oesophageal squamous cell carcinoma (ESCC). As a PD-1 inhibitor developed in China, camrelizumab is more accessible and available for Chinese ESCC patients. Camrelizumab plus neoadjuvant chemotherapy has shown promising efficacy with acceptable toxicity for resectable ESCC in the NIC-ESCC2019 trial. However, this was a single-arm trial, so we conducted a retrospective cohort study to compare neoadjuvant camrelizumab plus chemotherapy with neoadjuvant chemotherapy alone in terms of the safety and efficacy in patients with locally advanced ESCC. METHODS Between January 2017 and December 2021, patients with stage II-IVa ESCC who received neoadjuvant therapy at the First Affiliated Hospital of Chongqing Medical University and underwent radical oesophagectomy were enrolled in our study. These included 19 patients who received neoadjuvant chemotherapy plus camrelizumab (group 1) and 40 patients who only received neoadjuvant chemotherapy (group 2). RESULTS The baseline characteristics of the patients were comparable between the two groups. The pathological complete response (pCR) rate in group 1 was significantly higher than that in group 2 (26.3% vs. 2.5%, P = 0.018). All patients in group 1 achieved complete resection (R0), compared with 39 (97.5%) patients in group 2. Adverse events occurred in 16 (84%) patients in group 1 versus 35 (87.5%) patients in group 2. No grade ≥ 4 adverse events occurred in either group. No significant difference was found in surgical outcomes or postoperative complications. The 90-day mortality rate was comparable between the two groups (1 patient died in group 1 versus 2 patients in group 2). CONCLUSIONS Neoadjuvant camrelizumab plus chemotherapy followed by surgery was associated with a promising pCR rate and a manageable safety profile for patients with locally advanced ESCC.
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Affiliation(s)
- Rui-Qin Zhou
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Jun Luo
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Lin-Jun Li
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Ming Du
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Qing-Chen Wu
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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14
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Ma R, Yuan D, Mo C, Zhu K, Dang C, Zhang Y, Yin J, Li K. Factors affecting the ORR after neoadjuvant therapy of TP regimen combined with PD-1 inhibitors for esophageal cancer. Sci Rep 2023; 13:6080. [PMID: 37055490 PMCID: PMC10102326 DOI: 10.1038/s41598-023-33038-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 04/06/2023] [Indexed: 04/15/2023] Open
Abstract
The aim of this study is to evaluate the factors affecting the objective response rate (ORR) after neoadjuvant therapy of taxol plus platinum (TP) regimen combined with programmed cell death protein-1 (PD-1) inhibitors for esophageal cancer, and establish a predictive model for forecasting ORR. According to the inclusion and exclusion criteria, consecutive esophageal cancer patients who were treated in the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to February 2022 were enrolled in this study as a training cohort, while patients who were treated in the Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi'an Jiaotong University from January 2020 to December 2021 were enrolled as a validation cohort. All patients were treated with resectable locally advanced esophageal cancer and received neoadjuvant chemotherapy combined with immunotherapy. The ORR was defined as the sum of complete pathological response, major pathological response and partial pathological response. Logistic regression analysis was performed to determine the factors that might be related to the ORR of the patients after neoadjuvant therapy. The nomogram based on the result of regression analysis was established and verified to predict the ORR. In this study, 42 patients were included as training cohort and 53 patients were included as validation cohort. Chi-square analysis showed that neutrophil, platelet, platelet-to-lymphocytes ratio (PLR), systemic immune-inflammation index (SII), D-dimer and carcinoembryonic antigen (CEA) between ORR group and non-ORR group were significantly different. Logistic regression analysis showed that aspartate aminotransferase (AST), D-dimer and CEA were independent predictors of ORR after neoadjuvant immunotherapy. Finally, a nomogram was established based on AST, D-dimer and CEA. Internal validation and external validation revealed that the nomogram had a good ability to predict ORR after neoadjuvant immunotherapy. In conclusion, AST, D-dimer and CEA were the independent predictors of ORR after neoadjuvant immunotherapy. The nomogram based on these three indicators showed a good predictive ability.
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Affiliation(s)
- Rulan Ma
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China
| | - Dawei Yuan
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China
| | - Caijing Mo
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China
| | - Kun Zhu
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China
| | - Chengxue Dang
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China
| | - Yong Zhang
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China
| | - Jianhao Yin
- Department of General Surgery, Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi'an Jiaotong University, 309 West Yanta Road, Xi'an, 710061, Shaanxi, China.
| | - Kang Li
- Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
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15
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Yin J, Lin S, Fang Y, Jiao H, Chen Z, Tang H, Gu J, Zhang S, Sun L, Li Y, Han Y, Chen Q, Chen H, Li Z, Tan L. Neoadjuvant therapy with immunoagent (nivolumab) or placebo plus chemotherapy followed by surgery and adjuvant treatment in subjects with resectable esophageal squamous cell carcinoma: study protocol of a randomized, multicenter, double blind, phase II trial (NATION-2203 trial). J Thorac Dis 2023; 15:718-730. [PMID: 36910109 PMCID: PMC9992557 DOI: 10.21037/jtd-22-1789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 01/10/2023] [Indexed: 02/10/2023]
Abstract
Background Neoadjuvant chemotherapy (nCT) has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to nCT may improve oncologic outcome and survival. However, high-level evidence of neoadjuvant immunotherapy (nIT) combined with nCT in locally advanced resectable ESCC patients are still lacking. Hence, we describe this randomized controlled trial in order to assess the efficacy and safety of neoadjuvant nivolumab in combination with chemotherapy for locally advanced (stage II-III) ESCC patients. Methods This prospective, randomized, multicenter phase II trial aims to enroll 90 locally advanced (stage II-III) ESCC patients who will undergo nivolumab or placebo plus chemotherapy followed by surgery. Patients will be 2:1 randomized to nivolumab/chemo and placebo/chemo group by method of stratified randomization. In both arms, patients who have not achieved complete pathological complete response (pCR) will be administered with adjuvant nivolumab for up to 1 year. The primary endpoint is pCR rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events (AEs). The safety will be evaluated by AEs, grading by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 classifications. The double-blind will be maintained between subjects and investigators until the final unblinding process. Discussion This protocol has been reviewed and approved by the Ethics Committee of Zhongshan Hospital (B2022-004R). This is the first prospective, multicenter, randomized controlled trial to compare the combination of immunotherapy and chemotherapy with standard chemotherapy in neoadjuvant treatment for ESCC, also to explore whether adjuvant immunotherapy offers additional benefit in non-pCR patients after nCT with/without immunotherapy and R0 resection. We hypothesize that the pCR rate, R0 resection rate, EFS and OS of the study group (nivolumab/chemo) is significantly better than those of control group. Registration ClinicalTrial.gov: NCT05213312.
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Affiliation(s)
- Jun Yin
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyun Lin
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Fang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Heng Jiao
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zongwei Chen
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Tang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianmin Gu
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shaoyuan Zhang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Linyi Sun
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yin Li
- 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
| | - Yongtao Han
- Department of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qixun Chen
- Department of Thoracic Oncological Surgery, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China
| | - Haiquan Chen
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center & Institute of Thoracic Oncology & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
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16
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Chen Q, Mo S, Aizemaiti R, Cheng J, Wu Z, Ye P. Minimally invasive versus open McKeown esophagectomy for patients with esophageal squamous cell carcinoma after neoadjuvant PD-1 inhibitor plus chemotherapy. Front Oncol 2023; 13:1103421. [PMID: 36776336 PMCID: PMC9912456 DOI: 10.3389/fonc.2023.1103421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 01/05/2023] [Indexed: 02/14/2023] Open
Abstract
Introduction The purpose of this study was to compare short and mid-term outcomes in esophageal squamous cell carcinoma (ESCC) patients undergoing open or minimally invasive McKeown esophagectomy (MIE) after neoadjuvant PD-1 inhibitor plus chemotherapy. Methods Patients with locally advanced ESCC underwent open or minimally invasive McKeown esophagectomy after neoadjuvant PD-1 inhibitor plus chemotherapy were retrospectively included from June 2019 to June 2021. The baseline characteristics, pathological data, short-and mid-term outcomes were collected and compared based on the surgical approach. Results A total of 35 patients were included in the study. An open procedure was performed for 13 patients (37.1%), and 22 (62.9%) patients underwent MIE after neoadjuvant therapy. Compared with open group, MIE group had shorter operative times (350.8± 117.8 vs. 277.9 ± 30.2 min, P = 0.009). The total number of resected lymph nodes was not significantly different, but more left recurrent laryngeal lymph nodes were harvested from the Open group (2.6 ± 3.2 vs. 0.9 ± 1.7, P = 0.047). The median follow-up time was 1.42 years (range, 0.35-2.59 years) from the first day of treatment. Three patients (8.6%) died during follow-up, one in the open surgery group and two in the MIE group. There were six (17.1%) patients developed recurrence, three in each group. The 2-year cumulative survival rates were 92.3 ± 7.4% and 89.5 ± 7.1% for the open and MIE groups, respectively. Overall survival was not different between the two surgical approaches. Conclusions MIE might be safe and feasible for patients with locally advanced ESCC undergoing neoadjuvant PD-1 inhibitor plus chemotherapy.
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Affiliation(s)
- Qiuming Chen
- Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shaocong Mo
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Rusidanmu Aizemaiti
- Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jun Cheng
- Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Ziheng Wu
- Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Peng Ye
- Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China,*Correspondence: Peng Ye,
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17
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Xu L, Wei XF, Li CJ, Yang ZY, Yu YK, Li HM, Xie HN, Yang YF, Jing WW, Wang Z, Kang XZ, Zhang RX, Qin JJ, Xue LY, Bi N, Chen XK, Li Y. Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Front Immunol 2022; 13:1052542. [PMID: 36466925 PMCID: PMC9713810 DOI: 10.3389/fimmu.2022.1052542] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 10/31/2022] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. METHODS Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. RESULTS After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). CONCLUSION For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.
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Affiliation(s)
- Lei Xu
- 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
| | - Xiu-feng Wei
- 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
| | - Can-jun Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Zhao-yang Yang
- 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
| | - Yong-kui Yu
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Hao-miao Li
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Hou-nai Xie
- 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
| | - Ya-fan Yang
- 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
| | - Wei-wei Jing
- 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
| | - Zhen Wang
- 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
| | - Xiao-zheng Kang
- 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
| | - Rui-xiang Zhang
- 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
| | - Jian-jun Qin
- 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
| | - Li-yan Xue
- 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
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xian-kai Chen
- 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
| | - Yin Li
- 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
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Muir D, Antonowicz S, Whiting J, Low D, Maynard N. Implementation of the Esophagectomy Complication Consensus Group definitions: the benefits of speaking the same language. Dis Esophagus 2022; 35:6603615. [PMID: 35673848 DOI: 10.1093/dote/doac022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/17/2022] [Indexed: 12/24/2022]
Abstract
In 2015 the Esophagectomy Complication Consensus Group (ECCG) reported consensus definitions for complications after esophagectomy. This aimed to reduce variation in complication reporting, attributed to heterogeneous definitions. This systematic review aimed to describe the implementation of this definition set, including the effect on complication frequency and variation. A systematic literature review was performed, identifying all observational and randomized studies reporting complication frequencies after esophagectomy since the ECCG publication. Recruitment periods before and subsequent to the index ECCG publication date were included. Coefficients of variance were calculated to assess outcome heterogeneity. Of 144 studies which met inclusion criteria, 70 (48.6%) used ECCG definitions. The median number of separately reported complication types was five per study; only one study reported all ECCG complications. The coefficients of variance of the reported frequencies of eight of the 10 most common complications were reduced in studies which used the ECCG definitions compared with those that did not (P = 0.036). Among ECCG studies, the frequencies of postoperative pneumothorax, reintubation, and pulmonary emboli were significantly reduced in 2020-2021, compared with 2015-2019 (P = 0.006, 0.034, and 0.037 respectively). The ECCG definition set has reduced variation in esophagectomy morbidity reporting. This adds greater confidence to the observed gradual improvement in outcomes with time, and its ongoing use and wider dissemination should be encouraged. However, only a handful of outcomes are widely reported, and only rarely is it used in its entirety.
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Affiliation(s)
- Duncan Muir
- Department of Upper GI Surgery, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Stefan Antonowicz
- Department of Upper GI Surgery, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Jack Whiting
- Department of Upper GI Surgery, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Donald Low
- Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Medical Center, Seattle, WA, USA
| | - Nick Maynard
- Department of Upper GI Surgery, Oxford University Hospitals NHS Trust, Oxford, UK
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Yang Y, Tan L, Hu J, Li Y, Mao Y, Tian Z, Zhang B, Ma J, Li H, Chen C, Chen K, Han Y, Chen L, Liu J, Yu B, Yu Z, Li Z. Safety and efficacy of neoadjuvant treatment with immune checkpoint inhibitors in esophageal cancer: real-world multicenter retrospective study in China. Dis Esophagus 2022; 35:6596998. [PMID: 35649396 DOI: 10.1093/dote/doac031] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 04/26/2022] [Indexed: 02/05/2023]
Abstract
Immune checkpoint inhibitors (ICIs) have shown a powerful benefit in the neoadjuvant therapy for esophageal cancer, but evidence for its safety and efficacy is limited and may not reflect real-world practice. We retrospectively reviewed the database of treatment-naive patients from 15 esophageal cancer centers in China who received ICIs as neoadjuvant treatment for locally advanced esophageal cancer from May 2019 to December 2020. The primary endpoints were rate and severity of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs). Secondary endpoints included pathologically complete response (pCR) rate, R0 resection rate, mortality and morbidity. Among the 370 patients, 311 (84.1%) were male with a median age of 63 (range: 30-81) years and stage III or IVa disease accounted for 84.1% of these patients. A total of 299 (80.8%) patients were treated with ICIs and chemotherapy. TRAEs were observed in 199 (53.8%) patients with low severity (grade 1-2, 39.2%; grade 3-4, 13.2%; grade 5, 1.4%), and irAEs occurred in 24.3% of patients and were mostly of grade 1-2 severity (21.1%). A total of 341 (92.2%) patients had received surgery and R0 resection was achieved in 333 (97.7%) patients. The local pCR rate in primary tumor was 34.6%, including 25.8% of ypT0N0 and 8.8% of ypT0N+. The rate of postoperative complications was 41.4% and grade 3 or higher complications occurred in 35 (10.3%) patients. No death was observed within 30 days after surgery, and three patients (0.9%) died within 90 days postoperatively. This study shows acceptable toxicity of neoadjuvant immunotherapy for locally advanced esophageal cancer in real-world data. Long-term survival results are pending for further investigations.
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Affiliation(s)
- Yang Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital Affiliated to Fudan University, Shanghai, P. R. China
| | - Jian Hu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University, School of Medicine, Zhejiang, P. R. China
| | - Yin Li
- Department of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, P. R. China
| | - Yousheng Mao
- Department of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, P. R. China
| | - Ziqiang Tian
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P. R. China
| | - Baihua Zhang
- Department of Thoracic Surgery, Hunan Cancer Hospital, Changsha, P. R. China
| | - Jianqun Ma
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, P. R. China
| | - Hecheng Li
- Department of Thoracic Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, P. R. China
| | - Keneng Chen
- Department of Thoracic Surgery, Beijing Cancer Hospital, Beijing, P. R. China
| | - Yongtao Han
- Department of Thoracic Surgery, Sichuan Cancer Hospital, Chengdu, P. R. China
| | - Longqi Chen
- Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, P. R. China
| | - Junfeng Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P. R. China
| | - Bentong Yu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, P. R. China
| | - Zhentao Yu
- Department of Thoracic Surgery, Tianjin Medical University Cancer Hospital, Tianjin, P. R. China.,Department of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, P. R. China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
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Chen F, Qiu L, Mu Y, Sun S, Yuan Y, Shang P, Ji B, Wang Q. Neoadjuvant chemoradiotherapy with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma. Front Surg 2022; 9:893372. [PMID: 35983558 PMCID: PMC9379096 DOI: 10.3389/fsurg.2022.893372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022] Open
Abstract
Background Neoadjuvant anti-programmed death receptor-1 (PD-1) blockade has been reported to improve the prognosis of locally advanced esophageal squamous cell carcinoma (ESCC). This study was aimed to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemoradiotherapy in locally advanced ESCC. Methods We retrospectively enrolled ESCC patients who received camrelizumab plus chemoradiotherapy as neoadjuvant therapy before surgery from May 2019 to September 2021. Results A total of 38 eligible patients were enrolled. The neoadjuvant treatment was well tolerated with no serious treatment-related adverse events. 36 (94.7%) patients achieved a R0 resection without hospital mortality or any other serious intraoperative complications. The objective response rate (ORR) was 63.2% and the disease control rate (DCR) was 100.0%. The major pathological response (MPR) was 50.0% and the complete pathological response (pCR) was 39.5%. With a median follow-up of 18.5 months, 6 (15.8%) patients had died. The overall survival (OS) and disease-free survival (DFS) at 12 months were 87.6% and 78.7%, respectively. Subgroup analysis demonstrated that patients who got MPR or pCR achieved improved survival, while PD-L1 expression did not reach statistically difference in predicting survival. Conclusions Neoadjuvant camrelizumab plus chemoradiotherapy is safe and efficacious in treating patients with locally advanced ESCC.
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Affiliation(s)
- Fei Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Lingdong Qiu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Yushu Mu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Shibin Sun
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Yulong Yuan
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Pan Shang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Bo Ji
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Qifei Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
- Correspondence: Qifei Wang
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21
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Yin GQ, Li ZL, Li D. The Safety and Efficacy of Neoadjuvant Camrelizumab Plus Chemotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Retrospective Study. Cancer Manag Res 2022; 14:2133-2141. [PMID: 35795828 PMCID: PMC9251418 DOI: 10.2147/cmar.s358620] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 05/10/2022] [Indexed: 11/23/2022] Open
Abstract
Background Neoadjuvant anti-programmed death receptor-1 (PD-1) blockade has been explored in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). We conducted this study to assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC. Methods We retrospectively enrolled ESCC patients who received surgery within 3 months of treatment with camrelizumab plus chemotherapy from June 2019 to January 2021. Results A total of 34 eligible patients were enrolled. The neoadjuvant treatment was well tolerated with no serious treatment-related adverse events. Thirty-two (94.1%) patients achieved a R0 resection, and 14 patients (41.2%) developed postoperative complications. The objective response rate (ORR) was 61.8% and the disease control rate (DCR) was 100.0%. The major pathological response (MPR), pathological complete response (pCR), and clinical to pathological downstaging rate were 50.0%, 35.3%, and 79.4%, respectively. With a median follow-up of 14.8 months, 30 (88.2%) patients who underwent surgical resection remain alive. The disease-free survival (DFS) and overall survival (OS) at 12 months were 86.4% and 92.8%, respectively. Conclusion Neoadjuvant camrelizumab plus chemotherapy is safe and efficacious in treating patients with locally advanced ESCC.
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Affiliation(s)
- Guo-Qiang Yin
- Department of Thoracic Surgery, Zibo Central Hospital, Zibo, Shandong Province, 255000, People's Republic of China
| | - Zu-Lei Li
- Department of Thoracic Surgery, Zibo Central Hospital, Zibo, Shandong Province, 255000, People's Republic of China
| | - Dong Li
- Department of Thoracic Surgery, Zibo Central Hospital, Zibo, Shandong Province, 255000, People's Republic of China
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22
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Wang Z, Chen X, Li Y, Qin J, Fang Y, Yang Z, Fang Y, Qu D, Zhang R, Zheng Q, Kang X, Xue L, Huang J, Li Y, He J. Phase Ib trial of camrelizumab combined with chemotherapy and apatinib for neoadjuvant treatment of locally advanced thoracic esophageal squamous cell carcinoma. JOURNAL OF THE NATIONAL CANCER CENTER 2022; 2:98-105. [PMID: 39034958 PMCID: PMC11256696 DOI: 10.1016/j.jncc.2022.04.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 04/16/2022] [Accepted: 04/22/2022] [Indexed: 11/25/2022] Open
Abstract
Objective This is a prospective, single-arm, phase Ib study to evaluate the safety and efficacy of camrelizumab combined with chemotherapy and apatinib as neoadjuvant therapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC). Methods The regimen encompassed 2-4 cycles of neoadjuvant camrelizumab, nab-paclitaxel, nedaplatin, and apatinib to treatment-naive patients with resectable locally advanced ESCC. The treatment was repeated every 14 days. Initially, six patients were planned to receive two cycles of neoadjuvant therapy as safety assessment, and then 24 patients received four cycles of neoadjuvant therapy, followed by esophagectomy after 4-8 weeks. The primary endpoint was safety. The key secondary endpoints were pathologic complete response (pCR) and major pathologic response (MPR). Results This study enrolled 30 patients, among whom, five patients received two cycles of neoadjuvant therapy, and one patient missed the second cycle of therapy due to grade 3 elevated alanine transaminase (ALT) level. The remaining 24 patients received four planned cycles of neoadjuvant therapy. Eleven patients (36.7%) developed grade 3 neoadjuvant treatment-related adverse events (TRAEs). No patient developed grade 4 or 5 TRAEs. Neutropenia (23.3%) was the most common grade 3 TRAE. Twenty-nine patients underwent esophagectomy after neoadjuvant therapy. Among them, 15 patients (51.7%) achieved MPR, including seven patients with pCR (24.1%). Radiographic analyses established a significant correlation between maximal standardized uptake value (SUVmax) reduction and pathologic regression (P = 0.00095). Conclusions Neoadjuvant camrelizumab combined with chemotherapy plus apatinib demonstrated a manageable safety profile for patients with locally advanced ESCC, and an encouraging efficacy was observed in most of the treated patients. A decrease in SUVmax of the primary tumor may be a predictor of pathologic response to neoadjuvant camrelizumab combined with chemotherapy plus apatinib in ESCC.
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Affiliation(s)
- Zhen Wang
- 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
| | - Xiankai Chen
- 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
| | - Yong Li
- 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
| | - Jianjun Qin
- 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
| | - Yuan Fang
- Clinical Cancer Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaoyang Yang
- 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
| | - Yan Fang
- Department of Nuclear Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dong Qu
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruixiang Zhang
- 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
| | - Qingfeng Zheng
- 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
| | - Xiaozheng Kang
- 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
| | - Liyan Xue
- 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
| | - Jing Huang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yin Li
- 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
| | - Jie He
- 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
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Gu YM, Shang QX, Zhang HL, Yang YS, Wang WP, Yuan Y, Hu Y, Che GW, Chen LQ. Safety and Feasibility of Esophagectomy Following Neoadjuvant Immunotherapy Combined with Chemotherapy for Esophageal Squamous Cell Carcinoma. Front Surg 2022; 9:851745. [PMID: 35711710 PMCID: PMC9195295 DOI: 10.3389/fsurg.2022.851745] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/03/2022] [Indexed: 12/24/2022] Open
Abstract
Background This study aimed to investigate the safety and feasibility of esophagectomy after neoadjuvant immunotherapy and chemotherapy for esophageal squamous cell carcinoma. Methods We retrospectively identified patients who received neoadjuvant immunotherapy combined with chemotherapy (n = 38) in our center between 2020 and 2021. The primary end point was the risk of major complications (grade ≥3) according to the Clavien–Dindo classification. Secondary end points were surgical details, 30-day mortality, and 30-day readministration. Results The most commonly used regimens of immunotherapy were camrelizumab (36.8%), pembrolizumab (31.5%), tislelizumab (15.8%), sintilimab (13.2%), and toripalimab (2.6%). The median interval to surgery was 63 days (range, 40–147). Esophagectomy was performed in 37 of 38 patients who received neoadjuvant immunotherapy and chemotherapy. All procedures were performed minimally invasively, except for 1 patient who was converted to thoracotomy. Of 37 surgical patients, R0 resection was achieved in 36 patients (97.3%). Pathologic complete response was observed in 9 patients (24.3%). Tumor regression grade I was identified in 17 patients (45.9%). Morbidity occurred in 12 of 37 patients (32.4%). The most common complication was pneumonia (16.2%). There were no deaths or readministration within 30 days. Conclusions Esophagectomy following neoadjuvant immune checkpoint inhibitor plus chemotherapy for patients with resectable esophageal squamous cell carcinoma appears to be safe and feasible, with acceptable complication rates.
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Yang Y, Zhu L, Cheng Y, Liu Z, Cai X, Shao J, Zhang M, Liu J, Sun Y, Li Y, Yi J, Yu B, Jiang H, Chen H, Yang H, Tan L, Li Z. Three-arm phase II trial comparing camrelizumab plus chemotherapy versus camrelizumab plus chemoradiation versus chemoradiation as preoperative treatment for locally advanced esophageal squamous cell carcinoma (NICE-2 Study). BMC Cancer 2022; 22:506. [PMID: 35524205 PMCID: PMC9074348 DOI: 10.1186/s12885-022-09573-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022] Open
Abstract
Background Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240). Methods The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events. Discussion This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021. Trial registration ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered.
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Affiliation(s)
- Yang Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai, 200030, China
| | - Li Zhu
- Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Cheng
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Zhichao Liu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai, 200030, China
| | - Xiaoyue Cai
- Department of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jinchen Shao
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ming Zhang
- Department of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jun Liu
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yifeng Sun
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai, 200030, China
| | - Yin Li
- Department of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Jun Yi
- Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Bentong Yu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hongjing Jiang
- Department of Thoracic Surgery, Tianjin Medical University Cancer Hospital, Tianjin, China
| | - Hezhong Chen
- Department of Thoracic Surgery, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai, China
| | - Hong Yang
- Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai, 200030, China.
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Liu J, Yang Y, Liu Z, Fu X, Cai X, Li H, Zhu L, Shen Y, Zhang H, Sun Y, Chen H, Yu B, Zhang R, Shao J, Zhang M, Li Z. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J Immunother Cancer 2022; 10:jitc-2021-004291. [PMID: 35338088 PMCID: PMC8961177 DOI: 10.1136/jitc-2021-004291] [Citation(s) in RCA: 137] [Impact Index Per Article: 45.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/03/2022] [Indexed: 12/24/2022] Open
Abstract
Background Camrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC. Methods Patients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab. Results From November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality. Conclusions The robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC. Trial registration number ChiCTR1900026240.
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Affiliation(s)
- Jun Liu
- Department of Radiation Oncology, Shanghai Jiao Tong University, Shanghai, China
| | - Yang Yang
- Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China
| | - Zhichao Liu
- Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaolong Fu
- Department of Radiation Oncology, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoyue Cai
- Department of Integrative Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hongxuan Li
- Department of Radiation Oncology, Shanghai Jiao Tong University, Shanghai, China
| | - Li Zhu
- Department of Radiology, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Shen
- Department of Radiology, Shanghai Jiao Tong University, Shanghai, China
| | - Hong Zhang
- Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China
| | - Yifeng Sun
- Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China
| | - Hezhong Chen
- Department of Thoracic Surgery, Changhai Hospital, Shanghai, China
| | - Bentong Yu
- Department of Thoracic Surgery, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Renquan Zhang
- Department of Thoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jinchen Shao
- Department of Pathology, Shanghai Jiao Tong University, Shanghai, China
| | - Ming Zhang
- Department of Integrative Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Jiao Tong University, Shanghai, China
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Advances in the curative management of oesophageal cancer. Br J Cancer 2022; 126:706-717. [PMID: 34675397 PMCID: PMC8528946 DOI: 10.1038/s41416-021-01485-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 06/01/2021] [Accepted: 06/30/2021] [Indexed: 12/24/2022] Open
Abstract
The incidence of oesophageal cancer, in particular adenocarcinoma, has markedly increased over the last four decades with adenocarcinoma becoming the dominant subtype in the West, and mortality rates are high. Nevertheless, overall survival of patients with oesophageal cancer has doubled in the past 20 years, with earlier diagnosis and improved treatments benefiting those patients who can be treated with curative intent. Advances in endotherapy, surgical approaches, and multimodal and other combination therapies have been reported. New vistas have emerged in targeted therapies and immunotherapy, informed by new knowledge in genomics and molecular biology, which present opportunities for personalised cancer therapy and novel clinical trials. This review focuses exclusively on the curative intent treatment pathway, and highlights emerging advances.
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Zander T, Wagner AD. (Neo)Adjuvant Treatment of Locally Advanced Esophageal and Gastroesophageal Adenocarcinoma: Special Focus on Sex Differences. Cancers (Basel) 2022; 14:cancers14041088. [PMID: 35205835 PMCID: PMC8869883 DOI: 10.3390/cancers14041088] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/06/2022] [Accepted: 02/14/2022] [Indexed: 11/29/2022] Open
Abstract
Simple Summary Multimodal therapy is standard in locally advanced esophageal and gastroesophageal adenocarcinoma. Although substantial differences in incidence and outcome between women and men have been observed, no clear sex-specific treatment guide has been developed. In this summary, we described known sex differences focusing on locally advanced esophageal and gastroesophageal adenocarcinoma. Abstract Adenocarcinoma of the esophagus and gastroesophageal junction is a common disease. This disease is significantly more prevalent in men, although the main underlying risk factor has an equal sex distribution. In locally advanced disease, multimodal therapy has been developed as the standard in the western world. Neoadjuvant chemoradiotherapy or perioperative chemotherapy using the FLOT regimen was established as the standard. Most recently, adjuvant immunotherapy after neoadjuvant chemoradiotherapy and surgery has been introduced into the multimodal therapy. Substantial sex-specific differences in outcome in multimodal therapy have been described in retrospective subgroup analysis. Further studies are warranted to dissect the sex-specific differences in these treatment regimens.
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Affiliation(s)
- Thomas Zander
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Gastrointestinal Cancer Group Cologne (GCGC), University of Cologne, 50937 Cologne, Germany
- Correspondence:
| | - Anna Dorothea Wagner
- Department of Oncology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), 1011 Lausanne, Switzerland;
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He W, Leng X, Mao T, Luo X, Zhou L, Yan J, Peng L, Fang Q, Liu G, Wei X, Wang K, Wang C, Zhang S, Zhang X, Shen X, Huang D, Yi H, Bei T, She X, Xiao W, Han Y. Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma. Oncologist 2022; 27:e18-e28. [PMID: 35305102 PMCID: PMC8842349 DOI: 10.1093/oncolo/oyab011] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 11/18/2021] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. METHODS In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. RESULTS Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03). CONCLUSIONS The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. CLINICAL TRIAL REGISTRATION NCT04177797.
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Affiliation(s)
- Wenwu He
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Xuefeng Leng
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Tianqin Mao
- School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Xi Luo
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Lingxiao Zhou
- Department of Endoscopy Center, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Jiaxin Yan
- Department of Pathology, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Lin Peng
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Qiang Fang
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Guangyuan Liu
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Xing Wei
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Kangning Wang
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Chenghao Wang
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Sha Zhang
- Department of Endoscopy Center, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Xudong Zhang
- Department of Drug Clinical Trial, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Xudong Shen
- The Medical Department, 3D Medicines Inc., Shanghai, People’s Republic of China
| | - Depei Huang
- The Medical Department, 3D Medicines Inc., Shanghai, People’s Republic of China
| | - Huan Yi
- The Medical Department, 3D Medicines Inc., Shanghai, People’s Republic of China
| | - Ting Bei
- The Medical Department, 3D Medicines Inc., Shanghai, People’s Republic of China
| | - Xueke She
- Shanghai Junshi Biosciences Co., Ltd, Shanghai, People’s Republic of China
| | - Wenguang Xiao
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
| | - Yongtao Han
- Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People’s Republic of China
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Jin Z, Shen J, Wang C, Chen D, Zhang B, Zhang J, Ajani JA, Bennouna J, Chao J, Yoon HH, Zhu H, Ruan Y, Zhu C, Xu A. Narrative review of pembrolizumab for the treatment of esophageal cancer: evidence and outlook. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1189. [PMID: 34430630 PMCID: PMC8350624 DOI: 10.21037/atm-21-2804] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 06/28/2021] [Indexed: 12/24/2022]
Abstract
Objective Based on the current evidence, review the efficacy and safety profile of pembrolizumab, along with its shortcomings, in an effort to define future research directions. Background The survival outcome of esophageal cancer (EC) is poor, especially in patients with advanced stage. Palliative surgery, chemotherapy, radiotherapy and chemoradiotherapy have limited efficacy in prolonging the survival time. Currently, immunotherapies, including adoptive cell therapy-based, antibody-based, and vaccine-based therapies, are attracting considerable attention. The mechanism of immunotherapy lies in the modification of immune response and prevention of immune escape. Immunomodulatory agents can block the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, thereby allowing lymphocytes to attack tumor cells. This class of drugs has the potential to treat a variety of tumors and may substantially improve overall survival (OS) in some patients. Multiple clinical trials have shown that pembrolizumab has good efficacy and safety, enhances the EC treatment paradigm, and has even become the first-line treatment of choice for patients with PD-L1-positive recurrent or metastatic EC. Methods We reviewed the results of clinical trials of pembrolizumab for EC and gastroesophageal cancer presented at Embase, PubMed, the American Society of Clinical Oncology (ASCO) annual meetings, and the Cochrane Central Register of Controlled Trials. Conclusions Pembrolizumab has good efficacy and tolerability profiles, and has emerged as a second-line option for the treatment of PD-L1-positive locally advanced or metastatic ESCC. Pembrolizumab has many promising applications, and further investigations into its mechanisms should be conducted.
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Affiliation(s)
- Zixian Jin
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Jianfei Shen
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Chunguo Wang
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Dong Chen
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Bo Zhang
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Jian Zhang
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Jaffer A Ajani
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jaafar Bennouna
- Department of Medical Oncology, University Hospital of Nantes, France.,Inserm, CRCINA, Université de Nantes, Nantes, France
| | - Joseph Chao
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Harry H Yoon
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
| | - Hongyu Zhu
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Yuhang Ruan
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Chengchu Zhu
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Anyi Xu
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.,Department of Emergency, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
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Shen D, Chen Q, Wu J, Li J, Tao K, Jiang Y. The safety and efficacy of neoadjuvant PD-1 inhibitor with chemotherapy for locally advanced esophageal squamous cell carcinoma. J Gastrointest Oncol 2021; 12:1-10. [PMID: 33708420 DOI: 10.21037/jgo-20-599] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background Neoadjuvant therapy followed by esophagectomy has been recognized as an effective treatment for locally advanced esophageal cancer, though still has a dismal prognosis. Antibodies against programmed death 1 (PD-1) protein improve survival in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with chemotherapy in second-line therapy. However, neoadjuvant PD-1 inhibitor combined with chemotherapy has not been tested in locally advanced ESCC. We conducted this study to evaluate the efficacy and safety of pd-1 inhibitor in neoadjuvant chemotherapy. Methods In this study, we administered 28 adults with untreated, surgically resectable locally advanced ESCC. PD-1 inhibitor with chemotherapy [albumin paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin with an area under the curve (AUC) of 5 on day 1] were administered every 3 weeks intravenously, and surgery was performed approximately 3-5 weeks after the second dose. The primary purpose of the study was to evaluate the feasibility and safety of this regimen. Results In all, 28 locally advanced ESCC patients were enrolled, 27 patients received surgery, 9 (33.3%) patients' postoperative pathological specimens suggested pCR, and 11 (40.7%) patients' primary tumor suggested complete response. Neoadjuvant PD-1 inhibitor with chemotherapy had an acceptable side-effect profile, 26 patients' tumors were completely resected (96.3% were R0). According to the RESIST v.1.1, the response in all 27 patients was evaluated by a computed tomography (CT) scan before surgery, showing 12 patients with complete response (CR), 12 with partial response (PR), and 3 with stable disease (SD). For surgical procedures, 15 (55.6%) patients underwent minimal invasive surgery, 4 (14.8%) underwent right transthoracic open esophagectomy, and 8 (29.6%) underwent hybrid approaches. Conclusions The novel treatment of PD-1 inhibitor with chemotherapy in the neoadjuvant setting for locally advanced ESCC produced satisfactory outcomes: an unprecedentedly high pCR rate for neoadjuvant chemotherapy, a high R0 resection rate, and a low-toxicity profile were achieved. The long-term efficiency of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.
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Affiliation(s)
- Dijian Shen
- Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China
| | - Qixun Chen
- Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China
| | - Jie Wu
- Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China
| | - Jianqiang Li
- Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China
| | - Kaiyi Tao
- Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China
| | - Youhua Jiang
- Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.,Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China
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