1112 - Long-Term Outcomes of Dose Escalation in Definitive Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Randomized Phase III Trial
Presenter(s)
Y. Xu1, B. Dong2, Q. Cheng1, W. Zhu3, J. Li4, R. Huang5, Z. Sun6, X. Yang7, L. Liu6, H. He8, Z. Liao9, Y. Kong1, W. Wang3, J. Chen1, H. He10, G. Qiu1, M. Zeng11, J. Pu12, W. Hu13, Y. Bao14, Z. Liu15, J. Ma16, H. Jiang17, X. Du1, J. Hu18, T. Zhuang19, J. Huang20, T. Hua21, Y. Liu22, X. Liang23, J. Zhou24, X. Zheng1, B. Chen2, M. Xi2, and M. Chen2; 1Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou, Guangdong, China, 3Department of Radiotherapy, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China, 4Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China, 5Cancer Center, The First People’s Hospital of Foshan, Foshan, Guangdong, China, 6Department of Oncology, Jining No. 1 People's Hospital, Jining, Shandong, China, 7Department of Oncology, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China, 8Cancer Center, Foshan First People's Hospital, Foshan, Guangdong, China, 9The University of Texas MD Anderson Cancer Center, Houston, TX, 10Department of Radiation Oncology, Quzhou People’s Hospital, Quzhou, Zhejiang, China, 11Cancer Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China, 12Department of Radiation Oncology, Lianshui People's Hospital, Lianshui, Jiangsu, China, 13Department of Radiation Oncology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China, 14Department of Radiation Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China, 15Hunan Cancer Hospital, Changsha, China, 16Department of Radiation Oncology, First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, China, 17The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, 18Department of Radiation Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China, 19Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China, 20Department of Radiation Oncology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, China, 21Department of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China, 22Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China, 23Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China, 24Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Purpose/Objective(s): Definitive chemoradiotherapy (CRT) is the standard treatment for locally advanced, unresectable esophageal squamous cell carcinoma (ESCC). We previously demonstrated that escalating the radiation dose to 60 Gy did not enhance local control but did lead to increased radiation toxicity compared to 50 Gy (NCT01937208). Here, we present long-term results and exploratory analyses to further explore prognostic biomarkers.
Materials/Methods: Between May 2013 and May 2017, 331 patients with stage IIA-IVA ESCC were enrolled across multiple centers. A total of 324 patients were randomly assigned in a 1:1 ratio to receive either a 60 Gy (30 fractions) or 50 Gy (25 fractions) to the primary tumor and regional lymph nodes with CRT. Treatments were delivered over five consecutive days per week using intensity-modulated radiation therapy (IMRT). Chemotherapy included five cycles of concurrent weekly docetaxel and cisplatin, followed by two cycles of consolidation chemotherapy. The primary endpoint was locoregional progression-free survival (LRPFS). NanoString GeoMx digital spatial profiling (DSP) was performed on pretreatment biopsies for transcriptomic and proteomic characterization.
Results: The full analysis set included 319 patients (60 Gy group, n=160, 50 Gy group, n=159). With a median follow-up of 99.5 months, there were no statistically significant differences in LRPFS, overall survival (OS), or progression-free survival (PFS) rates. The 5-, 7- and 10-year LRPFS rates for the 60 Gy group were 41.8%, 35.8%, and 21.1% compared to 43.3%, 37.7%, and 24.2% for the 50 Gy group (HR = 1.06, 95% CI: 0.80-1.39, p = 0.70). The 5-, 7- and 10-year OS rates were 45.4%, 36.0% and 21.2% versus 45.6%, 40.1%, and 25.8%, respectively (HR = 1.09, 95% CI: 0.83-1.44, p = 0.53). The 5-, 7- and 10-year PFS rates were 38.0%, 34.0%, and 20.5% versus 42.8%, 37.2%, and 23.9%, respectively (HR = 1.06, 95% CI: 0.81-1.40, p = 0.66). Treatment toxicity has been previously reported. Spatial multi-omic analyses indicated that patients with early progression (PFS < 24 months) exhibited distinct immune microenvironment features, including higher expression levels of LAG3, CTLA4, and increased Treg infiltration compared to those with longer survival (OS > 60 months).
Conclusion: The extended follow-up data supports 50 Gy as the recommended radiation dose in definitive CRT for ESCC. This landmark prospective phase III trial provides the first long-term outcomes comparing radiation dose escalation in definitive CRT for locally advanced ESCC using IMRT, with mature 10-year follow-up data. In addition, our findings identify spatial biomarkers for CRT, potentially guiding the selection of ESCC patients who are more likely to benefit from treatment.