|
1
|
Liu J, Wu Z, Zhou S, Lv W, Wang Y, Xia P, Zhu L, Hu J. Neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma in real-world practice: an analysis of the clinical outcomes and long-term survival, and the feasibility of using major pathological response as a surrogate endpoint. Eur J Med Res 2025; 30:342. [PMID: 40301916 PMCID: PMC12038973 DOI: 10.1186/s40001-025-02599-z] [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: 12/04/2024] [Accepted: 04/15/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND Neoadjuvant immunochemotherapy is expected to become the standard treatment mode for locally advanced esophageal squamous cell carcinoma (ESCC). This study aims to analyze the clinical outcomes and long-term survival of neoadjuvant immunochemotherapy for locally advanced ESCC, and explore the feasibility of using major pathological response (MPR) as a surrogate endpoint. METHODS This real-world retrospective study consecutively included eligible patients with stage II-IVA locally advanced ESCC who received neoadjuvant immunochemotherapy and surgery between 2019 and 2022 at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. RESULTS This study collected a total of 166 patients, and ultimately included 126 patients after screening. The objective response rate (ORR) was 69.8% (88/126). The incidence of grade 3-4 adverse events (AEs) was 13.5% (17/126). MPR was observed in 49 (38.9%) patients, and 24 (19.0%) patients achieved a complete pathological response (pCR). The median progression-free survival (PFS) was 31.7 months and the 3-year PFS rate was 56.3%. The median overall survival (OS) was not reached and the 3-year OS rate was 70.6%. The median PFS of the non-MPR group was 25.0 months, with the MPR group not achieved (hazard ratio [HR], 2.503; 95% CI 1.359-4.610; P = 0.0022). The median OS in the non-MPR group was 31.7 months and not reached in the MPR group (HR, 3.607; 95% CI 1.576-8.254; P = 0.0012). MPR is an independent prognostic factor affecting OS (HR, 2.522; 95% CI 1.018-6.401; P = 0.046). CONCLUSIONS Neoadjuvant immunochemotherapy is safe and effective for locally advanced ESCC, and can result in certain survival benefits. MPR can serve as a surrogate endpoint for predicting long-term OS.
Collapse
Affiliation(s)
- Jiacong Liu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Ziheng Wu
- Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shihong Zhou
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Wang Lv
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Yiqing Wang
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Pinghui Xia
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Linhai Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.
| | - Jian Hu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.
- Key Laboratory of Clinical Evaluation Technology for Medical Device of Zhejiang Province, Hangzhou, 310003, China.
| |
Collapse
|
|
2
|
Yang Y, Zhang H, Yu B, He B, Li B, Hua R, Yang Y, He Y, Yao Y, Li C, Li Z. Risk factors and prediction of intensive care unit readmission after oesophagectomy for cancer‡. Eur J Cardiothorac Surg 2025; 67:ezaf124. [PMID: 40178967 DOI: 10.1093/ejcts/ezaf124] [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: 12/04/2024] [Revised: 03/19/2025] [Accepted: 04/02/2025] [Indexed: 04/05/2025] Open
Abstract
OBJECTIVES Intensive care unit (ICU) readmission has been proposed as a metric for quality of surgical care. The current study investigated potential factors and developed a prediction model for ICU readmission in patients following oesophagectomy for cancer. METHODS A total of 3028 patients from January 2019 to December 2022 were retrospectively collated as training cohort, with 829 patients from January 2023 to August 2023 enrolled for validation, respectively. Univariable and multivariable analyses were performed to identify potential factors after which a nomogram based on results from multivariable analysis was constructed and validated. RESULTS In the training cohort, the rate of ICU readmission was 3.6% (110/3028). Readmitted patients were associated with more reoperations, higher 90-day mortality and prolonged postoperative stay (all P < 0.001). Multivariable analysis demonstrated that older age ≥75 years, neoadjuvant therapy, preoperative albuminaemia, diffusing lung capacity for carbon monoxide (DLCO)%, longer operative duration and retention of endotracheal intubation when entering ICU were independently associated with ICU readmission. Based on these results, a nomogram for predicting readmission was constructed and validated. The Hosmer-Lemeshow test showed the model in the training cohort was well calibrated (χ2 = 5.259, P = 0.73) and area under the receiver operating characteristic curve was 0.739 (95% confidence interval 0.691-0.787). Moreover, the application of the nomogram in the validation cohort showed an improved area under the receiver of 0.780 (95% confidence interval 0.703-0.857). CONCLUSIONS ICU readmission after oesophagectomy although uncommon (3.6%) was associated with prolonged hospitalization and significant mortality. A nomogram based on 6 variables may assist intensivists to early identifying patients at high risk of readmission.
Collapse
Affiliation(s)
- Yuxin Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Zhang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Boyao Yu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin He
- Department of Critical Care, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Hua
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi He
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuanshan Yao
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chunguang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
3
|
Huang JS, Yang LT, Zhu JF, Zhong QH, Guo FL, Zhang ZY, Lin JB. Prediction of esophagogastric anastomotic leakage by nomogram combined with preoperative nutritional status and clinical factors: a retrospective study of 775 patients. Perioper Med (Lond) 2025; 14:36. [PMID: 40133981 PMCID: PMC11934493 DOI: 10.1186/s13741-024-00487-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 12/25/2024] [Indexed: 03/27/2025] Open
Abstract
AIM The purpose was to explore the independent risk factors for esophagogastric anastomotic leakage (EGAL) and establish a nomogram. METHODS Patients who underwent esophagectomy were enrolled and randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The differences between the two groups of factors were analyzed by difference analysis, and multivariate regression analysis was subsequently performed. A nomogram was established, and the feasibility of the nomogram was verified by analyzing the discrimination, calibration, and decision curves. RESULTS A total of 775 patients were enrolled, including 532 in the training cohort and 223 in the validation cohort. Multivariate regression analysis revealed that age, smoking history, drinking history, nutritional indicators, and anastomotic location were independent risk factors. In terms of discrimination, in the training group, the area under the curve was 0.757 (P = 0.025). In the calibration curve, the curves and fitting lines before and after correction in the training group and the validation group were basically the same. The results of the Hosmer-Lemeshow test showed that the chi-square value of the training cohort was 5.48 (P = 0.791). In the decision curve analysis of the training set, when the threshold probability was in the range of 5-63%, the net benefit of patients was greater than that of the two extreme curves. CONCLUSION Preoperative malnutrition is an independent risk factor for EGAL. A diagnostic model, developed on age, anastomotic location, smoking status, and drinking history, was a reliable noninvasive tool to timely predict the occurrence of AL.
Collapse
Affiliation(s)
- Jiang-Shan Huang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Li-Tao Yang
- Department of Thoracic Surgery, Baoji Traditional Chinese Medicine Hospital, Baoji, Shaanxi, China
| | - Jia-Fu Zhu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qi-Hong Zhong
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Fei-Long Guo
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zhen-Yang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jiang-Bo Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fujian Province University, Fuzhou, China.
| |
Collapse
|
|
4
|
Liu D, Liang HW, Liu Y, Huang W, Pan XB. Causes of death in locally advanced esophageal cancer undergoing neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy: a retrospective cohort study. Dis Esophagus 2025; 38:doaf017. [PMID: 40059762 DOI: 10.1093/dote/doaf017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/26/2024] [Accepted: 02/21/2025] [Indexed: 05/13/2025]
Abstract
PURPOSE To compare the causes of death in patients with locally advanced esophageal cancer treated with neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy followed by surgery. MATERIALS AND METHODS A retrospective cohort study was conducted on patients with stage T3-4aN0M0/T1-4aN1-3 M0 esophageal cancer who underwent either neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. Overall survival (OS) and specific causes of death were analyzed and compared between the two treatment groups. RESULTS A total of 4528 patients were included: 333 (7.4%) received neoadjuvant chemotherapy, and 4195 (92.6%) underwent neoadjuvant chemoradiotherapy. The 5-year OS was comparable between the two groups, both before (42.4% vs. 39.7%; hazard ratio [HR] = 1.14, 95% confidence interval [CI]: 0.98-1.33; P = 0.097) and after (42.2% vs. 42.2%; HR = 1.07, 95% CI: 0.86-1.31; P = 0.567) propensity score matching. The cumulative 5-year absolute risk of death from esophageal cancer (49.9% vs. 50.6%, P = 0.470), death from non-tumor causes (7.8% vs. 9.7%, P = 0.160), death due to lung causes (2.8% vs. 1.4%, P = 0.432), and death from heart-related causes (2.2% vs. 2.0%, P = 0.524) were similar between the two treatment groups. CONCLUSION In patients with locally advanced esophageal cancer, OS and the causes of death were comparable between those receiving neoadjuvant chemotherapy and those undergoing neoadjuvant chemoradiotherapy.
Collapse
Affiliation(s)
- Dong Liu
- Department of Radiation Therapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 150 Dongfang Road, Qiantang District, Hangzhou, Zhejiang 310018, P.R. China
| | - Huan-Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Qingxiu District, Nanning, Guangxi 530021, P.R. China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Qingxiu District, Nanning, Guangxi 530021, P.R. China
| | - Wei Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Qingxiu District, Nanning, Guangxi 530021, P.R. China
| | - Xin-Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Qingxiu District, Nanning, Guangxi 530021, P.R. China
| |
Collapse
|
|
5
|
Noronha V, Patil VM, Menon N, Joshi A, Shah MJ, Singh A, Goud S, Shah S, More S, Nawale K, Nakti D, Yadav A, Jogdhankar S, Kaushal RK, Tiwari VK, Niyogi D, Purandare N, Janu A, Chakrabarty N, Mahajan A, Tibdewal A, Agarwal J, Pawar A, Chowdhury OR, Sharma V, Kapu V, Trikha M, Kumar SV, Kolkur M, Bhagyavant P, Peelay Z, Khedkar R, Jain M, Badwe RA, Prabhash K. Phase III randomized trial comparing neoadjuvant paclitaxel plus platinum with 5-fluorouracil plus platinum in esophageal or gastroesophageal junction squamous cell carcinoma. J Natl Cancer Inst 2025; 117:58-75. [PMID: 39222012 DOI: 10.1093/jnci/djae214] [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: 03/26/2024] [Revised: 07/25/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Standard neoadjuvant chemotherapy for locally advanced esophageal or gastroesophageal junction squamous cancer, 5-fluorouracil plus platinum, is toxic and logistically challenging; alternative regimens are needed. METHODS This was a phase III randomized open-label noninferiority trial at Tata Memorial Center, India, in resectable locally advanced esophageal or gastroesophageal junction squamous cancer. Patients were randomly assigned 1:1 to 3 cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin area under the curve 6) with paclitaxel 175 mg/m2 (day 1) or 5-fluorouracil 1000 mg/m2 continuous infusion (days 1-4), followed by surgery. RESULTS Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Statistically significantly more patients on paclitaxel plus platinum (n =194, 92.3%) received all 3 chemotherapy cycles than on 5-fluorouracil with platinum (n = 170, 85.9%; P = .009). 5-fluorouracil plus platinum caused more grade 3 or higher toxicities (n = 124, 69.7%) than paclitaxel plus platinum (n = 97, 51.9%; P = .001). Surgery was performed in 131 (62.4%) patients on 5-fluorouracil plus platinum vs 139 (66.2%) on paclitaxel plus platinum (P = .415). Paclitaxel plus platinum resulted in higher pathologic primary tumor clearance (n = 33, 25.8%, vs n = 17, 15%; P = .04) and pathologic complete responses in 21.9% compared with 12.4% from 5-fluorouracil plus platinum (P = .053). Median overall survival was 27.5 months (95% confidence interval [CI] = 18.6 to 43.5 months) from paclitaxel plus platinum, which was noninferior to 27.1 months (95% CI = 18.8 to 40.7 months) from 5-fluorouracil plus platinum (hazard ratio [HR] = 0.89, 95% CI = 0.72 to 1.09; P = .346). CONCLUSION Neoadjuvant paclitaxel plus platinum chemotherapy is safer and results in similar R0 resections, higher pathologic tumor clearance and noninferior survival compared with 5-fluorouracil plus platinum. Paclitaxel plus platinum should replace 5-fluorouracil plus platinum as neoadjuvant chemotherapy for resectable locally advanced esophagealor gastroesophageal junction squamous cancer. CLINICAL TRIALS REGISTRY INDIA NUMBER CTRI/2014/04/004516.
Collapse
Affiliation(s)
- Vanita Noronha
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vijay Maruti Patil
- Department of Medical Oncology, PD Hinduja Hospital Medical Research Centre, Mumbai, Khar and Mahim, India
| | - Nandini Menon
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amit Joshi
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Minit Jalan Shah
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Ajaykumar Singh
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Supriya Goud
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Srushti Shah
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sucheta More
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Kavita Nawale
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dipti Nakti
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Akanksha Yadav
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shweta Jogdhankar
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rajiv Kumar Kaushal
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Virendra Kumar Tiwari
- Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Devayani Niyogi
- Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Nilendu Purandare
- Department of Nuclear Medicine, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Amit Janu
- Department of Radiodiagnosis, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Nivedita Chakrabarty
- Department of Radiodiagnosis, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Abhishek Mahajan
- Department of Imaging, Clatterbridge Cancer Centre National Health Service Foundation Trust, Liverpool, United Kingdom and Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
| | - Anil Tibdewal
- Department of Radiation Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Jaiprakash Agarwal
- Department of Radiation Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Akash Pawar
- Department of Biostatistics, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Oindrila Roy Chowdhury
- Department of Biostatistics, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Vibhor Sharma
- Department of Medical Oncology, Yatharth Superspeciality Hospital, Noida Extension, Uttar Pradesh, India
| | - Venkatesh Kapu
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mehak Trikha
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Srigadha Vivek Kumar
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manali Kolkur
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Priyanka Bhagyavant
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Zoya Peelay
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rutvij Khedkar
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Medha Jain
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Rajendra Achyut Badwe
- Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Kumar Prabhash
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| |
Collapse
|
|
6
|
Yue H, Liu J, Zhao L, Kuang H, Cheng J, Li J, He M, Gong J, Wang J. A2HTL: An Automated Hybrid Transformer-Based Learning for Predicting Survival of Esophageal Cancer Using CT Images. IEEE Trans Nanobioscience 2024; 23:548-555. [PMID: 39133594 DOI: 10.1109/tnb.2024.3441533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
Esophageal cancer is a common malignant tumor, precisely predicting survival of esophageal cancer is crucial for personalized treatment. However, current region of interest (ROI) based methodologies not only necessitate prior medical knowledge for tumor delineation, but may also cause the model to be overly sensitive to ROI. To address these challenges, we develop an automated Hybrid Transformer based learning that integrates a Hybrid Transformer size-aware U-Net with a ranked survival prediction network to enable automatic survival prediction for esophageal cancer. Specifically, we first incorporate the Transformer with shifted windowing multi-head self-attention mechanism (SW-MSA) into the base of the U-Net encoder to capture the long-range dependency in CT images. Furthermore, to alleviate the imbalance between the ROI and the background in CT images, we devise a size-aware coefficient for the segmentation loss. Finally, we also design a ranked pair sorting loss to more comprehensively capture the ranked information inherent in CT images. We evaluate our proposed method on a dataset comprising 759 samples with esophageal cancer. Experimental results demonstrate the superior performance of our proposed method in survival prediction, even without ROI ground truth.
Collapse
|
|
7
|
Han D, Dong J, Wang Q, Li B, Liu J, Liu H, Qiu B, Zhang W, Yang H, Shen W, Zhang Y, Zhu X, Wang Y, Wu L, Sun H, Huang W. Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts. BMC Cancer 2024; 24:1086. [PMID: 39223503 PMCID: PMC11367793 DOI: 10.1186/s12885-024-12825-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. METHODS From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1-6 and the second for cases 7-9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. RESULTS The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76-0.81; mean Hmean = 2.11-3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63-0.64; mean Hmean = 5.66-7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature. CONCLUSIONS We have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.
Collapse
Affiliation(s)
- Dan Han
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China
| | - Jinling Dong
- Department of Oncology, Yankuang New Journey General Hospital, Zoucheng, 273500, China
| | - Qifeng Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China
| | - Jun Liu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200050, China
| | - Hui Liu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Bo Qiu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Wencheng Zhang
- Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Hong Yang
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Wenbin Shen
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050017, China
| | - Yaowen Zhang
- Department sixth of Radiotherapy, Anyang Cancer Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, 455001, China
| | - Xiangzhi Zhu
- Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, China
| | - Yi Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Lei Wu
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Hongfu Sun
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Huaiyin distract, Jinan, 250117, Shandong Province, China.
| |
Collapse
|
|
8
|
Ronellenfitsch U, Friedrichs J, Barbier E, Bass GA, Burmeister B, Cunningham D, Eyck BM, Grilli M, Hofheinz RD, Kieser M, Kleeff J, Klevebro F, Langley R, Lordick F, Lutz M, Mauer M, Michalski CW, Michl P, Nankivell M, Nilsson M, Seide S, Shah MA, Shi Q, Stahl M, Urba S, van Lanschot J, Vordermark D, Walsh TN, Ychou M, Proctor T, Vey JA. Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis. JAMA Netw Open 2024; 7:e2425581. [PMID: 39093560 PMCID: PMC11297377 DOI: 10.1001/jamanetworkopen.2024.25581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 06/05/2024] [Indexed: 08/04/2024] Open
Abstract
Importance The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures Overall and disease-free survival, postoperative morbidity, and mortality. Results The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.
Collapse
Affiliation(s)
- Ulrich Ronellenfitsch
- Department of Abdominal, Vascular and Endocrine Surgery, Medical Faculty of the Martin-Luther-University Halle-Wittenberg and University Hospital Halle (Saale), Halle (Saale), Germany
| | - Juliane Friedrichs
- Department of Abdominal, Vascular and Endocrine Surgery, Medical Faculty of the Martin-Luther-University Halle-Wittenberg and University Hospital Halle (Saale), Halle (Saale), Germany
| | - Emilie Barbier
- Fédération Francophone de Cancérologie Digestive, Centre de Recherche Institut, Institut National de la Santé et de la Recherche Médicale, Epidemiology of Digestive Cancers, University of Burgundy, Franche-Comté, France
| | - Gary A. Bass
- Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia
| | - Bryan Burmeister
- Department of Radiation Oncology, GenesisCare Fraser Coast and the Hervey Bay Hospital, Urraween, Australia
| | - David Cunningham
- Institute of Cancer Research, National Institute for Health and Care Research Biomedical Research Centre, The Royal Marsden Hospital, London, United Kingdom
| | - Ben M. Eyck
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Maurizio Grilli
- Library of the Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Ralf-Dieter Hofheinz
- Day Treatment Center, Interdisciplinary Tumor Center Mannheim and Third Department of Internal Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Meinhard Kieser
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| | - Jörg Kleeff
- Department of Abdominal, Vascular and Endocrine Surgery, Medical Faculty of the Martin-Luther-University Halle-Wittenberg and University Hospital Halle (Saale), Halle (Saale), Germany
| | - Fredrik Klevebro
- Department of Clinical Science, Intervention and Technology, Karolinska Institute, Center for Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Ruth Langley
- MRC (Medical Research Council) Clinical Trials Unit, University College London, London, United Kingdom
| | - Florian Lordick
- Department of Oncology, University Cancer Center Leipzig and Cancer Center Central Germany, University of Leipzig Medical Center, Leipzig, Germany
| | - Manfred Lutz
- Department of Gastroenterology, Endocrinology, and Infectiology, Caritasklinik St Theresia, Saarbrücken, Germany
| | - Murielle Mauer
- Statistics Department, European Organisation for Research and Treatment of Cancer, Brussels, Belgium
| | - Christoph W. Michalski
- Department of General, Abdominal and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Patrick Michl
- Department of Gastroenterology, Infectiology and Toxicology, University Hospital Heidelberg, Heidelberg, Germany
| | - Matthew Nankivell
- MRC (Medical Research Council) Clinical Trials Unit, University College London, London, United Kingdom
| | - Magnus Nilsson
- Department of Clinical Science, Intervention and Technology, Karolinska Institute, Center for Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Svenja Seide
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
- Boehringer Ingelheim, Ingelheim, Germany
| | - Manish A. Shah
- Solid Tumor Oncology, Weill Cornell Medicine, New York, New York
| | - Qian Shi
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Michael Stahl
- Department of Medical Oncology and Hematology With Integrated Palliative Medicine, Protestant Hospital Essen-Mitte, Essen, Germany
| | - Susan Urba
- Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor
| | - Jan van Lanschot
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Dirk Vordermark
- Department of Radiotherapy, Medical Faculty of the Martin-Luther-University Halle-Wittenberg and University Hospital Halle (Saale), Halle (Saale), Germany
| | | | - Marc Ychou
- Montpellier Cancer Institute, Montpellier, France
| | - Tanja Proctor
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| | - Johannes A. Vey
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| |
Collapse
|
|
9
|
Lv H, Zhang F, Huang C, Xu S, Li J, Sun B, Gai C, Liu Z, Wang M, Li Z, Tian Z. Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2024; 150:260. [PMID: 38760614 PMCID: PMC11101546 DOI: 10.1007/s00432-024-05793-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/08/2024] [Indexed: 05/19/2024]
Abstract
PURPOSE Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.
Collapse
Affiliation(s)
- Huilai Lv
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Fan Zhang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Chao Huang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Shi Xu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Jiachen Li
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Bokang Sun
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Chunyue Gai
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Zhao Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Mingbo Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Zhenhua Li
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China
| | - Ziqiang Tian
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, NO.12, JianKang Road, Shijiazhuang, Hebei, China.
- Hebei Key Laboratory of Accurate Diagnosis and Comprehensive Treatment of Esophageal Cancer, Shijiazhuang, Hebei, China.
| |
Collapse
|
|
10
|
Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
| |
Collapse
|
|
11
|
Liang Z, Chen T, Li W, Lai H, Li L, Wu J, Zhang H, Fang C. Efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in locally advanced esophageal cancer: An updated meta-analysis. Medicine (Baltimore) 2024; 103:e36785. [PMID: 38241577 PMCID: PMC10798774 DOI: 10.1097/md.0000000000036785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 08/17/2023] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. METHODS The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3 + AEs). RESULTS This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HR = 0.80; 95% CI: 0.68-0.94), PFS (HR = 0.78; 95% CI: 0.66-0.93), pCR (OR = 13.00; 95% CI: 7.82-21.61) and R0 resection (OR = 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (OR = 2.31; 95% CI: 1.26-4.25) and grade 3 + AEs (OR = 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (OR = 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HR = 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HR = 0.80; 95% CI: 0.63-1.08). CONCLUSIONS Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3 + AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.
Collapse
Affiliation(s)
- Zhanpeng Liang
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Ting Chen
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Wenxia Li
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Huiqin Lai
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Luzhen Li
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Jiaming Wu
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Huatang Zhang
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| | - Cantu Fang
- Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, China
| |
Collapse
|
|
12
|
Beier MA, Greenbaum AA, Kangas-Dick AW, August DA. Does Neoadjuvant Radiation Therapy Contribute to the Incidence of Pulmonary Complications Following Esophagectomy for Malignant Neoplasm? Am Surg 2023; 89:4780-4788. [PMID: 36286615 DOI: 10.1177/00031348221135788] [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] [Indexed: 12/06/2023]
Abstract
BACKGROUND Post-operative pulmonary complications (POPC) are common in patients undergoing esophagectomy and neoadjuvant radiotherapy may exacerbate POPC. This study assessed whether neoadjuvant radiation increases the incidence of POPC in patients undergoing esophagectomy for malignancy. METHODS The American College of Surgeons-National Surgical Quality Improvement Program database files from 2016 to 2018 were queried for patients undergoing esophagectomy for malignancy. Inverse probability treatment weighting (IPTW) was used to create balanced cohorts in which the control group received neoadjuvant chemotherapy (nCT) and the treatment cohort received neoadjuvant chemoradiotherapy (nCRT). A subset analysis was performed on patients with pre-existing pulmonary disease (PEPD). Primary outcomes were POPC and 30-day mortality. RESULTS The all-patient analysis did not demonstrate a consistent association between neoadjuvant radiation and POPC. However, in patients with PEPD, POPC occurred more often in the nCRT cohort. Comparing nCRT to nCT and after IPTW adjustment for confounders, there was higher odds of pneumonia (aOR = 3.0, P = .002), unplanned intubation (aOR = 2.0, P = .03), and extended mechanical ventilation (aOR = 3.6, P = .002). DISCUSSION In esophageal cancer patients with PEPD that undergo nCRT vs nCT prior to esophagectomy, the greater risk of POPCs must be weighed against the potential for improved oncologic outcomes.
Collapse
Affiliation(s)
- Matthew A Beier
- Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Alissa A Greenbaum
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Aaron W Kangas-Dick
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - David A August
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| |
Collapse
|
|
13
|
Okamura A, Watanabe M, Okui J, Matsuda S, Takemura R, Kawakubo H, Takeuchi H, Muto M, Kakeji Y, Kitagawa Y, Doki Y. Neoadjuvant Chemotherapy or Neoadjuvant Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Real-World Data Comparison from A Japanese Nationwide Study. Ann Surg Oncol 2023; 30:5885-5894. [PMID: 37264286 DOI: 10.1245/s10434-023-13686-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/11/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. METHODS Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. RESULTS Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p < 0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. CONCLUSIONS Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.
Collapse
Affiliation(s)
- Akihiko Okamura
- Department of Esophageal Surgery, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masayuki Watanabe
- Department of Esophageal Surgery, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Jun Okui
- Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Satoru Matsuda
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Ryo Takemura
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Yuko Kitagawa
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| |
Collapse
|
|
14
|
Wang YJ, Bao T, Li KK, Xie XF, He XD, Zhao XL, Guo W. Concurrent radiotherapy cannot provide superiority of surgical oncological outcome and long-term survival rate in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy followed by minimally invasive esophagectomy. Surg Endosc 2023; 37:7073-7082. [PMID: 37380741 DOI: 10.1007/s00464-023-10203-w] [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: 03/07/2023] [Accepted: 06/11/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. METHODS The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. RESULTS After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. CONCLUSIONS Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.
Collapse
Affiliation(s)
- Ying-Jian Wang
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China
| | - Tao Bao
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China
| | - Kun-Kun Li
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China
| | - Xian-Feng Xie
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China
| | - Xian-Dong He
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China
| | - Xiao-Long Zhao
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China
| | - Wei Guo
- Department of Thoracic Surgery, Army Medical Center of PLA (Daping Hospital), Changjiang Route #10, Daping, 400042, Chongqing, People's Republic of China.
| |
Collapse
|
|
15
|
Yang W, Niu Y, Sun Y. Current neoadjuvant therapy for operable locally advanced esophageal cancer. Med Oncol 2023; 40:252. [PMID: 37498350 DOI: 10.1007/s12032-023-02097-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/19/2023] [Indexed: 07/28/2023]
Abstract
Locally advanced esophageal cancer has a poor prognosis, while an increasing number of patients are diagnosed with that. Neoadjuvant therapy has become a hot topic in treating locally advanced esophageal cancer to improve its survival benefit. The efficacy of neoadjuvant therapy followed by surgery has been confirmed by many studies, and neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy are included in the guidelines. In recent years, targeted therapy and immunotherapy have emerged, and more studies are evaluating the efficacy of combining them with neoadjuvant therapy for operable esophageal cancer patients. Even though the preliminary data is disappointing, many trials are still under investigation without improving survival benefits. New indexes used as surrogate endpoints (e.g., major pathologic response and pathological complete response) are emerging to accelerate the development and approval of neoadjuvant drugs. This review summarized the research progress in neoadjuvant therapy for locally advanced esophageal cancer and discussed which primary endpoint should be used in neoadjuvant therapy trials.
Collapse
Affiliation(s)
- Wenwei Yang
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yaru Niu
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yongkun Sun
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
- National Cancer Center, National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang, 065001, China.
| |
Collapse
|
|
16
|
Wu X, Zhu MC, Li GL, Xiong P, Sun W, Zhang N, Zhao B, Li LQ, Fu XN, Zhu M. Treatment and survival analysis for 40-year SEER data on upper esophageal cancer. Front Med (Lausanne) 2023; 10:1128766. [PMID: 37529246 PMCID: PMC10387539 DOI: 10.3389/fmed.2023.1128766] [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: 12/21/2022] [Accepted: 04/21/2023] [Indexed: 08/03/2023] Open
Abstract
Background Upper esophageal cancer (UEC) is rare in both Eastern and Western countries. The epidemiological characteristics and long-term survival of UEC patients are less known. In addition, the choice of optimal treatment for UEC has been controversial. Methods Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected using the SEER database. Student's t-test and Pearson's chi-square test were used to compare the differences in parameters among different groups. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rates were calculated by using the Kaplan-Meier method. Cox proportional hazard regression was used to analyze predictive factors. Results In the past 40 years, the cases of UEC have gradually increased, and the proportion of adenocarcinoma (AD) has gradually increased (from 3.6% to 11.8%, p < 0.001). There has been a significant increase (1973-1982 vs. 2004-2013) in median OS (7 months vs. 10 months, p < 0.001) and median ECSS (7 months vs. 11 months, p < 0.001) among UEC patients from 1973 to 2013. For the impact of different treatments, the results showed that the ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). Subgroup analysis showed that ECSS and OS were highest among patients treated with SWR compared with R+S and RWS for patients with localized disease. For regional disease, ECSS and OS were highest among patients with R+S compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC. Conclusion Although the long-term survival of UEC remains poor, it has gradually increased since 1973. This should be closely related to the improvement of medical care over the past 40 years. Different treatment methods have a great influence on the long-term survival of UEC. For localized diseases, surgery may be a better choice. For regional disease, surgery plus adjuvant or neoadjuvant radiotherapy may be more beneficial to improve the long-term prognosis of UEC patients.
Collapse
Affiliation(s)
- Xi Wu
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming-Chuang Zhu
- Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Guo-Liang Li
- Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Peng Xiong
- Intensive Care Unit, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Sun
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ni Zhang
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Zhao
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Le-Qun Li
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang-Ning Fu
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Zhu
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
17
|
Stam WT, Schuring N, Hulshof M, van Laarhoven H, Derks S, van Berge Henegouwen MI, van der Peet DL, Gisbertz SS, Daams F. The effect of anastomotic leakage on the incidence of recurrence after tri-modality therapy for esophageal adenocarcinomas. J Surg Oncol 2023. [PMID: 37133757 DOI: 10.1002/jso.27293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/13/2023] [Indexed: 05/04/2023]
Abstract
BACKGROUND Neoadjuvant chemoradiotherapy (nCRTx) reduces the incidence of recurrence, while anastomotic leakage has shown increase the risk of recurrence. The primary objective of this retrospective study was to investigate the incidence and pattern of recurrence and secondary median recurrence-free interval and post-recurrence survival in patients with and without anastomotic leakage after multimodal therapy for esophageal adenocarcinoma. METHODS Patients with recurrence after multimodal therapy between 2010 and 2018 were included. RESULTS Six hundred and eighteen patients were included, 91 (14.7%) had leakage and 278 (45.0%) recurrence. Patients with leakage did not develop recurrence more often (48.4%) than those without (44.4%, [p = 0.484]). Recurrence-free interval for patients with (n = 44) and without leakage (n = 234) was 39 and 52 weeks, respectively (p = 0.049). Post-recurrence survival was 11 and 16 weeks, respectively (p = 0.702). Specified by recurrence site, post-recurrence survival for loco-regional recurrences was 27 versus 33 weeks (p = 0.387) for patients with and without leakage, for distant 9 versus 13 (p = 0.999), and for combined 11 versus 18 weeks (p = 0.492). CONCLUSION AND DISCUSSION No higher incidence of recurrent disease was observed in patients with anastomotic leakage, however it is associated with a shorter recurrence-free interval. This could have implications for surveillance, as early detection of recurrent disease could influence therapeutic options.
Collapse
Affiliation(s)
- Wessel T Stam
- Amsterdam UMC location Vrije Universiteit Amsterdam, Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
| | - Nannet Schuring
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Surgery, Amsterdam, The Netherlands
| | - Maarten Hulshof
- Amsterdam UMC location University of Amsterdam, Radiotherapy, Amsterdam, The Netherlands
| | - Hanneke van Laarhoven
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands
| | - Sarah Derks
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | - Mark I van Berge Henegouwen
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Surgery, Amsterdam, The Netherlands
| | - Donald L van der Peet
- Amsterdam UMC location Vrije Universiteit Amsterdam, Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
| | - Suzanne S Gisbertz
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Surgery, Amsterdam, The Netherlands
| | - Freek Daams
- Amsterdam UMC location Vrije Universiteit Amsterdam, Surgery, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
| |
Collapse
|
|
18
|
Ólafsdóttir HS, Dalqvist E, Onjukka E, Klevebro F, Nilsson M, Gagliardi G, Alexandersson von Döbeln G. Postoperative complications after esophagectomy for cancer, neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy: A single institutional cohort study. Clin Transl Radiat Oncol 2023; 40:100610. [PMID: 36936472 PMCID: PMC10018434 DOI: 10.1016/j.ctro.2023.100610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/22/2023] [Accepted: 03/03/2023] [Indexed: 03/07/2023] Open
Abstract
Background Complications after esophagectomy are common and the possible increase in postoperative complications associated with neoadjuvant chemoradiotherapy is of concern. The aim of our study was to analyze if the addition of radiotherapy to neoadjuvant chemotherapy increases the incidence and severity of postoperative complications, including evaluation of the relation between radiation doses to the heart and lungs and postoperative complications. Methods The study was based on an institutional surgical database for esophageal cancer. The study period was October 2008 to March 2020. Patients treated with neoadjuvant chemoradiotherapy were compared to patients treated with neoadjuvant chemotherapy and dose/volume parameters for the lungs and heart considered. The primary outcome was 30-day postoperative complications. Results During the study period, 274 patients underwent surgery for esophageal cancer, 93 patients after neoadjuvant chemotherapy and 181 patients after neoadjuvant chemoradiotherapy. The median prescribed radiation dose to the planning target volume was 41.4 Gy, the median of the mean lung dose was 6.2 Gy, and the median of the mean heart dose was 20.3 Gy. The addition of radiotherapy to neoadjuvant chemotherapy did not increase the incidence of postoperative complications. Neither were radiation doses to the lungs and heart associated with postoperative complications. Taxane-based chemotherapy regimens were however associated with an increased incidence of postoperative complications. Conclusions In our cohort, the addition of neoadjuvant radiotherapy to chemotherapy was not associated with postoperative complications. However, taxane-based chemotherapy regimens, with or without concomitant radiotherapy, were associated with postoperative complications.
Collapse
Affiliation(s)
- Halla Sif Ólafsdóttir
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-141 52 Huddinge, Sweden
- Department of Radiotherapy, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-171 64 Solna, Sweden
- Corresponding author at: Department of Radiotherapy, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Anna Steckséns gata 41, SE-171 76 Stockholm, Sweden.
| | - Emmy Dalqvist
- Section of Radiotherapy Physics and Engineering, Department of Medical Radiation Physics and Nuclear Medicine, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-171 64 Solna, Sweden
| | - Eva Onjukka
- Section of Radiotherapy Physics and Engineering, Department of Medical Radiation Physics and Nuclear Medicine, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-171 64 Solna, Sweden
- Department of Oncology-Pathology, Karolinska Institutet, SE-171 64 Solna, Sweden
| | - Fredrik Klevebro
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-141 52 Huddinge, Sweden
- Department of Upper Abdominal Diseases, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-141 57 Huddinge, Sweden
| | - Magnus Nilsson
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-141 52 Huddinge, Sweden
- Department of Upper Abdominal Diseases, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-141 57 Huddinge, Sweden
| | - Giovanna Gagliardi
- Section of Radiotherapy Physics and Engineering, Department of Medical Radiation Physics and Nuclear Medicine, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-171 64 Solna, Sweden
- Department of Oncology-Pathology, Karolinska Institutet, SE-171 64 Solna, Sweden
| | - Gabriella Alexandersson von Döbeln
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-141 52 Huddinge, Sweden
- Medical Unit of Head, Neck, Lung and Skin Cancer, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, SE-171 64 Solna, Sweden
| |
Collapse
|
|
19
|
Postoperative and Pathological Outcomes of CROSS and FLOT as Neoadjuvant Therapy for Esophageal and Junctional Adenocarcinoma: An International Cohort Study From the Oesophagogastric Anastomosis Audit (OGAA). Ann Surg 2023; 277:e1026-e1034. [PMID: 35099168 DOI: 10.1097/sla.0000000000005394] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This study aimed to compare the postoperative and pathological outcomes between carboplatin, paclitaxel, radiotherapy (CROSS) and 5-FU, leucovorine, oxaliplatin and docetaxel (FLOT) in esophageal adenocarcinoma (EAC) patients from an international, multicenter cohort. SUMMARY OF BACKGROUND DATA Ongoing debate exists around optimum approach to locally advanced EAC, with proponents for perioperative chemotherapy, such as FLOT, or multimodal therapy, in particular the CROSS regimen. METHODS Patients undergoing CROSS (n = 350) and FLOT (n = 368), followed by curative esophagectomy for EAC were identified from the Oesophagogastric Anastomosis Audit. RESULTS The 90-day mortality was higher after CROSS than FLOT (5% vs 1%, P = 0.005), even on adjusted analyses [odds ratio (OR): 3.97, confidence interval (CI) 95% : 1.34-13.67]. Postoperative mortality in CROSS were related to higher pulmonary (74% vs 60%) and cardiac complications (42% vs 20%) compared to FLOT. CROSS was associated with higher pathologic complete response (pCR) rates (18% vs 10%, P = 0.004) and margin-negative resections (93% vs 76%, P < 0.001) compared with FLOT. On adjusted analyses, CROSS was associated with higher pCR rates (OR: 2.05, CI 95% : 1.26-3.34) and margin-negative resections (OR: 4.55, CI 95% : 2.70-7.69) compared to FLOT. CONCLUSIONS This study provides real-world data CROSS was associated with higher 90-day mortality than FLOT, related to cardio-pulmonary complications with CROSS. These warrant a further review into causes and mechanisms in selected patients, and at minimum suggest the need for strict radiation therapy quality assurance. Research into impact of higher pCR rates and R0 resections with CROSS compared to FLOT on long-term survival is needed.
Collapse
|
|
20
|
Purkayastha A, Sharma N, Sundaram V, Jaiswal P, Husain A. To compare neoadjuvant concurrent chemo-radiotherapy followed by surgery and neoadjuvant chemotherapy followed by surgery in carcinoma esophagus patients: A single institutional study in the Indian population. J Cancer Res Ther 2023; 19:675-683. [PMID: 37470593 DOI: 10.4103/jcrt.jcrt_940_21] [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] [Indexed: 11/04/2022]
Abstract
Objective This single institutional study compared neoadjuvant concurrent chemo-radiotherapy (NACCRT) and neoadjuvant chemotherapy (NACT) followed by surgery in locally advanced middle and lower-1/3 carcinoma esophagus patients in terms of toxicity, clinical response, operative complications, disease downstaging, resection rates, pathological response, recurrence, and survival. Materials and Methods This randomized prospective comparative study comprised 40 consecutive patients divided equally between two study arms NACCRT (n = 20; 41.4 Gy radiation dose; carboplatin area under the curve (AUC) 2/paclitaxel 50 mg/m2; 5 cycles) and NACT (n = 20; carboplatin AUC 5/paclitaxel 175 mg/m2; 2 cycles) from March 2014 to December 2016. Follow-up was done for 4 years. Chi-square test, Fischer's-exact test were used for comparative analysis and Kaplan-Meier analysis for survival. Results Statistically significant esophagitis in NACCRT and peripheral-neuropathy in NACT was observed (P < 0.001). NACCRT recorded more postoperative complications, higher complete resection (R0) rates, and pathologically complete response (pCR). Tumor downstaging was significant in both study groups (n < 0.001). Four-year median disease-free survival (DFS) and overall survival (OS) were 28.50 months and 38 months in NACCRT versus 28 months and 35.5 months in NACT, respectively. In both NACCRT and NACT, pCR cases showed improved median DFS and OS compared to pathological partial response (pPR) (n < 0.001). Conclusion This study demonstrated significant activity and tolerable toxicity of taxane-based therapy in NACCRT and NACT. Both groups recorded no survival benefit over each other, although pCR cases resulted in statistically significant survival advantage compared to clinical partial response. NACCRT resulted in lesser toxicity, numerically higher R0-resection, pCRs, median DFS, and OS compared to NACT.
Collapse
Affiliation(s)
- Abhishek Purkayastha
- Department of Radiation Oncology, Command Hospital (Southern Command), Pune, Maharashtra, India
| | - Neelam Sharma
- Department of Radiation Oncology, Army Hospital (Research and Referral), New Delhi, India
| | - Viswanath Sundaram
- Department of Medical Oncology, Army Hospital (Research and Referral), New Delhi, India
| | - Pradeep Jaiswal
- Department of Surgical Oncology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Azhar Husain
- Department of Nuclear Medicine, Command Hospital (Southern Command), Pune, Maharashtra, India
| |
Collapse
|
|
21
|
Hao W, Gao K, Li K, Li Y, Wang Z, Sun H, Xing W, Zheng Y. The Feasibility of Early Oral Feeding After Neoadjuvant Chemotherapy Combined With "Non-Tube No Fasting"-Enhanced Recovery. Ann Surg Oncol 2023; 30:1564-1571. [PMID: 36417005 DOI: 10.1245/s10434-022-12620-y] [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: 04/12/2022] [Accepted: 08/28/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND This study aimed to investigate the feasibility of early oral feeding (EOF) after neoadjuvant chemotherapy (nCT) combined with "non-tube no fasting"-enhanced recovery after minimally invasive esophagectomy (MIE). METHODS This retrospective study investigated patients who underwent nCT combined with non-tube no fasting-enhanced recovery after MIE in the Department of Thoracic Surgery, Ward I, of the authors' hospital from January 2014 to August 2017. These patients were divided into an early oral feeding (EOF) group (n = 112) and a late oral feeding (LOF) group (n = 69). The postoperative complications were compared between the two groups. RESULTS The study enrolled 181 patients (112 patients in the EOF group and 69 patients in the LOF group). No significant differences were found between the two groups in the incidence rates of complications such as anastomotic leakage (P = 0.961), pneumonia (P = 0.450), respiratory failure (P = 0.944), heart failure (P = 1.000), acute respiratory distress syndrome (ARDS) (P = 0.856), and unplanned reoperation (P = 0.440), whereas the time to the first postoperative flatus/bowel movement (P < 0.001) and the postoperative length of stay (P < 0.001) were significantly better in the EOF group than in the LOF group.. CONCLUSIONS In this study, EOF after nCT combined with non-tube no fasting-enhanced recovery after MIE did not significantly increase complications, but significantly shortened the time to the first postoperative flatus/bowel movement and the postoperative length of stay.
Collapse
Affiliation(s)
- Wentao Hao
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
| | - Kun Gao
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
| | - Keting Li
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
| | - Yin Li
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zongfei Wang
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
| | - Haibo Sun
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
| | - Wenqun Xing
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China
| | - Yan Zheng
- Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, 450008, People's Republic of China.
| |
Collapse
|
|
22
|
Xu J, Yan C, Li Z, Cao Y, Duan H, Ke S. Efficacy and Safety of Neoadjuvant Chemoimmunotherapy in Resectable Esophageal Squamous Cell Carcinoma: A Meta-analysis. Ann Surg Oncol 2023; 30:1597-1613. [PMID: 36380254 DOI: 10.1245/s10434-022-12752-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 10/19/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE This study aimed to summarize the efficacy and safety of neoadjuvant chemoimmunotherapy in resectable esophageal squamous cell carcinoma (ESCC). METHODS Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in resectable ESCC published before June 2022 was retrieved from PubMed, Embase, Cochrane Library, and Web of Science. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool. Subgroup and sensitivity analyses were further performed. RESULTS A total of 452 patients from 15 studies were included in this meta-analysis. All of the studies explored the efficacy and safety of neoadjuvant chemoimmunotherapy. The pooled major pathological response (MPR) rate and pathological complete response (PCR) rate were 58.3% and 32.9%, respectively. The pooled incidence of treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were 91.6% and 19.4%, respectively. The pooled R0 resection rate was 92.8%, and the resection rate was 81.1%. Incidence of anastomotic leakage, pulmonary infection, and postoperative hoarseness were 10.7%, 21.3%, and 13.0%, respectively. Compared with 2 cycles of neoadjuvant therapy, patients who received > 2 cycles of neoadjuvant therapy showed higher MPR rate (57.3% vs. 61.1%) and PCR rate (30.6% vs. 37.9%), and the incidence of TRAEs (89.2% vs. 98.9%) tended to be higher. However, no significant difference was found (P > 0.05). Two cycles of neoadjuvant therapy showed higher R0 resection rate and resection rate (R0 resection rate: 96.0% vs. 87.8%, P = 0.02; resection rate: 85.6% vs. 74.7%, P = 0.01). Pembrolizumab- and tislelizumab-based neoadjuvant therapy showed higher MPR rate (72.4% and 72.2%) and PCR rate (41.5 % and 50.0%). Compared with other ICIs, tislelizumab-based neoadjuvant therapy showed lower R0 resection rate (80.5%). The pooled incidence of SAEs for pembrolizumab-based neoadjuvant therapy (2.0%) was lower. Camrelizumab-based neoadjuvant therapy showed lower incidence of pulmonary infection (11.5%). CONCLUSIONS Neoadjuvant chemoimmunotherapy is effective and safe for resectable ESCC.
Collapse
Affiliation(s)
- Jinxin Xu
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Chun Yan
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Zhe Li
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Yunpeng Cao
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Hongbing Duan
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Sunkui Ke
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China.
| |
Collapse
|
|
23
|
Motegi D, Ichikawa H, Bamba T, Muneoka Y, Kano Y, Usui K, Hanyu T, Ishikawa T, Hirose Y, Miura K, Tajima Y, Shimada Y, Sakata J, Nakagawa S, Kosugi SI, Wakai T. Ulcer Scarring in the Gastric Conduit Is a Risk Factor for Anastomotic Leakage After Esophagectomy for Esophageal Cancer. J Gastrointest Surg 2023; 27:250-261. [PMID: 36509899 DOI: 10.1007/s11605-022-05545-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/19/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL. METHODS Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively. RESULTS AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004). CONCLUSIONS Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.
Collapse
Affiliation(s)
- Daisuke Motegi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan.
| | - Takeo Bamba
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-Cho, Chuo-Ku, Niigata City, Niigata, 951-8566, Japan
| | - Yusuke Muneoka
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yosuke Kano
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Kenji Usui
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Takaaki Hanyu
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
- Department of Surgery, Shibata Prefectural Hospital, 1-2-8 Hon-Cho, Shibata City, Niigata, 957-8588, Japan
| | - Takashi Ishikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yosuke Tajima
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| | - Satoru Nakagawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-Cho, Chuo-Ku, Niigata City, Niigata, 951-8566, Japan
| | - Shin-Ichi Kosugi
- Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma City, Niigata, 949-7302, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata City, Niigata, 951-8510, Japan
| |
Collapse
|
|
24
|
Tang H, Wang H, Fang Y, Zhu JY, Yin J, Shen YX, Zeng ZC, Jiang DX, Hou YY, Du M, Lian CH, Zhao Q, Jiang HJ, Gong L, Li ZG, Liu J, Xie DY, Li WF, Chen C, Zheng B, Chen KN, Dai L, Liao YD, Li K, Li HC, Zhao NQ, Tan LJ. Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial. Ann Oncol 2023; 34:163-172. [PMID: 36400384 DOI: 10.1016/j.annonc.2022.10.508] [Citation(s) in RCA: 74] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 09/29/2022] [Accepted: 10/13/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
Collapse
Affiliation(s)
- H Tang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai
| | - H Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai
| | - Y Fang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai
| | - J Y Zhu
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai; Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai
| | - J Yin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai
| | - Y X Shen
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai
| | - Z C Zeng
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai; Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai
| | - D X Jiang
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai
| | - Y Y Hou
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai
| | - M Du
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing
| | - C H Lian
- Department of General Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi
| | - Q Zhao
- Department of General Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi
| | - H J Jiang
- Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - L Gong
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Z G Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai
| | - J Liu
- Department of Radiotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai
| | - D Y Xie
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou
| | - W F Li
- Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou
| | - C Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou
| | - B Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou
| | - K N Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing
| | - L Dai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing
| | - Y D Liao
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - K Li
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - H C Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai
| | - N Q Zhao
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China
| | - L J Tan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai.
| |
Collapse
|
|
25
|
Kundel Y, Kurman N, Sulimani O, Gavrielli S, Nachalon Y, Moore A, Kashtan H, Fenig E, Brenner B, Popovtzer A, Fredman E. The effect of gastric fundus radiation dose on postoperative anastomotic leakage in esophageal cancer. Front Oncol 2023; 13:1080089. [PMID: 36925923 PMCID: PMC10011689 DOI: 10.3389/fonc.2023.1080089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 02/10/2023] [Indexed: 03/08/2023] Open
Abstract
Introduction Standard-of-care treatment for locally advanced esophageal carcinoma (LAEC) includes neoadjuvant chemoradiotherapy followed by esophagectomy. A potentially catastrophic surgical complication is the development of a postoperative anastomotic leak. To date, the association with radiation dose exposure had been inconclusive. We examined the correlation between radiation exposure to the gastric fundus and risk of postoperative leakage using contemporary radiation doses and fractionation. Methods A total of 69 consecutive patients with LAEC who underwent neoadjuvant chemoradiotherapy followed by esophagectomy in our tertiary center were prospectively followed (median, 27 months). Neoadjuvant regimen included 50.4 Gy in 28 fractions with 5-fluorouracil and cisplatin and 41.4 Gy in 23 fractions with carboplatin and paclitaxel. The gastric fundus was contoured and dosimetric and radiation technique parameters were retrospectively evaluated. Results Of the total number of patients, 71% and 29% had esophageal and gastroesophageal junction (GEJ) tumors, respectively. Fourteen patients (20.3%) experienced anastomotic leaks within a median of 2 days postoperatively, 78.6% of whom had lower third esophagus or GEJ primaries. Mean and minimum fundus dose did not significantly differ between those with and those without leakage (p = 0.42, p = 0.51). Mean fundus V25, V30, and V35 doses were numerically but not statistically higher in those with anastomotic leak (p = 0.58, p = 0.39, and p = 0.30, respectively). No correlation with incidence of leakage was seen between 3D and IMRT treatment modalities. Conclusions In our comparatively large prospectively collected series of patients treated for LAEC, radiation dose to the gastric fundus during neoadjuvant combination therapy prior to surgery did not correlate with the risk of postoperative anastomotic leak.
Collapse
Affiliation(s)
- Yulia Kundel
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.,Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Noga Kurman
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel
| | - Omri Sulimani
- Department of Surgery, Rabin Medical Center, Petach Tikva, Israel
| | - Shlomo Gavrielli
- Department of Radiology, Rabin Medical Center, Petach Tikva, Israel
| | - Yuval Nachalon
- Department of Otolaryngology - Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel
| | - Assaf Moore
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.,Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hanoch Kashtan
- Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Surgery, Rabin Medical Center, Petach Tikva, Israel
| | - Eyal Fenig
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.,Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Baruch Brenner
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.,Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Aron Popovtzer
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.,Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Elisha Fredman
- Department of Radiation Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.,Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
26
|
Lin CH, Chuang HN, Hsiao TH, Kumar VB, Hsu CH, Huang CY, Lee LW, Mao CL, Ko JL, Hsu CP. AGR2 expression as a predictive biomarker for therapy response in esophageal squamous cell carcinoma. PLoS One 2022; 17:e0276990. [PMID: 36327302 PMCID: PMC9632826 DOI: 10.1371/journal.pone.0276990] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 10/17/2022] [Indexed: 11/06/2022] Open
Abstract
Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.
Collapse
Affiliation(s)
- Chih-Hung Lin
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Thoracic Surgery, Department of Surgery, Taichung Veteran General Hospital, Taichung, Taiwan
| | - Han-Ni Chuang
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Tzu-Hung Hsiao
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan
- Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan
| | - V. Bharath Kumar
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan
| | - Chiung-Hung Hsu
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Chih-Yang Huang
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Li-Wen Lee
- Division of Thoracic Surgery, Department of Surgery, Taichung Veteran General Hospital, Taichung, Taiwan
| | - Chien-Lin Mao
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jiunn-Liang Ko
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- * E-mail: (JLK); (CPH)
| | - Chung-Ping Hsu
- Division of Thoracic Surgery, Department of Surgery, Taichung Veteran General Hospital, Taichung, Taiwan
- Division of Thoracic Surgery, Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- * E-mail: (JLK); (CPH)
| |
Collapse
|
|
27
|
Quantitative RECIST derived from multiparametric MRI in evaluating response of esophageal squamous cell carcinoma to neoadjuvant therapy. Eur Radiol 2022; 32:7295-7306. [PMID: 36048205 DOI: 10.1007/s00330-022-09111-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 08/04/2022] [Accepted: 08/10/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To develop a quantitative Response Evaluation Criteria in Solid Tumors (qRECIST) for evaluating response to neoadjuvant therapy (nT) in ESCCs relying on multiparametric (mp) MRI. METHODS Patients with cT2-T4a/N0-N3/M0 ESCC undergoing pre-nT and post-nT esophageal mpMRI before radical resection were prospectively included. Images were reviewed by two experienced radiologists. qRECIST was redefined using four methods including conventional criterion (cRECIST) and three model-dependent RECIST relying on quantitative MRI measurements at pre-nT, post-nT, and delta pre-post nT, respectively. Pathological tumor regression grades (TRGs) were used as a reference standard. The rates of agreement between four qRECIST methods and TRGs were determined with a Cronbach's alpha test, area under the curve (AUC), and a diagnostic odds ratio meta-analysis. RESULTS Ninety-one patients were enrolled. All four methods revealed high inter-reader agreements between the two radiologists, with a Kappa coefficient of 0.96, 0.87, 0.88, and 0.97 for cRECIST, pre-nT RECIST, post-nT RECIST, and delta RECIST, respectively. Among them, delta RECIST achieved the highest overall agreement rate (67.0% [61/91]) with TRGs, followed by post-nT RECIST (63.8% [58/91]), cRECIST (61.5% [56/91]), and pre-nT RECIST (36.3% [33/91]). Especially, delta RECIST achieved the highest accuracy (97.8% [89/91]) in distinguishing responders from non-responders, with 97.3% (34/35) for responders and 98.2% (55/56) for non-responders. Post-nT RECIST achieved the highest accuracy (93.4% [85/91]) in distinguishing complete responders from non-pCRs, with 77.8% (11/18) for pCRs and 94.5% (69/73) for non-pCRs. CONCLUSION The qRECIST with mpMRI can assess treatment-induced changes and may be used for early prediction of response to nT in ESCC patients. KEY POINTS • Quantitative mpMRI can reliably assess tumor response, and delta RECIST model had the best performance in evaluating response to nT in ESCCs, with an AUC of 0.98, 0.95, 0.80, and 0.82 for predicting TRG0, TRG1, TRG2, and TRG3, respectively. • In distinguishing responders from non-responders, the rate of agreement between delta RECIST and pathology was 97.3% (34/35) for responders and 98.2% (55/56) for non-responders, resulting in an overall agreement rate of 97.8% (89/91). • In distinguishing pCRs from non-pCR, the rate of agreement between MRI and pathology was 77.8% (11/18) for pCRs and 94.5% (69/73) for non- pCRs, resulting in an overall agreement rate of 91.2% (83/91).
Collapse
|
|
28
|
Solidum JGN, Rojo RD, Wo JY, Dee EC. Proton Beam Therapy for Esophageal Cancer. Cancers (Basel) 2022; 14:cancers14164045. [PMID: 36011037 PMCID: PMC9407004 DOI: 10.3390/cancers14164045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/09/2022] [Accepted: 08/12/2022] [Indexed: 12/05/2022] Open
Abstract
Simple Summary Early-stage esophageal cancer is managed surgically, with the addition of radiotherapy for locally advanced disease. Current photon-based radiotherapy results in a high treatment-related complications, due to proximal organ involvement. The anatomic location of the esophagus raises challenges due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. In this review, we present the role of PBT for esophageal cancer, including treatment planning, early clinical comparisons with photon-based techniques, ongoing trials, current challenges, toxicities, and issues of equity and health services. Abstract Early-stage esophageal cancer is often primarily managed surgically, with the addition of radiotherapy for locally advanced disease. However, current photon-based radiotherapy regimens and surgery results in a high incidence of treatment-related cardiac and pulmonary complications due to the involvement of proximal organs at risk. In addition, the anatomic location of the esophagus raises challenges for radiotherapy due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These challenges propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. Several dosimetric studies support the potential advantages of PBT for esophageal cancer treatment however, translation of these results to improved clinical outcomes remains unclear with limited clinical data, especially in large populations. Studies on the effect on quality of life are likewise lacking. Here, we review the existing and emerging role of PBT for esophageal cancer, including treatment planning, early clinical comparisons of PBT with photon-based techniques, recently concluded and ongoing clinical trials, challenges and toxicities, effects on quality of life, and global inequities in the treatment of esophageal cancer.
Collapse
Affiliation(s)
- Jea Giezl N. Solidum
- College of Medicine, University of the Philippines Manila, Manila 1000, Metro Manila, Philippines
| | - Raniv D. Rojo
- College of Medicine, University of the Philippines Manila, Manila 1000, Metro Manila, Philippines
| | - Jennifer Y. Wo
- Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom St., Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Edward Christopher Dee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Correspondence:
| |
Collapse
|
|
29
|
Wang YJ, Li KK, Xie XF, Bao T, Hao ZP, Long J, Wang S, Zhong ZY, Guo W. Neoadjuvant Anlotinib and chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced esophageal squamous cell carcinoma: Short-term results of an open-label, randomized, phase II trial. Front Oncol 2022; 12:908841. [PMID: 35982957 PMCID: PMC9380438 DOI: 10.3389/fonc.2022.908841] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/08/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundClinical benefits of neoadjuvant Anlotinib for locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. This study evaluated the efficacy and safety of neoadjuvant Anlotinib plus chemotherapy followed by minimally invasive esophagectomy (MIE) for the treatment of patients with locally advanced ESCC.MethodsPatients with locally advanced ESCC were randomly assigned to neoadjuvant Anlotinib combined with chemotherapy (Anlotinib group) or neoadjuvant chemoradiotherapy alone (nCRT group) with an allocation ratio of 1:1. The primary endpoint was the R0 surgical resection rate. Secondary endpoints included postoperative pathologic stage, complete response (CR) rate, and safety. Safety was assessed by adverse events (AEs) and postoperative complications.ResultsFrom August 2019 to August 2021, 93 patients were assigned to the nCRT or Anlotinib group. Of the 93 patients, 79 underwent MIE and were finally included in the per-protocol set (nCRT group: n=39; Anlotinib group: n=40). The R0 resection rate was 97.4% for nCRT versus 100.0% for Anlotinib group (p>0.05). Compared with the nCRT group, patients in the Anlotinib group had shorter total operation duration (262.2 ± 39.0 vs. 200.7 ± 25.5 min, p=0.010) and less blood loss (161.3 ± 126.7 vs. 52.4 ± 39.3 mL, p<0.001). No significant differences were found in the postoperative pathologic stage between the Anlotinib group and nCRT group (all p>0.05). Besides, the incidences of AEs (80.0% vs. 92.3%) and postoperative complications (22.5% vs. 30.8%) were similar between the two groups (all p>0.05).ConclusionsNeoadjuvant Anlotinib plus chemotherapy had a similar safety profile and pathologic response, but better surgical outcomes than nCRT for locally advanced ESCC.
Collapse
Affiliation(s)
- Ying-Jian Wang
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Kun-Kun Li
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xian-Feng Xie
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Tao Bao
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhi-Peng Hao
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jiang Long
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shuai Wang
- Department of Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhao-Yang Zhong
- Department of Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Wei Guo, ; Zhao-Yang Zhong,
| | - Wei Guo
- Department of Thoracic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Wei Guo, ; Zhao-Yang Zhong,
| |
Collapse
|
|
30
|
A Transcriptomic Liquid Biopsy Assay for Predicting Resistance to Neoadjuvant Therapy in Esophageal Squamous Cell Carcinoma. Ann Surg 2022; 276:101-110. [PMID: 35703443 PMCID: PMC9276630 DOI: 10.1097/sla.0000000000005473] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to establish a liquid-biopsy assay to predict response to neoadjuvant therapy (NAT) in esophageal squamous cell carcinoma (ESCC) patients. SUMMARY BACKGROUND DATA Pretreatment prediction of resistance to NAT is of great significance for the selection of treatment options in ESCC patients. In this study, we comprehensively translated tissue-based microRNA (miRNA) and messenger RNA (mRNA) expression biomarkers into a liquid biopsy assay. METHODS We analyzed 186 clinical ESCC samples, which included 128 formalin-fixed paraffin-embedded and a matched subset of 58 serum samples, from 2 independent institutions. We performed quantitative reverse-transcription polymerase chain reaction, and developed a resistance-prediction model using the logistic regression analyses. RESULTS We first evaluated the potential of 4-miRNAs and 3-mRNAs panel, which robustly predicted resistance to NAT [area under the curve (AUC): 0.85]. Moreover, addition of tumor size to this panel increased predictive potential to establish a combination signature (AUC: 0.92). We successfully validated this signature performance in independent cohort, and our model was more accurate when the signature was combined with clinical predictors (AUC: 0.81) to establish a NAT resistance risk (NATRR) model. Finally, we successfully translated our NATRR model into a liquid biopsy assay (AUC: 0.78), and a multivariate regression analysis revealed this model as an independent predictor for response to NAT (odds ratio: 6.10; P < 0.01). CONCLUSIONS We successfully developed a liquid biopsy-based assay that allows robust prediction of response to NAT in ESCC patients, and our assay provides fundamentals of developing precision-medicine.
Collapse
|
|
31
|
Duan H, Shao C, Pan M, Liu H, Dong X, Zhang Y, Tong L, Feng Y, Wang Y, Wang L, Newman NB, Sarkaria IS, Reynolds JV, De Cobelli F, Ma Z, Jiang T, Yan X. Neoadjuvant Pembrolizumab and Chemotherapy in Resectable Esophageal Cancer: An Open-Label, Single-Arm Study (PEN-ICE). Front Immunol 2022; 13:849984. [PMID: 35720388 PMCID: PMC9202755 DOI: 10.3389/fimmu.2022.849984] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 04/28/2022] [Indexed: 12/13/2022] Open
Abstract
Background In this single-arm study, the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy were evaluated in patients with resectable esophageal squamous cell carcinoma (ESCC). Methods This study included patients with ESCC of clinical stages II–IVA who underwent surgery within 4 to 6 weeks after completing treatment with pembrolizumab (200 mg) combined with a conventional chemotherapy regimen (3 cycles). The safety and efficacy of this combination treatment were evaluated as primary endpoints of the study. Results From April 2019 to August 2020, a total of 18 patients (including 14 men) were enrolled, of whom 13 patients progressed to surgery. Postoperative pathology revealed a major pathological response (MPR) in 9 cases (9/13, 69.2%) and a pathological complete response (pCR) in 6 cases (6/13, 46.2%). Five patients (5/18, 27.8%) experienced serious treatment-related adverse events (AEs) of grades 3–4. At the time of data cutoff (Mar 25, 2022), the shortest duration of follow-up was 17.8 months. Programmed death-ligand 1 (PD-L1) expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT) (r=−0.55, P=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens were weakly correlated with RVT (r=0.71; P=0.07), while a positive correlation was observed between postoperative forkhead box P3-positive (Foxp3)+T cells/CD4+Tcells ratios and RVT (r=0.84, P=0.03). Conclusions The combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment (TME). It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials (RCTs). Trial Registration ChiCTR2100048917.
Collapse
Affiliation(s)
- Hongtao Duan
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Changjian Shao
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Minghong Pan
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Honggang Liu
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Xiaoping Dong
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Yong Zhang
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Liping Tong
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Yingtong Feng
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Yuanyuan Wang
- Department of Pathology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Lu Wang
- Department of Pathology, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Neil B Newman
- Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Inderpal S Sarkaria
- Department of Cardiothoracic Surgery, The University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - John V Reynolds
- Department of Surgery, Trinity Centre, St. James's Hospital, Dublin, Ireland
| | | | - Zhiqiang Ma
- Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Tao Jiang
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Xiaolong Yan
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| |
Collapse
|
|
32
|
Gong J, Zhang W, Huang W, Liao Y, Yin Y, Shi M, Qin W, Zhao L. CT-based radiomics nomogram may predict local recurrence-free survival in esophageal cancer patients receiving definitive chemoradiation or radiotherapy: a multicenter study. Radiother Oncol 2022; 174:8-15. [PMID: 35750106 DOI: 10.1016/j.radonc.2022.06.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/18/2022] [Accepted: 06/15/2022] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND PURPOSE To establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. MATERIALS AND METHODS This retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n=201) and internal validation set (n=101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n=95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. RESULTS The deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index:0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation set (C-index:0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: -0.06). Low-risk groups had better LRFS than high-risk groups in training (p<0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p<0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p<0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index:0.82), internal (Cindex: 0.78), and external validation set (C-index:0.76). Calibration curves showed good agreement. CONCLUSIONS The hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.
Collapse
Affiliation(s)
- Jie Gong
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University. Xi'an, China
| | - Wencheng Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
| | - Ye Liao
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University. Xi'an, China
| | - Yutian Yin
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University. Xi'an, China
| | - Mei Shi
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University. Xi'an, China.
| | - Wei Qin
- Life Sciences Research Center, School of Life Sciences and Technology, Xidian University, Xi'an, China
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University. Xi'an, China.
| |
Collapse
|
|
33
|
Ma X, Zhao W, Li B, Yu Y, Ma Y, Thomas M, Zhang Y, Xiang J, Zhang Y. Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Perioperative and Survival Outcomes. Front Oncol 2022; 12:810898. [PMID: 35756623 PMCID: PMC9226664 DOI: 10.3389/fonc.2022.810898] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 04/28/2022] [Indexed: 12/17/2022] Open
Abstract
Background Immune checkpoint inhibitors (ICI) improve survival in patients with late-stage esophageal squamous cell carcinoma (ESCC) but have not been fully evaluated in locally advanced ESCC. Method We retrospectively assessed outcomes of consecutive, treatment-naïve locally advanced ESCC (stage III or IVA) adults treated with neoadjuvant ICI plus chemotherapy followed by surgery, who refused or lacked access to radiotherapy, with regards to surgery feasibility, pathological response, and relapse-free survival (RFS). Results We uneventfully treated 34 patients with the combined regimen in 2020. None reported grade III or higher toxic effects. All underwent surgery as planned: 32 received complete (R0) resections and 2 had microscopically positive margins (R1). Tumor downstaging occurred in 33 (97.1%) patients and 11 (32.4%) had pathologically complete response of the primary lesion. Median postoperative length of stay was 12 days (interquartile range: 11 to 17). All patients resumed a semi-liquid diet on discharge. The 90-day postoperative morbidity rate was 20.6% (7/34) with no mortalities. The 1-year RFS was 77.8% [95% CI, 64.2-94.2]. Conclusion Neoadjuvant ICI plus chemotherapy was safe and resulted in significant downstaging, rendering inoperable tumors operable, relieving symptoms of dysphagia and prolonging survival for locally advanced ESCC patients who refused or lacked access to radiotherapy.
Collapse
Affiliation(s)
- Xiao Ma
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Weixin Zhao
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Bin Li
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yongfu Yu
- Department of Biostatistics, The Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai, China
| | - Yuan Ma
- Chinese Institute for Brain Research, Beijing, China
| | - Mathew Thomas
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL, United States
| | - Yawei Zhang
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiaqing Xiang
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yiliang Zhang
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Institute of Thoracic Oncology, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| |
Collapse
|
|
34
|
Surgical Treatment of Patients with Adenocarcinoma of the Distal Esophageal Portion and Gastroesophageal Junction Performed After Neoadjuvant Chemotherapy and Combined Chemoradiation. ACTA MEDICA BULGARICA 2022. [DOI: 10.2478/amb-2022-0007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Esophageal carcinoma is an extremely aggressive cancer with an early distant spread, high rate of local recurrence, and low overall survival. Herewith we present 3 patients with advanced moderately and low differentiated adenocarcinomas, who underwent neoadjuvant chemotherapy (nCT) (two patients) and combined nCT with neoadjuvant radiation therapy (nRT) (one patient), followed by radical surgery. Subtotal esophageal resection, proximal gastric resection, and intrathoracic right gastroesophagoplasty a modo Ivor-Lewis were performed in the first two patients, while total gastrectomy, distal third esophageal resection, splenectomy and left intrathoracic esophagojejunoplasty a modo Roux were performed in the third one. A literature review of the role of neoadjuvant chemoradiotherapy (nCRT) as part of a trimodality therapy for advanced esophageal carcinoma is presented.
Collapse
|
|
35
|
Samarasam I, Surendran S, Midha G, Paul N, Yacob M, Abraham V, Mathew M, Sasidharan B, Gunasingam R, Pavamani S, Irodi A, Mani T. Feasibility, safety and oncological outcomes of minimally invasive oesophagectomy following neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma – Experience from a tertiary care centre. J Minim Access Surg 2022; 18:545-556. [DOI: 10.4103/jmas.jmas_242_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
36
|
Feng JF, Wang L, Chen QX, Yang X. Development and Validation of a New Integrative Score Based on Various Systemic Inflammatory and Nutritional Indicators in Predicting Prognosis in Patients With Resectable Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study. Cancer Control 2022; 29:10732748221091394. [PMID: 35410489 PMCID: PMC9008826 DOI: 10.1177/10732748221091394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background Recent studies revealed that various inflammatory and nutritional indexes
were associated with prognosis in esophageal cancer (EC). However, these
studies only evaluated one or two indexes, and the prognostic value of these
indexes individually or in combination is unclear. This study aimed to
construct an integrative score based on various inflammatory and nutritional
indexes for prognosis in resectable esophageal squamous cell
carcinoma (ESCC). Methods A total of 421 consecutive patients were randomly divided into either a
training or validation cohort at a ratio of 7:3 for retrospective analysis.
Using logic regression analyses, independent risk factors from peripheral
blood indexes were screened to construct an integrative score. The
associations regarding the integrative score, clinical characteristics,
cancer-specific survival (CSS), and overall survival (OS) were analyzed. Results Out of 20 indexes, hemoglobin (HB), C-reactive protein to albumin ratio
(CAR), and platelet to lymphocyte ratio (PLR) were independent risk factors
based on logical regression analyses. Then, an integrative score with the
optimal cut-off value of .67 was established according to the Combination Of
HB, CAR, and PLR (COHCP). The area under the curve (AUC) indicated higher
predictive ability of COHCP on prognosis than other indicators. Multivariate
analyses revealed that COHCP serves as an independent prognostic score.
Patients with COHCP low group (≤.67) had better 5-year CSS (57.3% vs 13.5%,
P < .001) and OS (51.1% vs 12.3%, P
< .001) than those with high group, respectively. Finally, the nomogram
based on COHCP was established and validated regarding CSS and OS, which can
accurately and effectively predict individual survival in resected ESCC. Conclusion The COHCP was a novel, simple, and useful predictor in resectable ESCC. The
COHCP-based nomogram may accurately and effectively predict survival.
Collapse
Affiliation(s)
- Ji Feng Feng
- Department of Thoracic Oncological Surgery, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, 89680Zhejiang Cancer Hospital, Hangzhou, China
| | - Liang Wang
- Department of Thoracic Oncological Surgery, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, 89680Zhejiang Cancer Hospital, Hangzhou, China
| | - Qi-Xun Chen
- Department of Thoracic Oncological Surgery, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, 89680Zhejiang Cancer Hospital, Hangzhou, China
| | - Xun Yang
- Department of Thoracic Oncological Surgery, Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, 89680Zhejiang Cancer Hospital, Hangzhou, China
| |
Collapse
|
|
37
|
Schröder W, Gisbertz SS, Voeten DM, Gutschow CA, Fuchs HF, van Berge Henegouwen MI. Surgical Therapy of Esophageal Adenocarcinoma-Current Standards and Future Perspectives. Cancers (Basel) 2021; 13:5834. [PMID: 34830988 PMCID: PMC8616112 DOI: 10.3390/cancers13225834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/15/2021] [Accepted: 11/18/2021] [Indexed: 12/18/2022] Open
Abstract
Transthoracic esophagectomy is currently the predominant curative treatment option for resectable esophageal adenocarcinoma. The majority of carcinomas present as locally advanced tumors requiring multimodal strategies with either neoadjuvant chemoradiotherapy or perioperative chemotherapy alone. Minimally invasive, including robotic, techniques are increasingly applied with a broad spectrum of technical variations existing for the oncological resection as well as gastric reconstruction. At the present, intrathoracic esophagogastrostomy is the preferred technique of reconstruction (Ivor Lewis esophagectomy). With standardized surgical procedures, a complete resection of the primary tumor can be achieved in almost 95% of patients. Even in expert centers, postoperative morbidity remains high, with an overall complication rate of 50-60%, whereas 30- and 90-day mortality are reported to be <2% and <6%, respectively. Due to the complexity of transthoracic esophagetomy and its associated morbidity, esophageal surgery is recommended to be performed in specialized centers with an appropriate caseload yet to be defined. In order to reduce postoperative morbidity, the selection of patients, preoperative rehabilitation and postoperative fast-track concepts are feasible strategies of perioperative management. Future directives aim to further centralize esophageal services, to individualize surgical treatment for high-risk patients and to implement intraoperative imaging modalities modifying the oncological extent of resection and facilitating surgical reconstruction.
Collapse
Affiliation(s)
- Wolfgang Schröder
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;
| | - Suzanne S. Gisbertz
- Cancer Center Amsterdam, Department of Surgery, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (S.S.G.); (D.M.V.); (M.I.v.B.H.)
| | - Daan M. Voeten
- Cancer Center Amsterdam, Department of Surgery, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (S.S.G.); (D.M.V.); (M.I.v.B.H.)
| | - Christian A. Gutschow
- Department of General and Transplantation Surgery, University Hospital Zurich, 8091 Zurich, Switzerland;
| | - Hans F. Fuchs
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;
| | - Mark I. van Berge Henegouwen
- Cancer Center Amsterdam, Department of Surgery, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (S.S.G.); (D.M.V.); (M.I.v.B.H.)
| |
Collapse
|
|
38
|
Zhao Q, Zhu J, Liu Y, Qin S, Zhou J. Preliminary evaluation of postoperative radiotherapy with small T-shaped field in thoracic esophageal squamous cell carcinoma. J Gastrointest Oncol 2021; 12:2004-2012. [PMID: 34790368 DOI: 10.21037/jgo-21-604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 10/21/2021] [Indexed: 11/06/2022] Open
Abstract
Background The optimal extent of clinical target volume (CTV) for postoperative radiotherapy in complete resection thoracic esophageal squamous cell carcinoma (ESCC) patients remains controversial. This study aimed to evaluate the primary outcome of postoperative radiotherapy with small T-shaped field encompassing the tumor bed, positive lymph node areas, bilateral supraclavicular areas, and upper and middle mediastinal areas. Methods A total of 96 thoracic ESCC patients were enrolled, with 49 and 47 cases in the small T-shaped field group and tumor bed field group, respectively. All of the patients received intensity-modulated radiotherapy (IMRT), and chemotherapy was administrated concurrently or sequentially. The median time of follow-up was 25 (range, 7-47) months. Results At the end of the follow-up period, in the small T-shaped field group, 8 (16.3%) patients had locoregional recurrence (LRR) and 12 (24.5%) had distant metastasis (DM), while in the tumor bed field group, 15 (31.9%) patients had LRR and 11 (23.4%) had DM. Although the rates of LRR and DM were not statistically different, LRR incidence in the mediastinal lymph nodes of the small T-shaped field group was strikingly lower than that of the tumor bed field group. The overall survival (OS) of the small T-shaped field group was higher than that of the tumor bed field group, but the difference was not statistically significance. In addition, we observed grade 2 radiation pneumonitis and grade 2 radiation esophagitis in both groups; all of these side effects were tolerable and controllable, and none of the patients experienced ≥ grade 3 pneumonitis, esophagitis, esophageal stricture, or life-threatening hemorrhage. Conclusions In conclusion, radiotherapy with small T-shaped field might be a feasible and efficacious postoperative approach for ESCC patients.
Collapse
Affiliation(s)
- Qi Zhao
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiaxing Zhu
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yandong Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Songbing Qin
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Juying Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| |
Collapse
|
|
39
|
Duan H, Wang T, Luo Z, Wang X, Liu H, Tong L, Dong X, Zhang Y, Valmasoni M, Kidane B, Almhanna K, Wiesel O, Pang S, Ma J, Yan X. A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study). ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1700. [PMID: 34988209 PMCID: PMC8667140 DOI: 10.21037/atm-21-6102] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/24/2021] [Indexed: 12/16/2022]
Abstract
Background Preoperative chemotherapy or chemoradiotherapy is the standard treatment for resectable esophageal cancer (EC); however, it is associated with increased postoperative complications and mortality. Recently, Immune Checkpoint inhibitors have been incorporated in the treatment of advanced EC. Its role in the preoperative setting has not been established yet. In this multicenter, single-arm study, we evaluated the efficacy and safety of neoadjuvant therapy with sintilimab in combination with chemotherapy in treating EC. Methods Patients received neoadjuvant therapy with 3 cycles of sintilimab 200 mg Q3W in combination with platinum-based chemotherapy. Surgery was performed within 4–6 weeks after neoadjuvant therapy. The primary endpoints of the trial were pathological complete response (pCR) and safety. Results A total of 23 patients (21 men and 2 women) were enrolled. Surgery was completed in 17 participants, with 16 achieving R0 resection and 1 had R1 resection, 5 participants refused surgery. One patient progressed prior to surgery. Twenty one patients (91%) had significant improvement in their dysphagia following treatment as assessed by Stooler’s criteria. The majority of patients who underwent resection have a good pathological response and downstaging rate was 76.5% (13/17). A pCR was achieved in 6 cases (6/17, 35.3%) and major pathological response (MPR) in 9 cases (9/17, 52.9%). The main preoperative adverse events (AEs) were vomiting (13/23, 56.5%), leukopenia (12/23, 52.2%), neutropenia (9/23, 39.1%), and malaise (8/23, 34.8%). Immune-related AEs were mild and included hypothyroidism (2/23, 8.7%) and rash (4/23, 17.4%). The incidence of ≥ grade 3 treatment related AEs was 30.4% (7/23). There were no ≥ grade 4 AEs. Conclusions Sintilimab in combination with chemotherapy in the neoadjuvant treatment of EC is safe and lead to a high pCR. Therefore, further testing is warranted.
Collapse
Affiliation(s)
- Hongtao Duan
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Tianhu Wang
- Department of Thoracic Surgery, Third Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhilin Luo
- Department of Thoracic Surgery, Third Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiaoyuan Wang
- Thoracic Surgery Department, Harbin Medical University Cancer Hospital, Harbin, China
| | - Honggang Liu
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Liping Tong
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Xiaoping Dong
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Yong Zhang
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Michele Valmasoni
- Department of Surgery, Oncology and Gastroenterology, School of Medicine, University of Padova, Padova, Italy
| | - Biniam Kidane
- Section of Thoracic Surgery, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Khaldoun Almhanna
- Division of Hematology/Oncology, The Warren Alpert Medical School of Brown University, Lifespan Cancer Institute, Rhode Island Hospital, Providence, RI, USA
| | - Ory Wiesel
- Division of Foregut and Thoracic Surgery, Department of Surgery, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Sainan Pang
- Thoracic Surgery Department, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jianqun Ma
- Thoracic Surgery Department, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiaolong Yan
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| |
Collapse
|
|
40
|
Capovilla G, Moletta L, Pierobon ES, Salvador R, Provenzano L, Zanchettin G, Costantini M, Merigliano S, Valmasoni M. Optimal Treatment of cT2N0 Esophageal Carcinoma: Is Upfront Surgery Really the Way? Ann Surg Oncol 2021; 28:8387-8397. [PMID: 34142286 DOI: 10.1245/s10434-021-10194-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/19/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Staging is inaccurate for cT2N0 esophageal cancer, and patients often are clinically mis-staged. This study aimed to evaluate the outcome after upfront surgery or neoadjuvant therapy, considering the impact of clinical "mis-staging." METHODS This study reviewed patients with squamous cell carcinoma (SCC) or adenocarcinoma (ADK) of the esophagus who underwent upfront surgery (S group) or neoadjuvant treatment (chemoradiotherapy [CRT] group) for cT2N0 cancer. Overall survival (OS), disease-free survival (DFS), morbidity, and mortality were evaluated. Correctly staged (cTNM = pTNM), understaged (cTNM < pTNM), and overstaged (cTNM > pTNM) patients in the S group and the CRT group were analyzed. Risk factors for unexpected lymph-node involvement were identified in the S group and for cancer-related death in the whole study cohort. RESULTS The study enrolled 229 patients with cT2N0 esophageal cancer. The 5-year OS rate was 34.2% in the S group versus 55.7% in the CRT group (p = 0.0088). The DFS also was significantly higher (p = 0.01). The morbidity and mortality rates were similar. In the S group, the cTNM was correctly staged for 21.4% and understaged for 63.4% of the patients, with 48.7% of the patients showing unexpected nodal involvement. A tumor length of 3 cm or more was an independent predictor of nodal metastases in SCC (p = 0.03), as was lymphovascular invasion (LVI) in ADK (p < 0.01). Cancer-related mortality was independently associated with lymph-node metastases (p = 0.03) and treatment by upfront surgery (p = 0.01). CONCLUSION Given the high rate of understaged patients in this study (63.4%), the authors advocate for combining the induction therapy with surgery in cT2N0, achieving better survival with similar morbidity and mortality.
Collapse
Affiliation(s)
- Giovanni Capovilla
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Lucia Moletta
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Elisa Sefora Pierobon
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy.
| | - Renato Salvador
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Luca Provenzano
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Gianpietro Zanchettin
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Mario Costantini
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Stefano Merigliano
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| | - Michele Valmasoni
- Clinica Chirurgica 3, Department of Surgical, Oncological and Gastroenterological Sciences, Università di Padova, Padova, Italy
| |
Collapse
|
|
41
|
Zhu K, Ren P, Yang Y, Wang Y, Xiao W, Zhang H, Yu Z. Role of chemotherapy after curative esophagectomy in squamous cell carcinoma of the thoracic esophagus: A propensity score-matched analysis. Thorac Cancer 2021; 12:1800-1809. [PMID: 33943011 PMCID: PMC8201545 DOI: 10.1111/1759-7714.13981] [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: 01/27/2021] [Revised: 04/11/2021] [Accepted: 04/13/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The efficacy of postoperative treatment of squamous cell carcinoma of the esophagus has not yet been determined. In this retrospective study, we investigated whether postoperative adjuvant chemotherapy (POCT) confers a survival benefit on patients who undergo curative esophagectomy. METHODS A total of 782 patients were enrolled in our study. The patients were divided into surgery alone (S) and surgery plus postoperative chemotherapy (S + POCT) groups. Propensity score matching (PSM) was used to eliminate the differences in baseline characteristics. The primary endpoint was overall survival (OS), which was calculated by the Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazards model was used to identify factors influencing the prognosis. RESULTS Of 782 patients, 343 (43.9%) underwent S alone, and 439 (56.1%) underwent S + POCT before PSM. The five-year OS rates were 42.3% and 47.8% in the S and S + POCT groups (p = 0.080), respectively. After PSM (296 patients per group), the five-year OS rates were 48.7% and 56.2% in the S and S + POCT groups (p = 0.025), respectively. For different cycles of POCT, patients with more than three cycles had a better survival than those with less than three cycles. The significant predictive factors for OS were pN stage (HR = 1.861, 95% CI: 1.310-2.645, p = 0.001), number of dissected nodes (HR = 0.621, 95% CI: 0.494-0.781, p < 0.001) and POCT received (HR = 0.699, 95% CI: 0.559-0.875, p = 0.002), which were identified by multivariate Cox regression analyses in the matched samples. CONCLUSIONS POCT appears to improve the OS rate of patients with ESCC after resection, and at least four chemotherapy cycles are necessary. These conclusions warrant further confirmation in large-scale multicenter randomized controlled trials.
Collapse
Affiliation(s)
- Kai Zhu
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China
| | - Peng Ren
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China
| | - Yueyang Yang
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China
| | - Ying Wang
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China
| | - Wanyi Xiao
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China
| | - Hongdian Zhang
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China
| | - Zhentao Yu
- Department of Esophageal Cancer, Tianjin 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 Cancer, Tianjin, China.,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| |
Collapse
|
|
42
|
Herbella FAM, Patti MG. Safety of Neoadjuvant Chemoradiotherapy Followed by Surgery for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma. JAMA Surg 2021; 156:452. [PMID: 33729433 DOI: 10.1001/jamasurg.2021.0134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
| | - Marco G Patti
- Department of Surgery, University of North Carolina, Chapel Hill
| |
Collapse
|
|
43
|
Wang H, Tang H, Fang Y, Tan L, Yin J, Shen Y, Zeng Z, Zhu J, Hou Y, Du M, Jiao J, Jiang H, Gong L, Li Z, Liu J, Xie D, Li W, Lian C, Zhao Q, Chen C, Zheng B, Liao Y, Li K, Li H, Wu H, Dai L, Chen KN. Morbidity and Mortality of Patients Who Underwent Minimally Invasive Esophagectomy After Neoadjuvant Chemoradiotherapy vs Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Surg 2021; 156:444-451. [PMID: 33729467 PMCID: PMC7970392 DOI: 10.1001/jamasurg.2021.0133] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Question Is there any difference in the safety of neoadjuvant chemoradiotherapy (nCRT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC) compared with that of neoadjuvant chemotherapy (nCT) followed by MIE? Findings In this multicenter randomized clinical trial of 264 patients with ESCC, overall morbidity rates were 47% in the nCRT group and 43% in nCT group, which was not significantly different. Meaning This trial shows that the safety of nCRT followed by MIE is similar to that of nCT for the treatment of locally advanced ESCC. Importance Safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) vs neoadjuvant chemotherapy (nCT) for treatment of locally advanced esophageal squamous cell carcinoma (ESCC) remain uncertain given lack of high-level clinical evidence. Objective To compare safety and long-term survival of nCRT followed by minimally invasive esophagectomy (MIE) with that of nCT followed by MIE for patients with locally advanced ESCC. Design, Setting, and Participants A prospective, multicenter, open-label, randomized clinical trial that compared safety and efficacy of nCRT vs nCT followed by MIE for patients with locally advanced ESCC. From January 1, 2017, to December 31, 2018, 264 patients with ESCC of clinical stages from cT3 to T4aN0 to 1M0 were enrolled. Analysis was performed on an intention-to-treat basis from January 1, 2017, to August 30, 2020. Interventions Eligible patients were randomized to the nCRT group (n = 132) or the nCT group (n = 132) by a computer-generated random system. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while 40 Gy of concurrent radiotherapy was added for the nCRT group. At about 6 weeks after neoadjuvant therapy, MIE via thoracoscopy and laparoscopy was performed for the patients in both groups. Main Outcomes and Measures The primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcome, recurrence-free survival time, and quality of life. Results Among 264 patients (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years), postoperative morbidity was 47.4% in the nCRT group (54 of 114) and 42.6% in the nCT group (46 of 108), with no significant difference between groups (difference, 4.8%; 95% CI, −8.2% to 17.5%; P = .48). Distribution of the severity of complications was similar between the 2 groups based on Clavien-Dindo classification. The 90-day perioperative mortality rate was 3.5% for the nCRT group (4 of 114) and 2.8% for the nCT group (3 of 108) (P = .94). The R0 resection rates were similar between groups (109 of 112 [97.3%] vs 100 of 104 [96.2%]; P = .92). However, patients in the nCRT group had a higher pathologic complete response (residual tumor, 0%) rate (40 of 112 [35.7%] vs 4 of 104 [3.8%]; P < .001) and a higher rate of negative lymph nodes (ypN0, 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P = .03) than those in the nCT group. One-year overall survival using intention-to-treat analysis was 87.1% in the nCRT group (115 of 132) and 82.6% in the nCT group (109 of 132) (P = .30). Furthermore, deaths caused by tumor progression or recurrence were significantly less in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P = .046); however, deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P = .24). Conclusions and Relevance Initial results of the trial showed that nCRT followed by MIE has similar safety to and better histopathologic outcome than nCT followed by MIE for treatment of locally advanced ESCC. Trial Registration ClinicalTrials.gov Identifier: NCT03001596
Collapse
Affiliation(s)
- Hao Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Tang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Fang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jun Yin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yaxing Shen
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaochong Zeng
- Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiangyi Zhu
- Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yingyong Hou
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming Du
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jia Jiao
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hongjing Jiang
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Lei Gong
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jun Liu
- Department of Radiotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Deyao Xie
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Wenfeng Li
- Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Changhong Lian
- Department of General Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Qiang Zhao
- Department of General Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Bin Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Yongde Liao
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Kuo Li
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hecheng Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Han Wu
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liang Dai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing, China
| | - Ke-Neng Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing, China
| |
Collapse
|
|
44
|
Lai Y, Zeng X, Zhou K, Zhou X, Liu Y, Hu Y. End to end intussusception anastomosis decreases the risk of anastomotic leakage after neoadjvant chemoradiation and McKeown oesophagectomy. Radiother Oncol 2021; 158:285-292. [PMID: 33662437 DOI: 10.1016/j.radonc.2021.02.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 02/19/2021] [Accepted: 02/19/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND PURPOSE To investigate the relationship between the radiation dose to the anastomotic region and postoperative anastomotic leakage rates after McKeown oesophagectomy with cervical anastomosis. MATERIALS AND METHODS Between January 2017 and December 2019, 164 consecutive patients undergoing trimodal therapy including neoadjuvant chemoradiotherapy and sequential McKeown oesophagectomy were included. The demographic and clinical patient data were collected. Additionally, the radiation dose to the regions including the mediastinum, airway, gastric fundus and anastomotic region was recalculated. RESULTS Twelve patients presented with anastomotic leakage, accounting for 7.3% (12/164) of the cohort. The anastomoses were located in the radiation field for all patients with anastomotic leakage (12/12, 100%), and for 61.8% (94/152) of those without (P = 0.009). Higher radiation doses, including the D50 and the mean, maximal and minimal doses to the oesophageal anastomotic region were found in the anastomotic leak group. Subgroup analysis between patients with end to end (ETE) anastomosis and ETE intussusception anastomosis revealed a lower anastomotic leakage rate in the latter after 1:1 ratio propensity score-matching (10.4% vs. 1.3%, P = 0.034). CONCLUSION Anastomosis location in the radiation field and a higher radiation dose to the oesophageal anastomotic region were associated with the occurrence of anastomotic leakage after trimodal therapy. Compared with ETE anastomosis, ETE intussusception anastomosis might reduce the occurrence of anastomotic leakage after neoadjuvant chemoradiation and subsequent McKeown oesophagectomy.
Collapse
Affiliation(s)
- Yutian Lai
- Department of Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China
| | - Xiaoxiao Zeng
- Department of Oncology, the People's Hospital of Jian Yang, Jian Yang, PR China
| | - Kun Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, PR China
| | - Xiaojuan Zhou
- Department of Oncology, West China Hospital, Sichuan University, Chengdu, PR China
| | - Yongmei Liu
- Department of Oncology, West China Hospital, Sichuan University, Chengdu, PR China.
| | - Yang Hu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, PR China.
| |
Collapse
|
|
45
|
Schizas D, Mylonas KS, Hasemaki N, Mpaili E, Ntomi V, Michalinos A, Theochari NA, Theochari CA, Mpoura M, Bakopoulos A, Liakakos T. Esophageal cancer surgery in Greece during the era of the financial crisis. Dis Esophagus 2021; 34:5881832. [PMID: 32766686 DOI: 10.1093/dote/doaa067] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/12/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022]
Abstract
The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004-June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015-2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P = 0.17). Ivor-Lewis was the most commonly performed procedure (67.1%) across all eras (P = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P < 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P = 0.3) or morbidity rates (P = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P = 0.90) or radiation (8.4%, P = 0.44) as well as adjuvant chemotherapy (54.8%, P = 0.85) and irradiation (13.7%, P = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P = 0.17) and survival rates (P = 0.91). The establishment of capital controls also had no impact on recurrence (P = 0.18) and survival (P = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care.
Collapse
Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Konstantinos S Mylonas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Natasha Hasemaki
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Efstratia Mpaili
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Vasileia Ntomi
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | | | - Nikoletta A Theochari
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Christina A Theochari
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Maria Mpoura
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Anargyros Bakopoulos
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Theodoros Liakakos
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| |
Collapse
|
|
46
|
Fujita K, Motoyama S, Sato Y, Wakita A, Nagaki Y, Minamiya Y, Miura M. Effects of SLC31A1 and ATP7B polymorphisms on platinum resistance in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiotherapy. Med Oncol 2021; 38:6. [PMID: 33411033 DOI: 10.1007/s12032-020-01450-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 08/30/2020] [Indexed: 11/24/2022]
Abstract
The relationship between the SLC31A1 (protein: copper transporter 1) rs10981694 A > C and ATP7B (protein: P-type adenosine triphosphatase 7B) rs9535828 A > G polymorphisms on the overall survival and disease-free survival of 104 Japanese patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemoradiotherapy (CRT) was investigated. Chemotherapy consisted of protracted infusion of 5-fluoracil (800 mg/m2/day) on days 1-5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. The median (range) follow-up was 47 (6-127) months. The 5-year overall and disease-free survival rates were 71.2% and 60.6%, respectively. The 5-year overall survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (91.7% vs. 65.0%, P = 0.018). The 5-year disease-free survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (79.2% vs. 55.0%, P = 0.043). In addition, univariate and multivariate analyses showed the SLC31A1 rs10981694 A > C polymorphism to be a significant prognostic factor affecting 5-year overall survival after neoadjuvant CRT. However, the overall and disease-free survival rates after surgery did not differ significantly among the ATP7B rs9535828 genotypes. In conclusion, only the SLC31A1 rs10981694 A/A genotype was an independent predictor of a poorer 5-year overall survival. Therefore, in neoadjuvant CRT for ESCC patients, the effect of platinum was affected by the SLC31A1 rs10981694 A > C polymorphism. The presence of this polymorphism should be considered when devising neoadjuvant CRT regimens or treatment strategies for ESCC.
Collapse
Affiliation(s)
- Kazuma Fujita
- Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Satoru Motoyama
- Department of Esophageal Surgery, Akita University Hospital, Akita, Japan.,Department of Comprehensive Cancer Control, Akita University Graduate School of Medicine, Akita, Japan
| | - Yusuke Sato
- Department of Esophageal Surgery, Akita University Hospital, Akita, Japan
| | - Akiyuki Wakita
- Department of Esophageal Surgery, Akita University Hospital, Akita, Japan
| | - Yushi Nagaki
- Department of Esophageal Surgery, Akita University Hospital, Akita, Japan
| | - Yoshihiro Minamiya
- Department of Esophageal Surgery, Akita University Hospital, Akita, Japan
| | - Masatomo Miura
- Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan.
| |
Collapse
|
|
47
|
Cao R, Pei X, Ge N, Zheng C. Clinical Target Volume Auto-Segmentation of Esophageal Cancer for Radiotherapy After Radical Surgery Based on Deep Learning. Technol Cancer Res Treat 2021; 20:15330338211034284. [PMID: 34387104 PMCID: PMC8366129 DOI: 10.1177/15330338211034284] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Radiotherapy plays an important role in controlling the local recurrence of esophageal cancer after radical surgery. Segmentation of the clinical target volume is a key step in radiotherapy treatment planning, but it is time-consuming and operator-dependent. This paper introduces a deep dilated convolutional U-network to achieve fast and accurate clinical target volume auto-segmentation of esophageal cancer after radical surgery. The deep dilated convolutional U-network, which integrates the advantages of dilated convolution and the U-network, is an end-to-end architecture that enables rapid training and testing. A dilated convolution module for extracting multiscale context features containing the original information on fine texture and boundaries is integrated into the U-network architecture to avoid information loss due to down-sampling and improve the segmentation accuracy. In addition, batch normalization is added to the deep dilated convolutional U-network for fast and stable convergence. In the present study, the training and validation loss tended to be stable after 40 training epochs. This deep dilated convolutional U-network model was able to segment the clinical target volume with an overall mean Dice similarity coefficient of 86.7% and a respective 95% Hausdorff distance of 37.4 mm, indicating reasonable volume overlap of the auto-segmented and manual contours. The mean Cohen kappa coefficient was 0.863, indicating that the deep dilated convolutional U-network was robust. Comparisons with the U-network and attention U-network showed that the overall performance of the deep dilated convolutional U-network was best for the Dice similarity coefficient, 95% Hausdorff distance, and Cohen kappa coefficient. The test time for segmentation of the clinical target volume was approximately 25 seconds per patient. This deep dilated convolutional U-network could be applied in the clinical setting to save time in delineation and improve the consistency of contouring.
Collapse
Affiliation(s)
- Ruifen Cao
- College of Computer Science and Technology, 12487Anhui University, Hefei, Anhui, China
- Engineering Research Center of Big Data Application in Private Health Medicine, Fujian Province University, Putian, Fujian, China
| | - Xi Pei
- 12652University of Science and Technology of China, Hefei, Anhui, China
| | - Ning Ge
- The First Affiliated Hospital of USTC West District, 117556Anhui Provincial Cancer Hospital, Hefei, Anhui, China
| | - Chunhou Zheng
- College of Computer Science and Technology, 12487Anhui University, Hefei, Anhui, China
- Engineering Research Center of Big Data Application in Private Health Medicine, Fujian Province University, Putian, Fujian, China
| |
Collapse
|
|
48
|
Operative Results and Perioperative Morbidity After Intensified Neoadjuvant Chemotherapy with FLOT for Gastroesophageal Adenocarcinoma Impact of Intensified Neoadjuvant Treatment. J Gastrointest Surg 2021; 25:58-66. [PMID: 32040809 DOI: 10.1007/s11605-019-04511-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 12/29/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Perioperative treatment is the standard of care in Western Europe for locally advanced gastric cancer (GC) and adenocarcinoma of the gastroesophageal junction (GEJ). Intensified neoadjuvant treatment within the NeoFLOT trial proved to be safe and effective. Yet, the influence of such intensification with 6 cycles of FLOT in the neoadjuvant setting has not been analyzed regarding its possible impact on perioperative results. MATERIALS AND METHODS A total of 537 patients were enrolled in this study; of whom, 132 had followed a standard neoadjuvant protocol (CTx), 356 had not received any neoadjuvant treatment (NoCTx), and 49 patients had undergone an intensified chemotherapy within the NeoFLOT trial (IntCTx) with 6 cycles of FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) every 2 weeks. RESULTS Our results reveal no significant difference in perioperative morbidity or mortality with regard to the neoadjuvant treatment. Postoperative bleeding and hematoma occurred less frequently in the IntCTx group compared to the NoCTx and the CTx groups (2.0% vs. 5.33% vs. 5.1%). Postoperative lymph fistulas were slightly more frequent in the IntCTx group (4.1% vs. 0.3% vs. 1.6%). Patients treated within the NeoFLOT trial had a higher risk for blood transfusions (OR 5.5; 95%-KI, 2.49-12.19), whereas patients without neoadjuvant therapy had the longest ICU stay (mean 8.3 vs. CTx 4.5 vs. IntCTx 6.7 days). CONCLUSION The results of the current study indicate that also an intensification of neoadjuvant chemotherapy with 6 preoperative cycles of FLOT does not significantly increase perioperative complications. Thus, prolonged neoadjuvant chemotherapy with FLOT is safe for patients with locally advanced GC or GEJ tumors.
Collapse
|
|
49
|
Goel A, Nayak V. Robot-Assisted Esophagectomy After Neoadjuvant Chemoradiation-Current Status and Future Prospects. Indian J Surg Oncol 2020; 11:668-673. [PMID: 33281406 PMCID: PMC7714799 DOI: 10.1007/s13193-020-01230-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 09/15/2020] [Indexed: 10/23/2022] Open
Abstract
Multimodality treatment with neoadjuvant chemoradiation followed by surgery has become the standard of care for esophageal cancer. In the recent years, there has been a shift in focus of surgical approach from open esophagectomy to minimally invasive esophagectomy. Robot-assisted esophagectomy is being performed more often in centers across the world. However, there is limited data on role of robot-assisted esophagectomy in patients who have received neoadjuvant chemoradiation. Initial reports have shown that integrating neoadjuvant therapy to robot-assisted esophagectomy is feasible and safe. With the growing popularity of robot-assisted surgery worldwide among both surgeons and patients, understanding the impact of neoadjuvant chemoradiation on the procedure and its oncological outcome seems worthwhile. In the present study, we present a review of available literature on the feasibility and safety of robot-assisted minimally invasive esophagectomy in esophageal cancer patients after neoadjuvant chemoradiation.
Collapse
|
|
50
|
Krasnoff CC, Grigorian A, Smith BR, Jutric Z, Nguyen NT, Daly S, Lekawa ME, Nahmias J. Predictors of Anastomotic Leak After Esophagectomy for Cancer: Not All Leaks Increase Mortality. Am Surg 2020; 87:864-871. [PMID: 33233922 DOI: 10.1177/0003134820956329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The impact of preoperative chemotherapy/radiation on esophageal anastomotic leaks (ALs) and the correlation between AL severity and mortality risk have not been fully elucidated. We hypothesized that lower severity ALs have a similar risk of mortality compared to those without ALs, and preoperative chemotherapy/radiation increases AL risk. METHODS The 2016-2017 American College of Surgeons National Surgical Quality Improvement Program's procedure-targeted esophagectomy database was queried for patients undergoing any esophagectomy for cancer. A multivariable logistic regression analysis was performed for risk of ALs. RESULTS From 2042 patients, 280 (13.7%) had ALs. AL patients requiring intervention had increased mortality risk including those requiring reoperation, interventional procedure, and medical therapy (P < .05). AL patients requiring no intervention had similar mortality risk compared to patients without ALs (P > .05). Preoperative chemotherapy/radiation was not predictive of ALs (P > .05). CONCLUSION Preoperative chemotherapy/radiation does not contribute to risk for ALs after esophagectomy. There is a stepwise increased risk of 30-day mortality for ALs requiring increased invasiveness of treatment.
Collapse
Affiliation(s)
- Chloe C Krasnoff
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Areg Grigorian
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Brian R Smith
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Zeljka Jutric
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Ninh T Nguyen
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Shaun Daly
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Michael E Lekawa
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| | - Jeffry Nahmias
- Department of Surgery, University of California, Irvine, Orange, CA, USA
| |
Collapse
|