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Liu G, Su Y, He Y, Hu H. In-Depth Analysis of the Necessity and Optimization Strategies for Adjuvant Radiotherapy Following Neoadjuvant Immunotherapy in the New Era of Esophageal Cancer Treatment. CANCER INNOVATION 2025; 4:e70010. [PMID: 40415863 PMCID: PMC12099070 DOI: 10.1002/cai2.70010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 03/13/2025] [Accepted: 03/27/2025] [Indexed: 05/27/2025]
Abstract
As immunotherapy rises to prominence in cancer treatment, the therapeutic approach to esophageal cancer is undergoing significant transformations. This review emphasizes the necessity and optimization pathways for adjuvant postoperative radiotherapy after neoadjuvant therapy in patients with esophageal cancer in the immunotherapy era. Initially, we review the advancements in neoadjuvant treatment strategies. Subsequently, we evaluate the role of postoperative radiotherapy and the latest advancements in radiotherapy target volume definition and dose optimization following neoadjuvant therapy, as well as the implications of tumor immunotherapy on postoperative radiotherapy strategies. In conclusion, in the new era of immunotherapy, postoperative radiotherapy following neoadjuvant therapy for esophageal cancer holds significant value. Optimization strategies should follow individualized treatment principles and comprehensively consider tumor biology, patient status, and treatment resources to achieve optimal therapeutic outcomes and quality of life, thereby driving continuous innovation in esophageal cancer treatment.
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Affiliation(s)
- Guohui Liu
- Department of Radiation OncologyThe Harbin Medical University Cancer HospitalHarbinHeilongjiangChina
| | - Yao Su
- Obstetrical DepartmentThe First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina
| | - Yunlong He
- Department of Radiation OncologyThe Harbin Medical University Cancer HospitalHarbinHeilongjiangChina
| | - Hanqing Hu
- Department of Colorectal Cancer SurgeryThe Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina
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2
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AlMaazmi FI, Bou Malhab LJ, ElDohaji L, Saber-Ayad M. Deciphering the Controversial Role of TP53 Inducible Glycolysis and Apoptosis Regulator (TIGAR) in Cancer Metabolism as a Potential Therapeutic Strategy. Cells 2025; 14:598. [PMID: 40277923 PMCID: PMC12025843 DOI: 10.3390/cells14080598] [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: 02/06/2025] [Revised: 03/26/2025] [Accepted: 03/28/2025] [Indexed: 04/26/2025] Open
Abstract
Tumor metabolism has emerged as a critical target in cancer therapy, revolutionizing our understanding of how cancer cells grow, survive, and respond to treatment. Historically, cancer research focused on genetic mutations driving tumorigenesis, but in recent decades, metabolic reprogramming has been recognized as a hallmark of cancer. The TP53 inducible glycolysis and apoptosis regulator, or TIGAR, affects a wide range of cellular and molecular processes and plays a key role in cancer cell metabolism by regulating the balance between glycolysis and antioxidant defense mechanisms. Cancer cells often exhibit a shift towards aerobic glycolysis (the Warburg effect), which allows rapid energy production and gives rise to biosynthetic intermediates for proliferation. By inhibiting glycolysis, TIGAR can reduce the proliferation rate of cancer cells, particularly in early-stage tumors or specific tissue types. This metabolic shift may limit the resources available for rapid cell division, thereby exerting a tumor-suppressive effect. However, this metabolic shift also leads to increased levels of reactive oxygen species (ROS), which can damage the cell if not properly managed. TIGAR helps protect cancer cells from excessive ROS by promoting the pentose phosphate pathway (PPP), which generates NADPH-a key molecule involved in antioxidant defense. Through its actions, TIGAR decreases the glycolytic flux while increasing the diversion of glucose-6-phosphate into the PPP. This reduces ROS levels and supports biosynthesis and cell survival by maintaining the balance of nucleotides and lipids. The role of TIGAR has been emerging as a prognostic and potential therapeutic target in different types of cancers. This review highlights the role of TIGAR in different types of cancer, evaluating its potential role as a diagnostic marker and a therapeutic target.
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Affiliation(s)
- Fatima I. AlMaazmi
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.I.A.); (L.E.)
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates;
- Immunology and NAT, Dubai Blood Donation Center, Dubai Health, Dubai P.O. Box 505055, United Arab Emirates
| | - Lara J. Bou Malhab
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Leen ElDohaji
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.I.A.); (L.E.)
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Maha Saber-Ayad
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; (F.I.A.); (L.E.)
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates;
- Faculty of Medicine, Cairo University, Cairo 11562, Egypt
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Tamba M, Osumi H, Ogura M, Fukuoka S, Okamura A, Kanamori J, Imamura Y, Yoshino K, Udagawa S, Wakatsuki T, Shinozaki E, Watanabe M, Yamaguchi K, Chin K, Ooki A. Real-world safety and efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy for locally advanced esophageal squamous cell carcinoma. BMC Cancer 2025; 25:636. [PMID: 40200210 PMCID: PMC11980314 DOI: 10.1186/s12885-025-14011-4] [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: 11/27/2024] [Accepted: 03/24/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (DCF) has become the new standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). In a real-world setting, the efficacy, recurrence, and adverse events (AEs) remain unclear. METHODS This retrospective cohort study included 86 patients who received neoadjuvant DCF followed by esophagectomy for resectable ESCC. RESULTS Following neoadjuvant DCF treatment, 75 patients underwent R0 curative resection. At the median follow-up of 19.2 months, the median disease-free survival (DFS)/recurrence-free survival (RFS) was not yet reached, with estimated 3-year DFS/RFS rates of 65.2%, respectively. The incidence of primary tumor regression grading (TRG) grade 1a and pathological complete response (pCR) were 21.3% (16/75) and 14.7% (11/75), respectively. The estimated 1-year DFS/RFS rates were 93.8% for primary TRG grade 1a and 100% for pCR. Baseline elevated serum SCC-antigen levels were inversely associated with achieving primary TRG grade 1a or pCR. In 64 patients who did not achieve pCR, residual tumor cells in the lymph nodes (ypN; HR, 16.96; 95% CI, 2.11-136.12; P < 0.01) and Glasgow prognostic score (GPS; HR, 8.34; 95% CI, 1.73-40.31; P < 0.01) were independent predictors of shorter DFS/RFS. The most common grade ≥ 3 AEs were neutropenia (61.6%) and febrile neutropenia (26.7%), which were not associated with clinicopathological factors. The most common non-hematological AEs were appetite loss (9.3%), pulmonary embolism (8.1%), diarrhea (7.0%), and nausea (2.3%). Nine patients discontinued neoadjuvant DCF due to toxicities. CONCLUSIONS Neoadjuvant DCF was effective and well-tolerated in real-world ESCC patients. Primary TRG grade 1a or pCR showed a favorable DFS/RFS, while positive ypN and GPS were independent risk factors for worse DFS/RFS.
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Affiliation(s)
- Mikako Tamba
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Hiroki Osumi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Mariko Ogura
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Shota Fukuoka
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Jun Kanamori
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Koichiro Yoshino
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Shohei Udagawa
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Takeru Wakatsuki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Eiji Shinozaki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Keisho Chin
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Akira Ooki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
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Tamba M, Okamura A, Osumi H, Imamura Y, Kanamori J, Ogura M, Fukuoka S, Yoshino K, Udagawa S, Wakatsuki T, Shinozaki E, Watanabe M, Yamaguchi K, Chin K, Ooki A. Lymph-node ratio as a risk factor for recurrence following neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy for locally advanced esophageal squamous cell carcinoma. Esophagus 2025; 22:166-176. [PMID: 39755858 DOI: 10.1007/s10388-024-01103-6] [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: 05/24/2024] [Accepted: 12/26/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND AND PURPOSE It remains unclear whether the lymph-node ratio (LNR) is a relevant factor for the risk of recurrence following neoadjuvant chemotherapy (nCT) with docetaxel, cisplatin, and 5-fluorouracil (DCF), which is a new standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan. This study aimed to evaluate the clinical utility of LNR as a risk factor for recurrence. MATERIALS AND METHODS We retrospectively analyzed 75 patients who underwent nCT-DCF followed by curative surgery for resectable ESCC. The cut-off for the LNR was determined using receiver-operating characteristic curve analysis for recurrence. RESULTS A higher LNR was observed in 34 (45.3%) patients. At a median follow-up of 19.2 months, the median disease-free survival (DFS)/recurrence-free survival (RFS) rate was not reached in patients with a lower LNR and was 8.0 months in those with a higher LNR (P < 0.01). The estimated 1-year DFS/RFS rate was 47.8% and 100% for patients with a higher LNR and lower LNR, respectively. LNR remained a risk factor, even when stratified by non-pathological complete response, the presence of positive ypN, or ypStage III. In those with a higher LNR, the median DFS/RFS was 18.3 versus 8.0 months with and without adjuvant nivolumab treatment, respectively. CONCLUSIONS Higher LNR indicates a more aggressive phenotype with worse DFS/RFS rates and increased recurrence following nCT-DCF treatment and curative surgery for ESCC.
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Affiliation(s)
- Mikako Tamba
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan
| | - Hiroki Osumi
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan
| | - Jun Kanamori
- Department of Gastroenterological Surgery, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan
| | - Mariko Ogura
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Shota Fukuoka
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Koichiro Yoshino
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Shohei Udagawa
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Takeru Wakatsuki
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Eiji Shinozaki
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Keisho Chin
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Akira Ooki
- Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan.
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Zhang H, Wang Q, Wang P, Tang B. Consolidation Chemotherapy Provided Survival Benefit for Esophageal Squamous Cell Carcinoma Patients Who Underwent Concurrent Chemoradiotherapy Lower Than 60 Gy. Thorac Cancer 2025; 16:e70012. [PMID: 40176263 PMCID: PMC11965269 DOI: 10.1111/1759-7714.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 01/23/2025] [Accepted: 01/27/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND The efficacy of consolidation chemotherapy (CCT) following concurrent chemoradiotherapy (CCRT) has not been clearly defined in esophageal squamous cell carcinoma (ESCC). This study determined which patients with stage II-IVA ESCC benefitted from CCT. METHODS 351 patients with ESCC were retrospectively reviewed. 185 patients received CCRT alone and 166 received CCRT plus CCT. Subset analyses were conducted on all patients' characteristics. Factors associated with survival were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. The Propensity score matching (PSM) technique was used to compensate for differences in patients' characteristics. RESULTS The median OS were 17.7 months and 38.4 months in the CCRT alone group and CCRT+CCT group (p = 0.002), respectively. Multivariable Cox regression analysis determined that CCT was associated with improved OS (p = 0.002, HR 0.592, 95% CI 0.423-0.829); After PSM, relative to the CCRT group, patients who received CCT experienced improved OS (17.7 months vs. 38.4 months, p = 0.0139). Subgroup analysis showed that CCT was more effective in radiation dose < 60 Gy (p = 0.002, HR 0.368, 95% CI 0.194-0.700). After matching between radiation dose, in the low dose cohort, the median OS was 13.2 months and 20.7 months in the CCRT alone group and CCRT+CCT group, respectively (p = 0.0028), the multivariate analysis results showed that CCT retained its statistical significance (p = 0.002, HR 0.353, 95% CI 0.183-0.681). In the high dose cohort, the median OS were 21.6 months and 23.6 months in the CCRT alone group and CCRT+CCT group, respectively (p = 0.5512). CONCLUSIONS We recommend that CCT treatment should be considered for ESCC patients who underwent CCRT using < 60 Gy. Further studies are needed to confirm these results.
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Affiliation(s)
- Hualei Zhang
- Department of Radiation OncologyThe Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalZhengzhouChina
| | - Qi Wang
- Department of Radiation OncologyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Ping Wang
- Department of Radiation OncologyTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Bo Tang
- Department of Radiation OncologyThe Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalZhengzhouChina
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Jiang W, Zhang B, Xu J, Xue L, Wang L. Current status and perspectives of esophageal cancer: a comprehensive review. Cancer Commun (Lond) 2025; 45:281-331. [PMID: 39723635 PMCID: PMC11947622 DOI: 10.1002/cac2.12645] [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: 07/01/2024] [Revised: 12/08/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024] Open
Abstract
Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in-depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.
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Affiliation(s)
- Wei Jiang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdongP. R. China
| | - Bo Zhang
- Department of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Jiaqi Xu
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Liyan Xue
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Luhua Wang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdongP. R. China
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Malekzada F, Vladimiriov M, Leitz M, Michel J, Nimzewski F, Hoeppner J. Neoadjuvant treatment of esophageal cancer: chemotherapy, chemoradiation, immunotherapy, and future trends of therapy. Innov Surg Sci 2025; 10:3-9. [PMID: 40144785 PMCID: PMC11934940 DOI: 10.1515/iss-2023-0005] [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: 01/25/2023] [Accepted: 10/07/2024] [Indexed: 03/28/2025] Open
Abstract
In the Western hemisphere, nonmetastatic locally advanced esophageal carcinoma is mostly treated in multimodal therapy protocols according to current therapy guidelines. In squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation is the favorable option. Unimodal surgical and chemoradiation treatment alternatives show inferior results on this entity. For locally advanced adenocarcinoma of the esophagus perioperative chemotherapy and neoadjuvant chemoradiation have been competing treatment approaches in the recent past. Both are evidence based (class I evidence) and superior compared to unimodal surgery. However, the latest results of head-to-head comparative therapy studies show superior overall survival results for the FLOT regimen of perioperative chemotherapy. Furthermore, immunotherapy and targeted therapy with monoclonal antibodies have become a strong focus of current clinical research. Nivolumab as well as trastuzumab are already an important part of the current standard therapies. In both entities - SCC and AC - a significant quota of patients shows a locoregional complete remission of the tumor in the specimen after modern neoadjuvant therapy and surgical resection. The addition of immunotherapy and targeted therapy to neoadjuvant therapy further increases complete remission rates in defined subgroups according to the results of current studies. Currently, three prospective randomized trials are ongoing on the subject of future possibilities for organ-preserving concepts in case of complete clinical remission ("surgery as needed," "watch and wait"). It is to be expected for the future that curative short-term and long-term treatment results in locally advanced esophageal carcinoma will significantly improve, particularly due to the additional possibilities of immunotherapy and organ-preserving therapy concepts in postneoadjuvant complete remission.
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Affiliation(s)
- Freschta Malekzada
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Miljana Vladimiriov
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Michael Leitz
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Julia Michel
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Fabian Nimzewski
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Jens Hoeppner
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
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Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025; 10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [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: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
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Affiliation(s)
- Tianzuo Zhan
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johannes Betge
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nadine Schulte
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lena Dreikhausen
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moying Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Antonia Leipertz
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
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9
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Yu N, Ge X, Zuo L, Cao Y, Wang P, Liu W, Deng L, Zhang T, Wang W, Wang J, Lv J, Xiao Z, Feng Q, Zhou Z, Bi N, Zhang W, Wang X. Multi-Centered Pre-Treatment CT-Based Radiomics Features to Predict Locoregional Recurrence of Locally Advanced Esophageal Cancer After Definitive Chemoradiotherapy. Cancers (Basel) 2025; 17:126. [PMID: 39796752 PMCID: PMC11720276 DOI: 10.3390/cancers17010126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/30/2024] [Accepted: 12/05/2024] [Indexed: 01/13/2025] Open
Abstract
Purpose: We constructed a prediction model to predict a 2-year locoregional recurrence based on the clinical features and radiomic features extracted from the machine learning method using computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal cancer. Patients and methods: A total of 264 patients (156 in Beijing, 87 in Tianjin, and 21 in Jiangsu) were included in this study. All those locally advanced esophageal cancer patients received definite radiotherapy and were randomly divided into five subgroups with a similar number and divided into training groups and validation groups by five cross-validations. The esophageal tumor and extratumoral esophagus were segmented to extract radiomic features from the gross tumor volume (GTV) drawn by radiation therapists before radiotherapy, and six clinical features associated with prognosis were added. T stage, N stage, M stage, total TNM stage, GTV, and GTVnd volume were included to construct a prediction model to predict the 2-year locoregional recurrence of patients after definitive radiotherapy. Results: A total of 264 patients were enrolled from August 2012 to April 2018, with a median age of 62 years and 81% were males. The 2-year locoregional recurrence rate was 52.6%, and the 2-year overall survival rate was 45.6%. About 66% of patients received concurrent chemotherapy. In total, we extracted 786 radiomic features from CT images and the Principal Component Analysis (PCA) method was used to screen out the maximum 30 features. Finally, the Support Vector Machine (SVM) method was used to construct the integrated prediction model combining radiomics and clinical features. In the five training groups for predicting locoregional recurrence, the mean value of C-index was 0.9841 (95%CI, 0.9809-0.9873), and in the five validation groups, the mean value was 0.744 (95%CI, 0.7437-0.7443). Conclusions: The integrated radiomics model could predict the 2-year locoregional recurrence after dCRT. The model showed promising results and could help guide treatment decisions by identifying high-risk patients and enabling strategies to prevent early recurrence.
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Affiliation(s)
- Nuo Yu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Xiaolin Ge
- Department of Radiation Oncology, Jiangsu Province Hospital/The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Lijing Zuo
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Ying Cao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Peipei Wang
- Department of Radiation Oncology, Jiangsu Province Hospital/The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Wenyang Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Wenqing Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Jianyang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Jima Lv
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Qinfu Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Zongmei Zhou
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
| | - Wencheng Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institution & Hospital, Tianjin 300060, China
| | - Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (N.Y.)
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Teja R, Bhaskar R, Yadlapalli DC, Kukunuri S, Mohan R. Real-World Data of Esophageal Malignancies Managed Under the Government Scheme From a Tertiary Cancer Center in South India. Cureus 2025; 17:e77850. [PMID: 39991427 PMCID: PMC11845311 DOI: 10.7759/cureus.77850] [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] [Accepted: 01/22/2025] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND Esophageal cancer is a major problem in India. The incidence has a geographic variation, being more common in some parts of south India and pockets in the north. The patients usually present in late stages as the symptoms are non-specific, hence patients are treated for other causes over prolonged periods. There has been marked improvement due to the incorporation of a multi-modality approach in the management of these cancers over the last decade. OBJECTIVE This study included patients with non-metastatic esophageal cancer who presented to the department of medical oncology between January 2020 and December 2023. The aim was to analyze the clinical and demographic profiles and survival outcomes of patients. METHODOLOGY This is a retrospective study conducted at a tertiary cancer care center in southern India, primarily serving patients from rural areas. Approval from the Institutional Ethics Committee was secured prior to the study (GSLMC/RC:1259A-EC/1259A-05/2024). Case files for all esophageal cancer patients treated at our center between January 2020 and December 2023 were collected from the medical records department and analyzed. We focused on patients diagnosed with non-metastatic esophageal cancer who had received treatment. RESULTS A total of 47 patients participated in our study, with a mean age of 55 years. The male-to-female ratio was 2:3. Among the participants, 18 (38.3%) were smokers and 12 (25.5%) were alcohol users. The most frequently affected site was the middle thoracic esophagus, with 22 patients (46.8%), followed by the lower third in 15 patients (31.9%), and both the upper one-third and gastroesophageal junction cancers each accounting for five patients (10.6%). Squamous cell carcinoma was the predominant histological type, representing 82% of cases. Stage 2 was the most common stage at presentation, seen in 22 patients (46.8%), followed by stage 3 in 17 patients (36.2%). Twenty patients received neoadjuvant chemoradiotherapy (NACRT), with 13 (65%) receiving a weekly regimen of paclitaxel and carboplatin, while seven (35%) were treated with a CAPEOX (capecitabine and oxaliplatin) regimen alongside radiation (41.4 to 45 Gray). Of these, only eight patients (40%) proceeded to surgery, while 12 patients (60%) did not. Among those who underwent surgery, five patients (62.5%) achieved a pathological complete response. Additionally, 24 patients received definitive CRT, resulting in a complete response in 14 patients (58.3%) and a partial response in 10 patients (41.6%). Three patients defaulted on treatment. The median overall survival for the analyzed group was 10.5 months, with a subset analysis showing that those who had surgery had a survival duration of 12 months, compared to eight months for those who did not undergo surgery. CONCLUSION The study concluded that the middle thoracic esophagus is the most prevalent site for esophageal cancer, with squamous cell carcinoma being the predominant histological type. Stage 2 is frequently observed at presentation, followed by stage 3. The standard treatment for locally advanced esophageal malignancies now involves a combined approach with NACRT. Despite advancements in multimodal treatments, the prognosis for esophageal cancer remains poor and requires significant improvement.
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Affiliation(s)
- Ravi Teja
- Medical Oncology, GSL (Ganni Subbalakshmi) Medical College, Rajahmundry, IND
| | - Rekabtala Bhaskar
- Medical Oncology, GSL (Ganni Subbalakshmi) Medical College, Rajahmundry, IND
| | - Deepak C Yadlapalli
- Medical Oncology, GSL (Ganni Subbalakshmi) Medical College, Rajahmundry, IND
| | - Sindhusha Kukunuri
- Medical Oncology, GSL (Ganni Subbalakshmi) Medical College, Rajahmundry, IND
| | - Ravi Mohan
- Medical Oncology, GSL (Ganni Subbalakshmi) Medical College, Rajahmundry, IND
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11
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Wang X, Kang X, Zhang R, Xue L, Xu J, Zhao X, Ou Q, Yu N, Feng G, Li J, Zheng Z, Chen X, Wang Z, Zheng Q, Li Y, Qin J, Bi N, Li Y. Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial. Clin Cancer Res 2024; 30:5061-5072. [PMID: 39544026 DOI: 10.1158/1078-0432.ccr-24-1236] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/10/2024] [Accepted: 09/10/2024] [Indexed: 11/17/2024]
Abstract
PURPOSE This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. RESULTS Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. CONCLUSIONS Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.
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Affiliation(s)
- Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaozheng Kang
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruixiang Zhang
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiaqi Xu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaotian Zhao
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Qiuxiang Ou
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Nuo Yu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guojie Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiao Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ziyu Zheng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiankai Chen
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Wang
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingfeng Zheng
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Li
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Qin
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yin Li
- Section of Esophageal and Mediastinal Oncology, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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12
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Guo Y, Wang T, Liu Y, Gu D, Li H, Liu Y, Zhang Z, Shi H, Wang Q, Zhang R, Xiong L, Fang Y, Zhou G, Ye J. Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer. Int Immunopharmacol 2024; 141:112939. [PMID: 39151385 DOI: 10.1016/j.intimp.2024.112939] [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: 12/25/2023] [Revised: 07/01/2024] [Accepted: 08/12/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND Several studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. METHODS Pooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. RESULTS The median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). CONCLUSION The differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.
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Affiliation(s)
- Yiyu Guo
- Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Tian Wang
- Xuzhou Medical University, Xuzhou, China
| | - Ying Liu
- Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Dayong Gu
- Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Hui Li
- Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Yatian Liu
- Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Zhi Zhang
- Department of Thoracic Surgery, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Haifeng Shi
- Department of Oncology, Sheyang County People's Hospital, Yancheng, China
| | - Qiang Wang
- Department of Oncology, Affiliated Jiangyan Hospital of Nanjing University of Chinese Medicine, Taizhou, China
| | - Rongrong Zhang
- Department of Oncology, Affiliated Jiangyan Hospital of Nanjing University of Chinese Medicine, Taizhou, China
| | - Lei Xiong
- Department of Thoracic Surgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Ying Fang
- Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Guoren Zhou
- Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
| | - Jinjun Ye
- Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
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13
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van der Zijden CJ, Bouwman A, Mostert B, Nuyttens JJME, van der Sluis PC, Spaander MCW, Mens JWM, Homs MYV, van Doorn L, Wijnhoven BPL, Lagarde SM. Overall survival after definitive chemoradiotherapy for patients with esophageal cancer: a retrospective cohort study. Dis Esophagus 2024; 37:doae047. [PMID: 38836354 PMCID: PMC11447113 DOI: 10.1093/dote/doae047] [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: 03/13/2024] [Accepted: 05/22/2024] [Indexed: 06/06/2024]
Abstract
Definitive chemoradiotherapy (dCRT) is a potentially curative therapy for esophageal cancer. As indications for dCRT differ widely, it is challenging to draw conclusions on outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns according to indications for treatment. Patients who underwent dCRT (50.4 Gy concomitant with carboplatin/paclitaxel) for esophageal cancer between 2012 and 2022 were identified. Indications for dCRT were: cervical tumor, irresectable disease, unfit for surgery, and patient and/or physician preference. The primary endpoint was OS calculated with the Kaplan-Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality, and disease recurrence. One hundred and fifty-seven patients were included (72.6% esophageal squamous cell carcinoma) with a median follow-up of 20 months (IQR 10.0-43.9). The full dCRT regimen was completed by 116 patients (73.9%). Thirty- and 90-day mortality were 2.5% and 8.3%, respectively. Median and 5-year OS for all patients were 22.9 months (95% CI 18.0-27.9) and 31.4%, respectively. The median OS per indication was 23.7 months (95% CI 6.5-40.8) for patients with cervical tumors, 10.9 months (95% 0.0-23.2) for irresectable disease, 28.2 months (95% CI 12.3-44.0) for unfit patients, and 22.9 months (95% CI 15.4-30.5) for patients' preference for dCRT (P = 0.11). Disease recurrence was observed in 74 patients (46%), located locoregionally (46%), distant (19%), or combined (35%). Patients who underwent dCRT had a 5-year OS of 31.4%, but OS differed according to indications for treatment with patients who had irresectable disease having the worst prognosis.
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Affiliation(s)
| | - Anna Bouwman
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Joost J M E Nuyttens
- Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Jan Willem M Mens
- Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Leni van Doorn
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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14
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Jeon WJ, Park D, Al-Manaseer F, Chen YJ, Kim JY, Liu B, Wu S, Castillo D. Survival and Treatment Patterns in Stage II to III Esophageal Cancer. JAMA Netw Open 2024; 7:e2440568. [PMID: 39432303 PMCID: PMC11581628 DOI: 10.1001/jamanetworkopen.2024.40568] [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: 05/03/2024] [Accepted: 08/26/2024] [Indexed: 10/22/2024] Open
Abstract
Importance Existing clinical trials favor neoadjuvant chemoradiation therapy (NCRT) followed by surgery alone for locally advanced esophageal cancer (EC) and perioperative chemotherapy as the preferred modality for esophageal adenocarcinoma (EAC). However, it is unclear whether these trial findings are reflected in the patterns of care and survival outcomes among patients in the clinical setting. Objective To investigate survival outcomes in the clinical setting among patients with EC after various treatment modalities. Design, Setting, and Participants This retrospective cohort study examined data from the National Cancer Database maintained by the American College of Surgeons and focused on patients with clinical stage II or III EC, excluding those with gastroesophageal junction cancer, who underwent trimodality therapy (NCRT followed by esophagectomy), definitive chemoradiation therapy (DCRT), radiotherapy (RT) alone, or perioperative chemotherapy from January 2006 to December 2020. Analyses were conducted from December 2023 to August 2024. Exposures Perioperative chemotherapy, trimodality therapy, DCRT, and single-modality RT. Main Outcomes and Measures A Cox proportional hazards regression model was used to compare overall survival (OS) between treatment groups in the entire cohort, among patients with squamous cell carcinoma or adenocarcinoma, and among those older than 65 years. Landmark survival analysis at 6 months was performed to reduce survivorship bias. Results The study included 57 116 patients (median age, 64 [IQR, 57-72] years; 45 410 [79.5%] male); 21 619 patients (37.9%) received trimodality therapy, 32 493 (57.1%) received DCRT, 2692 (4.7%) received single-modality RT, and 312 (0.5%) received perioperative chemotherapy. In the overall study population, 37 698 patients (66.0%) had EAC, and of the 312 patients that received perioperative chemotherapy, 283 (90.7%) had EAC. In adjusted survival analysis, perioperative chemotherapy (adjusted hazard ratio [AHR], 0.33; 95% CI, 0.28-0.39; P <.001) and trimodality therapy (AHR, 0.45; 95% CI, 0.44-0.46; P < .001) were associated with improved OS compared with DCRT. In contrast, RT alone was associated with worse outcomes compared with DCRT (AHR, 1.37; 95% CI, 1.30-1.45; P < .001). The median OS for perioperative chemotherapy of 66.2 months (95% CI, 43.1-111.9 months; P < .001) was longer compared with that for DCRT alone (18.1 months; 95% CI, 17.8-18.4 months; P < .001). Trimodality therapy was associated with a median OS of 43.9 months (95% CI, 42.8-45.5 months; P < .001), which was shorter than that for perioperative chemotherapy but improved compared with DCRT and RT alone, which was associated with a median OS of 13.5 months (95% CI, 12.8-14.0 months; P < .001). In the subgroup of patients older than 65 years, those who received perioperative chemotherapy had longer median OS (56.7 months; 95% CI, 36.4-115.2 months; P < .001) compared with those receiving other treatment modalities (eg, trimodality therapy: 40.1 months; 95% CI, 38.1-42.0 months; P < .001). Patients who received RT alone had the worst median OS (13.6 months; 95% CI, 12.8-14.4 months; P < .001). Conclusions and Relevance In this cohort study of patients with stage II to III EC, trimodality therapy was associated with improved OS compared with DCRT or RT alone for locally advanced EC and perioperative chemotherapy was associated with improved OS for adenocarcinoma.
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Affiliation(s)
- Won Jin Jeon
- Division of Medical Oncology and Hematology, Department of Internal Medicine, Loma Linda University, Loma Linda, California
| | - Daniel Park
- Department of Internal Medicine, University of California, San Francisco-Fresno, Fresno
| | - Farris Al-Manaseer
- Department of Internal Medicine, Loma Linda University, Loma Linda, California
| | - Yi-Jen Chen
- Department of Radiation Oncology, City of Hope Medical Center, Duarte, California
| | - Jae Y. Kim
- Division of Thoracic Surgery, Department of Surgery, City of Hope Medical Center, Duarte, California
| | - Bo Liu
- Department of Diagnostic Radiation, City of Hope Medical Center, Duarte, California
| | - Shengyang Wu
- Department of Radiation Oncology, City of Hope Medical Center, Duarte, California
| | - Dani Castillo
- Department of Medical Oncology and Therapeutics Research, City of Hope Medical Center, Duarte, California
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15
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Kachnic LA, Winter K, Suntharalingam M, Ilson D, Konski A, Lloyd S, McAvoy SA, Lad T, Olowokure OG, Samson P, Gore EM, Meyer JE, Videtic GMM, Clump DA, Raben A, Kayaleh O, Barker J, Haddock MG, Hopkins JO, Bruner DW. Patient-reported outcomes (PROs) in NRG Oncology RTOG 0436: a phase III trial evaluating the addition of cetuximab to paclitaxel, cisplatin, and radiation for esophageal cancer treated without surgery. Qual Life Res 2024; 33:2833-2844. [PMID: 39066879 PMCID: PMC11577575 DOI: 10.1007/s11136-024-03736-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2024] [Indexed: 07/30/2024]
Abstract
PURPOSE/OBJECTIVES NRG/RTOG 0436 evaluated cetuximab added to chemoradiation (CRT) for non-operative esophageal cancer management. PRO objectives assessed improvement in the FACT-Esophageal cancer subscale (ECS), version 4, with cetuximab, and if improved ECS correlated with clinical complete response (cCR). MATERIALS/METHODS Patients were randomized to cisplatin/paclitaxel/radiation ± cetuximab. Overall survival (OS) was the primary endpoint, with a 420 patient target, which also provided 82% power to detect ≥ 15 increase in the proportion of cetuximab patients with ECS improvement from baseline to 6-8 weeks post-CRT; α = 0.05, using a χ2 test. Improvement in ECS and its Swallowing and Eating Indices (SI, EI) was defined as 5, 4 and 2 point increases, respectively, from baseline to 6-8 weeks post-CRT. Univariate logistic regression assessed if cCR was associated with improved ECS. RESULTS This study was stopped early for not meeting a pre-specified OS endpoint and did not show survival benefit. Of 420 planned patients, 344 enrolled and 281 consented to PROs. ECS was completed by 261 (93%) at baseline, 173 (66%) 6-8 weeks post-CRT, and 117 (64%) at 1 year. At 6-8 weeks, patients receiving CRT + Cetuximab didn't have improved ECS; they experienced a lower proportion of improvement compared to standard CRT (37% vs. 53%; P = 0.04). The proportion of CRT patients with improvement in SI was 9% higher than with cetuximab, but not statistically significant (39% vs. 30%, P = 0.22). There was no association between treatment and EI. When examining ECS scores at 1 year by cCR vs. residual disease, a higher proportion of cCR patients improved, but not statistically significant (48% vs. 45%, P = 0.74). CONCLUSIONS The addition of cetuximab to CRT for the nonoperative management of esophageal cancer did not improve PROs.
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Affiliation(s)
- Lisa A Kachnic
- Department of Radiation Oncology, Columbia University Irving Medical Center, 622 West 168th Street, CHONY North, B Level, Room 11, New York, NY, 10032, USA.
| | - Kathryn Winter
- NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA
| | | | - David Ilson
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - André Konski
- University of Pennsylvania, Philadelphia, PA, USA
| | - Shane Lloyd
- University of Utah Health Science Center, Salt Lake City, UT, USA
| | - Sarah A McAvoy
- University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA
| | - Thomas Lad
- John H Stroger Jr Hospital of Cook County, Chicago, IL, USA
| | | | | | - Elizabeth M Gore
- Medical College of Wisconsin and Zablocki VA Medical Center, Milwaukee, WI, USA
| | | | | | | | - Adam Raben
- Christiana Care Health Services, INC. CCOP, New Castle County, Delaware, USA
| | | | - Jerry Barker
- USON-Texas Oncology-Sugar Land, Sugar Land, TX, USA
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Zhou Z, Zhang H, Du J, Yang J, Pan W, Zhang Q, Wang H, Tang P, Ba Y, Zhang H. A spatiotemporal comparative analysis on tumor immune microenvironment characteristics between neoadjuvant chemotherapy and preoperative immunotherapy for ESCC. Cell Death Dis 2024; 15:663. [PMID: 39256364 PMCID: PMC11387609 DOI: 10.1038/s41419-024-06986-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: 03/07/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 09/12/2024]
Abstract
The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5's antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.
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Affiliation(s)
- Zhengyang Zhou
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Hongdian Zhang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Jian Du
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Jiayu Yang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Wen Pan
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Qiumo Zhang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Huiya Wang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Peng Tang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China.
| | - Yi Ba
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dongcheng District, Beijing, 100032, China.
| | - Haiyang Zhang
- Tianjin Institute of Coloproctology, Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, China.
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17
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Hokamura N, Fukagawa T, Fukushima R, Kiyokawa T, Horikawa M, Soeda N, Suzuki Y, Kaneshiro S, Abe K, Kodashima S, Yamamoto T, Oshima Y, Ishida T, Sasajima Y, Nomoto A, Shiraishi K, Ito A. Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma. BMC Gastroenterol 2024; 24:295. [PMID: 39223478 PMCID: PMC11370125 DOI: 10.1186/s12876-024-03382-w] [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: 06/11/2023] [Accepted: 08/23/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.
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Affiliation(s)
- Nobukazu Hokamura
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan.
| | - Takeo Fukagawa
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Ryoji Fukushima
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Takashi Kiyokawa
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Masahiro Horikawa
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Naruyoshi Soeda
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Yusuke Suzuki
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Shinya Kaneshiro
- Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan
| | - Koichiro Abe
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Shinya Kodashima
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Takatsugu Yamamoto
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Yasutoshi Oshima
- Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan
| | - Tsuyoshi Ishida
- Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan
| | - Yuko Sasajima
- Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan
| | - Akihiro Nomoto
- Department of Radiology, Teikyo University School of Medicine, Tokyo, Japan
| | - Kenshiro Shiraishi
- Department of Radiology, Teikyo University School of Medicine, Tokyo, Japan
| | - Ai Ito
- Department of Pharmacy, Teikyo University School of Medicine, Tokyo, Japan
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18
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Aparicio T, Carteaux-Taieb A, Arégui A, Estrada J, Beraud-Chaulet G, Fossey-Diaz V, Hammel P, Cattan P. Management of esogastric cancer in older patients. Ther Adv Med Oncol 2024; 16:17588359241272941. [PMID: 39224532 PMCID: PMC11367604 DOI: 10.1177/17588359241272941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 07/17/2024] [Indexed: 09/04/2024] Open
Abstract
Although esogastric cancers often affect patients over 75, there are no specific age-related guidelines for the care of these patients. Esogastric cancers have a poor prognosis and require multimodal treatment to obtain a cure. The morbidity and mortality of these multimodal treatments can be limited if care is optimized by selecting patients for neoadjuvant treatment and surgery. This can include a geriatric assessment, prehabilitation, renutrition, and more extensive use of minimally invasive surgery. Denutrition is frequent in these patients and is particularly harmful in older patients. While older patients may be provided with neoadjuvant chemotherapy or radiotherapy, it must be adapted to the patient's status. A reduction in the initial dose of palliative chemotherapy should be considered in patients with metastases. These patients tolerate immunotherapy better than systemic chemotherapy, and a strategy to replace chemotherapy with immunotherapy whenever possible should be evaluated. Finally, better supportive care is needed in patients with a poor performance status. Prospective studies are needed to improve the care and prognosis of elderly patients.
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Affiliation(s)
- Thomas Aparicio
- Gastroenterology Department, Saint Louis Hospital, APHP, Université Paris Cité, 1 Avenue Claude Vellefaux, Paris 75475, France
| | - Anna Carteaux-Taieb
- Department of Digestive Surgery, Saint Louis Hospital, APHP, Université Paris Cité, Paris, France
| | - Amélie Arégui
- Paris Nord Oncogeriatrics Coordination Unit, Bretonneau Hospital, APHP, Paris, France
| | - Janina Estrada
- Geriatric Out-Patient Unit, Bretonneau Hospital, APHP, Paris, France
| | - Geoffroy Beraud-Chaulet
- Digestive and Medical Oncology Department, Paul Brousse Hospital, APHP, Paris-Saclay University, Villejuif, France
| | - Virginie Fossey-Diaz
- Paris Nord Oncogeriatrics Coordination Unit, Bretonneau Hospital, APHP, Paris, France
| | - Pascal Hammel
- Digestive and Medical Oncology Department, Paul Brousse Hospital, APHP, Paris-Saclay University, Villejuif, France
| | - Pierre Cattan
- Department of Digestive Surgery, Saint Louis Hospital, APHP, Université Paris Cité, Paris, France
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19
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Xu Y, Chow R, Murdy K, Mahsin M, Chandereng T, Sinha R, Lee-Ying R, Abedin T, Cheung WY, Thanh NX, Lee SL. Definitive Chemoradiotherapy versus Trimodality Therapy for Locally Advanced Esophageal Adenocarcinoma: A Multi-Institutional Retrospective Cohort Study. Cancers (Basel) 2024; 16:2850. [PMID: 39199621 PMCID: PMC11353245 DOI: 10.3390/cancers16162850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/09/2024] [Accepted: 08/12/2024] [Indexed: 09/01/2024] Open
Abstract
The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24-0.62; p<0.001) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77-1.91; p=0.40). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56-1.09; p=0.14) or cancer-specific survival (HR, 0.83; 95% CI, 0.57-1.21; p=0.33). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies.
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Affiliation(s)
- Yang Xu
- Department of Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (Y.X.)
- Department of Oncology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Ronald Chow
- Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
| | - Kyle Murdy
- Faculty of Law, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Md Mahsin
- Precision Oncology Hub, Arnie Charbonneau Cancer Institute, Calgary, AB T2N 4Z6, Canada;
| | | | - Rishi Sinha
- Department of Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (Y.X.)
- Department of Oncology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Richard Lee-Ying
- Department of Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (Y.X.)
- Department of Oncology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Tasnima Abedin
- Clinical Research Unit, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada
| | - Winson Y. Cheung
- Department of Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (Y.X.)
- Department of Oncology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Nguyen X. Thanh
- Strategic Clinical Networks, Alberta Health Services, Calgary, AB T5J 3E4, Canada
- School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Sangjune Laurence Lee
- Department of Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (Y.X.)
- Department of Oncology, University of Calgary, Calgary, AB T2N 1N4, Canada
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20
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Shin YS, Jang JY, Yoo YJ, Yu J, Song KJ, Jo YY, Kim SB, Park SR, Song HJ, Kim YH, Kim HR, Kim JH. Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma. Gastroenterol Rep (Oxf) 2024; 12:goae060. [PMID: 38974878 PMCID: PMC11227365 DOI: 10.1093/gastro/goae060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 04/02/2024] [Accepted: 05/26/2024] [Indexed: 07/09/2024] Open
Abstract
Background In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.
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Affiliation(s)
- Young Seob Shin
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Yun Jang
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ye Jin Yoo
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jesang Yu
- Department of Radiation Oncology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
| | - Kye Jin Song
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yoon Young Jo
- Department of Radiation Oncology, Yeungnam University Medical Centre, University of Yeungnam College of Medicine, Daegu, Korea
| | - Sung-Bae Kim
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sook Ryun Park
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong-Hee Kim
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyeong Ryul Kim
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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21
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Gelzinis TA. The Society of Thoracic Surgeons/American Society for Radiation Oncology/American Society of Clinical Oncology Recommendations on the Care of Patients With Localized Esophageal Cancers. J Cardiothorac Vasc Anesth 2024; 38:1445-1450. [PMID: 38658248 DOI: 10.1053/j.jvca.2024.03.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 03/17/2024] [Indexed: 04/26/2024]
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22
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Deboever N, Jones CM, Yamashita K, Ajani JA, Hofstetter WL. Advances in diagnosis and management of cancer of the esophagus. BMJ 2024; 385:e074962. [PMID: 38830686 DOI: 10.1136/bmj-2023-074962] [Citation(s) in RCA: 34] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.
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Affiliation(s)
- Nathaniel Deboever
- Department of Thoracic and Cardiovascular Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Christopher M Jones
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Kohei Yamashita
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, MD Anderson Cancer Center, Houston, TX, USA
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23
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Tchelebi LT, Goodman KA. Esophagogastric Cancer: The Current Role of Radiation Therapy. Hematol Oncol Clin North Am 2024; 38:569-583. [PMID: 38485552 DOI: 10.1016/j.hoc.2024.02.001] [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: 05/06/2024]
Abstract
Radiation therapy is an effective treatment modality in the management of patients with esophageal cancer regardless of tumor location (proximal, middle, or distal esophagus) or histology (squamous cell vs adenocarcinoma). The addition of neoadjuvant CRT to surgery in patients who are surgical candidates has consistently shown a benefit in terms of locoregional recurrence, pathologic downstaging, and overall survival. For patients who are not surgical candidates, CRT has a role as definitive treatment.
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Affiliation(s)
- Leila T Tchelebi
- Northwell, Lake Success, NY, USA; Department of Radiation Medicine, Northern Westchester Hospital, 400 East Main Street, Mount Kisco, NY 10549, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1128, New York, NY 10029-6574, USA. https://twitter.com/KarynAGoodman
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Wang K, Yuan S. Current status and prospect of particle therapy for esophageal cancer. PRECISION RADIATION ONCOLOGY 2024; 8:92-98. [PMID: 40336644 PMCID: PMC11935211 DOI: 10.1002/pro6.1232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 05/29/2024] [Accepted: 05/29/2024] [Indexed: 05/09/2025] Open
Abstract
Esophageal cancer is among the top causes of cancer-related mortality worldwide, and the main treatment modality for locally advanced esophageal cancer is concurrent chemoradiotherapy. The current photon-based radiotherapy modalities and procedures have increased the incidence of treatment-related cardiac and pulmonary complications. Additionally, anatomical changes in the esophagus resulting from diaphragmatic movement, weight loss, and tumor progression present challenges for radiotherapy. These challenges have spurred interest in particle therapies, such as proton beam therapy (PBT) and heavy-ion therapy, for esophageal cancer. This paper comprehensively reviews the dosimetric advantages, clinical efficacy, and limitations of PBT and heavy-ion therapy for esophageal cancer and discusses their prospects. This highlights the unique dosimetric benefits of these therapies, particularly their ability to deliver high-dose radiation precisely to the tumor while sparing the surrounding normal organs and tissues. Although PBT and heavy-ion therapy demonstrate superior clinical efficacy compared to photon therapy, they are not without limitations. Multiple studies are needed to further validate and supplement the existing clinical and preclinical data to better exploit the benefits of PBT and thereby provide improved survival advantages to these patients.
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Affiliation(s)
- Kang Wang
- Department of Radiation OncologyShandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Shuanghu Yuan
- Department of Radiation OncologyShandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
- Department of Radiation OncologyFirst Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
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25
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Li K, Li C, Lu S, He W, Wang C, Han Y, Leng X, Peng L. Effect of cervical paraesophageal lymph node metastasis versus supraclavicular lymph node metastasis on the overall survival of patients with thoracic esophageal squamous cell carcinoma: an observational study. Ann Med Surg (Lond) 2024; 86:2518-2523. [PMID: 38694352 PMCID: PMC11060193 DOI: 10.1097/ms9.0000000000001955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 03/04/2024] [Indexed: 05/04/2024] Open
Abstract
Background Esophageal cancer (EC) is a major global health burden, with a particularly high incidence in East Asia. The authors aimed to investigate the effect of metastasis in cervical paraesophageal lymph nodes (station 101) and supraclavicular lymph nodes (station 104) on the survival of patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC). Materials and Methods Data were obtained from the database of the authors' hospital. The authors retrospectively analyzed the patients with EC who underwent esophagectomy from January 2010 to December 2017. These patients were allocated into two groups based on the presence of lymph node metastasis (LNM) in the cervical paraesophageal or supraclavicular regions. Clinical outcomes and survival data were compared using the TNM staging system of the 8th edition of the American Joint Committee on Cancer (AJCC). Results After a median follow-up of 62.1 months, 122 patients with LNM in the supraclavicular region were included in the study. Among these patients, 53 showed cervical paraesophageal LNM and an overall survival (OS) of 19.9 months [95% confidence interval (CI): 16.3-23.5]. In contrast, 69 patients showed supraclavicular LNM with an OS of 34.9 months (95% CI 25.7-44.1). The OS rates at 1, 3, and 5 years were 77%, 29%, and 21%, respectively, for patients with cervical paraesophageal LNM. Moreover, patients with supraclavicular LNM demonstrated OS rates of 88%, 48%, and 34%, respectively [Hazard ratio (HR): 0.634, 95% CI: 0.402-1.000, P=0.042]. Conclusions Patients with ESCC with cervical paraesophageal LNM had significantly worse OS than those with supraclavicular LNM. This study underscores the importance of accurately identifying and managing ESCC with cervical paraesophageal LNM, as it may require more tailored and aggressive treatment strategies to prolong patient survival.
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Affiliation(s)
| | | | | | | | | | | | - Xuefeng Leng
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (Sichuan Cancer Hospital), Chengdu, People’s Republic of China
| | - Lin Peng
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (Sichuan Cancer Hospital), Chengdu, People’s Republic of China
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Bandidwattanawong C. Multi-disciplinary management of esophageal carcinoma: Current practices and future directions. Crit Rev Oncol Hematol 2024; 197:104315. [PMID: 38462149 DOI: 10.1016/j.critrevonc.2024.104315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 01/30/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Esophageal cancer in one of the most malignant and hard-to-treat cancers. Esophageal squamous carcinoma (ESCC) is most common in Asian countries, whereas adenocarcinoma at the esophago-gastric junction (EGJ AC) is more prevalent in the Western countries. Due to differences in both genetic background and response to chemotherapy and radiotherapy, both histologic subtypes need different paradigms of management. Since the landmark CROSS study has demonstrated the superior survival benefit of tri-modality including neoadjuvant chemoradiotherapy prior to esophagectomy, the tri-modality becomes the standard of care; however, it is suitable for a highly-selected patient. Tri-modality should be offered for every ESCC patient, if a patient is fit for surgery with adequate cardiopulmonary reserve, regardless of ages. Definitive chemoradiotherapy remains the best option for a patient who is not a surgical candidate or declines surgery. On the contrary, owing to doubtful benefits of radiotherapy with potentially more toxicities related to radiotherapy in EGJ AC, either neoadjuvant chemotherapy or peri-operative chemotherapy would be more preferable in an EGJ AC patient. In case of very locally advanced disease (cT4b), the proper management is more challenging. Even though, palliative care is the safe option, multi-modality therapy with curative intent like neoadjuvant chemotherapy with conversion surgery may be worthwhile; however, it should be suggested on case-by-case basis.
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Affiliation(s)
- Chanyoot Bandidwattanawong
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Thailand.
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27
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Li K, Li C, Nie X, He W, Du K, Liu K, Wang C, Li J, Han Y, Peng L, Wang Q, Leng X. Surgical vs nonsurgical treatment for esophageal squamous cell carcinoma in patients older than 70 years: a propensity score matching analysis. J Gastrointest Surg 2024; 28:611-620. [PMID: 38704198 DOI: 10.1016/j.gassur.2024.01.010] [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: 11/09/2023] [Revised: 01/01/2024] [Accepted: 01/13/2024] [Indexed: 05/06/2024]
Abstract
PURPOSE With the rising life expectancy and an aging population, it has become increasingly important to investigate treatments suitable for older adult patients with esophageal cancer. This study investigated whether older adult patients who underwent esophagectomy had better clinical outcomes than those who were nonsurgically treated. METHODS We retrospectively analyzed patients with esophageal squamous cell carcinoma (ESCC) who were 70 years or older and underwent esophagectomy, radiotherapy (RT), and/or chemoradiotherapy (CRT) between January 2018 and December 2019. Patients were divided into 2 groups: the surgery group (S group) and the nonsurgery group (NS group). We then compared the clinical outcomes of the 2 groups. RESULTS After a median follow-up duration of 36.6 months, the S group showed better overall survival (OS). The 3-year OS was 59% in the S group and 27% in the NS group (hazard ratio [HR], 0.397; 95% CI, 0.278-0.549; P < .0001). In the S group, the median progression-free survival was 38.3 months (95% CI, 30.6-46.1) compared with 12.3 months in the NS group (HR, 0.511; 95% CI, 0.376-0.695; P < .0001). In addition, the number of adverse events in the NS group was higher than that in the S group (P < .001). CONCLUSION Overall, patients with ESCC at the age of ≥70 years who underwent esophagectomy had significantly better clinical outcomes than those who underwent nonsurgical treatment with RT and/or CRT.
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Affiliation(s)
- Kexun Li
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan; Department of Thoracic Surgery I, Key Laboratory of Lung Cancer of Yunnan Province, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan, Sichuan
| | - Changding Li
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Xin Nie
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Wenwu He
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Kunyi Du
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Kun Liu
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Chenghao Wang
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Jialong Li
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Yongtao Han
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Lin Peng
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Qifeng Wang
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan; Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital, Chengdu, Sichuan
| | - Xuefeng Leng
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Chengdu, Sichuan.
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Yu BB, Huang JQ, Liang HW, Liu Y, Chen L, Pei S, Huang W, Pan XB. Treatment patterns and survival in T4b esophageal cancer: a retrospective cohort study. Aging (Albany NY) 2024; 16:7131-7140. [PMID: 38643464 PMCID: PMC11087096 DOI: 10.18632/aging.205747] [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: 11/01/2023] [Accepted: 03/18/2024] [Indexed: 04/22/2024]
Abstract
PURPOSE This study aims to evaluate the efficacy of various treatment approaches in stage T4b esophageal cancer patients. MATERIALS AND METHODS Data were extracted from the Surveillance, Epidemiology, and End Results databases, covering patients diagnosed with esophageal cancer between 2000 and 2020. Kaplan-Meier analysis was used to assess cancer-specific survival (CSS) and overall survival (OS) across different treatment patterns. RESULTS The study included 482 patients: 222 (46.1%) received chemoradiotherapy, 58 (12.0%) underwent radiotherapy alone, 37 (7.7%) received chemotherapy alone, 50 (10.4%) underwent surgery, and 115 (23.8%) received no treatment. Median CSS were 12, 4, 6, 18, and 1 month for chemoradiotherapy, radiotherapy alone, chemotherapy alone, surgery, and non-treatment groups. Median OS for these groups were 11, 3, 6, 17, and 1 month, respectively. Multivariable proportional hazard regression analysis revealed that patients who underwent surgery experienced significantly improved CSS (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.24-0.72; P = 0.002) and OS (HR = 0.45, 95% CI: 0.28-0.74; P = 0.002) compared to those receiving chemoradiotherapy after propensity score matching. CONCLUSIONS Esophagectomy, with or without radiotherapy and/or chemotherapy, results in better survival outcomes than chemoradiotherapy in patients with stage T4b esophageal cancer.
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Affiliation(s)
- Bin-Bin Yu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Jiang-Qiong Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Huan-Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Long Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Su Pei
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Wei Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
| | - Xin-Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China
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29
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Oshima K, Tsushima T, Ito Y, Kato K. Recent progress in chemoradiotherapy for oesophageal squamous cell carcinoma. Jpn J Clin Oncol 2024; 54:395-402. [PMID: 38342589 PMCID: PMC10999767 DOI: 10.1093/jjco/hyae005] [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: 12/14/2023] [Accepted: 01/11/2024] [Indexed: 02/13/2024] Open
Abstract
Oesophageal squamous cell carcinoma is a common malignancy worldwide. Definitive chemoradiotherapy is the standard treatment for patients with resectable stage oesophageal squamous cell carcinoma who cannot undergo surgery, as well as those with locally advanced unresectable oesophageal squamous cell carcinoma. However, it has several disadvantages such as poor survival, radiation-related toxicities and severe and lethal complications related to salvage treatment for residual or recurrent disease. Numerous clinical trials on chemoradiotherapy have been conducted to confirm the optimal combination of irradiation and chemotherapy. For advanced disease, multimodal treatment strategies including salvage surgery are essential. Palliative chemoradiotherapy is also crucial for dysphagia in locally advanced oesophageal squamous cell carcinoma with or without metastatic lesions. Recently, the synergistic mechanism of radiotherapy combined with immunotherapy has been reported. Early phase clinical trials suggest that a combination of immunotherapy and chemoradiotherapy can improve clinical outcomes with manageable side effects, but further investigations are needed. Here, we reviewed the existing clinical data and current development of chemoradiotherapy combined with immunotherapy in patients with oesophageal squamous cell carcinoma.
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Affiliation(s)
- Kotoe Oshima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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30
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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
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31
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Porschen R, Fischbach W, Gockel I, Hollerbach S, Hölscher A, Jansen PL, Miehlke S, Pech O, Stahl M, Vanhoefer U, Ebert MPA. Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus. United European Gastroenterol J 2024; 12:399-411. [PMID: 38284661 PMCID: PMC11017771 DOI: 10.1002/ueg2.12523] [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: 05/30/2023] [Accepted: 11/21/2023] [Indexed: 01/30/2024] Open
Abstract
Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.
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Affiliation(s)
- Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus OsterholzOsterholz‐ScharmbeckGermany
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von MagenDarm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro‐Liga) e. V.GiessenGermany
| | - Ines Gockel
- Klinik für Viszeral‐, Transplantations‐, Thorax‐ und GefäßchirurgieLeipzigGermany
| | | | - Arnulf Hölscher
- Contilia Zentrum für SpeiseröhrenerkrankungenElisabeth Krankenhaus EssenEssenGermany
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für GastroenterologieVerdauungs‐ und StoffwechselkrankheitenBerlinGermany
| | | | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle EndoskopieKrankenhaus Barmherzige BrüderRegensburgGermany
| | - Michael Stahl
- Klinik für Internistische Onkologie & Onkologische PalliativmedizinEvang. Kliniken Essen‐MitteEssenGermany
| | - Udo Vanhoefer
- Klinik für Hämatologie und OnkologieKath. MarienkrankenhausHamburgGermany
| | - Matthias P. A. Ebert
- Medizinische Fakultät MannheimII. Medizinische KlinikUniversitätsmedizinUniversität HeidelbergMannheimGermany
- DKFZ‐Hector Krebsinstitut an der Universitätsmedizin MannheimMannheimGermany
- Molecular Medicine Partnership UnitEMBLHeidelbergGermany
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Pao TH, Chen YY, Chang WL, Wu SY, Lai WW, Tseng YL, Chung TJ, Lin FC. Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery. PLoS One 2024; 19:e0300173. [PMID: 38547184 PMCID: PMC10977715 DOI: 10.1371/journal.pone.0300173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 02/22/2024] [Indexed: 04/02/2024] Open
Abstract
Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.
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Affiliation(s)
- Tzu-Hui Pao
- Division of Radiation Oncology, Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ying-Yuan Chen
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shang-Yin Wu
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wu-Wei Lai
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yau-Lin Tseng
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ta-Jung Chung
- Department of Medical Imaging, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Forn-Chia Lin
- Division of Radiation Oncology, Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Lee MH, Park MI, Lee JW, Jung K, Kim JH, Kim SE, Moon W, Park SJ. Comparison of the Clinical Outcomes of Esophagectomy and Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:102-110. [PMID: 38522853 DOI: 10.4166/kjg.2023.100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 02/12/2024] [Accepted: 02/13/2024] [Indexed: 03/26/2024]
Abstract
BACKGROUND/AIMS The efficacy of concurrent chemoradiotherapy (CCRT) or esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC) is unclear. This study compared the survival and recurrence of patients with locally advanced ESCC after definitive CCRT and surgery. METHODS A retrospective study was conducted on patients with locally advanced ESCC who underwent CCRT or esophagectomy at Kosin University Gospel Hospital from January 2010 to December 2016. The patients' baseline characteristics, pathology, recurrence rate, and three-year/five-year overall survival were obtained. RESULTS This study evaluated ESCC patients with cT1-T2, N+ or cT3-T4, or N, who were treated by definitive CCRT (n=14) or esophagectomy (n=32). No significant difference was noted between the two groups, except for the location of the cancer and performance state. The respective three- and five-year overall survival rates were 30.8% and 23.1% in the CCRT group and 40.2% and 22.5% in the esophagectomy group (p=0.685). In the CCRT group, three patients (21.4%) had a complete response, and two (66.7%) had a recurrence. In the esophagectomy group, an R0 resection was achieved in 28 (87.5%) patients, and a recurrence occurred in 18 (64.3%). The median disease-free survival in the CCRT and esophagectomy groups was 14 and 17 months, respectively (p=0.882). CONCLUSIONS These results showed no significant difference in survival between the definitive CCRT and surgery as the initial treatment. Nevertheless, larger prospective studies will be needed because of the retrospective nature and small number of patients in this study.
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Affiliation(s)
- Myung Hun Lee
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Ju Won Lee
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Kyoungwon Jung
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Jae Hyun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Seun Ja Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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Fan C, Wang X, Zheng X, Sun Y, Ye K, Jiang Y, Liu X, Xu W, Liu Y, Yang Y, Liu J, Jiang Q, He C, Wu X, Nie X, Zhang J, Tan B, Wang W, Zhang Y, Feng Z, Yang C, Lu Y, Liu H, Chen X, Xu J, Liu F, Zheng X, Wang J, Wu S, Chen G, Zhang Y, Jin L, Ge H. Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial. BMC Cancer 2024; 24:321. [PMID: 38454345 PMCID: PMC10921589 DOI: 10.1186/s12885-024-12002-5] [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: 09/13/2023] [Accepted: 02/13/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION ChiCTR1800017646.
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Affiliation(s)
- Chengcheng Fan
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xu Wang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xiaoli Zheng
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yanan Sun
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Ke Ye
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yue Jiang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xiao Liu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Wencai Xu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yang Liu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yuanyuan Yang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Jinsong Liu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Qiong Jiang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Chunyu He
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xiaoyuan Wu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xin Nie
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Jingwei Zhang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Bo Tan
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Wen Wang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yougai Zhang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Zhuo Feng
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Chengliang Yang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yufei Lu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Hailong Liu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xijuan Chen
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Jing Xu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Fang Liu
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xuefeng Zheng
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Jianhua Wang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Shang Wu
- Xinyang Hospital Affiliated to Zhengzhou University & Xinyang Central Hospital, Xinyang, 464000, China
| | - Guofu Chen
- Xinyang Hospital Affiliated to Zhengzhou University & Xinyang Central Hospital, Xinyang, 464000, China
| | | | - Linzhi Jin
- Anyang Cancer Hospital, Anyang, 455000, China
| | - Hong Ge
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.
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Bostel T, Nikolaidou E, Wollschläger D, Mayer A, Kaufmann J, Hopprich A, Rühle A, Grosu AL, Debus J, Fottner C, Moehler M, Grimminger P, Schmidberger H, Nicolay NH. Multicenter analysis on the value of standard (chemo)radiotherapy in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction. Radiat Oncol 2024; 19:28. [PMID: 38433231 PMCID: PMC10910868 DOI: 10.1186/s13014-024-02414-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/30/2024] [Indexed: 03/05/2024] Open
Abstract
BACKGROUND To assess the tolerability and oncological results of chemoradiation in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction. METHODS This multi-center retrospective analysis included 86 elderly patients (≥ 65 years) with esophageal or gastroesophageal junction adenocarcinoma (median age 73 years; range 65-92 years) treated with definitive or neoadjuvant (chemo)radiotherapy. The treatment was performed at 3 large comprehensive cancer centers in Germany from 2006 to 2020. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities according to CTCAE criteria v5.0 were analyzed, and parameters potentially relevant to patient outcomes were evaluated. RESULTS Thirty-three patients (38%) were treated with neoadjuvant chemoradiation followed by surgery, while the remaining patients received definitive (chemo)radiation. The delivery of radiotherapy without dose reduction was possible in 80 patients (93%). In 66 patients (77%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 48% of patients (n = 32) required chemotherapy de-escalation due to treatment-related toxicities and comorbidities. Twenty-nine patients (34%) experienced higher-grade acute toxicities and 14 patients (16%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS amounted to 72%, 49%, 46%, and 52%, respectively. In multivariate analysis, neoadjuvant chemoradiation followed by surgery was shown to be associated with significantly better PFS (p = 0.006), DMFS (p = 0.006), and OS (p = 0.004) compared with all non-surgical treatments (pooled definitive radiotherapy and chemoradiation). No such advantage was seen over definitive chemoradiation. The majority of patients with neoadjuvant therapy received standard chemoradiotherapy without dose reduction (n = 24/33, 73%). In contrast, concurrent chemotherapy was only possible in 62% of patients undergoing definitive radiotherapy (n = 33/53), and most of these patients required dose-reduction or modification of chemotherapy (n = 23/33, 70%). CONCLUSIONS In our analysis, omission of chemotherapy or adjustment of chemotherapy dose during definitive radiotherapy was necessary for the overwhelming majority of elderly esophageal cancer patients not eligible for surgery, and hence resulted in reduced PFS and OS. Therefore, optimization of non-surgical approaches and the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly patients with (gastro)esophageal adenocarcinoma is required.
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Affiliation(s)
- Tilman Bostel
- Department of Radiation Oncology, University Medical Center Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany.
- Radiological Institute Dr. Von Essen, Koblenz, Germany.
| | - Eirini Nikolaidou
- Department of Radiation Oncology, University Medical Center Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
- Department of Radiation Oncology, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Daniel Wollschläger
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Mainz, Germany
| | - Arnulf Mayer
- Department of Radiation Oncology, University Medical Center Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Justus Kaufmann
- Department of Radiation Oncology, University Medical Center Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
| | - Anne Hopprich
- Department of Radiation Oncology, University Medical Center Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
| | - Alexander Rühle
- Department of Radiation Oncology, University of Freiburg - Medical Center, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Radiation Oncology, University of Leipzig Medical Center, Leipzig, Germany
- Cancer Center Central Germany (CCCG), Leipzig, Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, University of Freiburg - Medical Center, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jürgen Debus
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
- German Cancer Consortium (DKTK), Partner Site Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christian Fottner
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
- Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany
| | - Markus Moehler
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
- Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany
| | - Peter Grimminger
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
- Department of General, Visceral and Transplant Surgery, University Medical Center Mainz, Mainz, Germany
| | - Heinz Schmidberger
- Department of Radiation Oncology, University Medical Center Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
- German Cancer Consortium (DKTK) Partner Site Mainz, German Cancer Research Center (Dkfz), Heidelberg, Germany
| | - Nils Henrik Nicolay
- Department of Radiation Oncology, University of Freiburg - Medical Center, Freiburg, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Radiation Oncology, University of Leipzig Medical Center, Leipzig, Germany
- Cancer Center Central Germany (CCCG), Leipzig, Germany
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Abana CO, Damen PJ, van Rossum PS, Bravo PL, Wei X, Pollard-Larkin JM, Nitsch PL, Murphy MB, Hofstetter WL, Liao Z, Lin SH. Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy. Int J Part Ther 2024; 11:100009. [PMID: 38757075 PMCID: PMC11095094 DOI: 10.1016/j.ijpt.2024.100009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 12/16/2023] [Accepted: 01/31/2024] [Indexed: 05/18/2024] Open
Abstract
Purpose The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. Patients and Methods We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Results The median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. Conclusion Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes.
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Affiliation(s)
- Chike O. Abana
- Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Pim J. Damen
- Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands
| | - Peter S. van Rossum
- Department of Radiation Oncology, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Pablo Lopez Bravo
- Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Xiong Wei
- Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | | | - Paige L. Nitsch
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Mariela Blum Murphy
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Wayne L. Hofstetter
- Department of Thoracic & Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Zhongxing Liao
- Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Steven H. Lin
- Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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37
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Huang VP, Ding L, Kim AW, Wightman SC, Atay SM. Delayed esophagectomy for adenocarcinoma is associated with a negative impact on long-term survival and an increased risk of perioperative morbidity. J Surg Oncol 2024; 129:592-600. [PMID: 37986276 DOI: 10.1002/jso.27513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 10/29/2023] [Indexed: 11/22/2023]
Abstract
OBJECTIVE Delayed esophagectomy (DE) following chemoradiation therapy (CXRT) for esophageal carcinoma is undertaken in selected patients. This study aimed to assess both short-term outcomes and long-term survival for patients with adenocarcinoma undergoing DE. METHODS The National Cancer Database was queried for patients with American Joint Committee on Cancer clinical stage II-III esophageal adenocarcinoma undergoing esophagectomy after CXRT. Patients were categorized as (1) DE, ≥90 days between completion of CXRT and surgery or (2) nondelayed esophagectomy (NDE), <90 days. Cox regression was performed to identify factors associated with mortality. RESULTS A total of 8157 patients met criteria. Age >69, nonwhite race, Medicare/Medicaid insured patients preferentially underwent DE. Five-year overall survival (OS) favored NDE (36% vs. 31%, p = 0.008). Cox regression identified DE, clinical stage >T2, or >N0 as factors associated with mortality. Within the DE group, OS favored early cT-status. DE fared worse than NDE in 30- and 90-day mortality (4.5%/11.1% vs. 2.9%/6.5%, p < 0.01/p < 0.001) and margin positive resection (7.1% vs. 4.2%, p < 0.001). CONCLUSIONS For esophageal adenocarcinoma, DE is associated with decreased OS compared to NDE. For DE, cT-status is prognostic for OS, while cN-status was not. Increased 30-/90-day mortality and margin positive resection rates for DE question whether patients with locally advanced (cT3/T4) primary esophageal adenocarcinoma should undergo intentional DE.
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Affiliation(s)
- Valerie P Huang
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Li Ding
- Division of Thoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Anthony W Kim
- Division of Thoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Sean C Wightman
- Division of Thoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Scott M Atay
- Division of Thoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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38
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Sato Y, Tanaka Y, Yokoi R, Tsuchiya H, Sengoku Y, Fukada M, Yasufuku I, Asai R, Tajima JY, Kiyama S, Kato T, Murase K, Matsuhashi N. Oligometastases of Esophageal Squamous Cell Carcinoma: A Review. Cancers (Basel) 2024; 16:704. [PMID: 38398095 PMCID: PMC10886923 DOI: 10.3390/cancers16040704] [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: 01/11/2024] [Revised: 02/02/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Patients with oligometastases show distant relapse in only a limited number of regions. Local therapy such as surgical resection, radiotherapy, chemoradiotherapy, and radiofrequency ablation for the relapsed sites may thus improve patient survival. Oligometastases are divided into oligo-recurrence and sync-oligometastases. Oligo-recurrence indicates a primary lesion that is controlled, and sync-oligometastases indicate a primary lesion that is not controlled. The management of oligo-recurrence and sync-oligometastases in esophageal squamous cell carcinoma has not been clearly established, and treatment outcomes remain equivocal. We reviewed 14 articles, including three phase II trials, that were limited to squamous cell carcinoma. Multimodal treatment combining surgical resection and chemoradiotherapy for oligo-recurrence of esophageal squamous cell carcinoma appears to be a promising treatment. With the development of more effective chemotherapy and regimens that combine immune checkpoint inhibitors, it will become more likely that sync-oligometastases that were unresectable at the initial diagnosis can be brought to conversion surgery. Currently, a randomized, controlled phase III trial is being conducted in Japan to compare a strategy for performing definitive chemoradiotherapy and, if necessary, salvage surgery with a strategy for conversion surgery in patients who can be resected by induction chemotherapy.
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Affiliation(s)
- Yuta Sato
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Yoshihiro Tanaka
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Ryoma Yokoi
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Hiroshi Tsuchiya
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Yuki Sengoku
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Masahiro Fukada
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Itaru Yasufuku
- Department of Clinical Anatomy Development Studies, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Ryuichi Asai
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Jesse Yu Tajima
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Shigeru Kiyama
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Takazumi Kato
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Katsutoshi Murase
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
| | - Nobuhisa Matsuhashi
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu Prefecture, Japan
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Honing J, Koch AD, Siersema PD, Spaander M. Endoscopic resection for residual oesophageal neoplasia after definitive chemoradiotherapy. Best Pract Res Clin Gastroenterol 2024; 68:101885. [PMID: 38522883 DOI: 10.1016/j.bpg.2024.101885] [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: 08/31/2023] [Accepted: 01/22/2024] [Indexed: 03/26/2024]
Abstract
Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.
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Affiliation(s)
- Judith Honing
- Department of Gastroenterology and Hepatology, Rotterdam MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Arjun D Koch
- Department of Gastroenterology and Hepatology, Rotterdam MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Rotterdam MC Cancer Institute, University Medical Center Rotterdam, the Netherlands
| | - Manon Spaander
- Department of Gastroenterology and Hepatology, Rotterdam MC Cancer Institute, University Medical Center Rotterdam, the Netherlands.
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40
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Yang Z, Guan F, Bronk L, Zhao L. Multi-omics approaches for biomarker discovery in predicting the response of esophageal cancer to neoadjuvant therapy: A multidimensional perspective. Pharmacol Ther 2024; 254:108591. [PMID: 38286161 DOI: 10.1016/j.pharmthera.2024.108591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 12/02/2023] [Accepted: 01/04/2024] [Indexed: 01/31/2024]
Abstract
Neoadjuvant chemoradiotherapy (NCRT) followed by surgery has been established as the standard treatment strategy for operable locally advanced esophageal cancer (EC). However, achieving pathologic complete response (pCR) or near pCR to NCRT is significantly associated with a considerable improvement in survival outcomes, while pCR patients may help organ preservation for patients by active surveillance to avoid planned surgery. Thus, there is an urgent need for improved biomarkers to predict EC chemoradiation response in research and clinical settings. Advances in multiple high-throughput technologies such as next-generation sequencing have facilitated the discovery of novel predictive biomarkers, specifically based on multi-omics data, including genomic/transcriptomic sequencings and proteomic/metabolomic mass spectra. The application of multi-omics data has shown the benefits in improving the understanding of underlying mechanisms of NCRT sensitivity/resistance in EC. Particularly, the prominent development of artificial intelligence (AI) has introduced a new direction in cancer research. The integration of multi-omics data has significantly advanced our knowledge of the disease and enabled the identification of valuable biomarkers for predicting treatment response from diverse dimension levels, especially with rapid advances in biotechnological and AI methodologies. Herein, we summarize the current status of research on the use of multi-omics technologies in predicting NCRT response for EC patients. Current limitations, challenges, and future perspectives of these multi-omics platforms will be addressed to assist in experimental designs and clinical use for further integrated analysis.
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Affiliation(s)
- Zhi Yang
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, China
| | - Fada Guan
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, United States of America
| | - Lawrence Bronk
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, China.
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De Pasqual CA, Weindelmayer J, Gervasi MC, Torroni L, Pavarana M, Cenzi D, Togliani T, Rossi R, Giacopuzzi S. Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma. Br J Surg 2024; 111:znae036. [PMID: 38415879 DOI: 10.1093/bjs/znae036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/30/2023] [Accepted: 01/29/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. METHODS Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. RESULTS The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. CONCLUSION Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy.
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Affiliation(s)
- Carlo A De Pasqual
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
| | - Jacopo Weindelmayer
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
| | - Maria C Gervasi
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
| | - Lorena Torroni
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | | | - Daniela Cenzi
- Department of Radiology, OCM Hospital of Verona, Verona, Italy
| | - Thomas Togliani
- Gastroenterology and Digestive Endoscopy Unit, University of Verona, Verona, Italy
| | - Roberto Rossi
- Department of Radiation Oncology, University of Verona, Verona, Italy
| | - Simone Giacopuzzi
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
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Zheng H, Zhang H, Zhu Y, Wei X, Liu S, Ren W. Value of blood oxygenation level-dependent magnetic resonance imaging in early evaluation of the response and prognosis of esophageal squamous cell carcinoma treated with definitive chemoradiotherapy: a preliminary study. BMC Med Imaging 2024; 24:18. [PMID: 38216885 PMCID: PMC10787410 DOI: 10.1186/s12880-024-01193-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/04/2024] [Indexed: 01/14/2024] Open
Abstract
BACKGROUND To find a useful hypoxia non-invasive biomarker for evaluating early treatment response and prognosis to definitive chemoradiotherapy (dCRT) in patients with esophageal squamous cell carcinoma (ESCC), using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). METHODS The R2* values were obtained pre- and 2-3 weeks post-dCRT in 28 patients with ESCC using BOLD MRI. Independent samples t-test (normality) or Mann-Whitney U test (non-normality) was used to compare the differences of R2*-related parameters between the complete response (CR) and the non-CR groups. Diagnostic performance of parameters in predicting response was tested with receiver operating characteristic (ROC) curve analysis. The 3-year overall survival (OS) was evaluated using Kaplan Meier curve, log rank test, and Cox proportional hazards regression analysis. RESULTS The post-R2*, ∆R2*, and ∆%R2* in the CR group were significantly higher than those in the non-CR group (P = 0.002, 0.003, and 0.006, respectively). The R2*-related parameters showed good prediction of tumor response, with AUC ranging from 0.813 to 0.829. The 3-year OS rate in patients with ∆R2* >-7.54 s- 1 or CR were significantly longer than those with ∆R2* ≤ -7.54 s- 1 (72.37% vs. 0.00%; Hazard ratio, HR = 0.196; 95% confidence interval, 95% CI = 0.047-0.807; P = 0.024) or non-CR (76.47% vs. 29.27%; HR = 0.238, 95% CI = 0.059-0.963; P = 0.044). CONCLUSIONS The preliminary results demonstrated that the R2* value might be a useful hypoxia non-invasive biomarker for assessing response and prognosis of ESCC treated with dCRT. BOLD MRI might be used as a potential tool for evaluating tumor oxygenation metabolism, which is routinely applied in clinical practice and beneficial to clinical decision-making. A large sample size was needed for further follow-up studies to confirm the findings.
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Affiliation(s)
- Huanhuan Zheng
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China
| | - Hailong Zhang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China
| | - Yan Zhu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China
| | - Xiaolei Wei
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China
| | - Song Liu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China.
| | - Wei Ren
- The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.
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Walsh TN, Kharytaniuk N, Furlong H, Sorensen J, O'Neill BDP, Breathnach OS, Grogan L. Patient choice of surgery or surveillance following a clinical complete response to neoadjuvant chemoradiotherapy for oesophageal carcinoma. Br J Surg 2024; 111:znad352. [PMID: 37933675 DOI: 10.1093/bjs/znad352] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/21/2023] [Accepted: 08/26/2023] [Indexed: 11/08/2023]
Affiliation(s)
- Thomas N Walsh
- Department of Surgery, Royal College of Surgeons in Ireland, Connolly Hospital, Dublin, Ireland
- Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
| | - Natallia Kharytaniuk
- Department of Surgery, Royal College of Surgeons in Ireland, Connolly Hospital, Dublin, Ireland
- Ear Institute, University College London, London, UK
| | - Heidi Furlong
- Department of Surgery, Royal College of Surgeons in Ireland, Connolly Hospital, Dublin, Ireland
| | - Jan Sorensen
- Healthcare Outcomes Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Brian D P O'Neill
- Department of Radiation Oncology, Beaumont Hospital, Dublin, Ireland
| | | | - Liam Grogan
- Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland
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Liu YW, Lee JY, Wang YK, Chen YH, Fang PT, Chou SH, Chen MH, Bai LY, Yen CJ, Wu MT, Wu IC. Comparison of therapeutic outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A prospective observational cohort study. J Formos Med Assoc 2024; 123:106-115. [PMID: 37385933 DOI: 10.1016/j.jfma.2023.06.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 03/06/2023] [Accepted: 06/14/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.
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Affiliation(s)
- Yu-Wei Liu
- Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; PhD Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, 807, Taiwan
| | - Jui-Ying Lee
- Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Yao-Kuang Wang
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Yi-Hsun Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan
| | - Pen-Tzu Fang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan
| | - Shah-Hwa Chou
- Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Ming-Huang Chen
- Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan
| | - Chia-Jui Yen
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Tsang Wu
- PhD Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, 807, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Worrell SG, Goodman KA, Altorki NK, Ashman JB, Crabtree TD, Dorth J, Firestone S, Harpole DH, Hofstetter WL, Hong TS, Kissoon K, Ku GY, Molena D, Tepper JE, Watson TJ, Williams T, Willett C. The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction. Pract Radiat Oncol 2024; 14:28-46. [PMID: 37921736 DOI: 10.1016/j.prro.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 11/04/2023]
Abstract
Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.
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Affiliation(s)
- Stephanie G Worrell
- Section of Thoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Nasser K Altorki
- Division of Thoracic Surgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
| | | | - Traves D Crabtree
- Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | | | - David H Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Wayne L Hofstetter
- Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Geoffrey Y Ku
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniela Molena
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joel E Tepper
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Thomas J Watson
- Thoracic Surgery Group, Beaumont Health, Royal Oak, Michigan
| | - Terence Williams
- Department of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Christopher Willett
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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Worrell SG, Goodman KA, Altorki NK, Ashman JB, Crabtree TD, Dorth J, Firestone S, Harpole DH, Hofstetter WL, Hong TS, Kissoon K, Ku GY, Molena D, Tepper JE, Watson TJ, Williams T, Willett C. The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction. Ann Thorac Surg 2024; 117:15-32. [PMID: 37921794 DOI: 10.1016/j.athoracsur.2023.09.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/23/2023] [Accepted: 09/05/2023] [Indexed: 11/04/2023]
Abstract
Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.
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Affiliation(s)
- Stephanie G Worrell
- Section of Thoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Nasser K Altorki
- Division of Thoracic Surgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
| | | | - Traves D Crabtree
- Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | | | - David H Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Wayne L Hofstetter
- Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Geoffrey Y Ku
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniela Molena
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joel E Tepper
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Thomas J Watson
- Thoracic Surgery Group, Beaumont Health, Royal Oak, Michigan
| | - Terence Williams
- Department of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Christopher Willett
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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Veziant J, Bouché O, Aparicio T, Barret M, El Hajbi F, Lepilliez V, Lesueur P, Maingon P, Pannier D, Quero L, Raoul JL, Renaud F, Seitz JF, Serre AA, Vaillant E, Vermersch M, Voron T, Tougeron D, Piessen G. Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR). Dig Liver Dis 2023; 55:1583-1601. [PMID: 37635055 DOI: 10.1016/j.dld.2023.07.015] [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: 04/19/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 08/29/2023]
Abstract
INTRODUCTION This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.
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Affiliation(s)
- Julie Veziant
- Department of Digestive and Oncological Surgery, Claude Huriez Hospital, CHU Lille, University of Lille, Lille F-59000, France.
| | - Olivier Bouché
- Department of Digestive Oncology, CHU Reims, Reims, France
| | - T Aparicio
- Department of Gastroenterology and Digestive Oncology, AP-HP, Saint-Louis Hospital, Paris, France
| | - M Barret
- Gastroenterology Department, Cochin Hospital, APHP, Paris, France
| | - F El Hajbi
- Department of Oncology, Centre Oscar Lambret, Lille, France
| | - V Lepilliez
- Gastroenterology Department, Jean Mermoz Private Hospital, Ramsay Santé, Lyon, France
| | - P Lesueur
- Department of Radiation Oncology, Centre Guillaume le Conquérant, Le Havre, France
| | - P Maingon
- Department of Radiation Oncology, La Pitié-Salpêtrière, APHP, Sorbonne University, Paris, France
| | - D Pannier
- Department of Oncology, Centre Oscar Lambret, Lille, France
| | - L Quero
- Department of Radiation Oncology, Saint-Louis Hospital, APHP, Paris, France
| | - J L Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint-Herblain, France
| | - F Renaud
- Department of Pathology, La Pitié-Salpêtrière, APHP, Sorbonne University, Paris, France
| | - J F Seitz
- Department of Digestive Oncology, La Timone, Aix Marseille Université, Marseille, France
| | - A A Serre
- Department of Radiotherapy, Centre Léon Bérard, Lyon, France
| | | | - M Vermersch
- Medical Imaging Department, Valencienne Hospital Centre, Valencienne 59300, France
| | - T Voron
- Department of General and Digestive Surgery, Sorbonne Université, AP-HP, Hôpital Saint Antoine, 184 rue du faubourg Saint-Antoine, Paris 75012, France
| | - D Tougeron
- Department of Gastro-Enterology and Hepatology, Poitiers University Hospital, Poitiers, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez Hospital, CHU Lille, University of Lille, Lille F-59000, France
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Jones CM, Lyles A, Bownes P, Goody R, Hingorani M, Joseph E, Radhakrishna G. Conformal 3D computed tomography planned endoluminal brachytherapy for the local control of esophageal cancer. Brachytherapy 2023; 22:840-850. [PMID: 37743184 DOI: 10.1016/j.brachy.2023.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 08/01/2023] [Accepted: 08/21/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE To outline the toxicity, tolerability, and efficacy of a 3D conformal computed tomography planned endoluminal brachytherapy (ELBT) treatment for esophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). METHODS AND MATERIALS A retrospective single-center analysis of toxicity, tolerability, and outcomes for 65 consecutive patients with OAC/OSCC who received 6-8Gy in one fraction or 12-16Gy in two fractions of high-dose-rate ELBT as salvage postchemoradiotherapy (n = 7 and n = 14 respectively), or as a boost to external beam radiotherapy (n = 14 and n = 30, respectively). RESULTS Median overall survival from the first brachytherapy application was 7.4 (IQR 5.0-14.7) months for the boost cohort and 9.2 (IQR 5.8-20.1) months for the salvage cohort. In a univariate analysis, use of a higher, fractionated dose of radiotherapy was associated with longer overall survival. At least one-third (33%; n = 7) of the salvage cohort and 28% (n = 12) of the boost cohort exhibited a local recurrence prior to death. Overall, 66.7% of the salvage and 56.8% of the boost cohort experienced odynophagia. Swallow function stabilized or improved early after treatment, with only 11.6% of the boost and 14.3% of the salvage cohort demonstrating a long-term decline in dysphagia score. CONCLUSIONS 3D conformal planned ELBT is safe and tolerable. Most patients exhibit an early and sustained stabilization or improvement in their swallow function and greater survival is seen with higher brachytherapy doses. Further research is required to determine the place of brachytherapy in the management of esophageal cancer, particularly when planned using contemporary conformal approaches.
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Affiliation(s)
- Christopher M Jones
- Department of Clinical Oncology, Leeds Cancer Centre, The Leeds Teaching Hospitals NHS Trust, Leeds, UK; Department of Oncology, University of Cambridge, Cambridge, UK; Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
| | - Annabel Lyles
- Department of Clinical Oncology, Leeds Cancer Centre, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Peter Bownes
- Department of Clinical Oncology, Leeds Cancer Centre, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Rebecca Goody
- Department of Clinical Oncology, Leeds Cancer Centre, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Mohan Hingorani
- Queen's Centre for Oncology & Haematology, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Eldho Joseph
- Department of Clinical Oncology, Leeds Cancer Centre, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Ganesh Radhakrishna
- Department of Clinical Oncology, The Christie Hospital, The Christie Hospitals NHS Foundation Trust, Manchester, UK
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Chidambaram S, Owen R, Sgromo B, Chmura M, Kisiel A, Evans R, Griffiths EA, Castoro C, Gronnier C, MaoAwyes MA, Gutschow CA, Piessen G, Degisors S, Alvieri R, Feldman H, Capovilla G, Grimminger PP, Han S, Low DE, Moore J, Gossage J, Voeten D, Gisbertz SS, Ruurda J, van Hillegersberg R, D'Journo XB, Chmelo J, Phillips AW, Rosati R, Hanna GB, Maynard N, Hofstetter W, Ferri L, Berge Henegouwen MI, Markar SR. Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study. Ann Surg 2023; 278:701-708. [PMID: 37477039 DOI: 10.1097/sla.0000000000006028] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/22/2023]
Abstract
OBJECTIVE To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.
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Affiliation(s)
- Swathikan Chidambaram
- Academic Surgical Unit, Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Richard Owen
- Department of Surgery, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
- The Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK
| | - Bruno Sgromo
- Department of Surgery, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Magdalena Chmura
- Department of Surgery, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Aaron Kisiel
- Department of Surgery, Birmingham University Hospitals NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Richard Evans
- Department of Surgery, Birmingham University Hospitals NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Ewen A Griffiths
- Department of Surgery, Birmingham University Hospitals NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK
| | - Carlo Castoro
- General Gastric and Esophagus Surgery Unit, Humanitas Research Hospital, Rozzano, Italy
| | - Caroline Gronnier
- Esophageal and Endocrine Surgery Unit, Digestive Surgery Department, Centre Magellan, CHU de Bordeaux, Bordeaux, France
| | - Mometo Ali MaoAwyes
- Stomach and Oesophageal Tumor Centre, Comprehensive Cancer Center, University Hospital Zurich, Zurich, Switzerland
| | - Christian A Gutschow
- Stomach and Oesophageal Tumor Centre, Comprehensive Cancer Center, University Hospital Zurich, Zurich, Switzerland
| | - Guillaume Piessen
- Department of Digestive and General Surgery, University Hospital Claude Huriez, Lille, Cedex, France
| | - Sébastien Degisors
- Department of Digestive and General Surgery, University Hospital Claude Huriez, Lille, Cedex, France
| | - Rita Alvieri
- Oncological Surgery Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Hope Feldman
- University of Texas, MD Anderson Cancer Center, Houston, TX
| | - Giovanni Capovilla
- Department of Surgery, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Peter P Grimminger
- Department of Surgery, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Shiwei Han
- Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Hospital & Seattle Medical Center, Seattle, WA
| | - Donald E Low
- Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Hospital & Seattle Medical Center, Seattle, WA
| | - Jonathan Moore
- Department of Surgery, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK
| | - James Gossage
- Department of Surgery, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK
| | - Dan Voeten
- Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
| | - Suzanne S Gisbertz
- Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
| | - Jelle Ruurda
- Department of Upper Gastrointestinal Surgery, University Medical Center, Utrecht, The Netherlands
| | | | - Xavier B D'Journo
- Department of Thoracic Surgery, Diseases of the Esophagus & Lung Transplantations, Chemin des Bourrely, North Hospital, Marseille, France
| | - Jakub Chmelo
- Northern Esophago-Gastric Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Alexander W Phillips
- Northern Esophago-Gastric Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Riccardo Rosati
- Department of GI Surgery, San Raffaele Hospital, Milan, Italy
| | - George B Hanna
- Academic Surgical Unit, Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Nick Maynard
- Department of Surgery, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
| | | | - Lorenzo Ferri
- Department of Surgery and Oncology, McGill University, Montreal General Hospital, Montreal, QC, Canada
| | - Mark I Berge Henegouwen
- Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
| | - Sheraz R Markar
- Department of Surgery, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
- Nuffield Department of Surgery, University of Oxford, Oxford, UK
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Acharya R, Mahapatra A, Verma HK, Bhaskar LVKS. Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review. Curr Oncol 2023; 30:9542-9568. [PMID: 37999111 PMCID: PMC10670555 DOI: 10.3390/curroncol30110691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/19/2023] [Accepted: 10/27/2023] [Indexed: 11/25/2023] Open
Abstract
Esophageal cancer is a highly aggressive and deadly disease, ranking as the sixth leading cause of cancer-related deaths worldwide. Despite advances in treatment, the prognosis remains poor. A multidisciplinary approach is crucial for achieving complete remission, with treatment options varying based on disease stage. Surgical intervention and endoscopic treatment are used for localized cancer, while systemic treatments like chemoradiotherapy and targeted drug therapy play a crucial role. Molecular markers such as HER2 and EGFR can be targeted with drugs like trastuzumab and cetuximab, and immunotherapy drugs like pembrolizumab and nivolumab show promise by targeting immune checkpoint proteins. Epigenetic modifications offer new avenues for targeted therapy. Treatment selection depends on factors like stage, tumor location, and patient health, with post-operative and rehabilitation care being essential. Early diagnosis, appropriate treatment, and supportive care are key to improving outcomes. Continued research is needed to develop effective targeted drugs with minimal side effects. This review serves as a valuable resource for clinicians and researchers dedicated to enhancing esophageal cancer treatment outcomes.
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Affiliation(s)
- Rakesh Acharya
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, India; (R.A.); (A.M.)
| | - Ananya Mahapatra
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, India; (R.A.); (A.M.)
| | - Henu Kumar Verma
- Department of Immunopathology, Institute of lungs Health and Immunity, Comprehensive Pneumology Center, Helmholtz Zentrum, Neuherberg, 85764 Munich, Germany;
| | - L. V. K. S. Bhaskar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, India; (R.A.); (A.M.)
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