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Strader C, Groth SS. Perforated Esophageal Cancer. Thorac Surg Clin 2024; 34:377-383. [PMID: 39332862 DOI: 10.1016/j.thorsurg.2024.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2024]
Abstract
Esophageal perforation in the setting of malignancy is a surgical emergency for which there is little direct evidence in the literature to guide treatment. Instead, treatment is based on a combination of our understanding of managing benign esophageal perforations and a contemporary understanding of the treatment and prognosis of esophageal cancer. Due to the numerous challenges of managing perforated esophageal cancer, incorporating clinicians with expertise in esophageal cancer, advanced endoscopy, and esophageal surgery into shared decision-making discussions with patients and their families is essential.
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Affiliation(s)
- Christopher Strader
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Shawn S Groth
- Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
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Nakayama Y, Ando T, Takagi H, Motoo I, Ueda Y, Sakumura M, Kajiura S, Takahashi S, Shimada S, Takashima Y, Fujinami H, Ogawa K, Tamura H, Hosokawa A, Yasuda I. Efficacy and Safety of Immune Checkpoint Inhibitor Combination Therapy for Dysphagia in Patients with Advanced Esophageal Cancer. J Clin Med 2024; 13:4806. [PMID: 39200948 PMCID: PMC11355245 DOI: 10.3390/jcm13164806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/10/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Background/Objectives: Recently, pembrolizumab plus 5-fluorouracil and cisplatin (FP), nivolumab plus FP, and nivolumab plus ipilimumab have become the first-line treatments for patients with advanced esophageal cancer. However, the treatment efficacy in primary tumors has not been reported. We assessed the outcomes of these treatments in advanced esophageal cancer, specifically focusing on esophageal dysphagia improvements and the primary tumor response. Methods: This retrospective study was conducted between October 2021 and November 2023. We investigated 23 patients with esophageal cancer and dysphagia who received an immune checkpoint inhibitor (ICI) plus FP or nivolumab plus ipilimumab. Results: The median progression-free survival (PFS) was 10.6 months (95% confidence interval [CI]: 9.0-12.5), and the median overall survival was not reached (95%CI: 13.0-NA). Improvement in dysphagia was observed in 19/23 (82.6%) patients, with a median time to improvement of 26 days (range: 15-77 days) and a median dysphagia PFS of 12.6 months (range: 8.1-NA months). Ten patients experienced immune-related adverse events (irAEs): seven had interstitial pneumonia, and three had thyroid dysfunction, pituitary dysfunction, and rash, respectively. Conclusions: Although there was a high frequency of irAEs, ICI for esophageal cancer achieved high response rates and prolonged survival. The observed improvement in dysphagia suggests the potential efficacy of the treatment against primary tumors.
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Affiliation(s)
- Yurika Nakayama
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Takayuki Ando
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Hiroaki Takagi
- Department of Medical Oncology, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama 930-8550, Japan; (H.T.); (K.O.)
| | - Iori Motoo
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Yuko Ueda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Miho Sakumura
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Shinya Kajiura
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Saeko Takahashi
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Seitaro Shimada
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Yusuke Takashima
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Haruka Fujinami
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
| | - Kohei Ogawa
- Department of Medical Oncology, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama 930-8550, Japan; (H.T.); (K.O.)
| | - Hotaka Tamura
- Department of Clinical Oncology, University of Miyazaki Hospital, Kihara-5200 Kiyotakecho, Miyazaki 889-1692, Japan; (H.T.); (A.H.)
| | - Ayumu Hosokawa
- Department of Clinical Oncology, University of Miyazaki Hospital, Kihara-5200 Kiyotakecho, Miyazaki 889-1692, Japan; (H.T.); (A.H.)
| | - Ichiro Yasuda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (Y.U.); (M.S.); (S.K.); (S.T.); (S.S.); (Y.T.); (H.F.); (I.Y.)
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Huang M, Li J, Wang Y, Jia L, Guo J, Wu Z, Gao S, Li J, Zhang Y. Ethanol exposure exacerbates 4-nitroquinoline-1-oxide induced esophageal carcinogenesis and induces invasive carcinoma with muscularis propria infiltration in a mouse model. Toxicol Appl Pharmacol 2024; 489:117006. [PMID: 38880189 DOI: 10.1016/j.taap.2024.117006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/26/2024] [Accepted: 06/13/2024] [Indexed: 06/18/2024]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers worldwide. Most ESCC patients are diagnosed at an advanced stage; however, current research on in vivo animal models accurately reflecting their clinical presentation is lacking. Alcohol consumption is a major risk factor for ESCC and has been used in several disease models for disease induction. In this study, we used 4-nitroquinoline-1-oxide in combination with ethanol to induce an in vivo ESCC mouse model. Esophageal tissues were stained with hematoxylin and eosin for histopathological examination and lesion scoring. In cellular experiments, cell adhesion and migration invasion ability were observed using phalloidin staining, cell scratch and transwell assays, respectively, and the expression of epithelial-mesenchymal transition-related markers was detected using quantitative reverse transcription polymerase chain reaction and western blotting. The results showed that ethanol-exposed mice lost more weight and had an increased number of esophageal nodules. Histological examination revealed that the lesion scores of the ethanol-exposed esophageal samples were significantly higher than those of the unexposed esophageal samples. Furthermore, ethanol-exposed esophageal cancer samples had more severe lesions with infiltration of tumor cells into the muscularis propria. In vitro cellular experiments showed that ethanol exposure induced cytoskeletal microfilament formation, promoted cell migration invasion elevated the expression of N-cadherin and Snail, and decreased the expression of E-cadherin. In conclusion, ethanol exposure exacerbates ESCC, promotes tumor cell infiltration into the muscularis propria, and could be an effective agent for establishing innovative models of invasive carcinoma.
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Affiliation(s)
- Ming Huang
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; Institute of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Jing Li
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Yu Wang
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; Institute of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Lei Jia
- The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Jianxin Guo
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Zhongbing Wu
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Shuang Gao
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China; Institute of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Jinge Li
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
| | - Yushuang Zhang
- The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
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Leelayuwatanakul N, Thanthitaweewat V, Wongsrichanalai V, Lertbutsayanukul C, Prayongrat A, Kitpanit S, Sriprasart T. The Prognostic Predictors of Airway Stenting in Malignant Airway Involvement From Esophageal Carcinoma. J Bronchology Interv Pulmonol 2023; 30:277-284. [PMID: 35899980 PMCID: PMC10312900 DOI: 10.1097/lbr.0000000000000879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/23/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND In locoregional esophageal carcinoma (EC), airway involvement is the most common route of extraesophageal metastasis. The prognosis remains poor even with a multimodality approach. Although airway stenting is well known for restoration of the airway, the survival benefit is still lacking. METHODS A total of 37 of patients with airway involvement from EC who underwent airway stenting at a single institution from 2015 to 2020 were retrospectively reviewed. Survival curves after stent placement among different groups were analyzed using Kaplan-Meier method. RESULTS Of 37 patients, 34 were male, and the mean age was 58.9 years (42 to 80). EC was commonly located at midesophagus (51.4%). The site of airway involvement was left main bronchus (48.6%), trachea (32.4%), multiple sites (16.2%), and right main bronchus (2.7%). The nature of airway involvement was tumor invasion (91.9%), compression (62.2%), and fistula (37.8%). Twenty-three patients (62.2%) had airway involvement at the time of esophageal cancer diagnosis. Only 4 patients underwent esophageal stenting. The median survival time after stent placement was 97 days (5 to 539). Chemotherapy and/or radiotherapy were given before stent placement in 18 patients (48.6%). Treatment-naive before airway stenting and diagnosis of airway involvement at the same time of EC diagnosis were independent predictors for the increased survival after stent placement ( P <0.05). Poststent treatment was associated with improved survival ( P =0.002). CONCLUSION In patients with malignant airway involvement from EC who underwent airway stenting, the prognostic predictors for improved survival were treatment-naive status, receiving treatment after airway stenting, and early-onset of airway involvement.
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Affiliation(s)
- Nophol Leelayuwatanakul
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University
- Department of Medicine, Chulalongkorn Comprehensive Cancer Center
| | - Vorawut Thanthitaweewat
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University
| | - Virissorn Wongsrichanalai
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University
| | - Chawalit Lertbutsayanukul
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Anussara Prayongrat
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Sarin Kitpanit
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
| | - Thitiwat Sriprasart
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University
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Lee CC, Soon YY, Vellayappan B, Ho F, Tey JCS. Survival rates and safety associated with chemoradiotherapy followed by surgery and chemoradiotherapy alone for patients with T4 esophageal cancer: a systematic review and meta-analysis. Acta Oncol 2022; 61:738-748. [PMID: 35450511 DOI: 10.1080/0284186x.2022.2062680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND The optimal treatment approach for T4 esophageal cancer is not well established. We aimed to perform a systematic review and meta-analysis to determine the survival rates and safety of chemoradiotherapy followed by surgery (CRT-S) and chemoradiotherapy alone (CRT) in patients with T4 Nany M0 esophageal cancer. MATERIALS AND METHODS We searched databases for eligible prospective or retrospective studies. The outcomes of interest were overall survival (OS) at 1, 3 and 5 years, treatment-related fistula formation and mortality rates. Meta-analyses were performed using the random effects models separately for studies evaluating CRT-S and CRT. Subgroup analyses were performed based on histology, radiation dose, chemotherapy regimen and duration of the interval between CRT and surgery. RESULTS We identified 23 studies including 1,119 patients with predominantly squamous cell carcinoma (93%) and adenocarcinoma (3%) histology. The OS rates of patients receiving CRT-S were 65%, 36% and 20% at 1, 3 and 5 years, respectively. The OS rates of patients receiving CRT were 30%, 11% and 10% at 1, 3 and 5 years, respectively. Treatment-related fistula formation rates were 4% for CRT-S and 9% for CRT. Treatment-related mortality rates were 3% for both groups. Subgroup analyses showed that the interval of >2 months between CRT and surgery was associated with significantly improved OS rates at 1, 3 and 5 years. CONCLUSION Chemoradiotherapy is an efficacious treatment approach for T4 esophageal cancer, with clinically acceptable rates of treatment-related fistula formation and mortality. Tri-modality approach with surgery can be considered in carefully selected patients. Our study findings should be interpreted with caution due to the lack of high-quality evidence. Randomized controlled trials are warranted to confirm these findings.
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Affiliation(s)
- Chia Ching Lee
- Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore; National University Hospital, Singapore, Singapore; National University Health System, Singapore, Singapore; National University of Singapore, Singapore, Singapore
| | - Yu Yang Soon
- Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore; National University Hospital, Singapore, Singapore; National University Health System, Singapore, Singapore; National University of Singapore, Singapore, Singapore
| | - Balamurugan Vellayappan
- Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore; National University Hospital, Singapore, Singapore; National University Health System, Singapore, Singapore; National University of Singapore, Singapore, Singapore
| | - Francis Ho
- Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore; National University Hospital, Singapore, Singapore; National University Health System, Singapore, Singapore; National University of Singapore, Singapore, Singapore
| | - Jeremy C. S. Tey
- Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore; National University Hospital, Singapore, Singapore; National University Health System, Singapore, Singapore; National University of Singapore, Singapore, Singapore
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Pao TH, Chen YY, Chang WL, Chang JSM, Chiang NJ, Lin CY, Lai WW, Tseng YL, Yen YT, Chung TJ, Lin FC. Esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal squamous cell carcinoma. PLoS One 2021; 16:e0251811. [PMID: 33989365 PMCID: PMC8121322 DOI: 10.1371/journal.pone.0251811] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 05/04/2021] [Indexed: 12/24/2022] Open
Abstract
Background The literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique. Methods A total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis. Results Median follow-up was 14.9 months (IQR, 7.0–28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3–10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383–10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053–6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058). Conclusions T4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.
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Affiliation(s)
- Tzu-Hui Pao
- Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ying-Yuan Chen
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jeffrey Shu-Ming Chang
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Nai-Jung Chiang
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Chia-Ying Lin
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wu-Wei Lai
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yau-Lin Tseng
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Ting Yen
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ta-Jung Chung
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Forn-Chia Lin
- Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- * E-mail:
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High incidence of esophageal fistula on patients with clinical T4b esophageal squamous cell carcinoma who received chemoradiotherapy: A retrospective analysis. Radiother Oncol 2021; 158:191-199. [PMID: 33667583 DOI: 10.1016/j.radonc.2021.02.031] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 02/09/2021] [Accepted: 02/19/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND PURPOSE Despite definitive chemoradiotherapy (CRT) being a recommended therapeutic method for patients with T4b esophageal squamous cell carcinoma (ESCC), treatment response and complications remain unclear. Esophageal fistula is a severe CRT-related complication when treating locally advanced ESCC, but data on risk factors that lead to esophageal fistula formation are limited. The aim of this analysis is to characterize the outcomes of T4b ESCC treated by CRT and investigate the risk factors of esophageal fistula. MATERIALS AND METHODS We retrospectively analyzed 136 patients with clinically unresectable T4b ESCC who were treated with CRT. Response, survival, and complication rates, particularly the rate of esophageal fistula and its associated risk factors were analyzed. RESULTS The median progression-free survival and overall survival (OS) of all patients were 7.9 (95% confidence interval [CI]: 6.1-9.7) and 12.2 months (95% [CI]: 8.9-15.4), respectively. The Kaplan-Meier curves showed that the 3- and 5-year OS rates were 29.9% and 20.2%, respectively. The incidence rate of esophageal fistulas was 30.1%. The median OS for patients with esophageal fistula was only 6.9 (95%[CI] = 6.0-7.8) months. The risk for developing esophageal fistulas was significantly high for ulcerative-type tumors (odds ratio [OR] = 3.202; 95%[CI] = 1.036-7.850, P = 0.011) and for those invading the bronchus/trachea (OR = 3.378; 95%[CI] = 1.223-9.332, P = 0.048). CONCLUSION We demonstrated that CRT for T4b ESCC patients has a curative potential, despite a high incidence of esophageal fistula, which was the main cause of treatment failure. The higher risk for fistula formation were tumors with ulceration or bronchus/trachea invasion.
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Ohkura Y, Ueno M, Udagawa H. Advantageous factors of R0 curative conversion esophagectomy and the optimal extent of lymphadenectomy after induction therapy for cT4b thoracic esophageal cancer. Ann Gastroenterol Surg 2021; 5:204-214. [PMID: 33860140 PMCID: PMC8034692 DOI: 10.1002/ags3.12416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 11/16/2020] [Accepted: 11/17/2020] [Indexed: 12/03/2022] Open
Abstract
AIM This study aimed to clarify the prognostic factors, the advantageous factors of R0 curative resection, and optimal extents of lymph node dissection for conversion esophagectomy after induction therapy. METHODS Among 1903 patients with esophageal cancer at Toranomon Hospital between January 2006 to May 2020, 151 patients with locally advanced T4b thoracic esophageal cancer were divided into two groups according to treatment: conversion surgery group (n = 54) and non-surgical treatment group (n = 97) for comparison. RESULTS The patients who underwent R0 curative resection showed preferable survival comparable to the survival rate of patients with cCR in the non-surgical treatment group (1-, 3- and 5-year survival: 96.9%, 82.1% and 76.7% vs 94.1%, 86.3%, and 86.3%; P = 0.770). Multivariate analysis revealed that the T4b tumor invasion by primary site (odds ratio (OR) = 6.100; 95% CI, 1.439-25.865: P = 0.014) and time to conversion surgery from start of induction therapy within four months (OR = 5.229; 95% CI, 1.296-21.102: P = 0.020) were all independent advantageous factors of R0 curative resection. Actuarial 1-, 3- and 5-year survival rates in patients who underwent conversion surgery with D2-3 lymphadenectomy were 90.9%, 48.6%, and 40.8%, respectively. CONCLUSIONS R0 resection led to improved prognosis in conversion esophagectomy for cT4b esophageal cancer. The T4b tumor invasion by primary site and time to conversion surgery from start of induction therapy within 4 months were independent advantageous factors of R0 curative resection. In addition, standard radical esophagectomy including prophylactic D2-/3- lymphadenectomy should be performed if it is possible, while taking adequate care regarding the increased risk after induction therapy.
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Affiliation(s)
- Yu Ohkura
- Department of Gastroenterological SurgeryToranomon HospitalOkinaka Memorial Institute for Medical ResearchTokyoJapan
| | - Masaki Ueno
- Department of Gastroenterological SurgeryToranomon HospitalOkinaka Memorial Institute for Medical ResearchTokyoJapan
| | - Harushi Udagawa
- Department of Gastroenterological SurgeryToranomon HospitalOkinaka Memorial Institute for Medical ResearchTokyoJapan
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Wada Y, Anbai A, Takagi N, Kumagai S, Okuyama E, Nanjo H, Sato Y, Motoyama S, Hashimoto M. Outcomes of Definitive Chemoradiotherapy for Stage IVa (T4b vs. N4) Esophageal Squamous Cell Carcinoma Based on the Japanese Classification System: A Retrospective Single-Center Study. Cancers (Basel) 2020; 13:E8. [PMID: 33375169 PMCID: PMC7792968 DOI: 10.3390/cancers13010008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/07/2020] [Accepted: 12/18/2020] [Indexed: 11/17/2022] Open
Abstract
The differences in prognoses or progression patterns between T4b non-N4 and non-T4b N4 esophageal squamous cell carcinoma post chemoradiotherapy (CRT) is unclear. This study compared the outcomes of CRT for stage IVa esophageal squamous cell carcinoma according to T/N factors. We retrospectively identified 66 patients with stage IVa esophageal squamous cell carcinoma who underwent definitive CRT at our center between January 2009 and March 2013. The treatment outcomes, i.e., progression patterns, prognostic factors, and toxicities based on version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, were studied. The patients (56 men and 10 women) had a median age of 67 (range: 37-87) years. The T/N classifications were T4b non-N4 (28/66), non-T4b N4 (24/66), and T4b N4 (14/66). Objective response was achieved in 57 patients (86.4%, (95% confidence interval, 74.6-94.1%)). There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, and progression pattern. We found no significant differences in prognoses or progression patterns among patients with T4b non-N4, non-T4b N4, and T4b N4 esophageal squamous cell carcinoma. Thus, it seems impractical to modify CRT regimens based on T/N factors.
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Affiliation(s)
- Yuki Wada
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8545, Japan; (A.A.); (N.T.); (S.K.); (E.O.); (M.H.)
| | - Akira Anbai
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8545, Japan; (A.A.); (N.T.); (S.K.); (E.O.); (M.H.)
| | - Noriko Takagi
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8545, Japan; (A.A.); (N.T.); (S.K.); (E.O.); (M.H.)
| | - Satoshi Kumagai
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8545, Japan; (A.A.); (N.T.); (S.K.); (E.O.); (M.H.)
| | - Eriko Okuyama
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8545, Japan; (A.A.); (N.T.); (S.K.); (E.O.); (M.H.)
| | - Hiroshi Nanjo
- Division of Clinical Pathology, Akita University Hospital, 1-1-1 Hondo, Akita 010-8545, Japan;
| | - Yusuke Sato
- Esophageal Surgery, Akita University Hospital, 1-1-1 Hondo, Akita 010-8545, Japan; (Y.S.); (S.M.)
| | - Satoru Motoyama
- Esophageal Surgery, Akita University Hospital, 1-1-1 Hondo, Akita 010-8545, Japan; (Y.S.); (S.M.)
| | - Manabu Hashimoto
- Department of Radiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8545, Japan; (A.A.); (N.T.); (S.K.); (E.O.); (M.H.)
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10
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Saeki H, Sohda M, Sakai M, Sano A, Shirabe K. Role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma. Ann Gastroenterol Surg 2020; 4:490-497. [PMID: 33005843 PMCID: PMC7511562 DOI: 10.1002/ags3.12364] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/07/2020] [Accepted: 05/17/2020] [Indexed: 12/13/2022] Open
Abstract
We reviewed the current status and future perspectives regarding the role of surgery in multidisciplinary treatment strategies for locally advanced esophageal squamous cell carcinoma (ESCC). The treatment and management of ESCC have been improved by dramatic advances in diagnostic techniques and the development of surgery, chemotherapy, radiotherapy, and immunotherapy. The current standard treatment for locally advanced ESCC is preoperative chemotherapy followed by surgery in Japan, whereas preoperative chemoradiotherapy is a globally recommended approach. Differences of recognition regarding the role for surgery between Japan and many Western countries may have created peculiar preferences for preoperative therapy. The clinical significance of conversion strategy and salvage surgery for patients with ESCC should be further evaluated in terms of curability and safety. Although strategies to identify patients who would benefit from preoperative therapy are strongly required to avoid performing unnecessary treatment, it remains difficult to predict the efficacy of preoperative therapy prior to treatment. Prospective clinical trials and basic research to identify predictive biomarkers for response to chemotherapy, radiotherapy, and immunotherapy are needed to promote the development of multidisciplinary treatment strategies for patients with ESCC.
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Affiliation(s)
- Hiroshi Saeki
- Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
| | - Makoto Sohda
- Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
| | - Makoto Sakai
- Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
| | - Akihiko Sano
- Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
| | - Ken Shirabe
- Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
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11
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Ohsawa M, Hamai Y, Ibuki Y, Emi M, Okada M. Successful Management of Esophageal Cancer With Perforation Using Bypass Surgery Followed by Definitive Chemoradiotherapy. In Vivo 2020; 34:2169-2172. [PMID: 32606200 DOI: 10.21873/invivo.12025] [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: 03/18/2020] [Revised: 03/31/2020] [Accepted: 04/01/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND Esophageal perforation in advanced esophageal cancer requires immediate treatment. However, no clear treatment protocol has been established for this condition. We report a case of advanced esophageal cancer with esophageal perforation treated with esophageal bypass surgery and definitive chemoradiotherapy (CRT). CASE REPORT A 45-year-old woman was diagnosed with locally advanced esophageal cancer with esophageal perforation. Although the patient's general condition was relatively stable, no improvement was expected through conservative treatment. Esophageal gastric bypass surgery was performed; her symptoms improved postoperatively and oral ingestion became possible. Definitive CRT with 66 Gy radiotherapy and chemotherapy with cisplatin and 5-fluorouracil was administered. A complete clinical response was achieved. The patient is alive and well without recurrence 20 months after treatment. CONCLUSION Definitive CRT after esophageal bypass surgery is a potential treatment option for locally advanced esophageal cancer with esophageal perforation to improve treatment response and quality of life.
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Affiliation(s)
- Manato Ohsawa
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Yoichi Hamai
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Yuta Ibuki
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Manabu Emi
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
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12
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Chen PJ, Yap WK, Chang YC, Tseng CK, Chao YK, Hsieh JCH, Pai PC, Lee CH, Yang CK, Ho ATY, Hung TM. Prognostic value of lymph node to primary tumor standardized uptake value ratio in unresectable esophageal cancer. BMC Cancer 2020; 20:545. [PMID: 32522275 PMCID: PMC7288503 DOI: 10.1186/s12885-020-07044-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 06/04/2020] [Indexed: 01/25/2023] Open
Abstract
Background Unresectable esophageal cancer harbors high mortality despite chemoradiotherapy. Better patient selection for more personalized management may result in better treatment outcomes. We presume the ratio of maximum standardized uptake value (SUV) of metastatic lymph nodes to primary tumor (NTR) in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) may provide prognostic information and further stratification of these patients. Methods The patients with non-metastatic and unresectable esophageal squamous cell carcinoma (SCC) receiving FDG PET/CT staging and treated by chemoradiotherapy were retrospectively reviewed. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for NTR. Kaplan-Meier method and Cox regression model were used for survival analyses and multivariable analyses, respectively. Results From 2010 to 2016, 96 eligible patients were analyzed. The median follow-up time was 10.2 months (range 1.6 to 83.6 months). Using ROC analysis, the best NTR cut-off value was 0.46 for prediction of distant metastasis. The median distant metastasis-free survival (DMFS) was significantly lower in the high-NTR group (9.5 vs. 22.2 months, p = 0.002) and median overall survival (OS) (9.5 vs. 11.6 months, p = 0.013) was also significantly worse. Multivariable analysis revealed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR] 1.81, p = 0.023) and OS (HR 1.77, p = 0.014). Conclusions High pretreatment NTR predicts worse treatment outcomes and could be an easy-to-use and helpful prognostic factor to provide more personalized treatment for patients with non-metastatic and unresectable esophageal SCC.
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Affiliation(s)
- Po-Jui Chen
- Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan
| | - Wing-Keen Yap
- Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan
| | - Yu-Chuan Chang
- Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Kwei-Shan, Taoyuan, Taiwan
| | - Chen-Kan Tseng
- Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan
| | - Yin-Kai Chao
- Division of Thoracic Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Jason Chia-Hsun Hsieh
- Division of Medical Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Chemical and Materials Engineering, Chang Gung University, No.259, Wenhua 1st Rd., Kwei-Shan, Taoyuan, Taiwan
| | - Ping-Ching Pai
- Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan
| | - Ching-Hsin Lee
- Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan
| | - Chan-Keng Yang
- Division of Medical Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Albert Tsung-Ying Ho
- Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tsung-Min Hung
- Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan. .,Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Kwei-Shan, Taoyuan, Taiwan.
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13
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Yamasaki M, Yamashita K, Saito T, Tanaka K, Makino T, Miyazaki Y, Takahashi T, Kurokawa Y, Nakajima K, Motoori M, Kimura Y, Mori M, Doki Y. Tracheal resection and anterior mediastinal tracheostomy in the multidisciplinary treatment of esophageal cancer with tracheal invasion. Dis Esophagus 2020; 33:5735623. [PMID: 32055845 DOI: 10.1093/dote/doz101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 11/04/2019] [Indexed: 12/11/2022]
Abstract
Combined tracheal resection and anterior mediastinal tracheostomy (AMT) for esophageal cancer with tracheal invasion is a challenging treatment because of its high morbidity and the lack of evidence regarding long-term outcomes. The aim of this study was to assess the short- and long-term outcomes of AMT as part of the multidisciplinary treatment for esophageal cancer with tracheal invasion. This retrospective study included 27 consecutive patients with esophageal cancer with tracheal invasion who underwent combined tracheal resection and AMT in their multidisciplinary treatment for esophageal cancer. We evaluated postoperative complications, body weight loss, and survival and examined the prognostic value of preoperative factors. All patients underwent chemotherapy and/or chemoradiotherapy as prior treatment. R0 resection was achieved in all cases. Clavien-Dindo grade I or greater complications occurred in 17 patients (63%), and grade III or greater complications occurred in 12 (44%). Overall in-hospital mortality was 4%, with one patient dying on postoperative day 48 when the brachiocephalic artery ruptured from tracheal compression. The 30- and 90-day mortality rates were 0% and 4%, respectively. Median weight change in patients without recurrence in the year after surgery was -1.7% (-9.6-21%). All of these patients received nutrition by oral intake and were living independently at home without public assistance. The 3- and 5-year disease-free survival rates were 25.9% and 18.5%, respectively; 3- and 5-year overall survival rates were 38.6% and 25.7%, respectively. Multivariate analysis identified response to prior treatment as an independent prognostic factor in these patients. Combined tracheal resection and AMT may be adapted as part of the multidisciplinary treatment of esophageal cancer with tracheal invasion. Improving AMT safety and optimizing patient selection may improve prognosis among patients with this cancer.
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Affiliation(s)
- Makoto Yamasaki
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Kotaro Yamashita
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Takuro Saito
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Koji Tanaka
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tomoki Makino
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yasuhiro Miyazaki
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tsuyoshi Takahashi
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yukinori Kurokawa
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Kiyokazu Nakajima
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Masaaki Motoori
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
| | - Yutaka Kimura
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Masaki Mori
- Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Yuichiro Doki
- Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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14
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Hu B, Jia F, Zhou H, Zhou T, Zhao Q, Chen Y, Li B, Huang W. Risk Factors Associated with Esophageal Fistula after Radiotherapy for Esophageal Squamous Cell Carcinoma. J Cancer 2020; 11:3693-3700. [PMID: 32284766 PMCID: PMC7150448 DOI: 10.7150/jca.39033] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 02/25/2020] [Indexed: 12/18/2022] Open
Abstract
Purpose: The aim of this study was to investigate risk factors for esophageal squamous cell carcinoma (ESCC) treated with radiotherapy (RT) with or without chemotherapy to guide how to reduce the occurrence of esophageal fistula (EF). Methods: 414 patients with ESCC who underwent RT with or without chemotherapy were collected in Shandong Cancer Hospital from February 2012 to June 2018 retrospectively. The clinical characters and dosimetric parameters were recorded. Univariate and multivariate logistic regression analyses were provided to determine the risk factors associated with EF. Results: The cumulative incidences of EF were 11.1% (46/414 patients). The median follow-up period was 15.8 months (range: 0.2-82.6months). The median survival time (MST) of patients with EF was 5.3 months. In univariate analysis, age, T4 stage, N3 stage, chemotherapy regimens, re-RT, ulcerative esophageal cancer (EC), esophageal stenosis, the maximum thickness of the tumor and the length of tumor had a correlation with the prevalence of EF. In multivariable logistic regression analysis, T4 stage, N3 stage, re-RT, ulcerative EC, esophageal stenosis, the maximum thickness of the tumor was confirmed as risk factors for EF. Conclusion: This study revealed that T4 stage, N3 stage, re-RT, ulcerative EC, esophageal stenosis, the maximum thickness of the tumor were risk factors associated with EF. We ought to attach importance to the prevention of EF. Patients with risk factors for EF should be paid close attention.
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Affiliation(s)
- Bing Hu
- School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong province, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
| | - Feng Jia
- Department of Oncology, Jinxiang people's hospital, Shandong province, China
| | - Haiyan Zhou
- Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
| | - Tao Zhou
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
| | - Qian Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
| | - Yiru Chen
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong province, China
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15
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Furuta M, Yokota T, Tsushima T, Todaka A, Machida N, Hamauchi S, Yamazaki K, Fukutomi A, Kawai S, Kawabata T, Onozawa Y, Yasui H. Comparison of enteral nutrition with total parenteral nutrition for patients with locally advanced unresectable esophageal cancer harboring dysphagia in definitive chemoradiotherapy. Jpn J Clin Oncol 2020; 49:910-918. [PMID: 31219161 DOI: 10.1093/jjco/hyz089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/16/2019] [Accepted: 06/10/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The nutritional status of patients with esophageal squamous cell carcinoma (ESCC) harboring dysphagia is often poor. The efficacy and safety of enteral nutrition (EN) versus total parenteral nutrition (TPN) have not been addressed in patients with ESCC requiring nutritional support during definitive chemoradiotherapy (dCRT). METHODS We performed a retrospective analysis of 51 locally advanced unresectable ESCC patients with dysphagia receiving EN (n = 28) or TPN (n = 23) during dCRT between 2009 and 2016. RESULTS Patient characteristics in EN vs. TPN were as follows: median age (range), 67 (34 to 82) vs. 66 (57 to 83); ECOG performance status 0/1/2, 11/15/2 vs. 7/14/2; dysphagia score 2/3/4, 11/15/2 vs. 14/8/1; and primary tumor location Ce/Ut/Mt/Lt/Ae, 4/6/14/3/1 vs. 2/2/16/1/2. Median changes in serum albumin level one month after dCRT were +8.8% (-36 to 40) in EN and -12% (-64 to 29) in TPN (P = 0.00377). Weight, body mass index, and skeletal muscle area were not significantly different between the groups. Median durations of hospitalization were 50 days (18 to 72) in EN and 63 days (36 to 164) in TPN (P = 0.00302). Adverse events during dCRT in EN vs. TPN were as follows: catheter-related infection, 0 vs. 6 (27%); aspiration pneumonia, 3 (11%) vs. 2 (9%); mediastinitis, 3 (11%) vs. 1 (5%); grade ≥3 neutropenia, 6 (21%) vs. 14 (64%) (P = 0.00287); and febrile neutropenia, 0 vs. 6 (27%) (P = 0.00561). CONCLUSIONS EN may be advantageous for improving serum albumin level, and reducing hematological toxicity and duration of hospitalization compared with TPN during dCRT in ESCC patients.
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Affiliation(s)
- Mitsuhiro Furuta
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Tomoya Yokota
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Akiko Todaka
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Nozomu Machida
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Satoshi Hamauchi
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Kentaro Yamazaki
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Akira Fukutomi
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
| | - Sadayuki Kawai
- Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takanori Kawabata
- Division of Medical Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yusuke Onozawa
- Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hirofumi Yasui
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center Shizuoka, Japan
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16
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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] [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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17
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Zhu C, Wang S, You Y, Nie K, Ji Y. Risk Factors for Esophageal Fistula in Esophageal Cancer Patients Treated with Radiotherapy: A Systematic Review and Meta-Analysis. Oncol Res Treat 2020; 43:34-41. [DOI: 10.1159/000503754] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
<b><i>Objective:</i></b> Esophageal fistula is a critical and fatal complication of esophageal cancer. The aim of this meta-analysis was to explore the risk factors for esophageal perforation in esophageal cancer patients treated with radiotherapy. <b><i>Methods:</i></b> Data from the PubMed and Embase databases were retrieved for clinical research published between 1990 and 2018. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. A meta-analysis was performed using the RevMan 5.3 software provided by the Cochrane Collaboration Network. <b><i>Results:</i></b> Seventeen articles were eligible for the meta-analysis. In these articles, over 35 risk factors for esophageal fistula formation were described and 17 risk factors were analyzed. Significant differences in the odds of developing an esophageal perforation were found with regard to age (OR 2.34, 95% CI 1.08–5.03, <i>p</i> = 0.001), ulcerative type (OR 2.72, 95% CI 1.43–5.16, <i>p</i> = 0.002), histology (OR 4.16, 95% CI 1.14–15.12, <i>p</i> = 0.03), T stage (OR 2.66, 95% CI 1.44–4.91, <i>p</i> = 0.002), short-term response (OR 2.21, 95% CI 1.06–4.62, <i>p</i> = 0.03), chemotherapy regimen (OR 2.80, 95% CI 1.38–5.68, <i>p</i> = 0.005), and stenosis (OR 2.00, 95% CI 1.03–3.89, <i>p</i> = 0.04). <b><i>Conclusions:</i></b> An age of <60–65 years, ulcerative type, squamous cell cancer, T4 stage, incomplete response, fluorouracil-based regimen, and stenosis were associated with an increased risk of esophageal fistula during or after radiotherapy. However, further, large-scale prospective studies are needed to establish the validity of this association.
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18
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Miyata H, Sugimura K, Motoori M, Omori T, Yamamoto K, Yanagimoto Y, Shinno N, Yasui M, Takahashi H, Wada H, Ohue M, Yano M. Clinical Implications of Conversion Surgery After Induction Therapy for T4b Thoracic Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2019; 26:4737-4743. [PMID: 31414291 DOI: 10.1245/s10434-019-07727-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Definitive chemoradiation therapy or chemotherapy alone is generally recommended for patients with unresectable cT4b esophageal cancer. However, conversion surgery has emerged as a therapeutic option when downstaging is achieved by induction therapy. METHODS We studied 169 patients with cT4 esophageal cancer who underwent induction therapy. Survival and prognostic factors were examined. RESULTS Of 169 patients, 25 who achieved a clinical complete response (cCR) underwent surveillance, 72 patients underwent conversion surgery, while another 72 patients whose tumors were regarded as unresectable after induction therapy did not undergo surgery. Among 169 patients, the 3- and 5-year survival rates were 31.0% and 25.9%, respectively. Sixty-four patients who underwent curative resection showed better survival comparable with survival of 25 patients who achieved cCR (3- and 5-year survival; 56.8% and 48.6% versus 64.0% and 52.0%, respectively). However, the survival of eight patients who underwent noncurative resection was as dismal as that of patients who did not undergo conversion surgery. Multivariate analysis in 169 patients identified female sex and achieving cCR or R0 resection as independent prognostic factors. Multivariate analysis in 72 patients who underwent conversion surgery identified sex, lymph node status, and R0 resection as independent prognostic factors in patients with cT4b esophageal cancer. CONCLUSIONS The present study showed that conversion surgery after induction therapy can be a potentially curative treatment option for select patients with cT4b esophageal cancer. An important issue for further research is to establish a method for more accurately diagnosing tumor resectability after induction therapy for cT4b esophageal cancer.
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Affiliation(s)
- Hiroshi Miyata
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan.
| | - Keijirou Sugimura
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masaaki Motoori
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Takeshi Omori
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Yamamoto
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Yoshitomo Yanagimoto
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Naoki Shinno
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masayoshi Yasui
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidenori Takahashi
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroshi Wada
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masayuki Ohue
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masahiko Yano
- Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Japan
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19
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Makino T, Yamasaki M, Tanaka K, Miyazaki Y, Takahashi T, Kurokawa Y, Motoori M, Kimura Y, Nakajima K, Mori M, Doki Y. Treatment and clinical outcome of clinical T4 esophageal cancer: A systematic review. Ann Gastroenterol Surg 2019; 3:169-180. [PMID: 30923786 PMCID: PMC6422802 DOI: 10.1002/ags3.12222] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/29/2018] [Accepted: 11/12/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Survival of patients with cT4 esophageal cancer is dismal. Although the optimal treatment strategy remains to be established, two treatment options are available for cT4 esophageal cancers: definitive chemoradiation (dCRT) and induction treatment followed by conversion surgery (CS). However, little is known concerning the differences in clinical outcome between patients with T4 esophageal tumors treated with dCRT and those eventually treated with CS. METHODS A systematic search of the scientific literature on PubMed/MEDLINE was carried out using the keywords "T4 esophageal cancer," "invading (involving) adjacent organ," "definitive chemoradiation," "induction therapy," "salvage surgery," and "conversion surgery," obtaining 28 reports published up to July 2018. RESULTS/CONCLUSION We found that CS was superior to dCRT with respect to local disease control and short-term survival; however, CS was associated with relatively higher perioperative mortality and morbidity. Alternatively, although dCRT might often cause fistula formation, a clinical complete response to dCRT is likely to lead to a better prognosis. Recent advances in chemotherapeutic agents have led to triple induction chemotherapy, with docetaxel, cisplatin, and 5-fluorouracil (DCF), which has shown promise as an initial induction treatment for cT4 esophageal cancer. Indeed, this regimen could control both local and systemic disease, which enables curative resection without preoperative CRT. Moreover, some appropriate changes in perioperative management and intensive systemic chemotherapy might enhance patient outcome. Randomized controlled trials with a large sample size are needed to establish the standard treatment for cT4 esophageal cancer.
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Affiliation(s)
- Tomoki Makino
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Makoto Yamasaki
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Koji Tanaka
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Yasuhiro Miyazaki
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Yukinori Kurokawa
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | | | - Yutaka Kimura
- Department of SurgeryFaculty of MedicineKindai UniversityOsakaJapan
| | - Kiyokazu Nakajima
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Masaki Mori
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
| | - Yuichiro Doki
- Department of Gastroenterological SurgeryGraduate School of MedicineOsaka UniversityOsakaJapan
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20
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Ohkura Y, Ueno M, Iizuka T, Udagawa H. Prognostic Factors and Appropriate Lymph Node Dissection in Salvage Esophagectomy for Locally Advanced T4 Esophageal Cancer. Ann Surg Oncol 2018; 26:209-216. [PMID: 30465220 DOI: 10.1245/s10434-018-7074-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Indexed: 01/11/2023]
Abstract
BACKGROUND A suitable treatment strategy for esophageal cancer after definitive chemoradiotherapy for T4 cases has not been established and remains unclear. This study aimed to clarify the independent prognostic factors, surgical indications, and optimal extent of lymphadenectomy for T4 esophageal cancer. METHODS Of 803 patients who underwent esophagectomy for esophageal cancer at the authors' institution from 2006 to March 2018, the study included 33 patients who underwent salvage esophagectomy with locally advanced T4 cancer. The study examined the baseline attributes and treatment results of these cases and evaluated the prognostic factors and treatment strategies. RESULTS The independent favorable prognostic factors in T4 cancer (T4a/T4b = 11/22) included non-T4b status [hazard ratio (HR), 15.311; 95% confidence-interval (CI), 1.277-183.5] and R0 resection (HR, 14.706; 95% CI, 1.193-166.67). For the cases in which R0 resection was possible (n = 14), both the 1- and 5-year survival rates were 90.9%, whereas for the cases without R0 dissection (n = 19), the 1- and 5-year survival rates were respectively 44.9% and 0%. In the univariate analysis, the patients who underwent two- or three-field lymph node dissection tended to have a better prognosis (p = 0.062), and those with 60 or more lymph nodes dissected had a significantly better prognosis (p = 0.038). For the patients who underwent salvage esophagectomy with typical lymph node dissection, the rate of complications classified as Clavien-Dindo grade 3 or higher (33.3%) was not increased, indicating that the procedure was relatively safe. CONCLUSIONS The results showed that in salvage esophagectomy for T4 esophageal cancer, R0 resection led to improved prognosis. Because typical two- or three-field lymph node dissection including prophylactic dissection could be performed safely and led to a better prognosis in salvage esophagectomy, typical esophagectomy including prophylactic lymph node dissection should be performed if possible.
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Affiliation(s)
- Yu Ohkura
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan. .,Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
| | - Masaki Ueno
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Toshiro Iizuka
- Okinaka Memorial Institute for Medical Research, Tokyo, Japan.,Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Harushi Udagawa
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.,Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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21
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Prognostic Factors of Salvage Esophagectomy for Residual or Recurrent Esophageal Squamous Cell Carcinoma After Definitive Chemoradiotherapy. World J Surg 2018; 42:2887-2893. [PMID: 29423738 DOI: 10.1007/s00268-018-4536-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND The aim of this study was to confirm prognostic factors for salvage esophagectomy for remnant or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy. STUDY DESIGN We retrospectively analyzed clinicopathological backgrounds of 50 patients who underwent salvage esophagectomy between April 2005 and January 2016. Salvage esophagectomy comprised 40 three-incision esophagectomies, two transhiatal esophagectomies and eight pharyngolaryngoesophagectomies. Independent prognostic factors for overall survival were assessed using Cox regression analysis of the factors. RESULTS Salvage esophagectomy remains a highly invasive surgery and correlated with a higher incidence of all morbidities of Clavien-Dindo classification (CDc) ≥II, severe morbidities of CDc ≥ IIIb, any pulmonary morbidities and chylorrhea, compared with those in patients without preoperative definitive chemoradiotherapy. Cox regression analysis suggested that R0 resection (hazard ratio [HR] 6.39; 95% confidence interval [CI] 2.03-9.68, P = 0.002), absence of severe complications (HR 4.97; 95% CI 1.70-14.81, P = 0.004) and early pStage (0-II) (HR 3.42; 95% CI 1.24-10.12, P = 0.018) were independent prognostic factors for salvage esophagectomy. CONCLUSIONS Salvage esophagectomy remains correlated with a high incidence of postoperative complications. Avoiding non-curative surgery and reducing the incidence of severe postoperative complications are important if patients are to receive prognostic benefit of this highly invasive surgery.
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22
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Yamaguchi S, Morita M, Yamamoto M, Egashira A, Kawano H, Kinjo N, Tsujita E, Minami K, Ikebe M, Ikeda Y, Kunitake N, Toh Y. Long-Term Outcome of Definitive Chemoradiotherapy and Induction Chemoradiotherapy Followed by Surgery for T4 Esophageal Cancer with Tracheobronchial Invasion. Ann Surg Oncol 2018; 25:3280-3287. [PMID: 30051363 DOI: 10.1245/s10434-018-6656-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Indexed: 11/18/2022]
Abstract
BACKGROUND T4 esophageal cancer (EC) that invades the trachea or bronchus often has poorer prognosis than other T4 ECs. We investigated the long-term results of definitive chemoradiotherapy (dCRT) or induction chemoradiotherapy followed by surgery (iCRT-S) in patients with T4 EC with tracheobronchial invasion (TBI). PATIENTS AND METHODS From 2003 to 2013, 71 patients with T4 EC with TBI were treated in our institution; 58 underwent dCRT, and 13 underwent iCRT-S. The long-term results associated with survival were retrospectively analyzed, and prognostic factors were examined by univariable and multivariable analysis. RESULTS The 1-, 2-, and 5-year overall survival for all patients with T4 EC with TBI treated by dCRT or iCRT-S was 57, 29, and 19%, respectively. Multivariable analysis revealed that clinical lymph node (LN) metastasis and the treatment period were significant prognostic factors. Clinical LN positivity had significantly poorer prognosis than LN negativity. The treatment outcome in the later period was significantly better than that in the earlier period. In particular, the outcome after dCRT revealed significantly better prognosis in the later compared with the earlier period, whereas the outcome after iCRT-S did not show such a difference. With respect to treatment modality, no significant difference in survival was observed between dCRT and iCRT-S. CONCLUSIONS Clinical LN negativity and later treatment period were significantly good prognostic factors for T4 EC with TBI. The recent improvements in dCRT outcomes may help to achieve survival comparable to that of iCRT-S.
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Affiliation(s)
- Shohei Yamaguchi
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan. .,Department of Surgery, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
| | - Masaru Morita
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Manabu Yamamoto
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Akinori Egashira
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Hiroyuki Kawano
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Nao Kinjo
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Eiji Tsujita
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Kazuhito Minami
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Masahiko Ikebe
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Yasuharu Ikeda
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Naonobu Kunitake
- Department of Radiology, National Kyushu Cancer Center, Fukuoka, Japan
| | - Yasushi Toh
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
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Sakaguchi M, Maebayashi T, Aizawa T, Ishibashi N, Saito T. Clinical results of multimodality therapy for esophageal cancer with distant metastasis. J Thorac Dis 2018; 10:1500-1510. [PMID: 29707300 DOI: 10.21037/jtd.2018.03.45] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Background The purpose of this study is to evaluate outcomes in upfront local response and survival of patients with esophageal cancer and distant metastasis. Methods This retrospective study included 34 patients (25 males) aged 42-92 years (median, 70 years) with a histological diagnosis of esophageal squamous cell cancer with distant metastasis. Staging was performed according to the UICC's TNM (6th edition) classification of malignant tumor. Results The median survival time (MST) was 5 months. The 1-year overall survival (OS) was 20.6%. Improved OS was associated with receipt of surgery [hazard ratio (HR), 3.857; 95% CI, 1.142-13.024; P=0.030] on both univariate and multivariate analyses, and the MST was 11 months. The overall objective local response rate was 82%. Ten patients had complete response (CR), 18 had partial response (PR). The overall symptom response was 88% patients. Six had CR, 24 had PR. There was no significant difference in the objective and symptom response between ≤50 and >50 Gy. Concurrent chemoradiotherapy (CCRT) with 50 Gy gave results of objective and symptom responses comparable to those of 60 Gy, which has been reported previously. Conclusions CCRT with 50 Gy gave results comparable to those of 60 Gy, which has been reported previously, and the toxicity was acceptable. Our findings showed that a multimodality therapy that includes surgery may improve survival in only a select group.
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Affiliation(s)
- Masakuni Sakaguchi
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Toshiya Maebayashi
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Takuya Aizawa
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Naoya Ishibashi
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
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24
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Park IH, Kim JY. Surveillance or resection after chemoradiation in esophageal cancer. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:82. [PMID: 29666805 DOI: 10.21037/atm.2017.12.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The treatment of locally advanced esophageal cancer continues to evolve. Previously, surgery was considered the foundation of treatment, but chemoradiation (CRT) has taken on a larger role both in the neoadjuvant setting and as definitive treatment. It has become clear that although some patients benefit from esophagectomy after CRT, a large subset of patients likely derive no benefit, and may be harmed by surgery. Some patients are cured from CRT alone and therefore do not need surgery. Another group of patients likely have metastatic disease at the time of local therapy that is just undetected on imaging and also do not benefit from surgery. A third group of patients will have persistent locoregional disease only after CRT. This last group is the subset who will actually benefit from surgery, but this likely comprises only a minority of patients with locally advanced disease. A strategy to maximize survival while minimizing unnecessary surgery is a reasonable goal, but present technology does not allow us to do this with certainty. Thus, the decision of whether to pursue resection or surveillance after CRT can be difficult as clinicians and patients try to balance the goal of maximizing the likelihood of cure against the risk of surgery and its impact on quality of life.
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Affiliation(s)
- Il-Hwan Park
- Department of Chest Surgery, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Jae Y Kim
- Division of Thoracic Surgery, City of Hope Cancer Center, Duarte, CA, USA
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25
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Makino T, Yamasaki M, Tanaka K, Tatsumi M, Takiguchi S, Hatazawa J, Mori M, Doki Y. Importance of positron emission tomography for assessing the response of primary and metastatic lesions to induction treatments in T4 esophageal cancer. Surgery 2017; 162:836-845. [PMID: 28711321 DOI: 10.1016/j.surg.2017.06.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 06/02/2017] [Accepted: 06/06/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND There is no consensus strategy for treatment of T4 esophageal cancer, and because of this, a better evaluation of treatment response is crucial to establish personalized therapies. This study aimed to establish a useful system for evaluating treatment response in T4 esophageal cancer. METHODS This study included 130 patients with cT4 esophageal cancer without distant metastasis who underwent 18F-fluorodeoxyglucose-positron emission tomography before and after a series of induction treatments comprising chemoradiation or chemotherapy. We evaluated the maximal standardized uptake value and treatment response. RESULTS The mean ± standard deviation of standardized uptake value in the primary tumor before and after induction treatments were 13.8 ± 4.4 and 5.4 ± 4.1, respectively, and the mean standardized uptake value decrease was 58.4%. The most significant difference in survival between positron emission tomography-primary tumor responders and nonresponders was at a decrease of 60% standardized uptake value, based on every 10% stepwise cutoff analysis (2-year cause-specific survival: 60.2 vs 23.5%; hazard ratio = 2.705; P < .0001). With this cutoff value, the resectability (P = .0307), pathologic response (P = .0004), and pT stage (P < .0001) were associated with positron emission tomography-primary tumor response. Univariate analysis of 2-year cause-specific survival indicated a correlation between cause-specific survival and clinical stages according to TNM classification, esophageal perforation, positron emission tomography-primary tumor response, lymph node status evaluated by positron emission tomography before and after induction treatments, and operative resection. Multivariate analysis further identified positron emission tomography-primary tumor response (hazard ratio = 2.354; P = .0107), lymph node status evaluated by positron emission tomography after induction treatments (hazard ratio = 1.966; P = .0089), and operative resection (hazard ratio = 2.012; P = .0245) as independent prognostic predictors. CONCLUSION Positron emission tomography evaluation of the response of primary and metastatic lesions to induction treatments is important to formulate treatment strategies for cT4 esophageal cancer.
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Affiliation(s)
- Tomoki Makino
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Mitsuaki Tatsumi
- Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Jun Hatazawa
- Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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26
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Klevebro F, Ekman S, Nilsson M. Current trends in multimodality treatment of esophageal and gastroesophageal junction cancer - Review article. Surg Oncol 2017; 26:290-295. [PMID: 28807249 DOI: 10.1016/j.suronc.2017.06.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 05/25/2017] [Accepted: 06/09/2017] [Indexed: 12/21/2022]
Abstract
PURPOSE Multimodality treatment has now been widely introduced in the curatively intended treatment of esophageal and gastroesophageal junction cancer. We aim to give an overview of the scientific evidence for the available treatment strategies and to describe which trends that are currently developing. METHODS We conducted a review of the scientific evidence for the different curatively intended treatment strategies that are available today. Relevant articles of randomized controlled trials, cohort studies, and meta analyses were included. RESULTS After a systematic search of relevant papers we have included 64 articles in the review. The results show that adenocarcinomas and squamous cell carcinomas of the esophagus and gastroesophageal junction are two separate entities and should be analysed and studied as two different diseases. Neoadjuvant treatment followed by surgical resection is the gold standard of the curatively intended treatment today. There is no scientific evidence to support the use of chemoradiotherapy over chemotherapy in the neoadjuvant setting for esophageal or junctional adenocarcinoma. There is reasonable evidence to support definitive chemoradiotherapy as a treatment option for squamous cell carcinoma of the esophagus. CONCLUSION The evidence base for curatively intended treatments of esophageal and gastroesophageal junction cancer is not very strong. Several on-going trials have the potential to change the gold standard treatments of today.
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Affiliation(s)
- Fredrik Klevebro
- Division of Surgery, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet and Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
| | - Simon Ekman
- Department of Oncology and Pathology, Karolinska Institutet and Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Magnus Nilsson
- Division of Surgery, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet and Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
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27
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Ueda H, Takeda M, Ueda S, Kawakami H, Okuno T, Takegawa N, Hayashi H, Tsurutani J, Tamura T, Ishikawa K, Nishimura Y, Nakagawa K. Clinical evaluation of palliative chemoradiotherapy for metastatic esophageal cancer. Oncotarget 2017; 8:80286-80294. [PMID: 29113302 PMCID: PMC5655197 DOI: 10.18632/oncotarget.17925] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 05/03/2017] [Indexed: 11/25/2022] Open
Abstract
Platinum-based chemotherapy is considered a standard treatment option for patients with metastatic esophageal carcinoma. However, the overall survival of patients receiving such treatment is <1 year. A common presenting symptom of esophageal cancer is dysphagia, which has a substantial impact on quality of life. We have now retrospectively evaluated the efficacy and safety of palliative chemoradiotherapy for patients with stage IV esophageal cancer, most of whom are unfit for curative chemoradiotherapy. Fifty consecutive patients diagnosed with stage IV esophageal cancer were treated with concurrent chemoradiotherapy at Kindai University Hospital between April 2008 and December 2014. Most (90%) patients received a total radiation dose of at least 50 Gy, and the median number of treatment cycles per patient was four for the combination of 5-fluorouracil and cisplatin. The response of the primary tumor and the overall response were 80% and 44%, respectively. The dysphagia score was improved after chemoradiotherapy in 36 (72%) patients and did not change between before and after treatment in 14 (28%) patients. With a median follow-up time of 9.4 months from the start of chemoradiotherapy, the median progression-free survival and overall survival were 4.7 and 12.3 months, respectively. Three patients (T4b in two, T3 in one) developed esophagobronchial fistula after completion of chemoradiotherapy (n = 2) or after disease progression (n = 1), resulting in death in each case. Our results suggest that palliative chemoradioiotherapy was safe and contributed the improvement of dysphagia in patients with stage IV esophageal cancer.
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Affiliation(s)
- Hiroto Ueda
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Masayuki Takeda
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Shinya Ueda
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Tatsuya Okuno
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Naoki Takegawa
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Hidetoshi Hayashi
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Junji Tsurutani
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Takao Tamura
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Kazuki Ishikawa
- Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Yasumasa Nishimura
- Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Kazuhiko Nakagawa
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
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Sun X, Han S, Gu F, Lin G, Wang Z, Wang Y, Xu Y. A Retrospective Comparison of Taxane and Fluorouracil-based Chemoradiotherapy in Patients with Inoperable Esophageal Squamous Cell Carcinoma. J Cancer 2016; 7:1066-73. [PMID: 27326249 PMCID: PMC4911873 DOI: 10.7150/jca.13547] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 03/15/2016] [Indexed: 01/29/2023] Open
Abstract
Purpose: To retrospectively compare taxane-based with fluorouracil-based chemoradiotherapy in terms of toxicity profiles, efficacy and survival in patients with inoperable esophageal cancer. Methods and Materials: We analyzed retrospectively 179 consecutive patients who were unresectable or medically unfit for surgery between March 2009 and November 2014. Eight-three patients were included in the taxane group and 96 cases were in the fluorouracil group. Results: The overall response rate (ORR) in the taxane group was higher than fluorouracil group, but was not significantly different (71.6% vs. 63.5%, respectively, P=0.255). In total, 53.0% (44/83) of the patients in the taxane group had progressive disease versus 54.2% (52/96) in the fluorouracil group (not significantly different (P=0.758)). There was no significant difference in overall response rate, progression free survival and overall survival, as well as treatment-related death. In terms of non-hematological toxicity, patients in the taxane group experienced a lower incidence of ≥ grade 3 esophageal perforation or fistula (4.8% vs. 13.5%, P=0.047) and pneumonia (4.8% vs. 9.7%, P=0.242). Regarding hematological toxicity, thrombocytopenia in the taxane group was significantly lower (4.8% vs. 13.5%, P=0.047), but there was a trend towards a higher rate of ≥ grade 3 leukopenia (34.9% vs.26.0%, P=0.196). Conclusions: Chemoradiation with taxane-based regimens is well tolerated, with potentially promising efficacy, and could become a good alternative treatment in a first line setting for patients with inoperable esophageal squamous cell carcinoma.
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Affiliation(s)
- Xiaojiang Sun
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China
| | - Shuiyun Han
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China
| | - Feiying Gu
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China
| | - Gang Lin
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China
| | - Zhun Wang
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China
| | - Yuezhen Wang
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China
| | - Yaping Xu
- 1. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou China;; 2. Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China
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29
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Li M, Zhao F, Zhang X, Shi F, Zhu H, Han A, Zhang Y, Kong L, Yu J. Involved-field irradiation in definitive chemoradiotherapy for T4 squamous cell carcinoma of the esophagus. ACTA ACUST UNITED AC 2016; 23:e131-7. [PMID: 27122981 DOI: 10.3747/co.23.2846] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Definitive concurrent chemoradiotherapy (ccrt) is currently a therapeutic option for locally advanced esophageal cancer. However, clinical practice differs with respect to the target volume for irradiation. The purpose of the present study was to analyze failure patterns and survival, and to determine the feasibility of using involved-field irradiation (ifi) with concurrent chemotherapy for T4 squamous cell carcinoma (scc) of the esophagus. METHODS Between January 2003 and January 2013, 56 patients with clinical T4M0 scc of the esophagus received ccrt using ifi. The radiation field included the primary tumour and clinically involved lymph nodes. Target volumes and sites of failure were analyzed, as were treatment-related toxicity and survival time. RESULTS In this 56-patient cohort, 13 patients (23.2%) achieved a complete response, and 21 (37.5%) achieved a partial response, for a total response rate of 60.7%. The major toxicities experienced were leucocytopenia and esophagitis, with 14 patients (25.0%) experiencing grade 3 toxicities. At a median follow-up of 34 months, 48 patients (85.7%) had experienced failure: 39 (69.6%) in-field, 7 (12.5%) elective nodal, and 19 (33.9%) distant. Only 1 patient (1.8%) experienced isolated elective nodal failure. The 1-, 2-, and 3-year survival rates were 39.3%, 21.4%, and 12.5% respectively. CONCLUSIONS For patients with T4M0 scc of the esophagus, definitive ccrt using ifi resulted in an acceptable rate of isolated elective nodal failure and an overall survival comparable to that achieved with elective nodal irradiation. A limited radiation therapy target volume, including only clinically involved lesions, would therefore be a feasible choice for this patient subgroup.
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Affiliation(s)
- M Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - F Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - X Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - F Shi
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - H Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - A Han
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - Y Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - L Kong
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
| | - J Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R.C
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30
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Li M, Zhang X, Zhao F, Luo Y, Kong L, Yu J. Involved-field radiotherapy for esophageal squamous cell carcinoma: theory and practice. Radiat Oncol 2016; 11:18. [PMID: 26846932 PMCID: PMC4743321 DOI: 10.1186/s13014-016-0589-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2015] [Accepted: 01/14/2016] [Indexed: 12/14/2022] Open
Abstract
Esophageal carcinoma (EC) is characterized by a high rate of lymph node metastasis and its spread pattern is not always predictable. Chemoradiotherapy has an important role in the treatment of EC in both the inoperable and the pre-operative settings. However, regarding the target volume for radiation, different clinical practices exist. Theoretically, in addition to the clinical target volume administered to the gross lesion, it might seem logical to deliver a certain dose to the uninvolved regional lymph node area at risk for microscopic disease. However, in practice, it is difficult because of the intolerance of normal tissue to radiotherapy (RT), particularly if all regions containing the cervical, mediastinal, and upper abdominal nodes are covered. To date, the use of elective nodal irradiation (ENI) is still controversial in the field of radiotherapy. Some investigators use involved-field radiotherapy (IFRT) in order to reduce treatment-related toxicities. It is thought that micrometastases can be controlled, to some extent, by chemotherapy and the abscopal effects of radiation. It is the presence of overtly involved lymph nodes rather than the micrometastatic nodes negatively affects survival in patients with EC. In another hand, lymph nodes stationed near primary tumors also receive considerable incidental irradiation doses that may contribute to the elimination of subclinical lesions. These data indicate that an irradiation volume covering only the gross tumor is appropriate. When using ENI or IFRT, very few patients experience solitary regional node failure and out-of-field lymph node failure is not common. Primary tumor recurrence and distant metastases, rather than regional lymph node failure, affect the overall survival in patients with EC. The available evidence indicates that the use of ENI seems to prevent or delay regional nodal relapse rather than improve survival. In a word, these data suggest that IFRT is feasible in EC patients.
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Affiliation(s)
- Minghuan Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong Province, 250117, China.
| | - Xiaoli Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong Province, 250117, China. .,Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
| | - Fen Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong Province, 250117, China.
| | - Yijun Luo
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong Province, 250117, China.
| | - Li Kong
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong Province, 250117, China.
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong Province, 250117, China.
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31
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Miyanaga S, Ninomiya I, Tsukada T, Okamoto K, Harada S, Nakanuma S, Sakai S, Makino I, Kinoshita J, Hayashi H, Nakamura K, Oyama K, Nakagawara H, Miyashita T, Tajima H, Takamura H, Fushida S, Ohta T. Concentration-dependent radiosensitizing effect of docetaxel in esophageal squamous cell carcinoma cells. Int J Oncol 2015; 48:517-24. [PMID: 26676807 DOI: 10.3892/ijo.2015.3291] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 11/13/2015] [Indexed: 11/05/2022] Open
Abstract
Taxanes, paclitaxel and docetaxel (DTX) are anticancer agents that exhibit cytotoxicity by inhibiting microtubule polymerization. They enhance the radiosensitivity of various cancers by blocking the cell cycle in the most radiosensitive G2/M phase. Recently, taxanes have been reported to have different mechanisms of action depending on dose intensity. However, the mechanism of the radio-enhancing effect of DTX in relation to the drug dose intensity is not clearly understood. In the present study, we experimentally investigated the radio-enhancing effects of various concentrations of DTX against esophageal squamous cell cancer (ESCC); KES cells were used for in vitro confirmation of the effective administration schedule for DTX in chemoradiotherapy involving ESCC. DTX enhanced radiation cell killing in a concentration-dependent manner in KES cells. High cytotoxic concentrations (>10 nM) of DTX strongly enhanced radiosensitivity. Low concentrations (<1 nM) of DTX that did not have a cytotoxic effect showed a radio-enhancing effect by inducing DNA double strand breaks and apoptosis after irradiation. Low and high concentrations of DTX induced radiosensitive G0/G1 and G2/M phase arrest, respectively in KES cells. Cells treated with high concentrations of DTX exhibited nuclear aggregation associated with apoptotic change. In contrast, cells treated with low concentrations of DTX displayed multi-nucleation or unequal division. In conclusion, enhancement of the radiosensitivity of ESCC cells by DTX was demonstrated, even using nanomolar concentrations that did not have a cytotoxic effect. DTX has different radio-enhancing mechanisms depending on its concentration. Therefore, weekly administration of DTX might effectively enhance radiation cytotoxicity in the treatment of ESCC.
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Affiliation(s)
- Shohei Miyanaga
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Itasu Ninomiya
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Tomoya Tsukada
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Koichi Okamoto
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Shinichi Harada
- Center for Biomedical Research and Education, School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Shinichi Nakanuma
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Seisho Sakai
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Isamu Makino
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Jun Kinoshita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hironori Hayashi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Keishi Nakamura
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Katsunobu Oyama
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hisatoshi Nakagawara
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Tomoharu Miyashita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hidehiro Tajima
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hiroyuki Takamura
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Tetsuo Ohta
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
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Qu X, Biagi J, Banashkevich A, Mercer C, Tremblay L, Mahmud A. Management and outcomes of localized esophageal and gastroesophageal junction cancer in older patients. Curr Oncol 2015; 22:e435-42. [PMID: 26715880 PMCID: PMC4687668 DOI: 10.3747/co.22.2661] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Older patients are commonly excluded from clinical trials in esophageal and gastroesophageal junction (gej) cancer. High-level evidence to guide management in this group is lacking. In the present study, we compared outcomes and described tolerance for curative- and noncurative-intent treatments among patients 70 years of age and older. METHODS We retrospectively reviewed all patients 70 years of age and older diagnosed with localized esophageal and gej cancer at our centre between 2005 and 2012. RESULTS The 74 patients identified had a median age of 77 years. Of those patients, 62% received curative-intent treatment, consisting mostly of concomitant chemoradiation therapy (n = 43, 93%). Median overall survival for patients receiving curative-intent treatment was 18.6 months [95% confidence interval (ci): 13.0 to 28.0 months], with 23% being long-term survivors (95% ci: 11.3% to 36.7%). In contrast, patients receiving noncurative-intent treatment had a median overall survival of 8.8 months (95% ci: 6.7 to 11.9 months), with none being long-term survivors (p < 0.0001). Improvement of dysphagia was seen after curative (81%) or palliative radiotherapy (78%) in symptomatic patients, and toxicities were manageable. The odds of not receiving curative treatment was higher by a factor of 8.5 among patients 80 years of age or older compared with those 70-79 years of age (95% ci: 2.5 to 28.7). CONCLUSIONS In managing older patients with esophageal and gej cancer, curative-intent treatment (compared with noncurative-intent treatment) leads to a significant survival benefit with a reasonable toxicity profile. Informed counselling of patients and their families about a curative treatment approach and efforts to increase awareness among oncology care providers are suggested.
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Affiliation(s)
- X. Qu
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - J. Biagi
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - A. Banashkevich
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - C.D. Mercer
- Department of Surgery, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - L. Tremblay
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
| | - A. Mahmud
- Department of Oncology, Queen’s University, Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON
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Jingu K, Umezawa R, Matsushita H, Sugawara T, Kubozono M, Yamamoto T, Ishikawa Y, Kozumi M, Takahashi N, Katagiri Y, Kadoya N, Takeda K. Chemoradiotherapy for T4 and/or M1 lymph node esophageal cancer: experience since 2000 at a high-volume center in Japan. Int J Clin Oncol 2015; 21:276-282. [PMID: 26324841 DOI: 10.1007/s10147-015-0896-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 08/13/2015] [Indexed: 11/29/2022]
Abstract
PURPOSE To review data for patients with stage T4 and/or M1 lymph node (lym) esophageal cancer who have been treated with definitive chemoradiotherapy since 2000 at a high-volume center in Japan. PATIENTS AND METHODS We retrospectively reviewed all patients with T4 and/or M1 lym esophageal cancer who were treated by definitive chemoradiotherapy between 2000 and 2010. The eligibility criteria included (1) histopathologically proven esophageal cancer, (2) T4 and/or M1 lym (UICC 2002), (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with ≥ 50 Gy, and (6) having no other active malignant tumor during treatment. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0). RESULTS Data from 128 patients (70 with clinical stage III, 58 with clinical stage IV) were used for analysis in this study. The median observation period for survivors was 46.3 months. The 2- and 4-year overall survival rates were 32.8 and 24.4 %, respectively. The overall survival of patients without M1 lym was significantly better than that of patients with Ml lym (4-year, 32.6 vs 11.7 %, log-rank test; p = 0.04). Overall survival in more recent patients (2006-2010) did not show improvement when compared with past patients (2000-2005). Eight patients had late toxicities of grade ≥3. CONCLUSIONS T4 patients without M1 lym showed a relatively good 4-year survival rate of approximately 33 %; however, the results did not show significant improvement after 2000.
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Affiliation(s)
- Keiichi Jingu
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan.
| | - Rei Umezawa
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Haruo Matsushita
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Toshiyuki Sugawara
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Masaki Kubozono
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Takaya Yamamoto
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Youjirou Ishikawa
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Maiko Kozumi
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Noriyoshi Takahashi
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Yu Katagiri
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Noriyuki Kadoya
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
| | - Ken Takeda
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan
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Makita N, Ninomiya I, Tsukada T, Okamoto K, Harada S, Nakanuma S, Sakai S, Makino I, Kinoshita J, Hayashi H, Oyama K, Nakagawara H, Miyashita T, Tajima H, Takamura H, Fushida S, Ohta T. Inhibitory effects of valproic acid in DNA double-strand break repair after irradiation in esophageal squamous carcinoma cells. Oncol Rep 2015; 34:1185-92. [PMID: 26135807 DOI: 10.3892/or.2015.4089] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 06/15/2015] [Indexed: 12/24/2022] Open
Abstract
Radiation therapy is one of the most promising therapeutic strategies in unresectable esophageal squamous cell carcinoma (ESCC). The histone deacetylase (HDAC) inhibitor has been shown to enhance radiosensitivity. Valproic acid (VPA) is a well-known drug used to treat seizure disorders and epilepsy, and has been shown to inhibit HDACs. We recently reported that a clinically safe dose of VPA enhances radiation‑induced cytotoxicity in human ESCC cells. However, the mechanism of radiosensitizing effect of VPA has not yet been confirmed. The present study examined the effect of VPA on DNA double-strand break (DSB) repair after radiation in the human ESCC cell lines KES, TE9 and TE11 by examining H2AX phosphorylation (γH2AX) levels as a marker of radiation‑induced DSBs. The present study also examined whether VPA inhibited radiation-induced DNA DSB repair by suppressing non-homologous end joining (NHEJ), focusing particularly on the acetylation of Ku70. VPA was shown to prolong γH2AX levels after irradiation in all three ESCC cell lines. Moreover, prolonged γH2AX foci formation after irradiation was also observed by immunocytochemistry following VPA pretreatment in KES and TE9 cells. VPA was shown to induce Ku70 acetylation after irradiation in all three ESCC cell lines. Our results suggest that VPA prolonged radiation‑induced DSBs by inhibiting NHEJ in DSB repair pathways in ESCC. VPA could therefore be used as an effective radiosensitizer in ESCC radiotherapy.
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Affiliation(s)
- Naoki Makita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Itasu Ninomiya
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Tomoya Tsukada
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Koichi Okamoto
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Shinichi Harada
- Center for Biomedical Research and Education, School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Shinichi Nakanuma
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Seisho Sakai
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Isamu Makino
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Jun Kinoshita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hironori Hayashi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Katsunobu Oyama
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hisatoshi Nakagawara
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Tomoharu Miyashita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hidehiro Tajima
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Hiroyuki Takamura
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
| | - Tetsuo Ohta
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8641, Japan
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Shinoda M, Ando N, Kato K, Ishikura S, Kato H, Tsubosa Y, Minashi K, Okabe H, Kimura Y, Kawano T, Kosugi SI, Toh Y, Nakamura K, Fukuda H. Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303). Cancer Sci 2015; 106:407-12. [PMID: 25640628 PMCID: PMC4409884 DOI: 10.1111/cas.12622] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2014] [Revised: 01/20/2015] [Accepted: 01/24/2015] [Indexed: 01/11/2023] Open
Abstract
Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.
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Affiliation(s)
- Masayuki Shinoda
- Department of Thoracic Surgery, Aichi Cancer Center, Nagoya, Japan
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Saeki H, Nakashima Y, Zaitsu Y, Tsuda Y, Kasagi Y, Ando K, Imamura Y, Ohgaki K, Ito S, Kimura Y, Egashira A, Oki E, Morita M, Maehara Y. Current status of and perspectives regarding neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. Surg Today 2015; 46:261-7. [PMID: 25740123 DOI: 10.1007/s00595-015-1144-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 02/15/2015] [Indexed: 12/15/2022]
Abstract
The significance of neoadjuvant chemoradiotherapy (NACRT) for esophageal squamous cell carcinoma (ESCC) remains controversial with regard to the pathological response and long-term survival. We herein review the current status of and future perspectives regarding NACRT followed by esophagectomy for locally advanced ESCC. Some studies have suggested that a pathological complete response with NACRT is more common in patients with ESCC than in those with adenocarcinoma and that NACRT provided a survival benefit limited to patients with ESCC. However, NACRT may increase the risk of postoperative complications after esophagectomy. It is obvious that a favorable pathological response is the most important factor for obtaining a survival benefit, although no established parameters have been implemented clinically to predict the response to NACRT. Prospective clinical studies and basic research studies to identify predictive biomarkers for the response to NACRT are needed to aid in the development of NACRT treatment strategies for patients with ESCC.
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Affiliation(s)
- Hiroshi Saeki
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Yuichiro Nakashima
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoko Zaitsu
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yasuo Tsuda
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuta Kasagi
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Koji Ando
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yu Imamura
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kippei Ohgaki
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Shuhei Ito
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yasue Kimura
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Akinori Egashira
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Eiji Oki
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Masaru Morita
- Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, Japan
| | - Yoshihiko Maehara
- Deptartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Zhang P, Xi M, Zhao L, Li QQ, He LR, Liu SL, Shen JX, Liu MZ. Efficacy and prognostic analysis of chemoradiotherapy in patients with thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis alone. Radiat Oncol 2014; 9:256. [PMID: 25424871 PMCID: PMC4251839 DOI: 10.1186/s13014-014-0256-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Accepted: 11/06/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. METHODS From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50-68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). RESULTS The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. CONCLUSIONS Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival.
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Affiliation(s)
- Peng Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Mian Xi
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Lei Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Qiao-Qiao Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Li-Ru He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Shi-Liang Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Jing-Xian Shen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Imaging Diagnosis and Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
| | - Meng-Zhong Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
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Shimoji H, Karimata H, Nagahama M, Nishimaki T. Induction chemotherapy or chemoradiotherapy followed by radical esophagectomy for T4 esophageal cancer: results of a prospective cohort study. World J Surg 2014; 37:2180-8. [PMID: 23649529 DOI: 10.1007/s00268-013-2074-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND We hypothesized that the survival rate of patients undergoing R0 esophagectomy after induction chemotherapy or chemoradiotherapy for unresectable T4 esophageal cancer (URT4) would be similar to that of patients undergoing esophagectomy for immediately resectable esophageal cancer with no unfavorable prognostic factors (RNU). METHODS Between April 2002 and June 2012, 87 of 283 patients with esophageal cancer who presented at the University Hospital of the Ryukyus were enrolled in this prospective cohort study. Tumors were classified as RNU and URT4 in 44 and 43 of the 87 patients, respectively. Outcomes of treatment for URT4 patients were compared with those of RNU patients. RESULTS The R0 resection rate (61 %) and in-hospital mortality rate (20 %) of URT4 patients were significantly poorer than those of RNU patients (98 and 2.3 %, respectively), although the morbidity rate was similar in the two groups (63 and 52 %, respectively). The 5-year survival rate (35 %) of URT4 patients was significantly poorer than that of RNU patients (67 %) in the intention-to-treat analysis. However, no significant difference was noted between the two survival curves for cases of R0 resection (5-year survival rate, 60 % vs. 69 %). Multivariate analysis revealed R status as the only significant independent prognostic factor for URT4 patients (P < 0.001; hazard ratio = 8.279). CONCLUSIONS Satisfactory survival rates can be achieved if R0 resection is performed after induction treatment in patients with T4 esophageal cancer, although secondary radical esophagectomy is associated with a higher risk of in-hospital mortality.
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Affiliation(s)
- Hideaki Shimoji
- Department of Digestive and General Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
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Karran A, Blake P, Chan D, Reid TD, Davies IL, Kelly M, Roberts SA, Crosby T, Lewis WG. Propensity score analysis of oesophageal cancer treatment with surgery or definitive chemoradiotherapy. Br J Surg 2014; 101:502-10. [PMID: 24615406 DOI: 10.1002/bjs.9437] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2013] [Indexed: 11/08/2022]
Abstract
BACKGROUND The role of treatments involving surgery versus definitive chemoradiotherapy (dCRT) for oesophageal cancer remains controversial. METHODS Consecutive patients with oesophageal cancer were studied. Those whose treatment involved surgery alone or who received neoadjuvant chemotherapy or chemoradiotherapy were compared with those receiving dCRT. Multiple regression models, including propensity scores, were developed to assess confounding factors associated with undergoing surgery or dCRT, and the risk-adjusted association between treatment and survival. RESULTS From a total of 727 patients, regression adjustment to control for bias created a cohort of 521 patients available for comparison (277 in the surgery group and 244 in the dCRT group). Local and distant recurrence rates were 10·1 and 22·0 per cent respectively after surgery, compared with 26·2 and 11·9 per cent following dCRT (P < 0·001). Median survival, and 2- and 5-year survival rates after surgery were 27 months, 53·8 and 31·0 per cent respectively, compared with 28 months, 54·2 and 31·9 per cent after dCRT (P = 0·918). On multivariable analysis, disease-free survival was related to endosonographic tumour category (hazard ratio (HR) 0·76, 95 per cent confidence interval 0·10 to 6·04 for T1; HR 1·57, 0·21 to 11·58 for T2; HR 2·12, 0·29 to 15·49 for T3; HR 3·07, 0·41 to 23·16 for T4; P = 0·003, in relation to T0 as reference), lymph node metastasis count (HR 1·10, 1·04 to 1·15; P < 0·001) and total disease length (HR 0·96, 0·93 to 1·00; P = 0·041). CONCLUSION There was no difference in survival after oesophageal cancer treatment involving surgery or dCRT.
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Affiliation(s)
- A Karran
- South East Wales Cancer Network, Department of Surgery, University Hospital of Wales, Cardiff, UK
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40
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Minegaki T, Kuwahara A, Yamamori M, Nakamura T, Okuno T, Miki I, Omatsu H, Tamura T, Hirai M, Azuma T, Sakaeda T, Nishiguchi K. Genetic polymorphisms in SLC23A2 as predictive biomarkers of severe acute toxicities after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. Int J Med Sci 2014; 11:321-6. [PMID: 24578608 PMCID: PMC3936025 DOI: 10.7150/ijms.7654] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 01/22/2014] [Indexed: 01/18/2023] Open
Abstract
OBJECTIVE Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed. METHODS A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated. RESULTS The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively. CONCLUSIONS Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.
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Affiliation(s)
- Tetsuya Minegaki
- 1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
| | - Akiko Kuwahara
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ; 3. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan
| | - Motohiro Yamamori
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ; 3. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan
| | - Tsutomu Nakamura
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Tatsuya Okuno
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Ikuya Miki
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Hideaki Omatsu
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Takao Tamura
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ; 4. Department of Medical Oncology, Nara Hospital, Kinki University Faculty of Medicine, Nara 630-0293, Japan
| | - Midori Hirai
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Takeshi Azuma
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Toshiyuki Sakaeda
- 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ; 5. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
| | - Kohshi Nishiguchi
- 1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. ; 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
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Hihara J, Hamai Y, Emi M, Aoki Y, Taomoto J, Miyata Y, Okada M. Esophageal bypass operation prior to definitive chemoradiotherapy in advanced esophageal cancer with tracheobronchial invasion. Ann Thorac Surg 2013; 97:290-5. [PMID: 24200399 DOI: 10.1016/j.athoracsur.2013.08.060] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 08/09/2013] [Accepted: 08/27/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND In T4 esophageal cancer with tracheobronchial invasion, an esophagorespiratory fistula (ERF) often occurs during or after chemoradiotherapy. We have performed esophageal bypass operations prior to definitive chemoradiotherapy for these patients to increase the chemoradiotherapy completion rate by minimizing the potential effect of an ERF. The aim of this study was to examine the clinical outcome of esophageal bypass surgery prior to chemoradiotherapy. METHODS Between 1997 and 2010, 17 patients underwent esophageal bypass surgery followed by definitive chemoradiotherapy for esophageal cancer with tracheobronchial invasion (bypass group). Ten patients in the same circumstances were treated with chemoradiotherapy alone (control group). Overall survival, the clinical effect of chemoradiotherapy, the ERF incidence rate, and the safety of esophageal bypass surgery were assessed. RESULTS The overall response rate to chemoradiotherapy was 64.7% in the bypass group and 90.0% in the control group. Except for 2 patients with ERF at initial diagnosis, 4 (26.7%) of the 15 patients developed ERF in the bypass group, and 3 (30.0%) of the 10 patients developed ERF in the control group during or after chemoradiotherapy. The 2-year and 3-year overall survival rates were 17.6% and 17.6% in the bypass group and 20.0% and 0% in the control group, respectively (p = 0.924); long-term survival of more than 3 years was seen only in the bypass group. CONCLUSIONS Esophageal bypass surgery prior to definitive chemoradiotherapy could be performed safely, and this strategy contributed to long-term survival in the patients who achieved a good response to chemoradiotherapy but developed an ERF.
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Affiliation(s)
- Jun Hihara
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
| | - Yoichi Hamai
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Manabu Emi
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yoshiro Aoki
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Junya Taomoto
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yoshihiro Miyata
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
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Saeki H, Morita M, Tsuda Y, Hidaka G, Kasagi Y, Kawano H, Otsu H, Ando K, Kimura Y, Oki E, Kusumoto T, Maehara Y. Multimodal Treatment Strategy for Clinical T3 Thoracic Esophageal Cancer. Ann Surg Oncol 2013; 20:4267-73. [DOI: 10.1245/s10434-013-3192-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2013] [Indexed: 01/04/2023]
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Laquière A, Grandval P, Heresbach D, Prat F, Arpurt JP, Bichard P, D'Halluin PN, Berthillier J, Boustière C, Laugier R. Self-expanding plastic stent removed after radiochemotherapy for advanced esophageal cancer. Dis Esophagus 2013; 27:176-81. [PMID: 23651038 DOI: 10.1111/dote.12078] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Endoscopic evaluation after chemoradiotherapy (CR) is impossible with an esophageal stent in place. The main study objective was to evaluate self-expanding plastic stent (SEPS) removal post-CR. Secondary end-points were the improvement of dysphagia and patients' quality of life. From October 2008 to March 2011, 20 dysphagic patients who suffered from advanced esophageal cancer were enrolled in a multicenter, prospective study. SEPS was inserted prior to CR and then removed endoscopically. SEPS efficiency (dysphagia score) and tolerance, as well as the patients' quality of life (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire validated for the esophagus), were monitored. Continuous variables were compared using a paired t-test analysis for matched data. A P-value of less than 0.05 was considered statistically significant. Twenty patients (15 men and 5 women), aged 61.5 years (±9.88) (range 43-82 years), with adenocarcinoma (n = 12) and squamous cell carcinoma (n = 8), were enrolled. SEPS were successfully inserted in all patients (100%). There was one perforation and three episodes of migration. All of these complications were medically treated. The mean dysphagia score at the time of stent placement was 2.79 (0.6). Mean dysphagia scores obtained on day 1 and day 30 post-SEPS placement were 0.7 (0.9) (P < 0.0001) and 0.45 (0.8) (P < 0.0001), respectively. Quality of Life Questionnaire validated for the esophagus score showed an improvement in dysphagia (P = 0.01) and quality of oral feeding (P = 0.003). All SEPS were removed endoscopically without complications. In two patients, the stent was left in place due to metastatic disease. SEPS are extractable after CR of esophageal cancer. Early stenting by SEPS prior to and during CR may reduce dysphagia and improve quality of oral alimentation.
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Affiliation(s)
- A Laquière
- Department of Gastroenterology, Saint Joseph Hospital, Marseille, France
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Pimiento JM, Weber J, Hoffe SE, Shridhar R, Almhanna K, Vignesh S, Karl RC, Meredith KL. Outcomes associated with surgery for T4 esophageal cancer. Ann Surg Oncol 2013; 20:2706-12. [PMID: 23504118 DOI: 10.1245/s10434-013-2885-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND T4 esophageal cancer often portends a dismal prognosis even after surgical resection. Historical incomplete resections and poor survival rates often make surgery palliative rather than curative. METHODS Using a comprehensive esophageal cancer database, we identified patients who underwent an esophagectomy for T4 tumors between 1994 and 2011. Neoadjuvant treatment (NT) and pathologic response variables were recorded, and response was denoted as complete response (pCR), partial response (pPR), and nonresponse (NR). Clinical and pathologic data were compared. Survival was calculated using Kaplan-Meier curves with log-rank tests for significance. RESULTS We identified 45 patients with T4 tumors all who underwent NT. The median age was 60 years (range, 31-79 years) with a median follow-up of 27 months (range, 0-122 months). There were 19 pCR (42 %), 22 pPR (49 %), and 4 NR (9 %). R0 resections were accomplished in 43 (96 %). There were 18 recurrences (40 %) with a median time to recurrence of 13.5 months (2.2-71 months). In this group pCR represented 7 (38.9 %), whereas pPR and NR represented 10 (55.5 %), and 1 (5.5 %) respectively. The overall and disease-free survival for all patients with T4 tumors were 35 and 36 %, respectively. Patients achieving a pCR had a 5 year overall and disease-free survival of 53 and 54 %, compared with pPR 23 and 28 %, while there were no 5 year survivors in the NR cohort. CONCLUSION We have demonstrated that neoadjuvant therapy and downstaging of T4 tumors leads to increased R0 resections and improvements in overall and disease-free survival.
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Affiliation(s)
- Jose M Pimiento
- Program of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
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Omatsu H, Kuwahara A, Yamamori M, Fujita M, Okuno T, Miki I, Tamura T, Nishiguchi K, Okamura N, Nakamura T, Azuma T, Hirano T, Ozawa K, Hirai M. TNF-α -857C>T genotype is predictive of clinical response after treatment with definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. Int J Med Sci 2013; 10:1755-60. [PMID: 24151445 PMCID: PMC3804799 DOI: 10.7150/ijms.6749] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 10/06/2013] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Genotypes of tumor necrosis factor alpha (TNF-α) and its surface receptors, TNFRSF1A and TNFRSF1B, have been examined in terms of the progression, metastasis, clinical efficacy, and prognosis of various cancers; however, little is known about their effects on clinical outcome in patients with esophageal squamous cell carcinoma (ESCC). In this study, TNF-α and TNFRSF1A genotypes were retrospectively evaluated in terms of predicting clinical response, long-term survival, and severe acute toxicities in 46 male Japanese ESCC patients treated with definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT). METHODS A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course being repeated after a 2-week interval. The TNF-α -1031T>C (rs1799964), -863C>A (rs1800630), -857C>T (rs1799724), -308G>A (rs1800629), -238G>A (rs361525), TNFRSF1A -609G>T (rs4149570), and 36A>G (rs767455) genotypes were evaluated. RESULTS The TNF-α -857C>T genotype was found to be predictive of clinical response, i.e., complete response or not (P = 0.010, Fisher's exact test), but had no effect on long-term survival (CC(-857) vs. CT(-857) + TT(-857), P = 0.072, Fisher's exact test, P = 0.070, Log-rank test). CONCLUSIONS The TNF-α -857C>T genotype was found to be predictive of clinical response and was more likely to predict long-term survival in Japanese ESCC patients receiving definitive 5-FU/CDDP-based CRT. Further clinical investigations with a larger number of patients or experiments in vitro should be performed to assess the predictive value of this genotype following CRT.
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Affiliation(s)
- Hideaki Omatsu
- 1. Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe 650-0017, Japan; ; 2. Department of Pharmacotherapy, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Zhong Z, Gu X, Zhang Z, Wang D, Qing Y, Li M, Dai N. Recombinant human endostatin combined with definitive chemoradiotherapy as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma of the oesophagus. Br J Radiol 2012; 85:e1104-9. [PMID: 22898155 PMCID: PMC3500809 DOI: 10.1259/bjr/15321801] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Revised: 10/07/2011] [Accepted: 10/31/2011] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE The objective of this study was to review the outcomes of recombinant human endostatin combined with chemoradiotherapy (CRT) as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma (SCC) of the oesophagus. METHODS A total of 38 patients with unresectable but without systemic metastatic SCC of the oesophagus (T(4) or stage IVA) were retrospectively studied. 18 patients were treated with recombinant human endostatin combined with 5-fluorouracil (5-FU)/cisplatin (CDDP)-based CRT and 20 were treated with 5-FU/CDDP-based CRT alone. Short- and long-term effects including initial treatment response, survival and treatment-related complications were assessed with a median follow-up period of 36.1 months. RESULTS CRT combined with endostatin resulted in a marked improvement in complete response rates (44.4% vs 30% in the CRT-alone group), and an increase in the 1-year and 3-year overall survival rates (72% vs 50.0% and 32% vs 22.0%, respectively), while the median time to progression was extended to 11.3 months in the combination group vs 8.1 months in the CRT-alone group. There were no treatment-related toxicities that could be attributed specifically to the endostatin, and the toxicities observed across the two groups are probably due to the CRT itself. CONCLUSIONS The short- and long-term effects of CRT combined with endostatin were an improvement over that of CRT alone in this retrospective cohort study. This combined treatment modality may be a promising treatment modality for the patients with unresectable but without systemic metastatic oesophageal cancer. Further prospective randomised control studies are needed to confirm this finding.
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Affiliation(s)
- Z Zhong
- Department of Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
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Shim HJ, Kim DE, Hwang JE, Bae WK, Nam TK, Na KJ, Cho SH, Chung IJ. A phase II study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin in advanced oesophageal cancer. Cancer Chemother Pharmacol 2012; 70:683-90. [PMID: 22932694 DOI: 10.1007/s00280-012-1962-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Accepted: 08/17/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Concurrent chemoradiotherapy (CRT) is a main treatment option for patients with advanced oesophageal cancer. However, improvement of survival outcomes and toxicities according to the selected treatment is still needed. This phase II trial was conducted to assess the efficacy and safety of concurrent CRT with weekly docetaxel and cisplatin in advanced oesophageal cancer. METHODS Patients with unresectable oesophageal cancer due to advanced stage or patients medically unfit for surgery were enrolled. Patients received 20 mg/m(2) docetaxel and 25 mg/m(2) cisplatin in weeks 1, 2, 3, 5, 6, and 7 with concurrent 54-Gy radiotherapy at 200 cGy/day. RESULTS Thirty-six patients with oesophageal squamous cell carcinoma were enrolled from December 2007 to December 2009. Among them, the toxicity and response rate of 35 were evaluated. Thirty-five patients completed radiotherapy as planned, and 33 completed chemotherapy as planned. Grade 3 or 4 toxicity during CRT included leucopenia (5.7 %), febrile neutropenia (2.9 %), oesophagitis (22.9 %), and tracheo-oesophageal fistula (5.7 %). After CRT, 8 patients (22.9 %) had a complete response, 22 (62.9 %) had a partial response, 4 (11.4 %) had stable disease, and 1 (2.9 %) had progressive disease. Improvement of dysphagia was observed in 85.3 %. At a median follow-up of 26.7 months, the median time to progression was 13.5 months, and median overall survival was 26.9 months. The 3-year progression-free survival rate was 16.7 %, and survival rate was 27.8 %. CONCLUSION Concurrent CRT with weekly docetaxel and cisplatin was well tolerated and is a convenient combination with promising efficacy. This result indicated favourable activity in terms of both tumour and symptom control.
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Affiliation(s)
- Hyun-Jeong Shim
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Republic of Korea
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Semrau R, Herzog SL, Vallböhmer D, Kocher M, Hölscher AH, Müller RP. Prognostic factors in definitive radiochemotherapy of advanced inoperable esophageal cancer. Dis Esophagus 2012; 25:545-54. [PMID: 22133297 DOI: 10.1111/j.1442-2050.2011.01286.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of this study was to assess the efficacy and prognostic factors of definitive radiochemotherapy (RCT) for inoperable esophageal cancer. Between 1995 and 2005 all patients with inoperable esophageal cancer that underwent concurrent RCT were included in this retrospective study. Conventional computed tomography-based treatment planning as well as 3D-conformal radiotherapy (RT) was used. Maximum radiotherapy dose was 63 Gy. Chemotherapy consisted of cisplatin (20 mg/m(2) d1-5 and 29-33) and 5-FU (650-1000 mg/m(2) d1-5 and 29-33). Patients not suitable for RCT received radiotherapy alone. Toxicity was measured according to common toxicity criteria (CTC). Two hundred three consecutive patients with inoperable esophageal cancer that received definitive therapy were identified in this time period (160 with squamous cell carcinoma and 43 with adenocarcinoma). The 2-year overall survival probability was 21.2% whereas the progression-free survival at 2 years was 13.8% for all patients. In the univariate analysis, type of histology, T-stage, N-stage, application of chemotherapy, and the radiation dose were significantly correlated with overall/progression-free survival. Moreover, multivariate analysis revealed an independent prognostic impact for N-stage, radiation dose, and concurrent chemotherapy. Definitive RCT is an important palliative treatment option for patients with inoperable esophageal cancer. N-stage, radiation dose, and concurrent chemotherapy are important prognostic factors for survival.
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Affiliation(s)
- R Semrau
- Department of Radiation Oncology, University of Cologne, Cologne, Germany.
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The value of ultrasound in the assessment of cervical and abdominal lymph node metastases and selecting surgical strategy in patients with squamous cell carcinoma of the thoracic esophagus treated with neoadjuvant therapy. Adv Med Sci 2012; 56:291-8. [PMID: 22119915 DOI: 10.2478/v10039-011-0055-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE To establish the role of ultrasound (US) in the assessment of cervical and abdominal lymph node metastases and its impact on making decision about surgical strategy in patients with squamous cell carcinoma of the thoracic esophagus. MATERIAL/METHODS The results of US lymph node assessment before and after a neoadjuvant treatment in 83 patients were compared with the results of histopathological evaluation of lymph nodes harvested during surgery (transthoracic esophagectomy and 2-field extended or 3-field lymph node dissection). A diagnostic value of cervical and abdominal US in terms of sensitivity, specificity, positive and negative predictive value after a neoadjuvant treatment were determined. RESULTS The sensitivity, specificity, positive and negative predictive value of the US assessment of cervical lymph node metastases were 100%, 96%, 81% and 100%, respectively. The sensitivity, specificity, positive and negative predictive value of the US assessment of abdominal lymph node metastases were 82%, 94%, 91.5% and 87%, respectively. CONCLUSIONS The high sensitivity and specificity of cervical US make this investigational method sufficient in the assessment of cervical nodal involvement. In esophageal cancer patients with negative cervical lymph nodes on US, three-field lymph node dissection could be avoided. In patients with positive cervical lymph nodes on US one should consider to extend lymph node dissection about lymph nodes of the neck to achieve a curative resection. In patients with negative abdominal US this investigation should be supplemented by more detailed diagnostic methods.
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Stage for stage comparison of recurrence patterns after definitive chemoradiotherapy or surgery for oesophageal carcinoma. Clin Oncol (R Coll Radiol) 2012; 24:617-24. [PMID: 22386923 DOI: 10.1016/j.clon.2012.02.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2011] [Revised: 01/12/2012] [Accepted: 02/01/2012] [Indexed: 11/24/2022]
Abstract
AIMS Definitive chemoradiotherapy (dCRT) has been advocated as an alternative treatment for oesophageal carcinoma, but received criticism for perceived poorer locoregional disease control when compared with surgery. The aim of this study was to determine the relative incidence and pattern of oesophageal carcinoma recurrence after dCRT and surgery in patients receiving stage-directed therapy with curative intent. MATERIALS AND METHODS In total, 623 consecutive patients with oesophageal carcinoma (207 squamous cell carcinoma, 416 adenocarcinoma) were studied. The primary outcome measure was disease-free survival, adjusted for baseline differences in gender, age and histological cell type. RESULTS Three hundred and eleven patients deemed unsuitable for surgery on the grounds of performance status (n = 137), bulky local disease (n = 121) or personal choice (n = 53) received dCRT and 312 surgery (200 received neoadjuvant chemotherapy). Oesophageal carcinoma recurrence was diagnosed in 44.1% of patients after dCRT compared with 40.7% after surgery (P = 0.222). Locoregional recurrence was more common after dCRT than after surgery (24.1% versus 9.3%, P < 0.0001). In contrast, distant metastases were more common after surgery than after dCRT (22.8% versus 12.9%, P = 0.001). The median time to recurrence in patients receiving dCRT and surgery were 15 and 17 months, respectively (P = 0.052). Stage-related disease-free 2 year survival for dCRT versus surgery was: stage I (68.6 versus 85.6%, P = 0.069), stage II (36.9 versus 47.4%, P = 0.011), stage III (31.0 versus 28.6, P = 0.878), stage IVa (21.4 versus 26.3%, P = 0.710). CONCLUSIONS These findings provide further support for a randomised trial of dCRT versus surgery in both oesophageal squamous cell carcinoma and adenocarcinoma.
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