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Geng Y, Zhao J, Li Y, Li Y. Adjuvant treatment after neoadjuvant chemoradiotherapy and surgery in patients with esophageal squamous cell carcinoma: a real-world study. Ther Adv Med Oncol 2025; 17:17588359251316179. [PMID: 39957805 PMCID: PMC11829303 DOI: 10.1177/17588359251316179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 01/09/2025] [Indexed: 02/18/2025] Open
Abstract
Background Neoadjuvant chemoradiotherapy (NCRT) combined with surgery is the standard treatment option for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, whether adjuvant chemotherapy (AC) administered postoperatively has a survival benefit remains inconclusive. Objectives To investigate whether AC is necessary after NCRT and esophagectomy and determine which patients might benefit from it. Design A retrospective study. Methods This retrospective study examined patients with ESCC treated with NCRT followed by radical esophagectomy at three hospitals between March 2016 and December 2022. Patients were assigned into the adjuvant and non-adjuvant therapy groups based on whether they received postoperative AC, allowing the comparison of disease-free survival (DFS) and overall survival (OS) between the two groups. In addition, based on whether postoperative pathology indicated pathological complete response (pCR), patients were classified into the pCR and non-pCR populations, with DFS and OS separately analyzed for each subgroup. Results Overall, 218 eligible patients were enrolled. No significant advantage was found in DFS (p = 0.540) and OS (p = 0.058) between the adjuvant and non-adjuvant therapy groups. In the non-pCR population, the adjuvant therapy groups had a significant advantage in DFS (p = 0.046) and OS (p = 0.011) compared to the non-adjuvant therapy group. However, in the pCR population, no significant advantage was found in DFS (p = 0.490) and OS (p = 0.110) analyses between the adjuvant and non-adjuvant therapy groups. Conclusion In the real world, patients with ESCC who underwent NCRT combined with radical esophagectomy and whose postoperative pathology was pCR did not benefit from AC. However, AC significantly improved DFS and OS in patients whose postoperative pathology did not reach pCR.
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Affiliation(s)
- Yuxin Geng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Junfeng Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Ying Li
- Department of Respiratory Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yintao Li
- Department of Respiratory Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Huaiyin District, Jinan, Shandong 250000, China
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Zhao F, Wang Q, Han W, Maitudi W, Cao F, Zhang T, Chen X, Dong J, Gong L, Shang X, Jiang H, Zhang W, Pang Q, Xiao Z, Wang P, Tang P. Multi-Institutional Analysis of Survival and Recurrence Patterns of Different Pathological Regression Types After Neoadjuvant Chemoradiotherapy or Radiotherapy for Esophageal Squamous Cell Carcinoma. Cancer Med 2025; 14:e70676. [PMID: 39945301 PMCID: PMC11822455 DOI: 10.1002/cam4.70676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 01/27/2025] [Accepted: 01/31/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND The recurrence patterns of different types of pathologic regression of the primary tumor and lymph nodes in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (NCRT) are little known, especially in ypT0N+ patients. METHODS We included 582 patients with ESCC who had esophagectomy after NCRT or neoadjuvant radiotherapy (NRT) from 3 institutions. The patients were divided into 4 groups: ypT0N0, ypT0N+, ypT+N0, and ypT+N+ according to the type of pathological regression of the primary tumor and lymph nodes. Survival, recurrence pattern and timing, and potential prognostic factors were compared. RESULTS A total of 179 patients were classified as ypT0N0, 227 patients as ypT + N0, 45 patients as ypT0N+, and 131 patients as ypT + N+. The median follow-up was 31.7 months in all patients. The restricted mean survival time (RMST) of ypT0N0, ypT + N0, ypT0N+, and ypT + N+ patients decreased sequentially (70.64, 63.84, 55.93 and 39.96 months) and the recurrence rates increased sequentially (22.3%, 29.5%, 44.4% and 54.2%). Both the overall survival (OS) and recurrence-free survival (RFS) in the ypT0N+ group were significantly lower than those in the ypT0N0 group (HR: 2.226, p = 0.007; HR: 2.271, p = 0.003). The distant metastasis (DM) pattern in ypT0N+ was similar to that of ypT + N+, and higher than that of ypN0 (25.6% vs 14.3%, HR: 1.970, p = 0.040). CONCLUSIONS ESCC patients with various pathological regression types after receiving NCRT or NRT had significantly different survival rates. ypT0N+ patients had a lower survival rate and higher DM rate than ypT0N0 patients. For these lymph node-positive patients, adjuvant chemotherapy does not appear to improve their prognosis.
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Affiliation(s)
- Fangdong Zhao
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Qifeng Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of MedicineUniversity of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan ProvinceChengduChina
| | - Weiming Han
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Wubulaishan Maitudi
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Fuliang Cao
- Department of Endoscopy Diagnosis and TherapyTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Tian Zhang
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Xi Chen
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Jie Dong
- Department of Nutrition TherapyTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Lei Gong
- Department of Esophageal CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Xiaobin Shang
- Department of Esophageal CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Hongjing Jiang
- Department of Esophageal CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Wencheng Zhang
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Qingsong Pang
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Zefen Xiao
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Ping Wang
- Department of Radiation OncologyTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Peng Tang
- Department of Esophageal CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
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Liu D, Liu A, Guo L, Li Y, Li Y, Chi Y, Lin H, Yu J, Li M. Postoperative Adjuvant Therapy Benefits Non-pCR Patients Rather Than pCR Patients for Locally Advanced ESCC: A Multicenter Real-World Study. Thorac Cancer 2025; 16:e70021. [PMID: 39988453 PMCID: PMC11847616 DOI: 10.1111/1759-7714.70021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 02/04/2025] [Accepted: 02/08/2025] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND There is no unified standard in adjuvant therapy (AT) for patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant therapy and surgery. We evaluated the significance of AT for these patients and explored its influencing factors. METHODS ESCC patients who underwent neoadjuvant therapy and surgery from 2019 to 2022 at three centers were divided into AT (n = 227) and non-AT groups (n = 435). Baseline characteristics were balanced using propensity score matching (PSM). Primary endpoints were disease-free survival (DFS) and overall survival (OS), assessed using the Kaplan-Meier method. Subgroup analyses and univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. RESULTS The median follow-up period is 36 (2-72) months. After PSM, the total population had 1-, 2-, and 3-year OS rates of 71.3%, 66.0%, and 64.1%, respectively. There were no statistically significant differences in DFS (HR: 0.79; 95% CI: 0.55-1.14, p = 0.21) or OS (HR: 0.75; 95% CI: 0.49-1.13, p = 0.17) between AT and non-AT groups. Subgroup analysis revealed that non-pCR patients benefited from AT in DFS (p = 0.042) and OS (p = 0.033). Moreover, in non-pCR patients who received AT, BMI ≥ 21.5 kg/m2 and ypN0 were independent protective factors of DFS. ypN0 was an independent protective factor of OS. In terms of AT regimens, the Kaplan-Meier analysis revealed that adjuvant immunochemotherapy (AICT) provided superior survival benefits than adjuvant radiotherapy and adjuvant chemotherapy. CONCLUSIONS Postoperative AT benefited ESCC patients with non-pCR, while AICT may be a relatively better AT regimen in real-world data, which deserves further exploration.
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Affiliation(s)
- Defeng Liu
- Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Ao Liu
- Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Longxiang Guo
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
- Department of OncologyDongying People's HospitalDongyingChina
| | - Yi Li
- Department of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Yuanlin Li
- Department of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Yuxiang Chi
- Cheeloo College of MedicineShandong UniversityJinanChina
- Institute of Oncology, Shandong Provincial HospitalShandong UniversityJinanChina
| | - Haiqun Lin
- Department of Radiation OncologyThe Second Hospital of Shandong UniversityJinanChina
| | - Jinming Yu
- Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
| | - Minghuan Li
- Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital, Cheeloo College of MedicineShandong UniversityJinanChina
- Department of Radiation Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina
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Feng J, Wang L, Yang X, Chen Q. Adjuvant immunotherapy after neoadjuvant immunochemotherapy and esophagectomy for esophageal squamous cell carcinoma: a real-world study. Front Immunol 2024; 15:1456193. [PMID: 39742260 PMCID: PMC11685212 DOI: 10.3389/fimmu.2024.1456193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 11/25/2024] [Indexed: 01/03/2025] Open
Abstract
Background The role of immunotherapy in the adjuvant setting seems promising in recent years. As per the findings of the CheckMate 577 trial, patients with esophageal cancer (EC) who had neoadjuvant chemoradiation with residual pathologic disease should be considered adjuvant immunotherapy (AIT). However, it is unknown if individuals with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant immunochemotherapy (NICT) followed by radical surgery also require AIT. Methods A retrospective analysis was performed on the data from patients who underwent NICT and radical surgery for ESCC between 2019 and 2020. To compare disease-free survival (DFS) and overall survival (OS), Kaplan-Meier survival curves were produced. To determine the parameters linked to DFS and OS, a Cox model using hazard ratios (HRs) was completed. Results Among the 292 eligible patients, 215 cases with a mean age of 63.3 ± 6.8 years, including 190 (88.4%) men and 25 (11.6%) women, were finally recruited. The percentage of R0 resection was 98.3%. After NICT, 65 (30.2%) patients achieved pathological complete response. AIT was given to 78 (36.3%) patients following radical resection. For all patients, the 3-year DFS and OS were 62.3% and 74.0%, respectively. In terms of 3-year DFS (61.5% vs. 62.8%, P=0.984) or OS (76.9% vs. 72.3%, P=0.384), no statistically significant difference was found between patients with and without AIT. AIT significantly improved survival in patients with ypT+N+ (DFS: 23.9% vs. 38.5%, P=0.036; OS: 37.0% vs. 61.5%, P=0.010), but not in those with ypT0N0 or ypT+N0. It was found that AIT was related to both DFS (HR: 0.297; P<0.001) and OS (HR: 0.321; P=0.001) in patients with ypT+N+. Conclusion In ypT+N+ ESCC patients, AIT after NICT followed by radical surgery reduces the recurrence and death, thereby improving the DFS and OS. Randomized controlled trials ought to be conducted to further assess the results of this retrospective investigation.
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Affiliation(s)
- Jifeng Feng
- Department of Thoracic Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus) of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou, China
| | - Liang Wang
- Department of Thoracic Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Xun Yang
- Department of Thoracic Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Qixun Chen
- Department of Thoracic Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
- Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus) of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou, China
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Pei S, Huang JQ, Liang HW, Liu Y, Chen L, Yu BB, Huang W, Pan XB. Adjuvant treatment patterns for pT3N0M0 esophageal cancer undergoing surgery. Dis Esophagus 2024; 37:doae026. [PMID: 38553783 DOI: 10.1093/dote/doae026] [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: 12/25/2023] [Revised: 02/17/2024] [Accepted: 03/12/2024] [Indexed: 08/02/2024]
Abstract
To assess adjuvant treatment patterns on survival in patients with pT3N0M0 esophageal cancer who underwent esophagectomy without neoadjuvant chemoradiotherapy. Stage pT3N0M0 esophageal cancer patients were assessed between 2000 and 2020 from the Surveillance, Epidemiology, and End Results databases. Kaplan-Meier analysis was used to compare overall survival (OS) among various treatment patterns. We identified 445 patients: 252 (56.6%) received surgery alone, 85 (19.1%) received surgery+chemoradiotherapy, 80 (18.0%) underwent surgery+chemotherapy, and 28 (6.3%) received surgery+ radiotherapy. For squamous cell carcinoma, surgery+chemoradiotherapy ([hazard ratio] HR = 1.04, 95% confidence interval (CI): 0.65-1.66; P = 0.873), surgery+chemotherapy (HR = 0.72, 95% CI: 0.42-1.22; P = 0.221), and surgery+radiotherapy (HR = 1.33, 95% CI: 0.74-2.39; P = 0.341) had similar OS compared to surgery alone. For adenocarcinoma, surgery+chemoradiotherapy (HR = 0.51, 95% CI: 0.36-0.74; P < 0.001) and surgery+chemotherapy (HR = 0.61, 95% CI: 0.42-0.87; P = 0.006) had better OS compared to surgery alone. However, surgery+radiotherapy had a comparable OS (HR = 0.81, 95% CI: 0.44-1.49; P = 0.495).Adjuvant treatments did not improve survival in stage pT3N0M0 esophageal squamous cell carcinoma patients. In contrast, adjuvant chemoradiotherapy and chemotherapy were recommended for esophageal adenocarcinoma patients.
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Affiliation(s)
- Su Pei
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jiang-Qiong Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Huan-Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Long Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Bin-Bin Yu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Wei Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xin-Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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Tang JM, Huang SJ, Chen QB, Wu HS, Qiao GB. Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity score-matched analysis. World J Gastrointest Surg 2024; 16:1537-1547. [PMID: 38983355 PMCID: PMC11230019 DOI: 10.4240/wjgs.v16.i6.1537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 04/29/2024] [Accepted: 05/16/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma (ESCC) patients remained debatable. AIM To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery. METHODS In this retrospective, propensity score-matched study, we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019. Patients who underwent neoadjuvant therapy were excluded. We collected patients' clinicopathological features and information regarding lymph nodes, including the total number of resected lymph nodes (NRLN), and pathologically diagnosed positive lymph nodes (RPLN). SPSS and R software were used for statistical analysis. RESULTS Among the included 1042 patients, two cohorts: ≤ 21 (n = 664) and > 21 NRLN (n = 378) were identified. The final prognostic model included four variables: T stage, N, venous thrombus, and the number of removed lymph nodes. Among them, NRLN > 21 was determined as an independent prognosticator after surgery for esophageal cancer (hazards regression = 0.66, 95% confidence interval: 0.50-0.87, P = 0.004). A nomogram was created based on the regression coefficients of the variables in the final model. In the training cohort, the predictive model displayed an uncorrected five-year overall survival C-index of 0.659, with a bootstrap-corrected C-index of 0.654. In the subgroup analysis, adjuvant chemotherapy was beneficial in the subgroup with NRLN > 21 and RPLN ≤ 0.16 and NRLN ≤ 21 and RPLN > 0.16. CONCLUSION NRLN > 21 was an independent prognostic factor after ESCC surgery. The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.
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Affiliation(s)
- Ji-Ming Tang
- Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangzhou 510080, Guangdong Province, China
| | - Shu-Jie Huang
- Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangzhou 510080, Guangdong Province, China
| | - Qi-Bin Chen
- Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangzhou 510080, Guangdong Province, China
| | - Han-Sheng Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Gui-Bin Qiao
- Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangzhou 510080, Guangdong Province, China
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Creden S, Groth SS. Commentary: Making the grade: Prognostic, therapeutic, and staging implications of tumor differentiation in esophageal adenocarcinoma. J Thorac Cardiovasc Surg 2024; 167:1953-1954. [PMID: 37838335 DOI: 10.1016/j.jtcvs.2023.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/16/2023]
Affiliation(s)
- Samuel Creden
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex
| | - Shawn S Groth
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex.
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West MA, Rahman S, Jack S, Grocott MP, Levett DZ, the Perioperative Exercise Testing and Training Society (POETTS), Rashid Y, Griffiths J, Ezra M, Ayres L, Neville-Webbe H, Javed MS, Shrotri M, Khan I, Whitmore D, Prabhu P, Timbrell D, Allen S, Packham AO, Sharpe D, Anderson H, Minto G, McAleer S, McPhail S, Alasmar M, Hartley RA, Sultan J, Grace B, Underwood TJ, Byrne J, Noble F, Kelly J, Ansell G, Edwards M. Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study. BJA OPEN 2024; 10:100289. [PMID: 38947220 PMCID: PMC11214286 DOI: 10.1016/j.bjao.2024.100289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 05/01/2024] [Indexed: 07/02/2024]
Abstract
Background Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration NCT03637647.
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Affiliation(s)
- Malcolm A. West
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
| | - Saqib Rahman
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Sandy Jack
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Michael P.W. Grocott
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Denny Z.H. Levett
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - the Perioperative Exercise Testing and Training Society (POETTS)
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Countess of Chester Hospital NHS Foundation Trust, Chester, UK
- Department of Anaesthetics, The Royal Surrey Foundation NHS Trust, Guildford, UK
- Anaesthetic Department, Frimley Park Hospital, Frimley Health NHS Foundation Trust, UK
- Department of General Surgery, The Royal Surrey NHS Foundation Trust Hospital, Minimal Access Therapy Training Unit (MATTU), Guildford, UK
- Department of Anaesthesia, University Hospitals of Leicester NHS Trust, Leicester, UK
- Department of Gastro-Intestinal Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
- Emergency Medical Retrieval and Transfer Service, Cymru, Joint Hospital Group (Southwest), UK
- Institute of Naval Medicine, Alverstoke, UK
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Yasir Rashid
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - John Griffiths
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Martin Ezra
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Lyndsay Ayres
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Helen Neville-Webbe
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Muhammad Shafiq Javed
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Milind Shrotri
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Iftikhar Khan
- Department of General Surgery, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - David Whitmore
- Departments of Anaesthesia and Critical Care, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Countess of Chester Hospital NHS Foundation Trust, Chester, UK
| | - Pradeep Prabhu
- Department of Anaesthetics, The Royal Surrey Foundation NHS Trust, Guildford, UK
| | - David Timbrell
- Department of Anaesthetics, The Royal Surrey Foundation NHS Trust, Guildford, UK
- Anaesthetic Department, Frimley Park Hospital, Frimley Health NHS Foundation Trust, UK
| | - Sophie Allen
- Department of General Surgery, The Royal Surrey NHS Foundation Trust Hospital, Minimal Access Therapy Training Unit (MATTU), Guildford, UK
| | - Andrew O. Packham
- Department of Anaesthesia, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - David Sharpe
- Department of Gastro-Intestinal Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Helen Anderson
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Gary Minto
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Samuel McAleer
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
- Emergency Medical Retrieval and Transfer Service, Cymru, Joint Hospital Group (Southwest), UK
| | - Stuart McPhail
- Directorate of Anaesthesia, University Hospitals Plymouth NHS Trust, Plymouth, UK
- Institute of Naval Medicine, Alverstoke, UK
| | - Mohamed Alasmar
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
| | - Robert A. Hartley
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
| | - Javed Sultan
- Department of General Surgery, The Royal Surrey NHS Foundation Trust Hospital, Minimal Access Therapy Training Unit (MATTU), Guildford, UK
- Salford Royal NHS Foundation Trust, Salford Royal, Salford, UK
- Division of Cancer Sciences, School of Medical Sciences, University of Manchester, UK
| | - Ben Grace
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Timothy J. Underwood
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - James Byrne
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Fergus Noble
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Jamie Kelly
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Gillian Ansell
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
| | - Mark Edwards
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
- Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- University Hospitals Southampton, Department of Surgery, Southampton, UK
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9
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Gao X, Overtoom HCG, Eyck BM, Huang SH, Nieboer D, van der Sluis PC, Lagarde SM, Wijnhoven BPL, Chao YK, van Lanschot JJB. Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis. Br J Surg 2024; 111:znae083. [PMID: 38721902 DOI: 10.1093/bjs/znae083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 02/23/2024] [Accepted: 03/05/2024] [Indexed: 05/15/2024]
Abstract
OBJECTIVE Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.
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Affiliation(s)
- Xing Gao
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
- Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Hidde C G Overtoom
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Ben M Eyck
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Shi-Han Huang
- Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Daan Nieboer
- Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Sjoerd M Lagarde
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Yin-Kai Chao
- Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan, Taiwan
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10
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Liu G, Hu B, Chen T, Zhang X, Tang Y, Chen Q, Shi H. Recurrence timing and patterns incorporating lymph node status after neoadjuvant chemoradiotherapy plus esophagectomy for esophageal squamous cell carcinoma. Front Oncol 2024; 14:1310073. [PMID: 38511145 PMCID: PMC10951093 DOI: 10.3389/fonc.2024.1310073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 02/05/2024] [Indexed: 03/22/2024] Open
Abstract
Purpose About 40% of esophageal squamous cell carcinoma (ESCC) patients experienced recurrence after neoadjuvant chemoradiotherapy (nCRT) plus esophagectomy. While limited information was available on recurrence risk stratification in ESCC after neoadjuvant treatment. Our previous study showed ypN status was a reliable tool to differentiate and predict the prognosis in the recurrent population. Here, we evaluated recurrence timing and patterns in ESCC patients, taking into consideration lymph node status after nCRT. Materials and methods A total of 309 ESCC patients treated with nCRT plus esophagectomy between 2018 and 2021 were enrolled in this observational cohort study. Lymph node status was recorded by the pathologist according to the surgical specimens. We retrospectively investigated the timing and patterns of recurrence and the prognoses in ESCC patients, taking into consideration lymph node status after nCRT. Results After nCRT plus surgery in ESCC patients, lymph node metastasis was associated with unfavorable clinicopathological factors and high risks of recurrence. In the recurrent subgroup, ypN+ patients experienced earlier recurrence, especially for locoregional recurrence within the first year. Moreover, ypN+ patients had poorer prognosis. However, the recurrence patterns in the ypN- and ypN+ groups were similar. Besides, there were no significant differences in surgery to recurrence, recurrence to death, or overall survival among patients with locoregional or distant recurrence for overall patients and within ypN- or ypN+ groups. Conclusions Lymph node metastasis was correlated with unfavorable clinicopathological factors and high risks of recurrence. Despite a similar recurrence pattern in the recurrent subgroup between the ypN- and ypN+ groups, ypN+ patients exhibited earlier recurrence and a worse prognosis.
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Affiliation(s)
- Guihong Liu
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Binbin Hu
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tao Chen
- Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xin Zhang
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yu Tang
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qian Chen
- Center of Biostatistics, Design, Measurement and Evaluation, Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Huashan Shi
- Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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11
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Worrell SG, Goodman KA, Altorki NK, Ashman JB, Crabtree TD, Dorth J, Firestone S, Harpole DH, Hofstetter WL, Hong TS, Kissoon K, Ku GY, Molena D, Tepper JE, Watson TJ, Williams T, Willett C. The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction. Pract Radiat Oncol 2024; 14:28-46. [PMID: 37921736 DOI: 10.1016/j.prro.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 11/04/2023]
Abstract
Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.
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Affiliation(s)
- Stephanie G Worrell
- Section of Thoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Nasser K Altorki
- Division of Thoracic Surgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
| | | | - Traves D Crabtree
- Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | | | - David H Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Wayne L Hofstetter
- Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Geoffrey Y Ku
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniela Molena
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joel E Tepper
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Thomas J Watson
- Thoracic Surgery Group, Beaumont Health, Royal Oak, Michigan
| | - Terence Williams
- Department of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Christopher Willett
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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12
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Clements HA, Underwood TJ, Petty RD. Total neoadjuvant therapy in oesophageal and gastro-oesophageal junctional adenocarcinoma. Br J Cancer 2024; 130:9-18. [PMID: 37898721 PMCID: PMC10781745 DOI: 10.1038/s41416-023-02458-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 09/07/2023] [Accepted: 09/28/2023] [Indexed: 10/30/2023] Open
Abstract
Adenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery. In this review, we discuss the current evidence for total neoadjuvant therapy and options for assessment of treatment response.
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Affiliation(s)
- Hollie A Clements
- Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
| | - Tim J Underwood
- School of Cancer Sciences, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Russell D Petty
- Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
- Tayside Cancer Centre, Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK
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13
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Worrell SG, Goodman KA, Altorki NK, Ashman JB, Crabtree TD, Dorth J, Firestone S, Harpole DH, Hofstetter WL, Hong TS, Kissoon K, Ku GY, Molena D, Tepper JE, Watson TJ, Williams T, Willett C. The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction. Ann Thorac Surg 2024; 117:15-32. [PMID: 37921794 DOI: 10.1016/j.athoracsur.2023.09.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/23/2023] [Accepted: 09/05/2023] [Indexed: 11/04/2023]
Abstract
Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.
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Affiliation(s)
- Stephanie G Worrell
- Section of Thoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Nasser K Altorki
- Division of Thoracic Surgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
| | | | - Traves D Crabtree
- Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | | | - David H Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Wayne L Hofstetter
- Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Geoffrey Y Ku
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniela Molena
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joel E Tepper
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Thomas J Watson
- Thoracic Surgery Group, Beaumont Health, Royal Oak, Michigan
| | - Terence Williams
- Department of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Christopher Willett
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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14
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Teranishi R, Makino T, Tanaka K, Yamashita K, Saito T, Yamamoto K, Takahashi T, Kurokawa Y, Motoori M, Yamasaki M, Nakajima K, Eguchi H, Doki Y. Long-term survival and prognostic factors associated with curative conversion surgery for ct4b esophageal squamous cell carcinoma: Analysis of 200 consecutive cases. Surgery 2023; 174:558-566. [PMID: 37385868 DOI: 10.1016/j.surg.2023.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 04/27/2023] [Accepted: 05/24/2023] [Indexed: 07/01/2023]
Abstract
BACKGROUND The optimal treatment strategy for cT4b esophageal cancer has not been established yet. Although curative surgery is sometimes performed after induction treatments, the prognostic factor of cT4b esophageal cancer cases who underwent R0 resection remains unknown. METHODS A total of 200 patients with cT4b esophageal cancer who underwent R0 resection after induction treatments between 2001 and 2020 in our institute were included in the present study. The relationship between clinicopathological factors and patient survival is evaluated to identify useful prognostic factors. RESULTS The median and 2-year overall survival were 40.1 months and 62.8%, respectively. Disease recurrence occurred in 98 (49%) patients after surgery. Compared to induction chemotherapy alone, chemoradiation-based induction treatments were associated with decreased locoregional recurrence (34.0% vs 60.8%, P = .0077) but increased pulmonary metastases (27.7% vs 9.8%, P = .0210) and dissemination (19.1% vs 3.9%, P = .0139) after surgery. Multivariate analysis of overall survival identified the preoperative C-reactive protein/albumin ratio (hazard ratio 1.7957, P = .0031), response to induction treatments (hazard ratio 2.9663, P = .0009), postoperative pneumonia (hazard ratio 2.3784, P = .0010), and pN (2-3) (hazard ratio 1.5693, P = .0355) as independent prognostic factors. Preoperative C-reactive protein/albumin ratio (hazard ratio 1.6760, P = .0068) and postoperative pneumonia (hazard ratio 1.8365, P = .0200) were also independent prognostic factors for recurrence-free survival. CONCLUSION Curative surgery after induction therapy for cT4b esophageal cancer achieved favorable survival. Preoperative C-reactive protein/albumin ratio, postoperative pneumonia, response to induction treatments, and pN were useful prognostic factors.
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Affiliation(s)
- Ryugo Teranishi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan.
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Kotaro Yamashita
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Takuro Saito
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Kazuyoshi Yamamoto
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | | | - Makoto Yamasaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
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15
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Zhou G, Yin M, He W, Ma Y, Li C, Li Z, Li X, Wang S, Wu G. Transarterial infusion chemotherapy for advanced esophageal cancer with airway stenosis. Front Oncol 2023; 13:1238287. [PMID: 37727208 PMCID: PMC10505802 DOI: 10.3389/fonc.2023.1238287] [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: 06/11/2023] [Accepted: 08/02/2023] [Indexed: 09/21/2023] Open
Abstract
Purpose This study aimed to investigate the safety and efficacy of transarterial infusion chemotherapy for the treatment of esophageal cancer with airway stenosis. Methods Data of patients with advanced esophageal cancer complicated with airway stenosis treated with transarterial infusion chemotherapy were retrospectively analyzed. Dyspnea, clinical efficacy and adverse reactions were evaluated. Results Of these patients, 27 had grade II preoperative dyspnea, and 31 had grade III preoperative dyspnea, 26 had grade I postoperative dyspnea, 25 had grade II postoperative dyspnea, and 7 had grade III postoperative dyspnea. Among 3 patients with left main bronchial stenosis and atelectasis, 2 had complete remission after transarterial infusion chemotherapy, and 1 demonstrated partial remission. After treatment, complete response, partial response, and stable disease were observed in 7, 34, and 17 cases, respectively. Total objective effective rate and disease control rate were 70.6% (41/58) and 100.0%, respectively. During follow up, 24 patients died of organ failure, and 17 patients died of tumor-related respiratory failure. Seven patients died of gastrointestinal bleeding, 1 patient died of myocardial infarction, and 9 patients survived. Conclusions Transarterial infusion chemotherapy is safe and effective for the treatment of advanced esophageal cancer with airway stenosis.
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Affiliation(s)
- Gang Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Meipan Yin
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei He
- Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yaozhen Ma
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunxia Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhen Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaobing Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuai Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Gang Wu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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16
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Raja S, Rice TW, Lu M, Semple ME, Blackstone EH, Murthy SC, Ahmad U, McNamara M, Toth AJ, Hemant I, Worldwide Esophageal Cancer Collaboration Investigators. Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer: Who Needs It? Ann Surg 2023; 278:e240-e249. [PMID: 35997269 PMCID: PMC10955553 DOI: 10.1097/sla.0000000000005679] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy. BACKGROUND Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown. METHODS From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality. RESULTS Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3-4 patients without nodal involvement and those with ypN2-3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1-2N0 cancers had either no benefit or a detriment in survival. CONCLUSIONS Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting.
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Affiliation(s)
- Siva Raja
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Thomas W. Rice
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Min Lu
- Department of Public Health Sciences, Division of Biostatistics, University of Miami, Miami, Florida
| | - Marie E. Semple
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Eugene H. Blackstone
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Sudish C. Murthy
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Usman Ahmad
- Heart, Vascular, and Thoracic Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Michael McNamara
- Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio
| | - Andrew J. Toth
- Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Ishwaran Hemant
- Department of Public Health Sciences, Division of Biostatistics, University of Miami, Miami, Florida
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Zhang Y, Zhang L, Li B, Ye T, Zhang Y, Yu Y, Ma Y, Sun Y, Xiang J, Li Y, Chen H. Machine learning to predict occult metastatic lymph nodes along the recurrent laryngeal nerves in thoracic esophageal squamous cell carcinoma. BMC Cancer 2023; 23:197. [PMID: 36864444 PMCID: PMC9979471 DOI: 10.1186/s12885-023-10670-3] [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: 08/31/2022] [Accepted: 02/22/2023] [Indexed: 03/04/2023] Open
Abstract
PURPOSE Esophageal squamous cell carcinoma (ESCC) metastasizes in an unpredictable fashion to adjacent lymph nodes, including those along the recurrent laryngeal nerves (RLNs). This study is to apply machine learning (ML) for prediction of RLN node metastasis in ESCC. METHODS The dataset contained 3352 surgically treated ESCC patients whose RLN lymph nodes were removed and pathologically evaluated. Using their baseline and pathological features, ML models were established to predict RLN node metastasis on each side with or without the node status of the contralateral side. Models were trained to achieve at least 90% negative predictive value (NPV) in fivefold cross-validation. The importance of each feature was measured by the permutation score. RESULTS Tumor metastases were found in 17.0% RLN lymph nodes on the right and 10.8% on the left. In both tasks, the performance of each model was comparable, with a mean area under the curve ranging from 0.731 to 0.739 (without contralateral RLN node status) and from 0.744 to 0.748 (with contralateral status). All models showed approximately 90% NPV scores, suggesting proper generalizability. The pathology status of chest paraesophgeal nodes and tumor depth had the highest impacts on the risk of RLN node metastasis in both models. CONCLUSION This study demonstrated the feasibility of ML in predicting RLN node metastasis in ESCC. These models may potentially be used intraoperatively to spare RLN node dissection in low-risk patients, thereby minimizing adverse events associated with RLN injuries.
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Affiliation(s)
- Yiliang Zhang
- grid.452404.30000 0004 1808 0942Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Institute of Thoracic Oncology, Fudan University, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Longfu Zhang
- Department of Pulmonary Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031 China
| | - Bin Li
- grid.452404.30000 0004 1808 0942Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Institute of Thoracic Oncology, Fudan University, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ting Ye
- grid.452404.30000 0004 1808 0942Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Institute of Thoracic Oncology, Fudan University, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yang Zhang
- grid.452404.30000 0004 1808 0942Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Institute of Thoracic Oncology, Fudan University, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yongfu Yu
- grid.8547.e0000 0001 0125 2443Department of Biostatistics, School of Public Health, and The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Yuan Ma
- grid.510934.a0000 0005 0398 4153Chinese Institute for Brain Research, Beijing, China
| | - Yihua Sun
- grid.452404.30000 0004 1808 0942Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Institute of Thoracic Oncology, Fudan University, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiaqing Xiang
- grid.452404.30000 0004 1808 0942Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Institute of Thoracic Oncology, Fudan University, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yike Li
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN, 37232, USA.
| | - Haiquan Chen
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. .,Institute of Thoracic Oncology, Fudan University, Shanghai, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Chufal KS, Ahmad I, Bajpai R, Miller AA, Chowdhary RL, Makker J, Batra U, Nathany S, Sharief MI, Umesh P, Sharma M, Amrith P, Pahuja AK, Sethi J, Antony V, Gairola M. Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort. Br J Radiol 2023; 96:20220413. [PMID: 36541255 PMCID: PMC9975378 DOI: 10.1259/bjr.20220413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 11/07/2022] [Accepted: 12/08/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). METHODS Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. RESULTS The median OS was 71.4 months (interquartile range: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89-0.98); 0.94 (0.89-0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09-0.53); 0.30 (0.12-0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01-1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08-6.57)] and adventitial involvement [2.54 (1.36-4.72)] also influenced OS, while involved margins [3.12 (1.24-7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44-0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57-0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. CONCLUSION NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. ADVANCES IN KNOWLEDGE The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.
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Affiliation(s)
- Kundan Singh Chufal
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Irfan Ahmad
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Ram Bajpai
- Centre for Prognosis Research, School of Medicine, Keele University, Staffordshire, United Kingdom
| | - Alexis Andrew Miller
- Department of Radiation Oncology, Illawara Cancer Care Center, Wollongong, New South Wales, Australia
| | - Rahul Lal Chowdhary
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | | | - Ullas Batra
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Shrinidhi Nathany
- Department of Molecular Diagnostics, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Muhammed Ismail Sharief
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Preetha Umesh
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Mansi Sharma
- Centre for Prognosis Research, School of Medicine, Keele University, Staffordshire, United Kingdom
| | - Patel Amrith
- Centre for Prognosis Research, School of Medicine, Keele University, Staffordshire, United Kingdom
| | - Anjali Kakria Pahuja
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Jaskaran Sethi
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Varghese Antony
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Munish Gairola
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
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Li X, Liu S, Jin L, Ma Y, Liu T. NOD2 inhibits the proliferation of esophageal adenocarcinoma cells through autophagy. J Cancer Res Clin Oncol 2023; 149:639-652. [PMID: 36316517 PMCID: PMC9931811 DOI: 10.1007/s00432-022-04354-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 09/07/2022] [Indexed: 02/16/2023]
Abstract
AIM To study the regulatory mechanism of NOD2 in the inhibition of esophageal adenocarcinoma cell proliferation. METHODS Cell experiments: after confirming the decrease in NOD2 expression in esophageal adenocarcinoma, we overexpressed NOD2 in esophageal adenocarcinoma cells via lentivirus, compared and verified the changes in esophageal adenocarcinoma cell proliferation before and after NOD2 overexpression, and compared the overexpression group with the control group by mRNA sequencing to identify pathways that may affect cell proliferation. Then, the autophagy level of multiple groups were assessed, and the results were verified by rescue experiments. In vivo experiments: we administered esophageal adenocarcinoma cells to nude mice to form tumors under their skin and then injected the tumors with NOD2 overexpression lentivirus and negative control lentivirus. After a period of time, the growth curve of the tumor was generated, and the tumor was removed to generate sections. Ki67 was labeled with immunohistochemistry to verify cell proliferation, and the protein was extracted from the tissue to detect the molecular indices of the corresponding pathway. RESULTS Upregulation of NOD2 expression inhibited the proliferation of esophageal adenocarcinoma cells. Upregulation of NOD2 expression increased the autophagy level of esophageal adenocarcinoma cells via ATG16L1. After ATG16L1 was inhibited, NOD2 had no significant effect on autophagy and proliferation of esophageal adenocarcinoma cells. Enhanced autophagy in esophageal adenocarcinoma cell lines inhibited cell proliferation. In vivo, the upregulation of NOD2 expression improved the autophagy level of tumor tissue and inhibited cells proliferation. CONCLUSION NOD2 can activate autophagy in esophageal adenocarcinoma cells through the ATG16L1 pathway and inhibit cell proliferation.
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Affiliation(s)
- Xiaozhi Li
- Emergency Department, The Third XiangYa Hospital, Central South University, Changsha, 410013, Hunan, China
| | - Suo Liu
- Cardiothoracic Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Longyu Jin
- Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, 410013, Hunan, China.
| | - Yuchao Ma
- Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, 410013, Hunan, China.
| | - Tao Liu
- Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, 410013, Hunan, China
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20
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Li K, Wang K, Wei X, Leng X, Fang Q. Optimal discharge planning for esophagectomy patients with enhanced recovery after surgery: Recommendations. Front Surg 2023; 10:1112675. [PMID: 36793310 PMCID: PMC9922840 DOI: 10.3389/fsurg.2023.1112675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/10/2023] [Indexed: 01/31/2023] Open
Abstract
Background Studies have suggested that the postoperative length of stay (PLOS) of esophagectomy patients under the enhanced recovery after surgery (ERAS) pathway should be >10 days as against the previously recommended 7 days. We investigated the distribution and influencing factors of PLOS in the ERAS pathway in order to recommend an optimal planned discharge time. Methods This was a single-center retrospective study of 449 patients with thoracic esophageal carcinoma who underwent esophagectomy and perioperative ERAS between January 2013 and April 2021. We established a database to prospectively document the causes of delayed discharge. Results The mean and median PLOS were 10.2 days and 8.0 days (range: 5-97), respectively. Patients were divided into four groups: group A (PLOS ≤ 7 days), 179 patients (39.9%); group B (8 ≤ PLOS ≤ 10 days), 152 (33.9%); group C (11 ≤ PLOS ≤ 14 days), 68 (15.1%); group D (PLOS > 14 days), 50 patients (11.1%). The main cause of prolonged PLOS in group B was minor complications (prolonged chest drainage, pulmonary infection, recurrent laryngeal nerve injury). Severely prolonged PLOS in groups C and D were due to major complications and comorbidities. On multivariable logistic regression analysis, open surgery, surgical duration >240 min, age >64 years, surgical complication grade >2, and critical comorbidities were identified as risk factors for delayed discharge. Conclusions The optimal planned discharge time for patients undergoing esophagectomy with ERAS should be 7-10 days with a 4-day discharge observation window. Patients at risk of delayed discharge should be managed adopting PLOS prediction.
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21
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da Costa WL, Gu X, Farjah F, Groth SS, Burt BM, Ripley RT, Massarweh NN. Clinical Understaging, Treatment Response, and Survival Among Esophageal Adenocarcinoma Patients. J Surg Res 2022; 279:256-264. [PMID: 35797753 DOI: 10.1016/j.jss.2022.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 05/09/2022] [Accepted: 06/04/2022] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.
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22
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Hu SY, Gao HJ, Jiang ZH, Shi GD, Wang HF, Ai JS, Wei YC. A Recurrence Predictive Model for Node-negative Esophageal Squamous Cell Carcinoma After Upfront Esophagectomy. Semin Thorac Cardiovasc Surg 2022; 36:102-111. [PMID: 36089122 DOI: 10.1053/j.semtcvs.2022.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 08/31/2022] [Indexed: 11/11/2022]
Abstract
The prognosis for pathologically node-negative (pN0) esophageal squamous cell carcinoma (ESCC) with surgery alone remains poor. We aimed to develop a model for a more precise prediction of recurrence, which will allow personalized management for pN0 ESCC after upfront complete resection. Clinical and pathological records of patients with completely resected pT1-3N0M0 ESCC were retrospectively analyzed between January 2014 and December 2019. A nomogram for the prediction of recurrence was established based on the Cox regression analysis and evaluated by C-index, AUC, and calibration curves. The model was further validated using bootstrap resampling and k-fold cross-validation and compared with the 8th edition of the AJCC TNM staging system using Td-ROC, NRI, IDI, and DCA. Two-hundred-and seventy cases were included in this study. The median follow-up was 45 months. Distant and/or loco-regional recurrences were noted in 89 (33.0%) patients. The predictive model revealed pT-category, differentiation, perineural invasion, examined lymph nodes (ELN), and prognostic nutritional index (PNI) as independent risk factors for recurrence, with a c-index of 0.725 in the bootstrapping cohort. Td-ROC, NRI, and IDI showed a better predictive ability than the AJCC 8th TNM staging system. Based on this model, patients in the low-risk group had a significantly lower recurrence incidence than those in the high-risk group (p < .001). The predictive model developed in this study may facilitate the precise prediction of recurrences for pN0 ESCC after upfront surgery. Stratifying management of those patients might bring significantly better survival benefits.
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Affiliation(s)
- Shi-Yu Hu
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui-Jiang Gao
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhi-Hui Jiang
- Department of General Surgery, Qingdao women and Children's Hospital, Qingdao, China
| | - Guo-Dong Shi
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hua-Feng Wang
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jiang-Shan Ai
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yu-Cheng Wei
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
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Li X, Luan S, Yang Y, Zhou J, Shang Q, Fang P, Xiao X, Zhang H, Yuan Y. Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery. Cancers (Basel) 2022; 14:cancers14153721. [PMID: 35954385 PMCID: PMC9367572 DOI: 10.3390/cancers14153721] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/18/2022] [Accepted: 07/27/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846−1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436−2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.
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Adjuvant Chemotherapy for Pathological Node-Positive Disease in Squamous Cell Carcinoma of the Esophagus after Neoadjuvant Chemoradiotherapy Plus Surgery. J Pers Med 2022; 12:jpm12081252. [PMID: 36013201 PMCID: PMC9409802 DOI: 10.3390/jpm12081252] [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: 06/30/2022] [Revised: 07/19/2022] [Accepted: 07/27/2022] [Indexed: 11/17/2022] Open
Abstract
Purpose: The purpose of the present study is to determine the impact on survival using adjuvant chemotherapy on patients with locally advanced esophageal cancer. Materials and Methods: From 2007 to 2016, we enrolled 127 locally advanced esophageal squamous cell carcinoma patients treated with combined neoadjuvant chemoradiotherapy (nCRT) and surgery. For patients with the pathological residual primary disease (pT+) and/or residual node disease (pN+) after nCRT, adjuvant chemotherapy was also given after consideration of the toxicity of nCRT, patient performance, and/or comorbidity. The regimen of adjuvant chemotherapy was cisplatin 20 mg/m2/day and 5-fluorouracil 800 mg/m2/day on days 1 through 4 and 22 through 25. The primary endpoint was overall survival (OS). Results: From a total of 127 patients, 26 of them (20.5%) received adjuvant chemotherapy. In the multivariate analysis, pN+ diseases were independently associated with poor OS (hazard ratio (HR): 4.117, 95% confidence interval (CI): 1.366–12.404; p = 0.012). For those with pN+ diseases, their 5-year OS was 36.4% in the follow-up arm compared with 45.8% in the adjuvant chemotherapy arm (p = 0.094). Conclusions: Pathologic node-positive disease is associated with poor OS in locally advanced esophagus cancer patients after combined treatments with nCRT and surgery. Adjuvant chemotherapy appeared to have improved OS in pathologic node-positive diseases.
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da Costa WL, Camp ER, Thrift AP. Sociodemographic and Facility-Related Disparities in the Delivery of Guideline-Concordant Therapy Among Patients With Esophageal Adenocarcinoma. JCO Oncol Pract 2022; 18:e1181-e1197. [DOI: 10.1200/op.21.00912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE: Evidence on health disparities among patients treated with multimodality therapy protocols is still limited. We aimed to evaluate the associations between patient-level and system-level factors and the receipt of guideline-concordant therapy among patients with esophageal adenocarcinoma (EA). METHODS: This is a national cohort study of patients with stage I-III EA in the National Cancer Database (2006-2018) treated with either upfront resection or neoadjuvant therapy followed by surgery. Clinical and pathologic staging data were used for defining guideline-concordant therapy. Logistic regression models were built to identify independent associations between deviations from treatment guidelines and clinical, sociodemographic, and hospital-related factors. RESULTS: Among 18,803 patients with EA treated at 1,049 hospitals, 4,511 had an endoscopic resection, 4,866 had upfront resection, and 9,426 had neoadjuvant therapy followed by surgery. A total of 16,002 patients (85.1%) received guideline-concordant therapy. Patients who were age 70 years or older (odds ratio [OR] 1.35; 95% CI, 1.14 to 1.60), had a Charlson-Deyo modified score of ≥ 1, and were treated at hospitals with a safety-net burden of ≥ 10% (OR 1.13; 95% CI, 1.02 to 1.25) had higher risk of deviations from guidelines, whereas treatment at high-volume facilities (OR 0.84; 95% CI, 0.74 to 0.95) and diagnosis after 2011 decreased this risk. Relative to cT0-1N0 patients, those with cT2N0 disease had the highest risk of deviations from guideline-concordant therapy (OR 3.76; 95% CI, 3.30 to 4.29). Among patients treated at high-volume facilities, safety-net burden over 10% increased the risk of deviations (OR 1.26; 95% CI, 1.01 to 1.57). CONCLUSION: The delivery of guideline-concordant therapy among patients with EA varies significantly across clinical stage groups and is associated with several sociodemographic disparities. This knowledge should be a resource for future quality improvement strategies intended to address inequitable care within vulnerable populations.
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Affiliation(s)
- Wilson L. da Costa
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX
| | - E. Ramsay Camp
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX
- Division of Surgical Oncology, Department of Surgery, Baylor College of Medicine, Houston, TX
| | - Aaron P. Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX
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Kamarajah SK, Markar SR, Phillips AW, Kunene V, Fackrell D, Salti GI, Dahdaleh FS, Griffiths EA. Survival benefit of adjuvant chemotherapy following neoadjuvant therapy and oesophagectomy in oesophageal adenocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1980-1987. [PMID: 35718676 DOI: 10.1016/j.ejso.2022.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 03/31/2022] [Accepted: 05/16/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND The evidence assessing the additional benefits of adjuvant chemotherapy (AC) following neoadjuvant therapy (NAT; i.e. chemotherapy or chemoradiotherapy) and oesophagectomy for oesophageal adenocarcinoma (EAC) are limited. This study aimed to determine whether AC improves long-term survival in patients receiving NAT and oesophagectomy. METHODS Patients receiving oesophagectomy for EAC following NAT from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). To account for immortality bias, patients with survival ≤3 months were excluded to account for immortality bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival. RESULTS Overall, 12,972 (91%) did not receive AC and 1,255 (9%) received AC. After PSM there were 2,485 who did not receive AC and 1,254 who did. After matching, AC was associated with improved survival (median: 38.5 vs 32.3 months, p < 0.001), which remained after multivariable adjustment (HR: 0.78, CI95%: 0.71-0.87). On multivariable interaction analyses, this benefit persisted in subgroup analysis for nodal status: N0 (HR: 0.85, CI95%: 0.69-0.96), N1 (HR: 0.66, CI95%: 0.56-0.78), N2/3 (HR: 0.80, CI95%: 0.66-0.97) and margin status: R0 (HR: 0.77, CI95%: 0.69-0.86), R1 (HR: 0.60, CI95%: 0.43-0.85). Further, patients with stable disease following NAT (HR: 0.60, CI95%: 0.59-0.80) or downstaged (HR: 0.80, CI95%: 0.68-0.95) disease had significant survival benefit after AC, but not patients with upstaged disease. CONCLUSION AC following NAT and oesophagectomy is associated with improved survival, even in node-negative and margin-negative disease. NAT response may be crucial in identifying patients who will benefit maximally from AC, and thus future research should be focused on identifying molecular phenotype of tumours that respond to chemotherapy to improve outcomes.
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Schneider BJ, Chang AC. ASO Perspectives: Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer: Never Stop Questioning. Ann Surg Oncol 2022; 29:2735-2738. [PMID: 35182309 DOI: 10.1245/s10434-021-11276-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 12/14/2021] [Indexed: 11/18/2022]
Abstract
This ASO perspective reviews the findings of a randomized placebo-controlled, clinical trial evaluating adjuvant nivolumab in esophageal or gastroesophageal junction carcinoma, reported recently by the Checkmate 577 investigators. The use of postoperative immunotherapy represents a significant paradigm shift for managing patients who have had limited evidence-based treatment options after completing neoadjuvant chemoradiation followed by resection for these aggressive malignancies.
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Affiliation(s)
- Bryan J Schneider
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Andrew C Chang
- Department of Surgery, University of Michigan, TC2120/5344, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA.
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Lin JX, Tang YH, Lin GJ, Ma YB, Desiderio J, Li P, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu RH, Zheng CH, Parisi A, Truty MJ, Huang CM. Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. JAMA Netw Open 2022; 5:e225557. [PMID: 35363268 PMCID: PMC8976237 DOI: 10.1001/jamanetworkopen.2022.5557] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 02/15/2022] [Indexed: 11/26/2022] Open
Abstract
IMPORTANCE Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced gastric cancer (LAGC); however, the indications for adjuvant chemotherapy (AC) in patients with LAGC who received NAC remain controversial. OBJECTIVE To compare survival rates between patients with LAGC who received AC and those who did not after NAC followed by surgery. DESIGN, SETTING, AND PARTICIPANTS This multicenter, international cohort study included 353 patients with LAGC undergoing curative-intent gastrectomy after NAC at 2 tertiary referral teaching hospitals in China between June 1, 2008, and December 31, 2017. To externally validate the findings in the Chinese patients, 109 patients from the US and Italy between June 1, 2006, and June 30, 2013, were reviewed. The follow-up period of the Chinese patients was completed in December 2020, and the follow-up period of the Western patients was completed between February and July 2017. Data analysis was performed from December 1, 2020, to February 28, 2021. EXPOSURES Patients who received AC and those who did not were propensity score matched to evaluate the association of AC with survival. MAIN OUTCOMES AND MEASURES Overall survival (OS), disease-free survival, and disease-specific survival. RESULTS Of 353 patients from China (275 [78.1%] male; mean [SD] age, 58.0 [10.7] years), 262 (74.1%) received AC and 91 (25.9%) did not. After propensity score matching, the 3-year OS was significantly higher in patients who received AC (60.1%; 95% CI, 53.1%-68.1%) than in those who did not (49.3%; 95% CI, 39.8%-61.0%) (P = .02). Lymph node ratio (LNR) was significantly associated with AC benefit (P < .001 for interaction), and a plot of the interaction between LNR and AC demonstrated that AC was associated with improved OS in patients with higher (≥9%) LNRs (3-year OS: 46.6% vs 21.7%; P < .001), but not in patients with LNRs less than 9% (3-year OS: 73.9% vs 71.3%; P = .30). When stratified by AC cycles, only those patients who completed at least 4 AC cycles exhibited a significant survival benefit in the 6-month (hazard ratio, 0.56; 95% CI, 0.33-0.96; P = .03) and 9-month landmark analysis (hazard ratio, 0.50; 95% CI, 0.27-0.94; P = .03). In the external cohort, improved OS with AC administration was also found in patients with LNRs of 9% or greater (3-year OS: 53.0% vs 26.3%; P = .04). CONCLUSIONS AND RELEVANCE In this cohort study, the administration of AC after NAC and resection of LAGC was associated with improved prognosis in patients with LNRs of 9% or greater. These findings suggest that LNR might be valuable in AC selection in future decision-making processes.
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Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Yi-Hui Tang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Guan-Jie Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Yu-Bin Ma
- Department of Gastrointestinal Surgery, Qinghai University Affiliated Hospital, Xining, China
| | - Jacopo Desiderio
- Department of Digestive Surgery, St Mary’s Hospital, Terni, Italy
- Department of Surgical Sciences, La Sapienza University of Rome, Rome, Italy
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Amilcare Parisi
- Department of Digestive Surgery, St Mary’s Hospital, Terni, Italy
- Department of Surgical Sciences, La Sapienza University of Rome, Rome, Italy
| | - Mark J. Truty
- Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
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Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery. Esophagus 2022; 19:214-223. [PMID: 34757482 DOI: 10.1007/s10388-021-00891-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 10/19/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery. METHODS A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed. RESULTS The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P < 0.001), lymphovascular invasion (LVI) (HR = 2.608, P < 0.001) were independent factors associated with OS. The LVI+/ypN+ group had a significantly poorer outcome than the other groups (P < 0.001). The 5-year RFS rates for patients with ypStage IIIA or higher among the LVI-negative cases and ypStage II or higher among the LVI-positive cases were around 0.6 or under. The novel pathological staging which was based on the present results was proposed and RFS curves of each novel stage suggested the suitability of these staging for our cohort. CONCLUSIONS The present results suggest that a novel pathological staging system using the ypTNM classification, in which the supraclavicular lymph node was regarded as a regional lymph node and the presence of LVI was included as a category, was appropriate for patients with LAESCC after NAC prior to surgery.
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Raman V, Jawitz OK, Farrow NE, Voigt SL, Rhodin KE, Yang CFJ, Turner MC, D’Amico TA, Harpole DH, Tong BC. The Relationship Between Lymph Node Ratio and Survival Benefit With Adjuvant Chemotherapy in Node-positive Esophageal Adenocarcinoma. Ann Surg 2022; 275:e562-e567. [PMID: 32649467 PMCID: PMC7790855 DOI: 10.1097/sla.0000000000004150] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND We hypothesized that the ratio of positive lymph nodes to total assessed lymph nodes (LNR) is an indicator of cancer burden in esophageal adenocarcinoma and may identify patients who may most benefit from AC. OBJECTIVE The aim of this study was to discern whether there is a threshold LNR above which AC is associated with a survival benefit in this population. METHODS The 2004-2015 National Cancer Database was queried for patients who underwent upfront, complete resection of pT1-4N1-3M0 esophageal adenocarcinoma. The primary outcome, overall survival, was examined using multivariable Cox proportional hazards models employing an interaction term between LNR and AC. RESULTS A total of 1733 patients were included: 811 (47%) did not receive AC whereas 922 (53%) did. The median LNR was 20% (interquartile range 9-40). In a multivariable Cox model, the interaction term between LNR and receipt of AC was significant (P = 0.01). A plot of the interaction demonstrated that AC was associated with improved survival beyond a LNR of about 10%-12%. In a sensitivity analysis, the receipt of AC was not associated with improved survival in patients with LNR <12% (hazard ratio 1.02; 95% confidence interval 0.72-1.44) but was associated with improved survival in those with LNR ≥12% (hazard ratio 0.65; 95% confidence interval 0.50-0.79). CONCLUSIONS In this study of patients with upfront, complete resection of node-positive esophageal adenocarcinoma, AC was associated with improved survival for LNR ≥12%. LNR may be used as an adjunct in multidisciplinary decision-making about adjuvant therapies in this patient population.
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Affiliation(s)
- Vignesh Raman
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Oliver K. Jawitz
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Norma E. Farrow
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Soraya L. Voigt
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Kristen E. Rhodin
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Chi-Fu J. Yang
- Department of Cardiothoracic Surgery, Stanford University Medical Center
| | - Megan C. Turner
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Thomas A. D’Amico
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - David H. Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
| | - Betty C. Tong
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC
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Yıldırım ÖA, Erdur E. Medical Oncology or Surgical Oncology: Which Branch Should Be Started in Esophageal Cancer Diagnostic Evaluation? Cureus 2022; 14:e22286. [PMID: 35350502 PMCID: PMC8932595 DOI: 10.7759/cureus.22286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2022] [Indexed: 11/05/2022] Open
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Rahman S, Thomas B, Maynard N, Park MH, Wahedally M, Trudgill N, Crosby T, Cromwell DA, Underwood TJ. Impact of postoperative chemotherapy on survival for oesophagogastric adenocarcinoma after preoperative chemotherapy and surgery. Br J Surg 2022; 109:227-236. [PMID: 34910129 PMCID: PMC10364695 DOI: 10.1093/bjs/znab427] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/15/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Perioperative chemotherapy is widely used in the treatment of oesophagogastric adenocarcinoma (OGAC) with a substantial survival benefit over surgery alone. However, the postoperative part of these regimens is given in less than half of patients, reflecting uncertainty among clinicians about its benefit and poor postoperative patient fitness. This study estimated the effect of postoperative chemotherapy after surgery for OGAC using a large population-based data set. METHODS Patients with adenocarcinoma of the oesophagus, gastro-oesophageal junction or stomach diagnosed between 2012 and 2018, who underwent preoperative chemotherapy followed by surgery, were identified from a national-level audit in England and Wales. Postoperative therapy was defined as the receipt of systemic chemotherapy within 90 days of surgery. The effectiveness of postoperative chemotherapy compared with observation was estimated using inverse propensity treatment weighting. RESULTS Postoperative chemotherapy was given to 1593 of 4139 patients (38.5 per cent) included in the study. Almost all patients received platinum-based triplet regimens (4004 patients, 96.7 per cent), with FLOT used in 3.3 per cent. Patients who received postoperative chemotherapy were younger, with a lower ASA grade, and were less likely to have surgical complications, with similar tumour characteristics. After weighting, the median survival time after postoperative chemotherapy was 62.7 months compared with 50.4 months without chemotherapy (hazard ratio 0.84, 95 per cent c.i. 0.77 to 0.94; P = 0.001). CONCLUSION This study has shown that postoperative chemotherapy improves overall survival in patients with OGAC treated with preoperative chemotherapy and surgery.
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Affiliation(s)
- Saqib Rahman
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- Clinical Effectiveness Unit, Royal College of Surgeons of England, London, UK
| | - Betsan Thomas
- Department of Oncology, Velindre University NHS Trust, Cardiff, UK
| | - Nick Maynard
- Department of Upper Gastrointestinal Surgery, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Min Hae Park
- Clinical Effectiveness Unit, Royal College of Surgeons of England, London, UK
| | - Muhammad Wahedally
- Clinical Effectiveness Unit, Royal College of Surgeons of England, London, UK
| | - Nigel Trudgill
- Department of Gastroenterology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | - Tom Crosby
- Department of Oncology, Velindre University NHS Trust, Cardiff, UK
| | - David A. Cromwell
- Clinical Effectiveness Unit, Royal College of Surgeons of England, London, UK
| | - Tim J. Underwood
- School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Crull DJ, Hogenes MCH, Hoekstra R, Hendriksen EM, van Det MJ, Kouwenhoven EA. The Impact of Tumor Regression on Prognosis After Neoadjuvant Chemoradiotherapy in Surgically Treated Esophageal Adenocarcinoma. Ann Surg Oncol 2022; 29:3658-3666. [DOI: 10.1245/s10434-022-11336-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/18/2021] [Indexed: 12/24/2022]
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Lee Y, Samarasinghe Y, Lee MH, Thiru L, Shargall Y, Finley C, Hanna W, Levine O, Juergens R, Agzarian J. Role of Adjuvant Therapy in Esophageal Cancer Patients After Neoadjuvant Therapy and Esophagectomy: A Systematic Review and Meta-analysis. Ann Surg 2022; 275:91-98. [PMID: 34596073 DOI: 10.1097/sla.0000000000005227] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The aim of this study was to analyze esophageal cancer patients who previously underwent neoadjuvant therapy followed by a curative resection to determine whether additional adjuvant therapy is associated with improved survival outcomes. SUMMARY BACKGROUND DATA Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal cancer, whereas adjuvant therapy is typically employed for patients with residual disease. However, the role of adjuvant therapy after a curative resection is still uncertain. METHODS MEDLINE, EMBASE, and CENTRAL databases were searched for studies comparing patients with esophageal cancer who underwent neoadjuvant therapy and curative resection with and without adjuvant therapy. Primary outcome was overall survival (OS), and random effects meta-analysis was conducted where appropriate. Grading of recommendations, assessment, development, and evaluation was used to assess the certainty of evidence. RESULTS Ten studies involving 6462 patients were included. When compared to patients who received neoadjuvant therapy and esophagectomy alone, adjuvant therapy groups experienced a significant decrease in mortality by 48% at 1 year (Risk Ratio (RR) 0.52, 95% confidence interval [CI] 0.41-0.65, P < 0.001, moderate certainty). This reduction in mortality was carried through to 5-year follow-up (RR 0.91, 95% CI 0.86-0.96, P < 0.001, moderate certainty). The difference between the adjuvant therapy and the control group was uncertain regarding the secondary outcomes. CONCLUSION Adjuvant therapy after neoadjuvant treatment and esophagectomy with negative resection margins provide an improved OS at 1 and 5 years with moderate to high certainty of evidence, but the benefit for disease-free survival and locoregional/distal recurrence remain uncertain due to limited reporting of these outcomes.
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Affiliation(s)
- Yung Lee
- Division of General Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Yasith Samarasinghe
- Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Michael H Lee
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Luxmy Thiru
- Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Yaron Shargall
- Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Christian Finley
- Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Wael Hanna
- Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Oren Levine
- Deparment of Oncology, McMaster University, Hamilton, Ontario, Canada
| | - Rosalyn Juergens
- Deparment of Oncology, McMaster University, Hamilton, Ontario, Canada
| | - John Agzarian
- Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada
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Bott RK, Beckmann K, Zylstra J, Wilkinson MJ, Knight WRC, Baker CR, Kelly M, Maisey N, Waters J, Van Hemelrijck M, Smyth EC, Allum WH, Lagergren J, Gossage JA, Cunningham D, Davies AR. Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins. Acta Oncol 2021; 60:672-680. [PMID: 33586602 DOI: 10.1080/0284186x.2021.1885057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins. METHODS This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment. RESULTS Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40-1.06; p .0.087). Responders to NAC (Mandard 1-3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15-1.11; p .1.081). CONCLUSIONS Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours.
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Affiliation(s)
- Rebecca K. Bott
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
| | - Kerri Beckmann
- School of Cancer and Pharmaceutical Sciences, Translational Oncology and Urology Research (TOUR), King’s College London, London, UK
- University of South Australia Cancer Research Institute, University of South Australia, Adelaide, Australia
| | - Janine Zylstra
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
| | - Michelle J. Wilkinson
- Department of Upper Gastrointestinal Surgery, The Royal Marsden Hospital, London, UK
| | - William R. C. Knight
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
| | - Cara R. Baker
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
| | - Mark Kelly
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
| | - Nick Maisey
- Department of Medical Oncology, Guy’s Hospital, London, UK
| | - Justin Waters
- Department of Medical Oncology, Maidstone Hospital, Kent, UK
| | - Mieke Van Hemelrijck
- School of Cancer and Pharmaceutical Sciences, Translational Oncology and Urology Research (TOUR), King’s College London, London, UK
| | | | - William H. Allum
- Department of Upper Gastrointestinal Surgery, The Royal Marsden Hospital, London, UK
| | - Jesper Lagergren
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - James A. Gossage
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
| | - David Cunningham
- Department of Medical Oncology, The Royal Marsden Hospital, London, UK
| | - Andrew R. Davies
- Department of Upper Gastrointestinal and General Surgery, St Thomas’ Hospital, London, UK
- School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
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Al-Kaabi A, van der Post RS, van der Werf LR, Wijnhoven BPL, Rosman C, Hulshof MCCM, van Laarhoven HWM, Verhoeven RHA, Siersema PD. Impact of pathological tumor response after CROSS neoadjuvant chemoradiotherapy followed by surgery on long-term outcome of esophageal cancer: a population-based study. Acta Oncol 2021; 60:497-504. [PMID: 33491513 DOI: 10.1080/0284186x.2020.1870246] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND With increasing interest in organ-preserving strategies for potentially curable esophageal cancer, real-world data is needed to understand the impact of pathological tumor response after neoadjuvant chemoradiotherapy (CRT) on patient outcome. The objective of this study is to assess the association between pathological tumor response following CROSS neoadjuvant CRT and long-term overall survival (OS) in a nationwide cohort. MATERIAL AND METHODS All patients diagnosed in the Netherlands with potentially curable esophageal cancer between 2009 and 2017, and treated with neoadjuvant CRT followed by esophagectomy were included. Through record linkage with the nationwide Dutch Pathology Registry (PALGA), pathological data were obtained. The primary outcome was pathological tumor response based on ypTNM, classified into pathological complete response (ypT0N0) and incomplete responders (ypT0N+, ypT+N0, and ypT+N+). Multivariable logistic and Cox regression models were used to identify predictors of pathological complete response (pCR) and survival. RESULTS A total of 4946 patients were included. Overall, 24% achieved pCR, with 19% in adenocarcinoma and 42% in squamous cell carcinoma. Patients with pCR had a better estimated 5-year OS compared to incomplete responders (62% vs. 38%, p< .001). Of the patients with incomplete response, ypT+N+ patients (32% of total population) had the lowest estimated 5-year OS rate, followed by ypT0N+ and ypT+ N0 (22%, 47%, and 49%, respectively, p< .001). Adenocarcinoma, well to moderate differentiation, cT3-4, cN+, signet ring cell differentiation and lymph node yield (≥15) were associated with lower likelihood of pCR. CONCLUSION In this population-based study, pathological tumor response based on the ypTNM-stage was associated with different prognostic subgroups. A quarter of patients achieved ypT0N0 with favorable long-term survival, while one-third had an ypT+N+ response with very poor survival. The association between pathological tumor response and long-term survival could help in more accurate assessments of individual prognosis and treatment decisions.
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Affiliation(s)
- Ali Al-Kaabi
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | | | - Bas P. L. Wijnhoven
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Camiel Rosman
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Maarten C. C. M. Hulshof
- Department of Radiotherapy, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Hanneke W. M. van Laarhoven
- Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Rob H. A. Verhoeven
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Research & Development, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands
| | - Peter D. Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
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Du VX, Groth SS. Commentary: Adjuvant chemotherapy after trimodal therapy for esophageal carcinoma: A bitter pill to swallow. JTCVS OPEN 2021; 5:150-151. [PMID: 36003186 PMCID: PMC9390313 DOI: 10.1016/j.xjon.2020.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 12/22/2020] [Accepted: 12/23/2020] [Indexed: 11/29/2022]
Affiliation(s)
- Valerie X. Du
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex
| | - Shawn S. Groth
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex
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A Phase II Study Demonstrates No Feasibility of Adjuvant Treatment with Six Cycles of S-1 and Oxaliplatin in Resectable Esophageal Adenocarcinoma, with ERCC1 as Biomarker for Response to SOX. Cancers (Basel) 2021; 13:cancers13040839. [PMID: 33671266 PMCID: PMC7922275 DOI: 10.3390/cancers13040839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 02/07/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Neoadjuvant chemoradiotherapy followed by surgery is currently standard of care in esophageal adenocarcinoma. However, prognosis remains dismal. The aim of our study was to assess the feasibility of administering six cycles of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy and esophagectomy. Although six cycles of adjuvant S-1 and oxaliplatin were not feasible in pretreated patients, mainly due to toxicity, efficacy results were promising compared to a propensity-score matched cohort. Exploratory biomarker analyses demonstrated potential benefit for patients with Excision repair cross-complementation group 1 (ERCC1) negative tumor expression. A proteomics biomarker model provided valuable information for prediction of survival and pharmacokinetics of 5-FU showed a correlation with treatment-related toxicity. Although it remains unclear if additional chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity, could potentially benefit from this treatment option based on our exploratory biomarker research. Abstract We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m2) on day 1 and S-1 (25 mg/m2 twice daily) on days 1–14. The primary endpoint was feasibility, defined as ≥50% completing treatment. We performed exploratory propensity-score matching to compare survival, ERCC1 and Thymidylate Synthase (TS) immunohistochemistry analyses, proteomics biomarker discovery and 5-FU pharmacokinetic analyses. Forty patients were enrolled and 48% completed all adjuvant cycles. Median dose intensity was 98% for S-1 and 62% for oxaliplatin. The main reason for early discontinuation was toxicity (67%). The median recurrence-free and overall survival were 28.3 months and 40.8 months, respectively (median follow-up 29.1 months). Survival was not significantly prolonged compared to a matched cohort (p = 0.09). Patients with ERCC1 negative tumor expression had significantly better survival compared to ERCC1 positivity (p = 0.01). Our protein signature model was predictive of survival [p = 0.04; Area under the curve (AUC) 0.80]. Moreover, 5-FU pharmacokinetics significantly correlated with treatment-related toxicity. To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research.
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da Costa WL, Gu X, Farjah F, Groth SS, Burt BM, Ripley RT, Carrott PW, Massarweh NN. Staging Concordance and Guideline-Concordant Treatment for Esophageal Adenocarcinoma. Ann Thorac Surg 2021; 113:279-285. [PMID: 33484675 DOI: 10.1016/j.athoracsur.2020.12.046] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 12/08/2020] [Accepted: 12/30/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Treatment selection for patients with esophageal adenocarcinoma is predicated on clinical staging information, which is inaccurate in 20% to 30% of cases and could impact the delivery of guideline-concordant treatment. We aimed to evaluate the association between staging concordance at the patient and hospital levels with the delivery of guideline-concordant treatment among esophageal adenocarcinoma patients. METHODS This was a national cohort study of resected esophageal adenocarcinoma patients in the National Cancer Data Base (2006 to 2015) treated either with upfront resection or neoadjuvant therapy followed by surgery. Patient- and hospital-level clinical and pathologic staging concordance and deviations from treatment guidelines were ascertained. For neoadjuvant therapy patients, staging concordance was predicted through Bayesian analysis. Reliability adjustment was used when evaluating hospital-level concordance. RESULTS Among 9393 esophageal adenocarcinoma patients treated at 927 hospitals, 41% had upfront surgery. Among upfront surgery patients, staging concordance was 85.1% for T1N0 and 86.9% for T3-T4N+ disease, but less than 50% for all others. Among patients treated with neoadjuvant therapy, treatment downstaging was observed in 33.9%. Deviations from treatment guidelines were identified in 38.5% of upfront surgery patients and 3.3% of neoadjuvant therapy patients. The proportion of concordantly staged patients ranged from 60.1% to 87.9%, and deviations from treatment guidelines were observed among 14.9% to 22.7% of the patients. Patient staging concordance increased, and deviations from guidelines decreased, as hospital-level concordance increased (trend test, P values less than .001 for all). CONCLUSIONS Deviations from treatment guidelines in esophageal adenocarcinoma patients appear to be a function of inaccurate clinical staging information, which should be a new focus for quality improvement efforts.
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Affiliation(s)
- Wilson Luiz da Costa
- Department of Medicine, Epidemiology, and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
| | - Xiangjun Gu
- Department of Medicine, Epidemiology, and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Farhood Farjah
- Department of Thoracic Surgery, University of Washington, Seattle, Washington
| | - Shawn S Groth
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Bryan M Burt
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Robert T Ripley
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Phillip W Carrott
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Nader N Massarweh
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas
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Cai Z, Jin H, Chen J, Hu J, Li H, Yi Z, Zu X. Adjuvant chemotherapy in patients with locally advanced bladder cancer after neoadjuvant chemotherapy and radical cystectomy: a systematic review and pooled analysis. Transl Androl Urol 2021; 10:283-291. [PMID: 33532317 PMCID: PMC7844510 DOI: 10.21037/tau-20-571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 10/30/2020] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) could ameliorate the stage of locally advanced bladder cancer (LABC) which is defined in pT3/T4 and/or pN+, improve overall survival (OS) before radical cystectomy (RC). However, for LABC, the decision to use adjuvant chemotherapy (AC) after NAC and RC is still controversial. METHODS We performed a comprehensive search of the PubMed, Embase, and Cochrane Library databases for literature that reported prognosis after using AC following NAC and RC. Cumulative analyses of hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were performed. We performed all analyses by Review Manager software, version 5.3, and Stata 15.0. RESULTS Six retrospective cohort studies were included, involving 4,346 patients. Pooled analysis results showed that using AC after NAC and RC can improve OS (HR =0.83, 95% CI: 0.74-0.94, P=0.002; I2 =0%) and cancer-specific survival (CSS) (HR =0.56, 95% CI: 0.32-0.99, P=0.04; I2 =0%) but cannot extend recurrence-free survival (RFS) (HR =0.52, 95% CI: 0.27-1.01, P=0.05; I2 =53%) for LABC patients. CONCLUSIONS This pooled analysis shows that AC after NAC and RC can improve the prognosis for patients with LABC.
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Affiliation(s)
- Zhiyong Cai
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Hang Jin
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Jiao Hu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Huihuang Li
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhenglin Yi
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiongbing Zu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
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Depypere L, De Hertogh G, Moons J, Provoost AL, Lerut T, Sagaert X, Coosemans W, Van Veer H, Nafteux P. Importance of Lymph Node Response After Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma. Ann Thorac Surg 2020; 112:1847-1854. [PMID: 33352178 DOI: 10.1016/j.athoracsur.2020.09.074] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 09/07/2020] [Accepted: 09/14/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND Tumor response and lymph node involvement are the most important prognosticators in resected patients with esophageal adenocarcinoma after neoadjuvant chemoradiotherapy (nCRT). We hypothesize that lymph node response (LNR) is also a valuable prognosticator in these patients, potentially revealing the added effect of nCRT. METHODS Hematoxylin and eosin slides of 193 esophageal adenocarcinoma patients with clinical suspicion of lymph node involvement (cN+) and treated with nCRT between 2008 and 2015 were assessed. Lymph nodes containing viable tumor cells were considered ypN+, and those negative for viable tumor were ypN0. LNR was also described according to an earlier defined method. Three groups were obtained: ypN0/LNR-, ypN0/LNR+, and ypN+. They were compared with 188 cN+ patients being pN0 (n = 45) or pN+ (n = 143) after upfront esophageal resection. RESULTS Forty-four patients were ypN0/LNR-, 55 were ypN0/LNR+, and 94 were ypN+. Median overall survival was 96.4, 31.2, and 20.6 months, respectively, and was significantly different between ypN0/LNR- and ypN0/LNR+ groups (P = .020). Survival was comparable between ypN0/LNR- and pN0 (104.2 months) groups (P = .519) and between ypN+ and pN+ (21.6 months) groups (P = .966). In ypN0 patients, risk of death in LNR+ patients was tripled compared with LNR- patients. CONCLUSIONS In cN+ esophageal adenocarcinoma patients treated with nCRT with postoperative final pathology being ypN0, median overall survival is tripled when no signs of LNR were found and comparable to cN+/pN0 upfront esophagectomy patients, suggesting that 23% of patients treated with nCRT were in fact true N0 and overtreated by nCRT. ypN+ patients have no survival benefit compared with pN+ patients.
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Affiliation(s)
- Lieven Depypere
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.
| | - Gert De Hertogh
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium; Department of Imaging & Pathology, Biomedical Sciences Group, KU Leuven, Leuven, Belgium
| | - Johnny Moons
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - An-Lies Provoost
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Toni Lerut
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Xavier Sagaert
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium; Department of Imaging & Pathology, Biomedical Sciences Group, KU Leuven, Leuven, Belgium
| | - Willy Coosemans
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Hans Van Veer
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Philippe Nafteux
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
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Merritt RE, Abdel-Rasoul M, Souza DMD, Kneuertz PJ. Nomograms for predicting overall and recurrence-free survival after trimodality therapy for esophageal adenocarcinoma. J Surg Oncol 2020; 123:881-890. [PMID: 33333590 DOI: 10.1002/jso.26349] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 11/21/2020] [Accepted: 12/07/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND Locally advanced esophageal carcinoma is treated with neoadjuvant chemoradiation and esophagectomy. Patients may still experience recurrence and death despite undergoing potentially curative trimodality therapy. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after the completion of trimodality therapy. METHODS A total of 215 patients with esophageal adenocarcinoma underwent trimodality therapy from September 2010 to April 2018. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts. RESULTS On multivariate analysis, clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, body mass index, age, and number of lymph nodes removed were predictive variables for overall survival. Clinical N-stage, tumor differentiation, tumor regression grade, anastomotic leak, age, and positive lymph nodes were significant predictors of RFS in a multivariate model. The nomogram for OS had good predictive ability (Harrell's Concordance index [C-index]: 0.71 [95% confidence interval {CI}: 0.66-0.76]). The nomogram for RFS also performed well (C-index: 0.70 [95% CI: 0.65-0.74]). CONCLUSION Our nomograms can accurately predict OS and RFS after trimodality therapy and may provide guidance regarding adjuvant therapy and surveillance.
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Affiliation(s)
- Robert E Merritt
- Thoracic Surgery Division, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Mahmoud Abdel-Rasoul
- Department of Biomedical Informatics, Center for Biostatistics, College of Medicine, The Ohio State University, Columbus, Ohio, USA
| | - Desmond M D' Souza
- Thoracic Surgery Division, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Peter J Kneuertz
- Thoracic Surgery Division, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial. J Thorac Oncol 2020; 16:310-317. [PMID: 33307192 DOI: 10.1016/j.jtho.2020.10.157] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 10/14/2020] [Accepted: 10/15/2020] [Indexed: 12/28/2022]
Abstract
INTRODUCTION The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer. METHODS Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause. RESULTS Demographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52-58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727-1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636-1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III-IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140-5.183, p < 0.001). CONCLUSIONS For patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy.
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Zheng B, Chen M, Chen C, Xiao J, Cai B, Zhang S, Liang M, Zeng T, Chen H, Wu W, Xu G, Zheng W, Zhu Y, Chen C. Adjuvant chemoradiotherapy for patients with pathologic node-positive esophageal cancer following radical resection is associated with improved survival. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1633. [PMID: 33490145 PMCID: PMC7812226 DOI: 10.21037/atm-20-4893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background Depending on the pathological stage, patients with esophageal squamous cell carcinoma (ESCC) can experience poor prognosis after surgery. This study was designed to analyze the effect of various treatments on prognosis in pathologic node-positive esophageal cancer patients who undergo radical surgery. Methods We evaluated 210 pathologic stage IIb–IIIc patients (pT1-4aN + M0) who had undergone esophagectomy for thoracic ESCC from January 2013 to October 2015 at our institute. Surgery alone was applied in 65 patients, postoperative chemotherapy alone was applied in 112 patients, and postoperative adjuvant chemoradiotherapy was applied in 33 patients. Kaplan-Meier and Cox regression analysis were used to compare overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to visualize the multivariate Cox regression analysis model. Results The median follow-up period was 49.4 months. The 3- and 5-year OS rates of the patients in the surgery group, postoperative chemotherapy group, postoperative chemoradiotherapy group were 55.4%, 61.6%, and 75.8%, and 30.1%, 44.0%, and 63.0% respectively. The 3- and 5-year DFS rates of the patients in the surgery group, postoperative chemotherapy group, postoperative chemoradiotherapy group were 44.6%, 52.7%, and 72.7%, and 20.0%, 24.1%, and 39.4%, respectively. Both the OS and DFS of the patients in the postoperative chemoradiotherapy group were better than those of the patients in the surgery and postoperative chemotherapy group. Among them, the OS of the postoperative radiotherapy group was longer than that of the surgery group (P=0.011) and the postoperative chemotherapy group (P=0.190), while the DFS of postoperative chemoradiotherapy group was longer than that of the surgery group and postoperative chemotherapy group, but the difference was not statistically significant (P>0.05). Conclusions This study showed that postoperative adjuvant chemoradiotherapy could improve 3-year OS and DFS compared with treatment using surgery alone or postoperative chemotherapy alone. However, an evaluation of long-term prognosis requires a longer follow-up.
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Affiliation(s)
- Bin Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Maohui Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Cheng Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jiazhou Xiao
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Bingqiang Cai
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Shuliang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Mingqiang Liang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Taidui Zeng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Hao Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Weidong Wu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Guobing Xu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Wei Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Yong Zhu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
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Liu S, Wen J, Yang H, Li Q, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Zhao L, Liu H, Hu Y, Liu M, Fu J, Xi M. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010. Eur J Cancer 2020; 138:113-121. [PMID: 32877795 DOI: 10.1016/j.ejca.2020.08.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 07/21/2020] [Accepted: 08/03/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim of this study was to compare recurrence patterns and prognostic factors for developing recurrences in patients with oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (CRT) followed by surgery or surgery alone from a multicenter phase III trial NEOCRTEC5010. PATIENTS AND METHODS Patients with locally advanced ESCC were randomly assigned in a 1:1 ratio to receive neoadjuvant CRT plus surgery (CRT + S group) or surgery alone (S group). CRT consisted of two cycles of vinorelbine and cisplatin with concurrent radiotherapy of 40.0 Gy in 20 fractions. Recurrence patterns, sites, frequency, and timing and potential prognostic factors were compared. RESULTS Of the 451 patients enrolled from 2007 to 2014, 411 patients who underwent resection were analysed. After a median follow-up of 51.9 months, 62 patients (33.7%) in the CRT + S group versus 104 patients (45.8%) in the S group experienced recurrences (P = 0.013). The CRT + S group demonstrated a significantly better locoregional failure-free survival (P = 0.012) and a more favourable distant metastasis-free survival (P = 0.028) than the S group. Recurrences occurred earlier in the S group (P = 0.053), and late relapses were much more frequent in the CRT + S group (P = 0.029). On multivariate analysis, R1 resection and surgery alone were adverse factors for developing locoregional recurrences, whereas R1 resection was the only independent factor associated with distant metastases. CONCLUSIONS The neoadjuvant CRT regimen was associated with significantly reduced locoregional and distant recurrences compared with surgery alone. Recurrence patterns, sites and frequency were different between groups. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER NCT01216527.
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Affiliation(s)
- Shiliang Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jing Wen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China
| | - Hong Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qiaoqiao Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuping Chen
- Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Chengchu Zhu
- Department of Thoracic Surgery, Taizhou Hospital, Wenzhou Medical University, Linhai, China
| | - Wentao Fang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Zhentao Yu
- Department of Thoracic Surgery, Tianjin Medical University Cancer Hospital, Tianjin, China
| | - Weimin Mao
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Jiaqing Xiang
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yongtao Han
- Department of Thoracic Surgery, Sichuan Cancer Hospital, Chengdu, China
| | - Lei Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hui Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yonghong Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Mengzhong Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jianhua Fu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Mian Xi
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
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46
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da Costa WL, Tran Cao HS, Portuondo JI, Sada YH, Massarweh NN. Hospital clinical staging accuracy for upper gastrointestinal malignancy. J Surg Oncol 2020; 122:1630-1638. [PMID: 32976667 DOI: 10.1002/jso.26211] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/01/2020] [Accepted: 09/02/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND Decisions about multimodality treatment for upper gastrointestinal malignancies are largely predicted on clinical staging information. However, hospital-level accuracy of clinical staging is currently unknown. METHODS A national cohort study of patients with adenocarcinoma of the esophagus, stomach, or pancreas in the NCDB (2006-2015) who were treated with upfront resection. Hospital-level staging accuracy (ascertained by comparing clinical stage to pathologic stage) was calculated. Within hospital correlation of staging accuracy across disease sites was evaluated using risk and reliability adjustment. RESULTS Overall, 1246 hospitals were evaluated. Median hospital T-staging accuracy was 77.5%, 73.7%, and 60.8% for esophageal, gastric, and pancreatic cancer, respectively. Median hospital N-staging accuracy was 80.2%, 72.9%, and 61.8%, respectively. For T-stage, over-staging was most frequently observed in esophageal patients (11.2%) while under-staging was most frequent in pancreatic patients (36.1%). For N-stage, over-staging was infrequent for all three, while under-staging was most common in pancreatic patients (37.4%). Correlation across disease sites was weak for both T- (best observed, r = .34) and N-stages (r = .30). When high volume hospitals were evaluated, correlation improved but accuracy rates were similar. CONCLUSIONS Despite the importance of clinical staging in multimodality treatment planning, hospitals inaccurately stage 20-40% of patients, with low correlation across disease sites.
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Affiliation(s)
- Wilson Luiz da Costa
- Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Hop S Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jorge I Portuondo
- Center for Innovations In Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.,Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Yvonne H Sada
- Center for Innovations In Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.,Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Nader N Massarweh
- Center for Innovations In Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.,Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
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47
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Yu J, Wang W, Yao W, Yang Z, Gao P, Liu M, Wang H, Chen S, Wang D, Wang W, Sun G. Gambogic acid affects ESCC progression through regulation of PI3K/AKT/mTOR signal pathway. J Cancer 2020; 11:5568-5577. [PMID: 32913452 PMCID: PMC7477450 DOI: 10.7150/jca.41115] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is an invasive gastrointestinal malignancy and in urgent need of new effective therapies. Gambogic acid (GA) exhibits anti-cancer effects in many cancer cells, but it remains to be determined whether GA has the same effect on ESCC. Here, we reported that GA treatment caused an inhibition in ESCC cell proliferation, migration and invasion. Meanwhile, GA induced dose-dependent apoptosis of ESCC cells, repressed the expression of Bcl2 and up-regulated the levels of Bax protein, cleaved-PARP1 and cleaved-caspase 3/9. Further investigation showed that GA down-regulated the levels of PI3K, p-AKT and p-mTOR, while promoted PTEN expression in ESCC cells. Taken together, we provided the first demonstration that GA exerts anti-tumor effects on ESCC cells presumably through regulating PTEN-PI3K-AKT-mTORpathway, suggestive of a therapeutic potential for ESCC.
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Affiliation(s)
- Jiarui Yu
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Wei Wang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Weinan Yao
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Zhao Yang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Peng Gao
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Meiyue Liu
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Huan Wang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Siyuan Chen
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Dan Wang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Weixi Wang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
| | - Guogui Sun
- School of Clinical Medicine, Affiliated Hospital, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, China.,Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China
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48
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Liao X, Gao Y, Liu J, Tao L, Xie J, Gu Y, Liu T, Wang D, Xie D, Mo S. Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway. Front Oncol 2020; 10:1756. [PMID: 33014864 PMCID: PMC7511800 DOI: 10.3389/fonc.2020.01756] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 08/05/2020] [Indexed: 11/13/2022] Open
Abstract
Cisplatin (DDP) represents one of the common drugs used for esophageal squamous cell carcinoma (ESCC), but side effects associated with DDP and drug resistance lead to the failure of treatment. This study aimed to understand whether tanshinone IIA (tan IIA) and DDP could generate a synergistic antitumor effect on ESCC cells. Tan IIA and DDP are demonstrated to restrain ESCC cell proliferation in a time- and dose-dependent mode. Tan IIA and DDP at a ratio of 2:1 present a synergistic effect on ESCC cells. The combination suppresses cell migration and invasion abilities, arrests the cell cycle, and causes apoptosis in HK and K180 cells. Molecular docking indicates that tan IIA and DDP could be docked into active sites with the tested proteins. In all treated groups, the expression levels of E-cadherin, β-catenin, Bax, cleaved caspase-9, P21, P27, and c-Fos were upregulated, and the expression levels of fibronectin, vimentin, Bcl-2, cyclin D1, p-Akt, p-ERK, p-JNK, P38, COX-2, VEGF, IL-6, NF-κB, and c-Jun proteins were downregulated. Among these, the combination induced the most significant difference. Our results suggest that tan IIA could be a novel treatment for combination therapy for ESCC.
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Affiliation(s)
- Xiaozhong Liao
- Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ying Gao
- Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiahui Liu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lanting Tao
- Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jun Xie
- Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yueyu Gu
- The Second Clinical College, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Taoli Liu
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Dongmei Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Dan Xie
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Suilin Mo
- Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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49
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Sun JM. Adjuvant Therapy for Esophageal Squamous Cell Carcinoma. THE KOREAN JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2020; 53:168-171. [PMID: 32793447 PMCID: PMC7409891 DOI: 10.5090/kjtcs.2020.53.4.168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 05/20/2020] [Indexed: 11/16/2022]
Abstract
Adjuvant therapy for completely resected esophageal squamous cell carcinoma is less commonly applied in clinical practice than neoadjuvant therapy, but it plays a substantial role in improving survival for esophageal cancer patients. This article presents a concise review of the evidence regarding adjuvant therapy for esophageal squamous cell carcinoma and future directions, particularly immunotherapy.
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Affiliation(s)
- Jong-Mu Sun
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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50
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Xu QL, Li H, Zhu YJ, Xu G. The treatments and postoperative complications of esophageal cancer: a review. J Cardiothorac Surg 2020; 15:163. [PMID: 32631428 PMCID: PMC7336460 DOI: 10.1186/s13019-020-01202-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 06/22/2020] [Indexed: 12/24/2022] Open
Abstract
Abstract Esophageal cancer is still one of the most common cancers in the world. We review the appropriate treatments at different stages of esophageal cancer and also analyze the advantages and disadvantages of these treatments. The prognosis and recovery of different treatment regimens are further discussed. In particular, post-operative complications are the major causes of high mortality derived from the esophageal cancer. Therefore, we particularly discuss the main complications resulting in high mortality after surgery of esophageal cancer, and summarize their risk factors and treatment options. Background As the common cancer, the complications of esophageal cancer after surgery have been not obtained systematic treatment strategy, focusing on treatment regimens based on the different stages of esophageal cancers. Methods and overview This paper systematically summarizes the appropriate treatment strategies for different stages of esophageal cancers, and their advantages and disadvantages. We particularly focus on the postoperative survival rate of patients and postoperative complications, and discuss the causes of high mortality risk factors after surgery. The risk factors of death and corresponding treatment methods are further summarized in this study. Conclusion Postoperative complications is the main cause responsible for the hard cure of esophageal cancers. The existing literatures indicate that postoperative anastomotic fistula is one of the most important complications leading to death, while it has not received much attention yet. We suggest that anastomotic fistula should be detected and dealt with early by summarizing these literatures. It is, therefore, necessary to develop a set of methods to predict or check anastomotic fistula in advance.
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Affiliation(s)
- Qi-Liang Xu
- Department of Cardiothoracic Surgery, Heze Municipal Hospital, Heze, 274031, Shandong, China
| | - Hua Li
- Department of Information, Heze Municipal Hospital, Heze, 274031, Shandong, China
| | - Ye-Jing Zhu
- Department of Clinical Pharmacy, Heze Municipal Hospital, Heze, 274031, Shandong, China
| | - Geng Xu
- Department of Cardiothoracic Surgery, Heze Municipal Hospital, Heze, 274031, Shandong, China.
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