Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era
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
Affiliations
Wing-Keen Yap
Proton 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, Taiwan
Ming-Chieh Shih
Department of Applied Mathematics, National Dong Hwa University, Hualien 974, Taiwan
Yu-Chen Chang
Proton 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, Taiwan
Chia-Hsin Lin
Proton 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, Taiwan
Shih-Ming Huang
Department of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
Tsung-You Tsai
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Otolaryngology-Head and Neck Surgery, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Ching-Fu Chang
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Chih-Chung Hsu
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Chen-Kan Tseng
Proton 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, Taiwan
Miao-Fen Chen
Proton 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, Taiwan
Din-Li Tsan
Proton 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, Taiwan
Chi-Ting Liau
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Ming-Mo Hou
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Hematology-Oncology, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Yin-Kai Chao
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Thoracic Surgery, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Chien-Hung Chiu
Chang Gung Memorial Hospital-Linkou Medical Center, Department of Thoracic Surgery, Chang Gung University, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
Tsung-Min Hung
Proton 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, Taiwan
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, p = 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; p = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; p = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (p = 0.003) and a 48% reduction in risk of recurrence (p = 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 (p = 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.
