Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era
Background: The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes i...
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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2989 |
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| author | Wing-Keen Yap Ming-Chieh Shih Yu-Chen Chang Chia-Hsin Lin Shih-Ming Huang Tsung-You Tsai Ching-Fu Chang Chih-Chung Hsu Chen-Kan Tseng Miao-Fen Chen Din-Li Tsan Chi-Ting Liau Ming-Mo Hou Yin-Kai Chao Chien-Hung Chiu Tsung-Min Hung |
| author_facet | Wing-Keen Yap Ming-Chieh Shih Yu-Chen Chang Chia-Hsin Lin Shih-Ming Huang Tsung-You Tsai Ching-Fu Chang Chih-Chung Hsu Chen-Kan Tseng Miao-Fen Chen Din-Li Tsan Chi-Ting Liau Ming-Mo Hou Yin-Kai Chao Chien-Hung Chiu Tsung-Min Hung |
| author_sort | Wing-Keen Yap |
| collection | DOAJ |
| description | Background: The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients. Methods: we identified patients with esophageal squamous cell carcinoma who were staged as ypT3/T4 and/or ypN+ after being treated with neoadjuvant chemoradiotherapy followed by esophagectomy between the years 2013 and 2019. Patients were divided into two groups based on whether they received adjuvant chemoradiotherapy. The Kaplan-Meier method and Cox regression modeling were performed for survival analyses and multivariable analysis, respectively. Results: 76 eligible patients were included in the analyses. The median follow-up for the study cohort was 43.4 months. On Kaplan-Meier analyses of the overall population, adjuvant chemoradiotherapy was associated with significantly improved median overall survival (31.7 months vs. 16.3 months, <i>p</i> = 0.036). On Kaplan-Meier analyses of the 35 matched pairs generated by propensity score matching, adjuvant chemoradiotherapy was associated with significantly longer median overall survival (31.7 months vs. 14.3 months; <i>p</i> = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; <i>p</i> = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (<i>p</i> = 0.003) and a 48% reduction in risk of recurrence (<i>p</i> = 0.035) after adjusting for putative confounders. In addition, microscopic positive resection margin and Mandard tumor regression grade 3–4 were independently associated with increased mortality and risk of recurrence. While a greater number of lymph nodes dissected was independently associated with significantly improved overall survival, the number of positive lymph nodes was independently associated with significantly worse overall survival and a trend (<i>p</i> = 0.058) towards worse recurrence-free survival. Conclusions: This study demonstrated that adjuvant CRT was independently associated with a significantly improved survival and lower risk of recurrence than observation in esophageal squamous cell carcinoma patients staged as ypT3 and/or ypN+ after receiving neoadjuvant chemoradiotherapy and radical surgery. The results of this study have implications for the design of future clinical trials and may improve treatment outcomes of patients in this setting who cannot afford or are without access to adjuvant nivolumab. |
| first_indexed | 2024-03-09T18:27:01Z |
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| id | doaj.art-14e526ae29d541cb94ad37bbd028f3e0 |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T18:27:01Z |
| publishDate | 2022-11-01 |
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| series | Biomedicines |
| spelling | doaj.art-14e526ae29d541cb94ad37bbd028f3e02023-11-24T07:47:18ZengMDPI AGBiomedicines2227-90592022-11-011011298910.3390/biomedicines10112989Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy EraWing-Keen Yap0Ming-Chieh Shih1Yu-Chen Chang2Chia-Hsin Lin3Shih-Ming Huang4Tsung-You Tsai5Ching-Fu Chang6Chih-Chung Hsu7Chen-Kan Tseng8Miao-Fen Chen9Din-Li Tsan10Chi-Ting Liau11Ming-Mo Hou12Yin-Kai Chao13Chien-Hung Chiu14Tsung-Min Hung15Proton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanDepartment of Applied Mathematics, National Dong Hwa University, Hualien 974, TaiwanProton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanProton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanDepartment of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung 204, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Otolaryngology-Head and Neck Surgery, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanProton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanProton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanProton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Thoracic Surgery, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanChang Gung Memorial Hospital-Linkou Medical Center, Department of Thoracic Surgery, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanProton and Radiation Therapy Center, Chang Gung Memorial Hospital-Linkou Medical Center, Department of Radiation Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, TaiwanBackground: The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients. Methods: we identified patients with esophageal squamous cell carcinoma who were staged as ypT3/T4 and/or ypN+ after being treated with neoadjuvant chemoradiotherapy followed by esophagectomy between the years 2013 and 2019. Patients were divided into two groups based on whether they received adjuvant chemoradiotherapy. The Kaplan-Meier method and Cox regression modeling were performed for survival analyses and multivariable analysis, respectively. Results: 76 eligible patients were included in the analyses. The median follow-up for the study cohort was 43.4 months. On Kaplan-Meier analyses of the overall population, adjuvant chemoradiotherapy was associated with significantly improved median overall survival (31.7 months vs. 16.3 months, <i>p</i> = 0.036). On Kaplan-Meier analyses of the 35 matched pairs generated by propensity score matching, adjuvant chemoradiotherapy was associated with significantly longer median overall survival (31.7 months vs. 14.3 months; <i>p</i> = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; <i>p</i> = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (<i>p</i> = 0.003) and a 48% reduction in risk of recurrence (<i>p</i> = 0.035) after adjusting for putative confounders. In addition, microscopic positive resection margin and Mandard tumor regression grade 3–4 were independently associated with increased mortality and risk of recurrence. While a greater number of lymph nodes dissected was independently associated with significantly improved overall survival, the number of positive lymph nodes was independently associated with significantly worse overall survival and a trend (<i>p</i> = 0.058) towards worse recurrence-free survival. Conclusions: This study demonstrated that adjuvant CRT was independently associated with a significantly improved survival and lower risk of recurrence than observation in esophageal squamous cell carcinoma patients staged as ypT3 and/or ypN+ after receiving neoadjuvant chemoradiotherapy and radical surgery. The results of this study have implications for the design of future clinical trials and may improve treatment outcomes of patients in this setting who cannot afford or are without access to adjuvant nivolumab.https://www.mdpi.com/2227-9059/10/11/2989neoadjuvant chemoradiotherapytrimodality therapyadjuvant chemoradiotherapyIMRTVMATesophageal cancer |
| spellingShingle | Wing-Keen Yap Ming-Chieh Shih Yu-Chen Chang Chia-Hsin Lin Shih-Ming Huang Tsung-You Tsai Ching-Fu Chang Chih-Chung Hsu Chen-Kan Tseng Miao-Fen Chen Din-Li Tsan Chi-Ting Liau Ming-Mo Hou Yin-Kai Chao Chien-Hung Chiu Tsung-Min Hung Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era Biomedicines neoadjuvant chemoradiotherapy trimodality therapy adjuvant chemoradiotherapy IMRT VMAT esophageal cancer |
| title | Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era |
| title_full | Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era |
| title_fullStr | Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era |
| title_full_unstemmed | Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era |
| title_short | Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era |
| title_sort | adjuvant chemoradiotherapy associated with improved overall survival in resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy in intensity modulated radiotherapy era |
| topic | neoadjuvant chemoradiotherapy trimodality therapy adjuvant chemoradiotherapy IMRT VMAT esophageal cancer |
| url | https://www.mdpi.com/2227-9059/10/11/2989 |
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