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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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Chen C, Zeng B, Xue D, Cao R, Liao S, Yang Y, Li Z, Kang M, Chen C, Xu B. Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial. BMJ Open 2022; 12:e060619. [PMID: 36302570 PMCID: PMC9621153 DOI: 10.1136/bmjopen-2021-060619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 10/07/2022] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Radiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to reduce the injury is strict adherence to dose-volume restrictions of normal lungs. RILI can manifest as acute radiation pneumonitis with cellular injury, cytokine release and cytokine recruitment to inflammatory infiltrate, and subsequent chronic radiation pulmonary fibrosis. Pirfenidone inhibits the production of inflammatory cytokines, scavenges-free radicals and reduces hydroxyproline and collagen formation. Hence, pirfenidone might be a promising drug for RILI prevention. This study aims to evaluate the efficacy and safety of pirfenidone in preventing RILI in patients with locally advanced ESCC receiving chemoradiotherapy. METHODS AND ANALYSIS This study is designed as a randomised, placebo-controlled, double-blinded, single-centre phase 2 trial and will explore whether the addition of pirfenidone during concurrent chemoradiation therapy (CCRT) could prevent RILI in patients with locally advanced ESCC unsuitable for surgery. Eligible participants will be randomised at 1:1 to pirfenidone and placebo groups. The primary endpoint is the incidence of grade >2 RILI. Secondary endpoints include the incidence of any grade other than grade >2 RILI, time to RILI occurrence, changes in pulmonary function after CCRT, completion rate of CCRT, disease-free survival and overall survival. The follow-up period will be 1 year. In case the results meet the primary endpoint of this trial, a phase 3 multicentre trial with a larger sample size will be required to substantiate the evidence of the benefit of pirfenidone in RILI prevention. ETHICS AND DISSEMINATION This study was approved by the Ethics Committee of Fujian Union Hospital (No. 2021YF001-02). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations. TRIAL REGISTRATION NUMBER ChiCTR2100043032.
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Affiliation(s)
- Cheng Chen
- Department of Radiation Oncology, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological, and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, China
- Department of Medical Imaging Technology, School of Medical Imaging, Union Clinical Medical College, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, Fujian, China
| | - Bangwei Zeng
- Nosocomial Infection Control Branch, Fujian Medical University Union Hospital, Fuzhou, China
| | - Dan Xue
- Pulmonary Department, Fujian Medical University Union Hospital, Fuzhou, China
| | - Rongxiang Cao
- Pulmonary Department, Fujian Medical University Union Hospital, Fuzhou, China
| | - Siqin Liao
- Department of PET/CT Center, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yong Yang
- Department of Radiation Oncology, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological, and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, China
- Department of Medical Imaging Technology, School of Medical Imaging, Union Clinical Medical College, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, Fujian, China
| | - Zhihua Li
- Department of Oncology Department, The Second Hospital of Zhangzhou, Zhangzhou, People's Republic of China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Benhua Xu
- Department of Radiation Oncology, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological, and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, China
- Department of Medical Imaging Technology, School of Medical Imaging, Union Clinical Medical College, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, Fujian, China
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Liu Y, Beeraka NM, Liu J, Chen K, Song B, Song Z, Luo J, Liu Y, Zheng A, Cui Y, Wang Y, Jia Z, Song X, Wang X, Wang H, Qi X, Ren J, Wu L, Cai J, Fang X, Wang X, Sinelnikov MY, Nikolenko VN, Greeshma MV, Fan R. Comparative clinical studies of primary chemoradiotherapy versus S-1 and nedaplatin chemotherapy against stage IVb oesophageal squamous cell carcinoma: a multicentre open-label randomised controlled trial. BMJ Open 2022; 12:e055273. [PMID: 35470188 PMCID: PMC9039379 DOI: 10.1136/bmjopen-2021-055273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Oesophageal squamous cell carcinoma (OSCC) is one of the most commonly occurring devastating tumours worldwide, including in China. To date, the standard care of patients with stage IV OSCC is systemic chemotherapy and palliative care, which results in poor prognosis. However, no consensus has been established regarding the role of radiotherapy in targeting the primary tumour in patients with stage IVa OSCC. Thus, the aim of this study is to assess the effectiveness of primary radiotherapy combined with S-1 and nedaplatin (NPD) chemotherapy in the patients with stage IV OSCC. METHODS AND ANALYSIS The study is a multicentre, open-label, randomised controlled trial. A total of 180 eligible patients with stage IV OSCC will be randomised into a study group (90 patients) and a control group (90 patients). Patients in the study group will receive radiotherapy to the primary tumour at a dose of 50.4 Gy combined with 4-6 cycles of S-1 and NPD chemotherapy. In the control group, patients will only receive 4-6 cycles of S-1 and NPD chemotherapy. The primary and secondary outcomes will be measured. The differences between the two groups will be statistically analysed with regard to overall survival, the progression-free survival and safety. All outcomes will be ascertained before treatment, after treatment and after the follow-up period.The results of this study will provide evidence on the role of radiotherapy in patients with stage IV OSCC in China, which will show new options for patients with advanced oesophageal cancer. ETHICS AND DISSEMINATION This study was approved by the Institutional Ethics Committee of The First Hospital Affiliated of Zhengzhou University (approval number: SS-2018-04). TRIAL REGISTRATION The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1800015765) on 1 November 2018; retrospectively registered, http://www.chictr.org.cn/index.aspx.
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Affiliation(s)
- Yun Liu
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Radiation Oncology, Anhui Provincial Cancer Hospital/Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, P.R. China, Hefei, People's Republic of China
| | - Narasimha M Beeraka
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Human Anatomy, Sechenov University, Moskva, Moskva, Russian Federation
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), JSS Medical College, Mysuru, Karnataka, India
| | - Junqi Liu
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kuo Chen
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bo Song
- Department of Oncology, The Xinyang Central Hospital, Xinyang, China
| | - Zhang Song
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianchao Luo
- Department of Oncology, The Henan Provincial People's Hospital, Zhengzhou, China
| | - Yang Liu
- Department of Radiation Oncology, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China
| | - Anping Zheng
- Department of Radiation Oncology, Anyang Cancer Hospital, Anyang, China
| | - Yanhui Cui
- Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Yang Wang
- Department of Radiation Oncology, The Nanyang Central Hospital, Nanyang, China
| | - Zhenhe Jia
- Department of Oncology, The Xixia County People's Hospital, xixia, China
| | - Xiangyu Song
- Department of Radiation Oncology, The Linzhou People's Hospital, Linzhou, China
| | - Xiaohong Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Hongqi Wang
- Department of Radiation Oncology, General Hospital of Pingmei Shenma Medical Group Pingdingshan 467000, Pingmei, China
| | - Xuefeng Qi
- Department of Radiation Oncology, The Linying County People's Hospital, Linying, China
| | - Jinshan Ren
- Department of Radiation Oncology, The First Affiliated Hospital of Nanyang Medical College, Nanyang, China
| | - Liping Wu
- Department of Radiation Oncology, The Xinxiang Central Hospital, Xinxiang, China
| | - Jixing Cai
- Department of Radiation oncology, the Linzhou Cancer Hospital, 456550, P.R, Linzhou, People's Republic of China
| | - Xainying Fang
- Department of Oncology, The Xinyang Central Hospital, Xinyang, China
| | - Xin Wang
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mikhail Y Sinelnikov
- Department of Human Anatomy, Sechenov University, Moskva, Moskva, Russian Federation
| | - Vladimir N Nikolenko
- Department of Human Anatomy, Sechenov University, Moskva, Moskva, Russian Federation
- Department of Human anatomy, M.V. Lomonosov Moscow State University, Moscow, Russian Federation
| | - M V Greeshma
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), JSS Medical College, Mysuru, Karnataka, India
| | - Ruitai Fan
- Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Zhang L, Song Y, Jiang N, Huang Y, Dong B, Li W, He Y, Chen Y, Liu H, Yu R. Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis. BMJ Open 2021; 11:e046352. [PMID: 33753446 PMCID: PMC7986677 DOI: 10.1136/bmjopen-2020-046352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVES Despite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC. DESIGN Meta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. SETTING RCTs from any country and healthcare setting. PARTICIPANTS Patients with OC. INTERVENTIONS Combination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC. PRIMARY AND SECONDARY OUTCOME MEASURES Overall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures. RESULTS In total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia. CONCLUSIONS Overall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment. TRIAL REGISTRATION NUMBER CRD42020169230.
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Affiliation(s)
- Lijuan Zhang
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yanli Song
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Nan Jiang
- School of Nursing, Tianjin Medical University, Tianjin, China
| | - Yaqi Huang
- School of Nursing, Tianjin Medical University, Tianjin, China
| | - Bo Dong
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Wei Li
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yanze He
- School of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yun Chen
- Department of Colorectal Surgery, Liaoning Cancer Institute and Hospital, Shenyang, China
| | - Haibin Liu
- Department of Critical Care Medicine, Liaoning Cancer Institute and Hospital, Shenyang, China
| | - Rui Yu
- Department of Science and Technology, Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Liu Q, Xia Y, Chen Y, Zhang J, Deng J, Zhao K. A study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin for advanced esophageal squamous cell carcinoma with T4 and/or M1 lymph node metastasis or locoregional recurrence. Radiat Oncol 2020; 15:75. [PMID: 32268925 PMCID: PMC7140386 DOI: 10.1186/s13014-020-01518-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 03/19/2020] [Indexed: 12/02/2022] Open
Abstract
Background The improvement of survival outcomes and the reduction of toxicities for esophageal squamous cell carcinoma (SCC) are still needed. We conducted a pilot study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin for the treatment of esophageal SCC with T4 and/or M1 lymph node metastasis (LNM) or locoregional recurrence. Methods Fifty-four patients with advanced thoracic esophageal SCC having a stage T4 tumor or M1 LNM and/or locoregional recurrence were enrolled. Docetaxel and cisplatin were both administered weekly at a dose of 25 mg/m2 5–6 times in total concurrently with a specific dose of radiation. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), locoregional control and treatment-related toxicities. Results From October 2015 to December 2016, concurrent treatment with full-cycle docetaxel and cisplatin and radiotherapy was administered to 41 of 54 patients (75.9%). A total of 51 patients (94.4%) completed the radiation schedules. Twenty-one patients (44.4%) achieved a complete response, and 21 (44.4%) achieved a partial response after chemoradiotherapy. The median survival time was 18.2 months, and the median PFS time was 11.5 months. The 1-year and 3-year OS, locoregional control and PFS rates were 70.4, 80.6, 50.0 and 36.4%, 64.3, 31.5%, respectively. Grade 3 toxicities included neutropenia (13.0%), anemia (3.7%), thrombocytopenia (1.9%), fatigue (20.4%), anorexia (13.0%), esophagitis (11.1%), and pneumonitis (5.6%). Grade 4 neutropenia occurred in 16.7% of patients. Four patients (7.4%) died from grade 5 toxicities. There were no significant differences in both survival and grade 3 and higher toxicities between the newly diagnosed group and recurrent group. Conclusions Concurrent chemoradiotherapy with weekly docetaxel and cisplatin is a well-tolerated and effective treatment regimen for esophageal SCC with T4 or M1 LNM and/or locoregional recurrence. Clinical trials with larger sample size and comparisons with conventional fluorouracil and cisplatin regimens are needed.
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Affiliation(s)
- Qi Liu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Xia
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center Minhang Branch Hospital, Shanghai, China
| | - Yun Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Junhua Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiaying Deng
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Kuaile Zhao
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Chen D, Menon H, Welsh J. Using Real-World Historical Controls to Evaluate Radiation Dose Escalation in Esophageal Cancer—Reply. JAMA Oncol 2020; 6:583-584. [DOI: 10.1001/jamaoncol.2019.6412] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Dawei Chen
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Hari Menon
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - James Welsh
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston
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Hua Y, Wang W, Zheng X, Yang L, Wu H, Hu Z, Li Y, Yue J, Jiang Z, Zhang X, Hou Q, Wu S. NVP-BSK805, an Inhibitor of JAK2 Kinase, Significantly Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma in vitro and in vivo. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:745-755. [PMID: 32158193 PMCID: PMC7047839 DOI: 10.2147/dddt.s203048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 01/10/2020] [Indexed: 01/22/2023]
Abstract
Purpose Radiotherapy is one major curative treatment modality for esophageal squamous cell carcinoma (ESCC) patients. This study aimed to find out small-molecular kinase inhibitors, which can significantly enhance the radiosensitivity of ESCC in vitro and in vivo. Materials and Methods Ninety-three kinase inhibitors were tested for their radiosensitizing effect in ESCC cells through high-content screening. The radiosensitizing effect of kinase inhibitors was investigated in vitro by detection of DNA double-strand breaks (DSBs) and clonogenic survival assay. By the establishment of xenograft tumor models in BALB/c nude mice, the radiosensitizing effect of kinase inhibitors was investigated in vivo. Results Among the 93 kinase inhibitors tested, we found NVP-BSK805, an inhibitor of JAK2 kinase, significantly radiosensitized ESCC cells through enhancing DSBs, inhibiting DNA damage repair and arresting cell cycle in G2/M or G0/G1 phase. After treatment with NVP-BSK805, ESCC cells showed decreased clonogenic survival and delayed tumor growth in vivo. JAK2 kinase was highly expressed in tumor tissues of ESCC patients, while rarely expressed in matched normal esophageal epithelial tissues. Survival analysis revealed JAK2 kinase as a prognostic factor of ESCC patients treated with chemoradiotherapy. Conclusion Our study discovered JAK2 kinase as an attractive target to enhance the radiosensitivity of ESCC cells in vitro and in vivo.
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Affiliation(s)
- Yuhui Hua
- Department of Pharmacy, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Weijia Wang
- Department of Pharmacy, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Xiaoli Zheng
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Ling Yang
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Hongjin Wu
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Zhaoyang Hu
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Ying Li
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Jing Yue
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Zhenzhen Jiang
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Xiaoyan Zhang
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Qiang Hou
- Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou 310002, People's Republic of China
| | - Shixiu Wu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People's Republic of China
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Impact of Definitive Radiotherapy and Surgical Debulking on Treatment Outcome and Prognosis for Locally Advanced Masaoka-Koga stage III Thymoma. Sci Rep 2020; 10:1735. [PMID: 32015469 PMCID: PMC6997365 DOI: 10.1038/s41598-020-58692-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/16/2020] [Indexed: 11/08/2022] Open
Abstract
The role of definitive radiotherapy (dRT) and debulking surgery (DS) for patients with locally advanced, unresectable, Masaoka-Koga stage III thymomas was not well studied. Unresectable tumor refers to tumor that could not be completely resected because of invasion of surrounding organs. Consecutive patients with unresectable stage III thymomas between 2000 and 2017 were reviewed. According to the treatment intent and radiation dose, patients were categorized into a dRT group and a non-dRT group. The former group included patients who received radiotherapy at doses ≥ 54 Gy after DS or biopsy. The latter group included patients who did not receive radiotherapy and those who received a radiation dose < 54 Gy. A total of 82 patients were included. Compared with non-dRT, dRT significantly improved 5-year overall survival (OS, P = 0.003), progression-free survival (PFS, P = 0.008), and freedom from locoregional failure (FFLF, P < 0.001). Compared with biopsy alone, DS did not improve OS, PFS, FFLF. On multivariate analysis, dRT was an independent prognostic factor for OS (hazard ratio [HR]: 2.37, P = 0.024), PFS (HR: 2.40, P = 0.004), and FFLF (HR: 3.83, P = 0.001). In conclusion, dRT was an effective and beneficial treatment for patients with unresectable Masaoka-Koga stage III thymoma.
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9
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Onderdonk BE, Gutiontov SI, Chmura SJ. The Evolution (and Future) of Stereotactic Body Radiotherapy in the Treatment of Oligometastatic Disease. Hematol Oncol Clin North Am 2020; 34:307-320. [DOI: 10.1016/j.hoc.2019.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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10
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Tan L, Xiao Z, Zhang H, Chen D, Feng Q, Zhou Z, Lv J, Liang J, Yin W. Survival comparision of three-dimensional radiotherapy alone with concurrent chemoradiotherapy for non-surgical esophageal carcinoma. Cancer Radiother 2020; 24:21-27. [PMID: 32001131 DOI: 10.1016/j.canrad.2019.06.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 06/23/2019] [Accepted: 06/26/2019] [Indexed: 12/29/2022]
Abstract
PURPOSE Radiotherapy is the main treatment method for patients with locally advanced, unresectable esophageal cancer. The aim of this study is to compare overall survival (OS) using 3D radiotherapy (3DRT) alone with concurrent chemoradiotherapy (CCRT) in 296 non-surgical esophageal carcinoma patients. PATENTS AND METHODS Over 10 years, of the 480 patients with esophageal carcinoma treated with 3DRT with or without chemotherapy, 148 patients each comprised 3DRT and CCRT groups after propensity score matching. RESULTS The 5- and 10-year OS (P=0.337) and PFS (P=0.715) rates for 3DRT alone were 22.0%, 14.4% and 26.1%, 23.2%, respectively, compared with 28.8%, 18.6% and 34.7%, 29.1% for CCRT, respectively. CCRT did not improve 5-year and 10-year OS or PFS in 60-70Gy group (OS: 27.5% and 25.2%; 17.9% and 17.0%, P=0.938; PFS: 38.3% and 31.8%; 31.9% and 27.8%, P=0.890) nor reduce 10-year hematogenous metastasis (31.7% and 28.3%, P=0.698). CCRT improved 5-year OS and PFS of 50.0-59.9Gy group (OS: 33.3% and 12.0%, P=0.029; PFS: 33.1% and 10.6%, P=0.081). For 3DRT, the 5-year OS and PFS rates were significantly better in the 60-70Gy group (P=0.017) compared with 50.0-59.9Gy group (P=0.002). For CCRT group, 5-year OS and PFS favored the 50.0-59.9Gy group, but the difference was insignificant. Major toxicities were greater with CCRT compared with 3DRT. CONCLUSION For non-surgical esophageal carcinoma patients, 3DRT combined with CCRT was effective in prolonging both OS and PFS.
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Affiliation(s)
- L Tan
- Department of Oncology, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, 150001 Harbin, Heilongjiang, PR China
| | - Z Xiao
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China.
| | - H Zhang
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
| | - D Chen
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
| | - Q Feng
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
| | - Z Zhou
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
| | - J Lv
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
| | - J Liang
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
| | - W Yin
- Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
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11
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Effect of lung volume on helical radiotherapy in esophageal cancer: are there predictive factors to achieve acceptable lung doses? Strahlenther Onkol 2020; 196:805-812. [PMID: 31980833 DOI: 10.1007/s00066-020-01581-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 01/07/2020] [Indexed: 12/25/2022]
Abstract
PURPOSE The dose received by the lungs in radiotherapy (RT) is affected by the patient's current lung volume. The presence of predictive factors and cut-off points were investigated to achieve acceptable lung doses in esophageal cancer (EC) treatment. METHODS Virtual RT volumes of supracarinal EC were delineated. RT plans were designed with standard criteria in the TomoTherapy planning system (TomoTherapy Inc., Madison, WI, USA). The total dose was 50.4 Gy (1.8 Gy/fraction). ROC (Receiver operating characteristic) analysis and Mann-Whitney U tests were performed. RESULTS There was a total of 65 patient plans included. ROC analysis showed that lung/PTV (Planning target volume) volume ratio (AUC [Area under curve]: 0.91, 95% CI: 0.83-0.99, p = 0.000) and bilateral lung volume (AUC: 0.81, 95% CI: 0.70-0.92, p = 0.000) have diagnostic power to predict the suitability of RT plans according to QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) for lung dose constraints. The cut-off points of 7 and 3500 cc were selected for lung/PTV ratio and bilateral lung volume, respectively. The effect of the cut-off points on the dose data was assessed with the Mann-Whitney U test. The mean lung and heart doses, lung V5, V15, and V20, as well as heart V5, V20, V30, and V45 values were found to be lower in both groups separated by cut-off points (p < 0.05). CONCLUSION The lung/PTV ratio ≥7 and bilateral lung volume ≥3500 cc cut-off points are predictive of whether TomoTherapy plans may meet QUANTEC lung dose limits in patients with supracarinal esophageal cancer. The patients with lung/PTV ratio and lung volume above these cut-off points may be candidates for treatment with TomoTherapy.
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12
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Efficacy of Different Chemotherapy Regimens in Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy. J Clin Med 2020; 9:jcm9010197. [PMID: 31936858 PMCID: PMC7020070 DOI: 10.3390/jcm9010197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 12/15/2019] [Accepted: 01/07/2020] [Indexed: 12/14/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) are very common cancers worldwide, and there is higher incidence of synchronous ESCC/NSCC in Taiwan. The aim of the current study was to investigate the efficacy of different chemotherapy regimens in patients with locally advanced synchronous ESCC/HNSCC who received curative concurrent chemoradiotheapy (CCRT). A total of 75 patients were identified and assigned to one of two groups: 45 patients receiving cisplatin/5-fluorouracil (5-FU) regime in one group and 30 patients receiving a weekly cisplatin regime in the other. Overall survival (OS) was calculated from the date of diagnosis of the ESCC or HNSCC to the date of death from any cause or the most recent follow-up. Kaplan–Meier curves and log-rank tests were used to estimate OS and differences between the two groups, respectively. There was no significant difference in the analysis of OS between the cisplatin/5-FU and the weekly cisplatin groups. However, patients that interrupted their CCRT were found to have worse OS compared to those without interruptions (5.4 months versus 18.8 months, p = 0.002). In subgroup analysis, patients without interruptions of CCRT had a better OS than those with interruptions in the cisplatin/5-FU group (13.0 months versus 5.4 months, p = 0.041) as well as in the weekly cisplatin group (21.4 months versus 5.0 months, p = 0.017). Interruption of CCRT was the only independently poor prognostic factor of OS in the univariate and multivariate (hazard ratio 0.18, p < 0.001) analyses. Most interruption of CCRT resulted from adverse events (AEs) or serious AEs. Although there was no significant difference in the incidence of AEs between these two groups, lower incidence of adverse events was mentioned in the weekly cisplatin group. Our study suggests that interruption of CCRT is an independently poor prognostic factor of OS, and that completion of CCRT without interruption is more important than the choice of chemotherapeutic regimen for patients with synchronous ESCC/HNSCC.
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Nemoto K, Kawashiro S, Toh Y, Numasaki H, Tachimori Y, Uno T, Jingu K, Matsubara H. Comparison of the effects of radiotherapy doses of 50.4 Gy and 60 Gy on outcomes of chemoradiotherapy for thoracic esophageal cancer: subgroup analysis based on the Comprehensive Registry of Esophageal Cancer in Japan from 2009 to 2011 by the Japan Esophageal Society. Esophagus 2020; 17:122-126. [PMID: 31912332 PMCID: PMC7066307 DOI: 10.1007/s10388-019-00711-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/29/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND In definitive chemoradiotherapy (CRTx) for esophageal cancer, a radiotherapy (RT) dose of 50.4 Gy in 28 fractions has been the standard in many countries, while 60 Gy in 30 fractions has been frequently used in Japan. To clarify the optimal RT dose in CRTx for esophageal cancer, we compared clinical outcomes with the two doses using data from the Comprehensive Registry of Esophageal Cancer in Japan by the Japan Esophageal Society (JES). METHODS Of the patients enrolled in the registry for 2015-2017 surveys (patients treated between 2009 and 2011), 996 patients who received definitive CRTx with 50.4 Gy or 60 Gy for thoracic esophageal cancer were eligible for analysis. RESULTS The complete response (CR) rates in the 50.4 Gy and 60 Gy groups were 49.1% and 46.4%, respectively (p = 0.5851). The 5-year overall survival (OS) rates in the 50.4 Gy group and 60 Gy group for stages I, II/III and IV were 64.2% and 57.2%, 35.0% and 27.0%, and 18.0% and 15.3%, respectively. Since no significant difference was found between the two groups, the 50.4 Gy group was not inferior to the 60 Gy group with regard to OS. CONCLUSIONS The analysis revealed that the 50.4 Gy group had a non-inferior outcome in comparison with the 60 Gy group for stages I, II/III and IV thoracic esophageal cancer. These results were obtained from a large database for the first time in Japan.
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Affiliation(s)
- Kenji Nemoto
- Japan Esophageal Society, Tokyo, Japan ,grid.268394.20000 0001 0674 7277Department of Radiology, Yamagata University Graduate School of Medicine, 2-2-2, Iida-nishi, Yamagata, 990-9585 Japan
| | - Shohei Kawashiro
- Japan Esophageal Society, Tokyo, Japan ,grid.268394.20000 0001 0674 7277Department of Radiology, Yamagata University Graduate School of Medicine, 2-2-2, Iida-nishi, Yamagata, 990-9585 Japan
| | - Yasushi Toh
- Japan Esophageal Society, Tokyo, Japan ,grid.470350.5Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Hodaka Numasaki
- Japan Esophageal Society, Tokyo, Japan ,grid.136593.b0000 0004 0373 3971Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuji Tachimori
- Japan Esophageal Society, Tokyo, Japan ,Center for Cancer Treatment, Kawasaki Saiwai Hospital, Kawasaki, Japan
| | - Takashi Uno
- Japan Esophageal Society, Tokyo, Japan ,grid.411321.40000 0004 0632 2959Department of Radiology, Chiba University Hospital, Chiba, Japan
| | - Keiichi Jingu
- Japan Esophageal Society, Tokyo, Japan ,grid.69566.3a0000 0001 2248 6943Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hisahiro Matsubara
- Japan Esophageal Society, Tokyo, Japan ,grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
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Taniyama TK, Tsuda T, Miyakawa K, Arai H, Doi A, Hirakawa M, Horie Y, Mizukami T, Izawa N, Ogura T, Sunakawa Y, Nakajima TE. Analysis of fistula formation of T4 esophageal cancer patients treated by chemoradiotherapy. Esophagus 2020; 17:67-73. [PMID: 31506805 DOI: 10.1007/s10388-019-00691-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Accepted: 09/05/2019] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND AIM Fistula is one of the known complications of T4 esophageal cancer (T4-EC). The standard treatment for T4-EC is chemoradiotherapy, but detailed data about fistula resulting from chemoradiotherapy in this condition are limited. In particular, radiographic findings of T4-EC with fistula have not been reported. This study assessed the risk factors of fistula based on clinical information on patients with chemoradiotherapy for T4-EC. METHODS We retrospectively reviewed the clinical data of 59 T4-EC patients who had squamous cell carcinoma without any fistula before receiving definitive or palliative chemoradiotherapy. RESULTS A fistula was observed in 18 patients (31%) throughout their clinical course. The overall survival in the fistula group was significantly shorter than that in the non-fistula group (259 vs. 346 days; p = 0.0341). The axial tumor size on computed tomography (CT) was confirmed as an independent risk factor for esophageal fistula in multivariate analysis of stepwise methods [OR 1.226; 95% CI 1.109-1.411; p < 0.0001]. Twelve out of 14 patients with an axial tumor size of 50 mm or greater had developed a fistula. CONCLUSIONS A large tumor size on the axial plane on CT is a risk factor for fistula formation.
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Affiliation(s)
| | - Takashi Tsuda
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
| | - Kunihisa Miyakawa
- Department of Radiology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Hiroyuki Arai
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Ayako Doi
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Mami Hirakawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Yoshiki Horie
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Takuro Mizukami
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Naoki Izawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Takashi Ogura
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Yu Sunakawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Takako Eguchi Nakajima
- Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
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15
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Watanabe M, Otake R, Kozuki R, Toihata T, Takahashi K, Okamura A, Imamura Y. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today 2020; 50:12-20. [PMID: 31535225 PMCID: PMC6952324 DOI: 10.1007/s00595-019-01878-7] [Citation(s) in RCA: 290] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 09/04/2019] [Indexed: 02/06/2023]
Abstract
Esophageal cancer is one of the most aggressive gastrointestinal cancers. This review focuses on eight topics within the multidisciplinary approach for esophageal cancer. As esophagectomy is highly invasive and likely to impair quality of life, the development of less invasive strategies is expected. Endoscopic resection (ER) of early esophageal cancer is a less invasive treatment for early esophageal cancer. A recent phase II trial revealed that combined ER and chemoradiotherapy (CRT) is efficacious as an esophagus-preserving treatment for cT1bN0 squamous cell carcinoma (SCC). Esophagectomy and definitive CRT are equally effective for patients with clinical stage I SCC in terms of long-term outcome. For locally advanced resectable cancers, multidisciplinary treatment strategies have been established through several clinical trials of neoadjuvant or perioperative treatment. Minimally invasive esophagectomy may improve the outcomes of patients and CRT is a curative-intent alternative to esophagectomy. CRT with 50.4 Gy radiotherapy combined with salvage surgery is a promising option to preserve the esophagus. Induction chemotherapy followed by esophagectomy may improve the outcomes of patients with locally advanced unresectable tumors. Immune checkpoint inhibitors are effective for esophageal cancer, and their introduction to clinical practice is awaited.
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Affiliation(s)
- Masayuki Watanabe
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Reiko Otake
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Ryotaro Kozuki
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Tasuku Toihata
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Keita Takahashi
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
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16
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Boers J, Joldersma A, van Dalsen AD, Wiegman EM, Schenk BE, de Graaf JC, Pierik EGJM, Timmer PR, de Groot JWB. Intensified Neoadjuvant Chemoradiotherapy for Patients with Potentially Resectable Esophageal Cancer: A Retrospective Cohort Study. Ann Surg Oncol 2019; 27:1520-1528. [PMID: 31828691 DOI: 10.1245/s10434-019-08114-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND Neoadjuvant treatment consisting of five cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy), followed by esophagectomy, is the standard treatment for resectable esophageal cancer in The Netherlands. It remains unclear whether intensification of neoadjuvant therapy leads to better outcomes. This study analyzed the outcomes of intensified chemoradiotherapy. METHODS We included patients who were deemed eligible for esophagectomy between January 2008 and December 2014. Neoadjuvant therapy consisted of six cycles of carboplatin (area under the curve = 2 mg/mL/min) and paclitaxel (50 mg/m2 of body surface area) and concurrent radiotherapy (50.4 Gy administered in 28 fractions of 1.8 Gy each, 5 days per week), followed by esophagectomy. RESULTS Of the 176 patients included in this study, 73% underwent a resection. At a median follow-up of 29.3 months for the total cohort, median disease-free survival (DFS) was 22.5 months. DFS at 3 and 5 years was 42% and 36%, respectively, while the overall survival (OS) rates were 47% and 38%, respectively. In addition, the 5-year DFS and OS rates of our resection group were 44% and 48%, respectively. In 102 patients (58%), grade 3 or higher adverse events were observed, mainly hematological. The postoperative mortality rate within 30 days was 4%, and pathological complete response was achieved in 35% of patients. CONCLUSIONS Intensification of neoadjuvant chemoradiotherapy for patients with potentially resectable esophageal cancer is well tolerated, yielding high pathological complete response rates, but adverse events occurred frequently, and survival compared with conventional neoadjuvant chemoradiotherapy seems similar. Therefore, intensification of neoadjuvant chemoradiotherapy should not be routinely used.
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Affiliation(s)
- Jorianne Boers
- Department of Medical Oncology, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Annalie Joldersma
- Department of Surgery, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Annette D van Dalsen
- Department of Surgery, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Erwin M Wiegman
- Department of Radiation Oncology, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - B Ed Schenk
- Department of Gastroenterology and Hepatology, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Jacques C de Graaf
- Department of Medical Oncology, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Engelbertus G J M Pierik
- Department of Surgery, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Paul R Timmer
- Department of Radiation Oncology, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands
| | - Jan Willem B de Groot
- Department of Medical Oncology, Isala Oncology Center, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands.
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17
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Yoshii T, Hara H, Asayama M, Kumekawa Y, Miyazawa S, Takahashi N, Matsushima T, Shimizu S, Saito Y. Chemoradiotherapy with FOLFOX for esophageal squamous cell cancer with synchronous rectal cancer: Four case reports and a literature review. Mol Clin Oncol 2019; 12:23-30. [PMID: 31814973 PMCID: PMC6888043 DOI: 10.3892/mco.2019.1945] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 07/16/2019] [Indexed: 12/30/2022] Open
Abstract
Chemoradiotherapy (CRT) is a valuable treatment option for localized esophageal cancer. Conventional baseline chemotherapy for this type of cancer includes cisplatin and fluorouracil. Recently, CRT with leucovorin-fluorouracil-oxaliplatin (FOLFOX) has become popular due to its convenience and lower toxicity. In Japan, the use of oxaliplatin for esophageal cancer is not yet approved, so experience with this treatment is limited to cases with colorectal cancer. As such patients are not usually included in clinical trials, little is known on the efficacy and safety of this treatment for this patient subpopulation, and treatment generalization in Japan is not allowed. We herein share our experience with CRT and FOLFOX for cases with esophageal cancer and synchronous rectal cancer at our institution. The clinical data of 4 patients who were treated for esophageal cancer with CRT/FOLFOX at our hospital between 2007 and 2016, who also had synchronous rectal cancer, were retrieved and analyzed. All the patients were male and had esophageal squamous cell cancer and synchronous rectal cancer. The median patient age was 68 years (range, 65–77 years). One patient received neoadjuvant CRT followed by surgery, and the other 3 patients received definitive CRT for esophageal cancer. FOLFOX was administered biweekly during radiotherapy (41.4–60 Gy). All 4 patients completed the treatment schedule and responded to CRT. No patients experienced progression of rectal cancer during treatment. Notably, 1 patient also achieved a complete response (CR) of rectal cancer after CRT for esophageal cancer. Moreover, 2 patients without dysphagia were treated as outpatients and achieved a CR. Encephalopathy was the only reported grade 3 adverse event. Although the present study included a limited number of cases, the findings suggest that CRT with FOLFOX may be a valuable option for the treatment of patients with esophageal squamous cell cancer and synchronous rectal cancer.
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Affiliation(s)
- Takako Yoshii
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Hiroki Hara
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Masako Asayama
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Yosuke Kumekawa
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Shoichi Miyazawa
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Naoki Takahashi
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Tomohiro Matsushima
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Satoshi Shimizu
- Department of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan
| | - Yoshihiro Saito
- Department of Radiotherapy, Saitama Cancer Center, Saitama 362-0806, Japan
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18
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Novel Radiotherapy Technologies in the Treatment of Gastrointestinal Malignancies. Hematol Oncol Clin North Am 2019; 34:29-43. [PMID: 31739949 DOI: 10.1016/j.hoc.2019.08.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Over the past 2 decades, major technical advances in radiation therapy planning and delivery have made it possible to deliver higher doses to select high-risk volumes. This has helped to expand the role of radiation therapy in the treatment of gastrointestinal malignancies. Whereas dose escalation was previously limited by the radiosensitivity of normal tissues within and adjacent to the gastrointestinal tract, advances in target delineation, patient immobilization, treatment planning, and image-guided treatment delivery have greatly improved the therapeutic ratio. More conformal radiation modalities can offer further dose optimization to target volumes while sparing normal tissue from toxicity.
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19
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Worrell SG, Towe CW, A Dorth J, Machtay M, Perry Y, Linden PA. Higher Doses of Neoadjuvant Radiation for Esophageal Cancer Do Not Affect the Pathologic Complete Response Rate or Survival: A Propensity-Matched Analysis. Ann Surg Oncol 2019; 27:500-508. [PMID: 31571054 DOI: 10.1245/s10434-019-07849-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Traditional neoadjuvant therapy for esophageal cancer has used chemoradiation doses greater than 45 Gy. This study aimed to examine the dose of preoperative radiation in relation to the pathologic complete response (pCR) rate and overall survival (OS) for patients with resectable esophageal cancer. METHODS The National Cancer Database was queried for all patients with esophageal or gastroesophageal junction cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy between 2006 and 2015. The radiation doses were divided into four ranges based on Grays (Gy) received: less than 39.6 Gy, 39.60-44.99 Gy, 45-49.99 Gy, and 50 Gy or more. RESULTS The inclusion criteria were met by 10,293 patients. All patients received neoadjuvant CRT, with 689 patients (6.7%) receiving less than 39.6 Gy, 973 patients (9.5%) receiving 39.6-44.9 Gy, 3837 patients (37.3%) receiving 45-49.9 Gy, and 4794 patients (46.6%) receiving 50 Gy or more. The overall pCR rate was 17.2% (1769/10,293) and was significantly lower for those who received less than 39.6 Gy of radiation than for those who received 39.6 Gy or more (13.9% [96/689] vs. 17.4% [1673/9604]; p = 0.017). The median OS of 37.2 months was significantly better for those who received 39.6 Gy or more than for those who received less than 39.6 Gy (38 vs. 29.6 months (p < 0.0001). The pCR and OS did not differ between the three higher radiation doses (39.6-44.9 vs. 45-49.9 Gy vs. ≥ 50 Gy; pCR [p = 0.1] vs. OS [p = 0.097]). The patients who received 39.6-44.9 Gy were propensity matched with those who received 45 Gy or more of radiation. There remained no difference in pCR (p = 0.375) or OS (p = 0.957). CONCLUSIONS In the United States, the heterogeneity in neoadjuvant CRT dosing is significant, with 84% of patients receiving more than 45 Gy. The benefit of neoadjuvant CRT in terms of pCR and overall survival is seen with doses of 39.6 Gy or more, but not with doses higher than 45 Gy.
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Affiliation(s)
- Stephanie G Worrell
- Division of Thoracic and Esophageal Surgery, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
| | - Christopher W Towe
- Division of Thoracic and Esophageal Surgery, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jennifer A Dorth
- Division of Radiation Oncology, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Mitchell Machtay
- Division of Radiation Oncology, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Yaron Perry
- Division of Thoracic and Esophageal Surgery, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Philip A Linden
- Division of Thoracic and Esophageal Surgery, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA
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20
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Wang X, Liu X, Li B. ASO Author Reflections: Concurrent Selective Lymph Node Radiotherapy and S-1 Plus Cisplatin for Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2019; 26:741-742. [PMID: 31549314 DOI: 10.1245/s10434-019-07832-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Indexed: 11/18/2022]
Affiliation(s)
- Xintong Wang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, China
| | - Xiaomeng Liu
- School of Medicine and Life Sciences, University of Jinan Shandong Academy of Medical Sciences, Jinan, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, China.
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Tomotherapy as a neoadjuvant treatment for locally advanced esophageal cancer might increase bone marrow toxicity in comparison with intensity-modulated radiotherapy and volumetric-modulated arc therapy. Med Dosim 2019; 45:e6-e12. [PMID: 31176536 DOI: 10.1016/j.meddos.2019.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 04/07/2019] [Accepted: 05/01/2019] [Indexed: 12/25/2022]
Abstract
This study compares dosimetric parameters in these following 3 neoadjuvant chemoradiotherapy (NCRT) methods in treating locally advanced esophagus cancer: helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). It is aimed to ascertain the efficient technique that kept high target coverage and availed the dose sparing of bone marrow (BM). This research collected data on 11 patients from October 2014 to June 2017 who received NCRT for pathologically confirmed esophageal cancer. The prescription doses to the planning target volume (PTV) were all given as 60 Gy (2 Gy per fraction, 5 days a week). Three physicists via Varian Eclipse Treatment Planning System and Accuray planning stations redesigned 5 radiotherapy plans (fixed 5-field IMRT, fixed 7-field IMRT, 2-arc VMAT, 3-arc VMAT, and TOMO) for each of the patients. At the end of the planning, we then appraised the dosimetric quality based on the PTV parameters and the doses to organs at risk (OARs). In the study VMAT reached the highest conformity index (CI; 2 arcs VMAT: 0.74 ± 0.10; 3 arcs VMAT: 0.78 ± 0.07; p< 0.05), and IMRT the lowest homogeneity index (HI; fivefields IMRT: 0.12 ± 0.03; sevenfields IMRT: 0.10 ± 0.02; p< 0.05). Besides, 7 fields IMRT (0.10 ± 0.02) achieved superior HI to that of 5 fields IMRT (0.12 ± 0.03, p< 0.01). TOMO (p< 0.05) and VMAT (p< 0.05) were both significantly superior to IMRT in terms of the dose to lung (V5, V10, V15, V20, and V30). These 5 radiation techniques were similar regarding the dose to heart (V5, V20, and V30), but IMRT (5 fields IMRT: 19.27 ± 5.33; 7 fields IMRT: 20.05 ± 4.19) significantly raised the dose to the V50 of the heart when compared to VMAT (2 arcs VMAT: 16.6 ± 5.68; 3 arcs VMAT: 15.04 ± 5.75; p< 0.05) and TOMO (15.05 ± 4.7, p< 0.05). VMAT reduced the dose to BM (V5, V10, V20, and V30) as compared to TOMO (p< 0.05) and IMRT (p< 0.05). The CI of VMAT was the supreme one in those of the techniques in this study, so was the HI of IMRT. VMAT also provided another advantage that it reduced the dose to the BM. TOMO ameliorated the dose sparing of the lung, but the dose that the BM absorbed from TOMO was of some concern about BM toxicity.
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22
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Advantages of salvage photodynamic therapy using talaporfin sodium for local failure after chemoradiotherapy or radiotherapy for esophageal cancer. Surg Endosc 2019; 34:899-906. [DOI: 10.1007/s00464-019-06846-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Accepted: 05/16/2019] [Indexed: 11/25/2022]
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23
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Chen NB, Qiu B, Zhang J, Qiang MY, Zhu YJ, Wang B, Guo JY, Cai LZ, Huang SM, Liu MZ, Li Q, Hu YH, Li QW, Liu H. Intensity-Modulated Radiotherapy versus Three-Dimensional Conformal Radiotherapy in Definitive Chemoradiotherapy for Cervical Esophageal Squamous Cell Carcinoma: Comparison of Survival Outcomes and Toxicities. Cancer Res Treat 2019; 52:31-40. [PMID: 31048664 PMCID: PMC6962472 DOI: 10.4143/crt.2018.624] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 04/29/2019] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. RESULTS With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. CONCLUSION No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.
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Affiliation(s)
- Nai-Bin Chen
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bo Qiu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jun Zhang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Meng-Yun Qiang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yu-Jia Zhu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bin Wang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jin-Yu Guo
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ling-Zhi Cai
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shao-Min Huang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Meng-Zhong Liu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qun Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yong-Hong Hu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qi-Wen Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hui Liu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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24
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Hematologic Markers as Prognostic Factors in Nonmetastatic Esophageal Cancer Patients under Concurrent Chemoradiotherapy. BIOMED RESEARCH INTERNATIONAL 2019; 2019:1263050. [PMID: 30834254 PMCID: PMC6374875 DOI: 10.1155/2019/1263050] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 01/14/2019] [Indexed: 12/17/2022]
Abstract
Nonmetastatic esophageal cancer can demonstrate a high local recurrence rate even under the standard treatment. We evaluated platelet counts before and after concurrent chemoradiotherapy (CCRT), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting esophageal cancer prognosis under CCRT. Newly diagnosed patients with esophageal cancer (stages IA–IIIC) who underwent CCRT during January 2013–December 2017 were enrolled. The data were collected retrospectively. Overall survival (OS), time to progressive disease (TPD), and time to metastasis (TM) were recorded for indicating prognosis. Kaplan–Meier curves were plotted and univariate and multivariate analyses were performed. In total, 105 patients were enrolled. The stages of esophageal cancer and surgery were associated with prognosis (i.e., OS, TPD, and TM). Based on TPD and TM, women had better prognosis than men. In the univariate analysis, high pre- and post-CCRT platelet counts (>300,000/μL), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) as well as low lymphocyte percentage were significantly associated with poor prognosis. However, in the multivariate analysis, only post-CCRT high platelet count (>300,000/μL) remained significantly associated with poor prognosis (P = .041, .045, and .023 for OS, TPD, and TM, respectively). Poor prognosis was observed in patients with high platelet counts, PLR, NLR, and low lymphocyte percentage. Surgery was an independent factor predicting better prognosis. Our findings may have clinical significance with regard to therapeutic decision-making.
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Yamada K, Chigusa Y, Nomura M, Sakanaka K, Nakamura M, Yano S, Tsunoda S, Kondoh E, Mandai M. A Case of Recurrent Esophageal Cancer Treated with Concurrent Chemoradiation Therapy in Pregnancy. Case Rep Obstet Gynecol 2018; 2018:1280582. [PMID: 30627462 PMCID: PMC6304601 DOI: 10.1155/2018/1280582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 11/14/2018] [Accepted: 11/22/2018] [Indexed: 12/02/2022] Open
Abstract
Esophageal cancer rarely coincides with pregnancy, and only five cases have been reported thus far. The management of esophageal cancer during pregnancy is extremely challenging due to its aggressive nature. We herein report a case of recurrent esophageal cancer in pregnancy. A 41-year-old multigravida with a history of esophageal squamous cell cancer treated with esophagectomy and perioperative chemotherapy was diagnosed with local recurrent carcinoma of the residual esophagus at 16 weeks of gestation. The patient strongly desired to continue the pregnancy, and concurrent chemoradiation therapy (CRT) consisting of 50.4 Gy of radiation, cisplatin, and 5-fluorouracil was carried out from 19 weeks of gestation. CRT was dramatically effective, and the recurrent lesion disappeared. At 38 weeks of gestation, she underwent cesarean section and delivered a healthy female baby. Both maternal and fetal courses were satisfactory, and the patient has been free of disease for 12 months. This is the first case of recurrent esophageal cancer in pregnancy in which CRT was completed without reducing treatment intensity and led to a complete response. Nevertheless, little is known regarding the safety and possible adverse effects of CRT on the fetus. Therefore, deliberate selection of patients and long-term follow-up of the child are necessary.
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Affiliation(s)
- Kaori Yamada
- Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Yoshitsugu Chigusa
- Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Motoo Nomura
- Department of Therapeutic Oncology, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Katsuyuki Sakanaka
- Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Mitsuhiro Nakamura
- Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
- Division of Medical Physics, Department of Information Technology and Medical Engineering, Human Health Sciences, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Shinsuke Yano
- Division of Clinical Radiology Service, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Shigeru Tsunoda
- Department of Surgery, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Eiji Kondoh
- Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Masaki Mandai
- Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
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26
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Zhu H, Ge X, Lu Y, Zuo Y, Qin Q, Sun X, Yang M. Nedaplatin-based chemotherapy regimens combined with concurrent radiotherapy as first-line treatment for stage II-III esophageal squamous cell carcinoma. Oncol Lett 2018; 17:594-602. [PMID: 30655806 DOI: 10.3892/ol.2018.9564] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 10/04/2018] [Indexed: 12/23/2022] Open
Abstract
Concurrent chemoradiotherapy (CCRT) is an effective first-line treatment for esophageal squamous cell carcinoma (ESCC). The present study aimed to compare clinical outcomes between three nedaplatin-based regimens for CCRT of ESCC. Patients with stage II-III thoracic ESCC in China between January 2012 and May 2016 were included. Patients received esophageal ultrasonography prior to treatment. Chemotherapy was as follows: i) 100 mg/m2 nedaplatin intravenously on day 1 and 70 mg/m2 tegafur-gimeracil-oteracil potassium (S-1) orally twice daily for 2 weeks; ii) 50 mg/m2 nedaplatin intravenously on days 1 and 2 and 35 mg/m2 docetaxel intravenously on days 1 and 8; or iii) 60 mg/m2 nedaplatin intravenously on days 1 and 2. Intensity-modulated radiotherapy was used to administer a total dose of 60-66 Gy (1.8-2.0 Gy per fraction) to the primary tumor and 45-50 Gy to the subclinical region. A total of 70 patients were enrolled (median age, 66 years; range, 50-81 years). T4 disease was identified in 45 (64.3%) patients. All patients completed radiotherapy and received ≥2 chemotherapy cycles. Estimated 1-, 2- and 3-year overall survival (OS) rates were 82.9, 53.9 and 31.4%, respectively. OS and progression-free survival were similar between the three treatment groups. Grade 3/4 hematological toxicities were observed in 35 (50%) patients. The incidence of serious treatment-associated toxicities was numerically highest for the nedaplatin/docetaxel combination. Patients with thoracic ESCC had good clinical outcomes following CCRT. With similar survival rates and disease responses yet lower hematological toxicities, nedaplatin/S-1 and single-agent nedaplatin may be preferable to nedaplatin/docetaxel. Poor control of distant metastasis may be a disadvantage of single-agent chemotherapy use in CCRT, and a further study with larger cohorts is required to confirm this.
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Affiliation(s)
- Huiping Zhu
- The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.,Department of Oncology, Zhangjiagang First People's Hospital, Suchow, Jiangsu 215600, P.R. China
| | - Xiaolin Ge
- Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Yufeng Lu
- Department of Oncology, The Second Affiliated Hospital of Suchow University, Jiangsu 215004, P.R. China
| | - Yun Zuo
- Department of Oncology, Zhangjiagang First People's Hospital, Suchow, Jiangsu 215600, P.R. China
| | - Qin Qin
- Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xinchen Sun
- Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Min Yang
- The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.,Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, P.R. China
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27
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Sylvester CB, Abe JI, Patel ZS, Grande-Allen KJ. Radiation-Induced Cardiovascular Disease: Mechanisms and Importance of Linear Energy Transfer. Front Cardiovasc Med 2018; 5:5. [PMID: 29445728 PMCID: PMC5797745 DOI: 10.3389/fcvm.2018.00005] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 01/09/2018] [Indexed: 12/24/2022] Open
Abstract
Radiation therapy (RT) in the form of photons and protons is a well-established treatment for cancer. More recently, heavy charged particles have been used to treat radioresistant and high-risk cancers. Radiation treatment is known to cause cardiovascular disease (CVD) which can occur acutely during treatment or years afterward in the form of accelerated atherosclerosis. Radiation-induced cardiovascular disease (RICVD) can be a limiting factor in treatment as well as a cause of morbidity and mortality in successfully treated patients. Inflammation plays a key role in both acute and chronic RICVD, but the underling pathophysiology is complex, involving DNA damage, reactive oxygen species, and chronic inflammation. While understanding of the molecular mechanisms of RICVD has increased, the growing number of patients receiving RT warrants further research to identify individuals at risk, plans for prevention, and targets for the treatment of RICVD. Research on RICVD is also relevant to the National Aeronautics and Space Administration (NASA) due to the prevalent space radiation environment encountered by astronauts. NASA's current research on RICVD can both contribute to and benefit from concurrent work with cell and animal studies informing radiotoxicities resulting from cancer therapy. This review summarizes the types of radiation currently in clinical use, models of RICVD, current knowledge of the mechanisms by which they cause CVD, and how this knowledge might apply to those exposed to various types of radiation.
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Affiliation(s)
- Christopher B Sylvester
- Department of Bioengineering, Rice University, Houston, TX, United States.,Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, United States
| | - Jun-Ichi Abe
- Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Zarana S Patel
- Science and Space Operations, KBRwyle, Houston, TX, United States
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Barney CL, Zamora P, Ewing A, Old M, Chakravarti A, Bhatt A. Synchronous Supraglottic and Esophageal Squamous Cell Carcinomas Treated with a Monoisocentric Hybrid Intensity-Modulated Radiation Technique. Front Oncol 2018; 7:307. [PMID: 29359120 PMCID: PMC5766653 DOI: 10.3389/fonc.2017.00307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 11/28/2017] [Indexed: 12/18/2022] Open
Abstract
Risk factors for squamous cell carcinomas (SCCs) of the head and neck (HN) and esophagus are similar. As such, synchronous primary tumors in these areas are not entirely uncommon. Definitive chemoradiation (CRT) is standard care for locally advanced HNSCC and is a preferred option for inoperable esophageal SCC. Simultaneous treatment of both primaries with CRT can present technical challenges. We report a case of synchronous supraglottic and esophageal SCC primary tumors, highlighting treatment with a monoisocentric hybrid radiation technique and normal tissue toxicity considerations.
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Affiliation(s)
| | - Pedro Zamora
- Radiation Oncology, Ohio State University, Columbus, OH, United States
| | - Ashlee Ewing
- Radiation Oncology, Ohio State University, Columbus, OH, United States
| | - Matthew Old
- Head and Neck Surgery, Ohio State University, Columbus, OH, United States
| | - Arnab Chakravarti
- Radiation Oncology, Ohio State University, Columbus, OH, United States
| | - Aashish Bhatt
- Radiation Oncology, Ohio State University, Columbus, OH, United States
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29
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So B, Marcu LG, Olver I, Gowda R, Bezak E. Cocktail without hangover: in search for the optimal chemotherapy in the combined management of non-operable esophageal carcinomas. Acta Oncol 2017; 56:899-908. [PMID: 28375694 DOI: 10.1080/0284186x.2017.1307518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND The worldwide incidence of esophageal cancer has greatly increased over the past few decades making it the sixth deadliest cancer. The disease is often detected in advanced stages when surgery is no longer an option. The standard treatment in these situations is combined chemoradiotherapy, by employing drug cocktails that lead to optimal treatment outcomes both from the perspective of tumor control and normal tissue toxicity. METHODS The aim of this work was to collate the existing trials and clinical studies reported on non-operable esophageal cancer and to analyze the results based on treatment outcomes after various drug combinations. RESULTS Of all drug combinations, cisplatin/5-FU is the most well established chemotherapy regimen for esophageal cancer as both neoadjuvant therapy, an alternative option to surgery, and for palliative purposes. Although this regimen is associated with the most toxicity, it also appears to have the best survival benefit and relief of symptoms. CONCLUSIONS More research is warranted to further increase the therapeutic ratio in non-operable esophageal cancers.
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Affiliation(s)
- Bianca So
- Faculty of Medicine, University of New South Wales, Sydney, Australia
- School of Health Sciences, University of South Australia, Adelaide, Australia
| | - Loredana G. Marcu
- Department of Physics, Faculty of Science, University of Oradea, Oradea, Romania
- School of Physical Sciences, University of Adelaide, Adelaide, Australia
| | - Ian Olver
- Sansom Institute for Health Research, University of South Australia, Adelaide, Australia
| | - Raghu Gowda
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - Eva Bezak
- School of Health Sciences, University of South Australia, Adelaide, Australia
- Department of Physics, Faculty of Science, University of Oradea, Oradea, Romania
- Sansom Institute for Health Research, University of South Australia, Adelaide, Australia
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30
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Xi M, Lin SH. Recent advances in intensity modulated radiotherapy and proton therapy for esophageal cancer. Expert Rev Anticancer Ther 2017; 17:635-646. [PMID: 28503964 DOI: 10.1080/14737140.2017.1331130] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Radiotherapy is an important component of the standard of care for esophageal cancer. In the past decades, significant improvements in the planning and delivery of radiation techniques have led to better dose conformity to the target volume and improved normal tissue sparing. Areas covered: This review focuses on the advances in radiotherapy techniques and summarizes the availably dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, proton therapy, and four-dimensional radiotherapy for esophageal cancer, and discusses the challenges and future development of proton therapy. Expert commentary: Although three-dimensional conformal radiotherapy is the standard radiotherapy technique in esophageal cancer, the retrospectively comparative studies strongly suggest that the dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can translate into improved clinical outcomes, despite the lack of prospective randomized evidence. As a novel form of conventional IMRT technique, volumetric modulated arc therapy can produce equivalent or superior dosimetric quality with significantly higher treatment efficiency in esophageal cancer. Compared with photon therapy, proton therapy has the potential to achieve further clinical improvement due to their physical properties; however, prospective clinical data, long-term results, and cost-effectiveness are needed.
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Affiliation(s)
- Mian Xi
- a Department of Radiation Oncology, Cancer Center , Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine , Guangzhou , Guangdong , China
| | - Steven H Lin
- b Department of Radiation Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA
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31
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Yamashita H, Jingu K, Niibe Y, Katsui K, Matsumoto T, Nishina T, Terahara A. Definitive salvage radiation therapy and chemoradiation therapy for lymph node oligo-recurrence of esophageal cancer: a Japanese multi-institutional study of 237 patients. Radiat Oncol 2017; 12:38. [PMID: 28219406 PMCID: PMC5319190 DOI: 10.1186/s13014-017-0780-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 02/10/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND This study evaluated the treatment results of lymph node (LN) oligo-recurrence in esophageal cancer patients treated with salvage radiotherapy (RT) in a multi-institutional retrospective study. METHODS Eligibility criteria for this retrospective analysis were: the primary lesion of esophageal cancer was controlled; from one to five LN recurrences; total RT dose ≥45 Gy to exclude palliative RT; without recurrence other than LN; and salvage RT for LN recurrence was given between January 2000 and April 2015. The median follow-up time for the 93 living patients was 29.6 months. RESULTS Two hundred thirty-seven patients were matched in five hospitals. The 3-year overall survival (OS) was 37%, local control was 45%, progression-free survival was 24%, and esophageal cancer-specific survival was 42%. On univariate analysis for OS, combined chemotherapy (p = 0.000055), disease-free interval (DFI) ≥12 months (p = 0.0013), LN max diameter ≤22 mm (p = 0.0052), and Karnofsky performance status ≥80% (p = 0.030) were associated with a significantly better prognosis. On multivariate analysis, significant differences were seen for combined chemotherapy (p = 0.000018), DFI (p = 0.0027), and LN max diameter (p = 0.018). CONCLUSIONS LN oligo-recurrence following treatment for esophageal cancer was not a terminal-stage event. Moreover, cure may be possible by chemoradiation therapy with a long DFI (≥12 months) and small size (≤22 mm).
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Affiliation(s)
- Hideomi Yamashita
- Department of Radiology, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Keiichi Jingu
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1, Seiryou-cho, Aoba-ku, Sendai, 980-8575, Japan
| | - Yuzuru Niibe
- Department of Radiology, Toho University Omori Medical Center, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.
| | - Kuniaki Katsui
- Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Toshihiko Matsumoto
- Department of Gastrointestinal Medicine, Shikoku Cancer Center, Kou 160, Umemoto-cho, Matsuyama, Ehime, 791-0280, Japan.,Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo, 670-8540, Japan
| | - Tomohiro Nishina
- Department of Gastrointestinal Medicine, Shikoku Cancer Center, Kou 160, Umemoto-cho, Matsuyama, Ehime, 791-0280, Japan
| | - Atsuro Terahara
- Department of Radiology, Toho University Omori Medical Center, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan
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Mikhail S, Wei L, Salem ME, Bekaii-Saab T. Outcomes of definitive chemoradiation in patients with esophageal cancer. Dis Esophagus 2017; 30:1-7. [PMID: 27868290 DOI: 10.1111/dote.12506] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The incidence of esophageal cancer has risen dramatically in the Western world. Although surgical resection of esophageal tumors is considered the cornerstone of curative approaches in localized esophageal cancer, approximately 40% of patients who undergo chemoradiation followed by surgery will experience a recurrence. Additionally, surgical resection is not a viable option for many patients with locally advanced unresectable disease, poor general condition or whose condition deteriorated following chemoradiation. Several investigators have, therefore, attempted to evaluate the outcomes of definitive chemoradiation in patients with localized or locally advanced esophageal cancer. The outcomes of concurrent chemoradiation remain a matter of debate given the heterogenous study design and treatment regimens used in recent trials. Understanding the clinical benefit of chemoradiation is essential prior to recommending it as an alternative to surgery. In our review, we present the most recent studies evaluating the role of chemoradiation to better define the clinical outcomes of patients with special attention to overall survival.
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Affiliation(s)
| | - Lai Wei
- The Ohio State University-James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA
| | - Mohamed E Salem
- Georgetown University Hospital-Lombardi Comprehensive Cancer Center, Washington DC, USA
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Du D, Song T, Liang X, Fang M, Wu S. Concurrent chemoradiotherapy with elective lymph node irradiation for esophageal cancer: a systemic review and pooled analysis of the literature. Dis Esophagus 2017; 30:1-9. [PMID: 26918886 DOI: 10.1111/dote.12471] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Concurrent chemoradiotherapy (CCRT) has been accepted as the standard non-surgical treatment for esophageal cancer. However, no consistent conclusions have been reached whether elective lymph node irradiation (ENI) should be delivered. Therefore, we performed a systematic review and pooled analysis to evaluate the value of CCRT with ENI. A literature search based on PubMed, Embase and Google Scholar was carried out and all of the studies were evaluated carefully regarding with survival outcomes, response rates, patterns of failure rates and acute/late toxicities. Twenty-two studies were identified based on the criteria: median overall survival time was 21.0 months; pooled response rates were 56.8% (CR) and 85.8% (CR+PR), respectively; residual disease rate, local-regional recurrence rate, distant failure rate and both (local-regional recurrence plus distant failure) rate was 28%, 21%, 11%, and 7%, respectively; hematologic toxicities were the most sever acute toxicities and esophagus-related toxicity was the most common radiation-related toxicity both in acute (15.7%) and late (6.2%) phase. In conclusion, ENI is feasible with acceptable toxicities in esophageal carcinoma and the efficacy should be verified in randomized trials.
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Affiliation(s)
- Dexi Du
- Department of Radiation Oncology, Lishui's Central Hospital, Lishui , Zhejiang, China
| | - Tao Song
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
| | - Xiaodong Liang
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
| | - Min Fang
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
| | - Shixiu Wu
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
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Jeene PM, Versteijne E, van Berge Henegouwen MI, Bergmann JJGHM, Geijsen ED, Muller K, van Laarhoven HWM, Hulshof MCCM. Definitive chemoradiation for locoregional recurrences of esophageal cancer after primary curative treatment. Dis Esophagus 2017; 30:1-5. [PMID: 27766725 DOI: 10.1111/dote.12539] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of this study was to determine the outcome of salvage definitive chemoradiation (dCRT) for a locoregional recurrence after any prior curative treatment outside previously irradiated areas. Thirty-nine patients treated between January 2005 and December 2014 were reviewed for locoregional recurrent esophageal cancer outside previously irradiated areas. All patients received salvage treatment with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel and carboplatin. The median follow-up period was 15 months (range 1.7-120). The median overall survival (OS) for all patients after salvage dCRT was 22 months (95% CI 6.2-37.6). The 1-, 3-, and 5-year OS was 72%, 31%, and 28%, respectively. Median survival after salvage dCRT for a regional lymph node recurrence was 33 months (95% CI 5.8-60.3) versus 14 months (95% CI 6.8-21.6) for a recurrence at the anastomosis (P = 0.022, logrank). Median OS was 35 months for the squamous cell carcinoma group and 19 months for the adenocarcinoma group (P = 0.67). Sixteen of 39 patients developed a locoregional recurrence after salvaged dCRT. The median locoregional recurrence-free survival (LRFS) was 24 months. The 1-, 3-, and 5-year LRFS was 79%, 36%, and 36%, respectively. Median disease-free survival (DFS) was 15 months. The 1-, 3-, and 5-year DFS was 66%, 27%, and 27%, respectively. Of 16 patients, 8 (50%) with a primary failure at the site of the anastomosis developed a local recurrence after salvaged dCRT compared to 7 of 22 patients (32%) with a primary recurrence in a lymph node. Definitive chemoradiation is a feasible and effective treatment for locoregional recurrent esophageal cancer outside a previously irradiated area, and should be given with a curative intent. This holds true for recurrence of both squamous cell carcinoma and adenocarcinoma. Lymph node recurrences have a markedly better prognosis than recurrences at the site of the anastomosis.
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Affiliation(s)
- P M Jeene
- Departments of Radiotherapy, Academic Medical Center Amsterdam , Amsterdam , The Netherlands
| | - E Versteijne
- Departments of Radiotherapy, Academic Medical Center Amsterdam , Amsterdam , The Netherlands
| | | | - J J G H M Bergmann
- Departments of Gastroenterology, , Academic Medical Center Amsterdam , Amsterdam , The Netherlands
| | - E D Geijsen
- Departments of Radiotherapy, Academic Medical Center Amsterdam , Amsterdam , The Netherlands
| | - K Muller
- Department of Radiotherapy, Radiotherapiegroep, Deventer, The Netherlands
| | - H W M van Laarhoven
- Departments of Medical Oncology, Academic Medical center Amsterdam, Amsterdam
| | - M C C M Hulshof
- Departments of Radiotherapy, Academic Medical Center Amsterdam , Amsterdam , The Netherlands
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Wang YD, Lu N. Consensus and controversies on dose and target volume of three-dimensional conformal radiotherapy for esophageal carcinoma. Shijie Huaren Xiaohua Zazhi 2016; 24:4531-4536. [DOI: 10.11569/wcjd.v24.i34.4531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Radiotherpay is the mainstay treatment for esophageal cancer. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy have been widely applied in routine clinical work, because they can raise the target dose and reduce the injury to normal tissue, and therefore raise the five-year survival rate to > 20%. In recent years, a number of studies on 3DCRT have been carried out with regard to radiation dose, target volume contour, and preventive lymph node irradiation, and this article will summarize these issues.
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36
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SEOM Clinical Guideline for the diagnosis and treatment of esophageal cancer (2016). Clin Transl Oncol 2016; 18:1179-1186. [PMID: 27900538 PMCID: PMC5138258 DOI: 10.1007/s12094-016-1577-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 11/11/2016] [Indexed: 12/17/2022]
Abstract
Esophageal cancer (EC) is an aggressive tumor that represents the 6th most common cause of cancer death worldwide. The estimated incidence in Spain is 2090 cases/year. Two main pathological subtypes exist, squamous cell carcinoma and adenocarcinoma. The main differences between them are localization and underlying factors which are the principal cause of the recent incidence changes observed in west countries. Staging techniques and treatment options which combine surgery, chemotherapy and radiotherapy, reflected the high complexity of the EC management. An undeniably multidisciplinary approach is, therefore, required. In this guide, we review the status of current diagnosis and treatment, define evidence and propose recommendations.
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Kwak EL, Hong TS, Forcione DG, Kambadakone A, Lennerz JK. Case 35-2016. A 62-Year-Old Man with Dysphagia. N Engl J Med 2016; 375:1983-1991. [PMID: 27959609 DOI: 10.1056/nejmcpc1610714] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Eunice L Kwak
- From the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Massachusetts General Hospital, and the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Harvard Medical School - both in Boston
| | - Theodore S Hong
- From the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Massachusetts General Hospital, and the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Harvard Medical School - both in Boston
| | - David G Forcione
- From the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Massachusetts General Hospital, and the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Harvard Medical School - both in Boston
| | - Avinash Kambadakone
- From the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Massachusetts General Hospital, and the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Harvard Medical School - both in Boston
| | - Jochen K Lennerz
- From the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Massachusetts General Hospital, and the Departments of Medicine (E.L.K., D.G.F.), Radiation Oncology (T.S.H.), Radiology (A.K.), and Pathology (J.K.L.), Harvard Medical School - both in Boston
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38
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Intrafractional dose variation and beam configuration in carbon ion radiotherapy for esophageal cancer. Radiat Oncol 2016; 11:150. [PMID: 27846916 PMCID: PMC5109696 DOI: 10.1186/s13014-016-0727-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 11/09/2016] [Indexed: 12/04/2022] Open
Abstract
Background In carbon ion radiotherapy (CIR) for esophageal cancer, organ and target motion is a major challenge for treatment planning due to potential range deviations. This study intends to analyze the impact of intrafractional variations on dosimetric parameters and to identify favourable settings for robust treatment plans. Methods We contoured esophageal boost volumes in different organ localizations for four patients and calculated CIR-plans with 13 different beam geometries on a free-breathing CT. Forward calculation of these plans was performed on 4D-CT datasets representing seven different phases of the breathing cycle. Plan quality was assessed for each patient and beam configuration. Results Target volume coverage was adequate for all settings in the baseline CIR-plans (V95 > 98% for two-beam geometries, > 94% for one-beam geometries), but reduced on 4D-CT plans (V95 range 50–95%). Sparing of the organs at risk (OAR) was adequate, but range deviations during the breathing cycle partly caused critical, maximum doses to spinal cord up to 3.5x higher than expected. There was at least one beam configuration for each patient with appropriate plan quality. Conclusions Despite intrafractional motion, CIR for esophageal cancer is possible with robust treatment plans when an individually optimized beam setup is selected depending on tumor size and localization.
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Hihara J, Hamai Y, Emi M, Murakami Y, Kenjo M, Nagata Y, Okada M. Role of definitive chemoradiotherapy using docetaxel and 5-fluorouracil in patients with unresectable locally advanced esophageal squamous cell carcinoma: a phase II study. Dis Esophagus 2016; 29:1115-1120. [PMID: 26471962 DOI: 10.1111/dote.12433] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Definitive chemoradiotherapy (CRT) with docetaxel (DOC) and 5-fluorouracil (5-FU) is a unique regimen for esophageal cancer. In this prospective phase II study, antitumor effect and safety of CRT using DOC and 5-FU for inoperable locally advanced esophageal cancer were evaluated. DOC 7.5 mg/m2 was infused on days 1, 8, 22, and 29. 5-FU 250 mg/m2 /day was infused continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-45. Radiotherapy was given to 66 Gy in 33 fractions. Eleven patients with thoracic and five with cervical esophageal cancer were eligible. All patients had esophageal squamous cell carcinoma (ESCC). The response rate was 94%, with complete response in five patients (31%) and partial response in 10 (63%). Hematologic toxicity was mild; only one patient (6%) had Grade 1 leukopenia. Nonhematologic Grade 3 or higher adverse events were esophagitis (31%), anorexia (6%), and esophago-bronchial fistula (6%). No treatment-related deaths occurred. The median time to progression was 20 months and overall 3-year and 5-year survival were 44% and 31%, respectively. Definitive CRT using DOC and 5-FU could be performed safely, and it demonstrated a favorable antitumor effect for ESCC. This regimen might be indicated in patients in whom it is desirable to avoid myelosuppression and progression of renal impairment.
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Affiliation(s)
- J Hihara
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Y Hamai
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - M Emi
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Y Murakami
- Department of Radiation Oncology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - M Kenjo
- Department of Radiation Oncology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Y Nagata
- Department of Radiation Oncology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - M Okada
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
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40
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Farinella E, Safar A, Nasser HA, Bouazza F, Liberale G, Paesmans M, Marechal R, Van Laethem JL, Hendlisz A, VanHoutte P, El Nakadi I. Salvage esophagectomy after failure of definitive radiochemotherapy for esophageal cancer. J Surg Oncol 2016; 114:833-837. [PMID: 27778349 DOI: 10.1002/jso.24429] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 08/18/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Definitive radiochemotherapy (dRCT) in locally advanced esophageal cancer is associated with a high rate of loco-regional recurrence. In this condition, salvage esophagectomy may be considered as a therapeutic option. The aim of this analysis is to evaluate the feasibility and the morbi-mortality of this strategy. METHODS Between January 2006 and April 2014, 208 patients underwent esophagectomy for esophageal cancer at ULB-Erasme-Bordet. Thirty-two patients received a preoperative radiochemotherapy (pRCT) followed by planned esophagectomy (Group 1) for locally advanced disease. Sixteen patients underwent salvage esophagectomy for recurrence or failure after dRCT (Group 2). Data on post-operative morbidity and mortality and survival were collected and analyzed. RESULTS An increase of overall morbidity was detected in Group 2 as compared to Group 1 (43% vs. 37.5%), mainly related to respiratory complications (35.5% vs. 28%) and anastomotic leak (25% vs. 3%). No 90-days mortality was observed in the two surgical groups. The 1, 2, and 3-year survival rates after surgery were respectively 89%, 80%, and 71% for Group1 and 84%, 73%, and 63% for Group 2. CONCLUSIONS In our experience, both salvage esophagectomy and esophagectomy after pRCT showed good survival results with low postoperative morbidity and mortality. Salvage surgery remains a therapeutic indication in selected patients. J. Surg. Oncol. 2016;114:833-837. © 2016 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | - Adonis Safar
- Department of Digestive Surgery, ULB-Erasme-Bordet, Bruxelles, Belgium
| | - Haydar A Nasser
- Department of Digestive Surgery, ULB-Erasme-Bordet, Bruxelles, Belgium
| | - Fikri Bouazza
- Department of Digestive Surgery, ULB-Erasme-Bordet, Bruxelles, Belgium
| | - Gabriele Liberale
- Department of Digestive Surgery, ULB-Erasme-Bordet, Bruxelles, Belgium
| | - Marianne Paesmans
- Data Center, Institut Jules Bordet, Center des Tumeurs ULB Bruxelles, Bruxelles, Belgium
| | - Raphael Marechal
- Department of Gastroenterology, GI Cancer Unit, ULB-Erasme, Bruxelles, Belgium
| | | | - Alain Hendlisz
- Department of Medical Oncology, Institut Jules Bordet, Bruxelles, Belgium
| | - Paul VanHoutte
- Department of Radiotherapy, Institut Jules Bordet, Bruxelles, Belgium
| | - Issam El Nakadi
- Department of Digestive Surgery, ULB-Erasme-Bordet, Bruxelles, Belgium
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Abstract
Particle irradiation of cancerous disease has gained great traction in recent years. The ability for particle therapy centers to deliver radiation with a highly conformal dose distribution while maintaining minimal exit or excess dose delivered to normal tissue, coupled with various biological advantages particularly found with heavy-ion beams, enables treatment of diseases inapproachable with conventional radiotherapy. Here, we present a review of the current status of particle therapy with regard to cancers of the gastrointestinal tract, including esophagus, liver, pancreas, and recurrent rectal cancer.
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Affiliation(s)
- Makoto Shinoto
- Ion Beam Therapy Center, SAGA HIMAT Foundation, Saga, Japan
| | - Daniel K Ebner
- Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.,Brown University Alpert Medical School, Providence, RI, USA
| | - Shigeru Yamada
- Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
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Gemici C, Yaprak G, Batirel HF, Ilhan M, Mayadagli A. Radiation field size and dose determine oncologic outcome in esophageal cancer. World J Surg Oncol 2016; 14:263. [PMID: 27737673 PMCID: PMC5064926 DOI: 10.1186/s12957-016-1024-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 10/07/2016] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Locoregional recurrence is a major problem in esophageal cancer patients treated with definitive concomitant chemoradiotherapy. Approximately half of the patients fail locoregionally. We analyzed the impact of enlarged radiation field size and higher radiation dose incorporated to chemoradiotherapy on oncologic outcome. METHODS Seventy-four consecutive patients with histologically proven nonmetastatic squamous or adenocarcinoma of the esophagus were included in this retrospective analysis. All patients were locally advanced cT3-T4 and/or cN0-1. Treatment consisted of either definitive concomitant chemoradiotherapy (Def-CRT) (n = 49, 66 %) or preoperative concomitant chemoradiotherapy (Pre-CRT) followed by surgical resection (n = 25, 34 %). Patients were treated with longer radiation fields. Clinical target volume (CTV) was obtained by giving 8-10 cm margins to the craniocaudal borders of gross tumor volume (GTV) instead of 4-5 cm globally accepted margins, and some patients in Def-CRT group received radiation doses higher than 50 Gy. RESULTS Isolated locoregional recurrences were observed in 9 out of 49 patients (18 %) in the Def-CRT group and in 1 out of 25 patients (3.8 %) in the Pre-CRT group (p = 0.15). The 5-year survival rate was 59 % in the Def-CRT group and 50 % in the Pre-CRT group (p = 0.72). Radiation dose was important in the Def-CRT group. Patients treated with >50 Gy (11 out of 49 patients) had better survival with respect to patients treated with 50 Gy (38 out of 49 patients). Five-year survivals were 91 and 50 %, respectively (p = 0.013). CONCLUSIONS Radiation treatment planning by enlarged radiation fields in esophageal cancer decreases locoregional recurrences considerably with respect to the results reported in the literature by standard radiation fields (18 vs >50 %). Radiation dose is as important as radiation field size; patients in the Def-CRT group treated with ≥50 Gy had better survival in comparison to patients treated with 50 Gy.
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Affiliation(s)
- Cengiz Gemici
- Department of Radiation Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Cevizli, Istanbul, Turkey
| | - Gokhan Yaprak
- Department of Radiation Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Cevizli, Istanbul, Turkey
| | - Hasan Fevzi Batirel
- Department of Thoracic Surgery, Marmara University Medical Faculty, Istanbul, Turkey
| | - Mahmut Ilhan
- Department of Medical Oncology, Avrasya Hospital, Istanbul, Turkey
| | - Alpaslan Mayadagli
- Department of Radiation Oncology, Bezmialem Vakif University Medical Faculty, Istanbul, Turkey
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Takebayashi K, Tsubosa Y, Kamijo T, Iida Y, Imai A, Nagaoka M, Kitani T, Niihara M, Booka E, Shimada A, Nakagawa M, Onitsuka T. Comparison of Salvage Total Pharyngolaryngectomy and Cervical Esophagectomy Between Hypopharyngeal Cancer and Cervical Esophageal Cancer. Ann Surg Oncol 2016; 24:778-784. [PMID: 27714538 DOI: 10.1245/s10434-016-5474-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Indexed: 11/18/2022]
Abstract
BACKGROUND Total pharyngolaryngectomy and cervical esophagectomy (TPLCE) after chemoradiotherapy remains a challenge because of the high rate of complications and few available data on outcomes and safety. The purpose of this study was to evaluate the clinical significance of salvage TPLCE and to compare treatment outcomes between hypopharyngeal cancer and cervical esophageal cancer. METHODS Data from 37 consecutive patients who were diagnosed with potentially resectable hypopharyngeal and cervical esophageal cancer after chemoradiotherapy were retrospectively analyzed. The survival and surgical outcomes were investigated between the hypopharyngeal cancer and cervical esophageal cancer groups. RESULTS Twenty-six patients were included in hypopharyngeal cancer group and 11 patients were included in cervical esophageal cancer group. The baseline characteristics were balanced between the two groups. Compared to the hypopharyngeal cancer group, the cervical esophageal cancer group had significantly more frequent tracheal-related complications (p < 0.05) and stronger association of distal margin of the cervical esophagus and radiation field with tracheal ischemia after salvage surgery. CONCLUSIONS Salvage TPLCE can offer the exclusive chance of prolonged survival. Association of tracheal ischemia with salvage TPLCE was seen more frequently for cervical esophageal cancer. Therefore, the indication for salvage TPLCE must be carefully considered to maintain the balance between curability and safety.
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Affiliation(s)
- Katsushi Takebayashi
- Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan.,Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yasuhiro Tsubosa
- Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Tomoyuki Kamijo
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
| | - Yoshiyuki Iida
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Atsushi Imai
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masato Nagaoka
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takashi Kitani
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masahiro Niihara
- Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Eisuke Booka
- Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ayako Shimada
- Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masahiro Nakagawa
- Division of Plastic and Reconstructive Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Tetsuro Onitsuka
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
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Ohba A, Kato K, Ito Y, Katada C, Ishiyama H, Yamamoto S, Ura T, Kodaira T, Kudo S, Tamaki Y. Chemoradiation therapy with docetaxel in elderly patients with stage II/III esophageal cancer: A phase 2 trial. Adv Radiat Oncol 2016; 1:230-236. [PMID: 28740892 PMCID: PMC5514160 DOI: 10.1016/j.adro.2016.07.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 07/07/2016] [Indexed: 12/19/2022] Open
Abstract
PURPOSE The most effective treatments in elderly patients with esophageal cancer remain a subject of debate. This multicenter phase 2 study was designed to evaluate the efficacy and toxicity of chemoradiation therapy (CRT) with docetaxel (DTX) in elderly patients with stage II/III (non-T4) esophageal cancer. METHODS AND MATERIALS Patients ≥70 years of age with clinical stage II/III esophageal cancer received DTX at a weekly dose of 10 mg/m2 during 6 consecutive weeks and concurrent radiation therapy (60 Gy in 30 fractions). The primary endpoint was the 2-year survival rate, and the required number of enrolled patients was 37. RESULTS Between July 2008 and January 2011, 16 patients were enrolled. The study was prematurely closed because of slow accrual. Characteristics of the patients were as follows: median age, 77 years (range, 73-81); performance status 0/1, 4/12; and clinical stage IIA/IIB/III, 3/4/9. Of the 16 patients, 14 (87.5%) completed the CRT. The 2-year survival rate was 62.5% (90% confidence interval [CI], 42.5-82.5). The median survival time was 27.7 months (95% CI, 23.3-32.2 months) and the median progression-free survival was 15.2 months (95% CI, 5.4-25.0 months). Seven patients achieved complete response, resulting in a complete response rate of 43.8% (95% CI, 19.8-70.1). Grade 3 or higher acute toxicities included esophagitis (31.3%), anorexia (12.5%), leukopenia (6.3%), neutropenia (6.3%), thrombocytopenia (6.3%), mucositis (6.3%), and infection (6.3%). Grade 3 or higher late toxicities included esophagitis (12.5%), pleural effusion (12.5%), pneumonitis (6.3%), and pericardial effusion (6.3%). CONCLUSIONS CRT with DTX might be a treatment option for elderly patients with stage II/III esophageal cancer, particularly for patients who are medically unfit for surgery or cisplatin-containing therapy. However, further improvements of this therapy are required to decrease the incidence of esophagitis.
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Affiliation(s)
- Akihiro Ohba
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Ken Kato
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshinori Ito
- Radiation Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan
| | - Hiromichi Ishiyama
- Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Kanagawa, Japan
| | - Sachiko Yamamoto
- Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | - Takashi Ura
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan
| | - Takeshi Kodaira
- Department of Therapeutic Radiation Oncology, Aichi Cancer Center Hospital, Aichi, Japan
| | - Shigehiro Kudo
- Department of Radiation Oncology, Gunma Prefectural Cancer Center, Gunma, Japan
| | - Yoshio Tamaki
- Department of Radiation Oncology, Gunma Prefectural Cancer Center, Gunma, Japan
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45
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Kumagai K, Mariosa D, Tsai JA, Nilsson M, Ye W, Lundell L, Rouvelas I. Systematic review and meta-analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy. Dis Esophagus 2016; 29:734-739. [PMID: 26316181 DOI: 10.1111/dote.12399] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The therapeutic strategy to be recommended in case of recurrent or persistent squamous cell esophageal cancer after completed definitive chemoradiotherapy (dCRT) has to be documented. Salvage esophagectomy has traditionally been recognized as a viable option, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. 'Second-line' chemoradiotherapy (CRT) without surgery may offer a treatment alternative in these difficult and demanding clinical situations. Until now, no comprehensive attempt has been carried out to compare the respective therapeutic options. A systematic literature search was performed focusing on studies comparing survival and treatment-related mortality in patients submitted to salvage esophagectomy or second-line CRT for recurrent or persistent esophageal squamous cell carcinoma after dCRT. Hazard ratios and risk ratios were calculated to compare the effect of these therapeutic strategies on overall survival and treatment-related mortality, respectively. Four studies containing 219 patients, with persistent or recurrent esophageal squamous cell carcinoma after dCRT, were included in the meta-analysis. The analysis revealed an overall survival benefit following salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95% confidence interval 0.21-0.86, P = 0.017) compared with second-line CRT. A treatment-related mortality of 10.3% was recorded in the 36 patients who were submitted to salvage esophagectomy, while it was impossible to perform a meta-analysis comparing treatment-related mortality between the groups. Salvage esophagectomy offers significant gain in long-term survival compared with second-line CRT, although the surgery is potentially at a price of a high treatment-related mortality.
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Affiliation(s)
- K Kumagai
- Center for Digestive Diseases, Karolinska University Hospital, Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
| | - D Mariosa
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - J A Tsai
- Center for Digestive Diseases, Karolinska University Hospital, Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - M Nilsson
- Center for Digestive Diseases, Karolinska University Hospital, Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - W Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - L Lundell
- Center for Digestive Diseases, Karolinska University Hospital, Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - I Rouvelas
- Center for Digestive Diseases, Karolinska University Hospital, Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden
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46
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Lordick F, Mariette C, Haustermans K, Obermannová R, Arnold D. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27:v50-v57. [PMID: 27664261 DOI: 10.1093/annonc/mdw329] [Citation(s) in RCA: 663] [Impact Index Per Article: 73.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- F Lordick
- University Cancer Centre Leipzig, University Hospital Leipzig, Leipzig, Germany
| | - C Mariette
- Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France
| | - K Haustermans
- Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
| | - R Obermannová
- Clinic of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - D Arnold
- Instituto CUF de Oncologia, Lisbon, Portugal
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47
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Kobayashi Y, Myojin M, Shimizu S, Hosokawa M. Esophageal motion characteristics in thoracic esophageal cancer: Impact of clinical stage T4 versus stages T1-T3. Adv Radiat Oncol 2016; 1:222-229. [PMID: 28740891 PMCID: PMC5514169 DOI: 10.1016/j.adro.2016.08.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 07/07/2016] [Accepted: 08/11/2016] [Indexed: 01/19/2023] Open
Abstract
PURPOSE The main purpose was to investigate the differences of the esophageal motion (EM) and the internal target volume (ITV) margins for the esophagus between clinical T1-T3 (cT1-T3) and cT4 cases, using 4-dimensional computed tomography. A secondary purpose was to assess the metastatic lymph nodal motion (NM) and the ITV margins for lymph nodes (LNs) using the datasets of patients with nodal involvement pathologically defined. METHODS AND MATERIALS We analyzed patients with thoracic esophageal cancer consecutively treated with definitive chemoradiation, measuring the EM and the ITV margins in the left-right, anteroposterior, and superoinferior directions. All esophageal contours were divided at the carina. The EM and NM were measured from the displacement of the centroid point between 0% images (at the end of inhalation) and 50% images (at the end of exhalation). The ITV margins were defined as the maximum distance in each direction from the clinical target volume at the 4-dimensional computed tomography average images to the intersection of the clinical target volume at the 0% and 50% images of complete coverage in each patient. RESULTS The EM below the carina in cT4 was significantly smaller than that in cT1-T2 in all directions (P < .01) and than that in cT3 in all directions (left-right: P = .03, anteroposterior and superoinferior: P < .01). The EM in the case of a cT4 tumor located below the carina was smaller than that in the case of cT4 tumor located above the carina. The NM of abdominal-LNs was much larger than that of cervicothoracic-LNs and the EM below the carina. These tendencies were similar in the ITV measurements. CONCLUSIONS The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.
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Affiliation(s)
- Yuta Kobayashi
- Department of Radiation Oncology, Keiyukai Sapporo Hospital, Sapporo, Hokkaido
| | - Miyako Myojin
- Department of Radiation Oncology, Keiyukai Sapporo Hospital, Sapporo, Hokkaido
- Corresponding author. Department of Radiation Oncology, Keiyukai Sapporo Hospital, Hodori 14 Kita 1-1, Shiroishi-ku, Sapporo, Hokkaido 003-0027, Japan.Department of Radiation OncologyKeiyukai Sapporo HospitalHodori 14 Kita 1-1Shiroishi-kuSapporoHokkaido003-0027Japan
| | - Shinichi Shimizu
- Department of Radiation Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido
| | - Masao Hosokawa
- Department of Surgery, Keiyukai Sapporo Hospital, Sapporo, Hokkaido
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48
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Brower JV, Chen S, Bassetti MF, Yu M, Harari PM, Ritter MA, Baschnagel AM. Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012. Int J Radiat Oncol Biol Phys 2016; 96:985-993. [PMID: 27869098 DOI: 10.1016/j.ijrobp.2016.08.016] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 08/08/2016] [Accepted: 08/15/2016] [Indexed: 11/19/2022]
Abstract
PURPOSE To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. METHODS AND MATERIALS Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. RESULTS A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). CONCLUSIONS In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.
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Affiliation(s)
- Jeffrey V Brower
- Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Shuai Chen
- Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Michael F Bassetti
- Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Menggang Yu
- Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Paul M Harari
- Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Mark A Ritter
- Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
| | - Andrew M Baschnagel
- Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
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49
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Nabavizadeh N, Shukla R, Elliott DA, Mitin T, Vaccaro GM, Dolan JP, Maggiore RJ, Schipper PH, Hunter JG, Thomas CR, Holland JM. Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy. Dis Esophagus 2016; 29:614-20. [PMID: 26043837 DOI: 10.1111/dote.12377] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.
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Affiliation(s)
- N Nabavizadeh
- Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - R Shukla
- Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - D A Elliott
- Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - T Mitin
- Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - G M Vaccaro
- Division of Medical Oncology, Department of Internal Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - J P Dolan
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
| | - R J Maggiore
- Division of Medical Oncology, Department of Internal Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - P H Schipper
- Division of Cardiothoracic and General Thoracic Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
| | - J G Hunter
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
| | - C R Thomas
- Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA
| | - J M Holland
- Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA
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50
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Adebahr S, Schimek-Jasch T, Nestle U, Brunner TB. Oesophagus side effects related to the treatment of oesophageal cancer or radiotherapy of other thoracic malignancies. Best Pract Res Clin Gastroenterol 2016; 30:565-80. [PMID: 27644905 DOI: 10.1016/j.bpg.2016.07.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 07/20/2016] [Indexed: 01/31/2023]
Abstract
The oesophagus as a serial organ located in the central chest is frequent subject to "incidental" dose application in radiotherapy for several thoracic malignancies including oesophageal cancer itself. Especially due to the radiosensitive mucosa severe radiotherapy induced sequelae can occur, acute oesophagitis and strictures as late toxicity being the most frequent side-effects. In this review we focus on oesophageal side effects derived from treatment of gastrointestinal cancer and secondly provide an overview on oesophageal toxicity from conventional and stereotactic fractionated radiotherapy to the thoracic area in general. Available data on pathogenesis, frequency, onset, and severity of oesophageal side effects are summarized. Whereas for conventional radiotherapy the associations of applied doses to certain volumes of the oesophagus are well described, the tolerance dose to the mediastinal structures for hypofractionated therapy is unknown. The review provides available attempts to predict the risk of oesophageal side effects from dosimetric parameters of SBRT.
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Affiliation(s)
- Sonja Adebahr
- Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
| | - Tanja Schimek-Jasch
- Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
| | - Ursula Nestle
- Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany
| | - Thomas B Brunner
- Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany.
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