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Concurrent Chemoradiotherapy with Extended Nodal Irradiation and/or Erlotinib in Locally Advanced Esophageal Squamous Cell Cancer: Long-Term Follow-Up of a Randomized Phase 3 Trial

64 Pages Posted: 7 Jun 2019

See all articles by Congying Xie

Congying Xie

Wenzhou Medical University - Second Affiliated Hospital

Zhao Jing

Hangzhou Cancer Hospital - Department of Radiation Oncology

Honglei Luo

The First People’s Hospital of Huaihua

Wei Hu

Wenzhou Medical University - Taizhou Hospital of Zhejiang Province

Anping Zheng

Chinese Academy of Sciences (CAS) - Department of Radiation Oncology

Duojie Li

Bengbu Medical College - First Affiliated Hospital

Lingyu Ding

Hangzhou Cancer Hospital

Hongyan Zhang

Anhui Provincial Hospital

Conghua Xie

Wuhan University - Department of Radiation and Medical Oncology; Leishenshan Hospital - Department of Medical Quality Control

Xilong Lian

Kaohsiung Medical University - Kaohsiung Medical University Hospital

Dexi Du

Central Hospital of Lishui City

Ming Chen

Chinese Academy of Sciences (CAS) - Department of Radiation Oncology

Xiuhua Bian

Jiangsu Cancer Hospital

Bangxian Tan

North Sichuan Medical College - First Affiliated Hospital

Bing Xia

Hangzhou Cancer Hospital - Department of Radiation Oncology

Ni Zhang

Hangzhou Cancer Hospital - Department of Radiation Oncology

Ruifei Xie

Hangzhou Cancer Hospital - Information Center

Qing Liu

Sun Yat-sen University (SYSU)

Lvhua Wang

Chinese Academy of Medical Sciences - National Cancer Center

Shixiu Wu

Hangzhou Cancer Hospital - Hangzhou Cancer Institute

More...

Abstract

Background: The outcome of patients with locally advanced esophageal squamous cell cancer (ESCC) remain poor. The aim of this study was to report the long-term outcomes in a randomized controlled multicentre phase III study evaluating extended nodal irradiation (ENI) and erlotinib in locally advanced ESCC.

Methods: A 2x2 factorial design was used to test two hypotheses: (1) that ENI was superior to conventional field irradiation (CFI); (2) that chemoradiotherapy plus erlotinib was superior to chemoradiotherapy in patients with locally advanced ESCC. Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to receive concurrent chemotherapy with ENI or CFI with or without erlotinib (150 mg per day during chemoradiotherapy). The primary end point was overall survival (OS). We have explored the impact of epidermal growth factor receptor (EGFR) expression on efficacy of erlotinib plus chemradiotherapy.

Findings: A total of 352 patients (88 assigned to each treatment group) were enrolled. After a minimum follow-up of 5 years for surviving patients, the 5-year survival rate was 44·92%, 34·82%, 33·81% and 19·62% in group A, B, C and D (P = 0·013). The median OS was 49·97 months, 26·50 months, 23·83 months, and 20·87 months in group A, B, C and D. The radiation field-by-erlotinib interaction test was not significant for OS (HR, 0·96; P = 0·871) and progression-free-survival (PFS) (HR, 0·97; P = 0·908). The ENI significantly improved OS compared with the standard CFI (median, 38·53 v 22·60 months; HR, 0·74; P = 0·018). The addition of erlotinib significantly improved OS (median, 39·38 v 27·42 months; HR, 0·75; P = 0·025). The patients with ESCC over expressing EGFR treated by erlotinib had a better OS and PFS than patients without EGFR expression.

Interpretation: Concurrent chemoradiotherapy with ENI and/or erlotinib still improved survival outcomes with long-term follow-up in locally advanced ESCC. ENI should be adopted in concurrent chemoradiotherapy for ESCC patients. The patients with ESCC over expressing EGFR could significantly benefit from the erlotinib plus chemoradiotherapy.

Funding Statement: The authors state: "No commercial support was provided for this study."

Declaration of Interests: All authors declare no competing interests.

Ethics Approval Statement: All patients provided written informed consent, and the study was approved by the institutional review board or independent ethics committee of each participating center.

Keywords: esophageal squamous cell cancer, elective nodal irradiation, erlotinib

Suggested Citation

Xie, Congying and Jing, Zhao and Luo, Honglei and Hu, Wei and Zheng, Anping and Li, Duojie and Ding, Lingyu and Zhang, Hongyan and Xie, Conghua and Lian, Xilong and Du, Dexi and Chen, Ming and Bian, Xiuhua and Tan, Bangxian and Xia, Bing and Zhang, Ni and Xie, Ruifei and Liu, Qing and Wang, Lvhua and Wu, Shixiu, Concurrent Chemoradiotherapy with Extended Nodal Irradiation and/or Erlotinib in Locally Advanced Esophageal Squamous Cell Cancer: Long-Term Follow-Up of a Randomized Phase 3 Trial (June 5, 2019). Available at SSRN: https://ssrn.com/abstract=3399610 or http://dx.doi.org/10.2139/ssrn.3399610

Congying Xie

Wenzhou Medical University - Second Affiliated Hospital ( email )

China

Zhao Jing

Hangzhou Cancer Hospital - Department of Radiation Oncology

Hangzhou, 310002
China

Honglei Luo

The First People’s Hospital of Huaihua

Huaihua
China

Wei Hu

Wenzhou Medical University - Taizhou Hospital of Zhejiang Province

Zhejiang, Zhejiang 317000
China

Anping Zheng

Chinese Academy of Sciences (CAS) - Department of Radiation Oncology

China

Duojie Li

Bengbu Medical College - First Affiliated Hospital

China

Lingyu Ding

Hangzhou Cancer Hospital

34 Yanguan Lane
Hangzhou, Shangcheng District 310002
China

Hongyan Zhang

Anhui Provincial Hospital

Hefei
China

Conghua Xie

Wuhan University - Department of Radiation and Medical Oncology ( email )

169# Donghu Road
Wuhan
China
862767812607 (Phone)

Leishenshan Hospital - Department of Medical Quality Control

Wuhan
China

Xilong Lian

Kaohsiung Medical University - Kaohsiung Medical University Hospital

Kaohsiung
Taiwan

Dexi Du

Central Hospital of Lishui City

China

Ming Chen

Chinese Academy of Sciences (CAS) - Department of Radiation Oncology

China

Xiuhua Bian

Jiangsu Cancer Hospital

Nanjing
China

Bangxian Tan

North Sichuan Medical College - First Affiliated Hospital

Nanchong
China

Bing Xia

Hangzhou Cancer Hospital - Department of Radiation Oncology

Hangzhou, 310002
China

Ni Zhang

Hangzhou Cancer Hospital - Department of Radiation Oncology

Hangzhou, 310002
China

Ruifei Xie

Hangzhou Cancer Hospital - Information Center

Hangzhou, 310002
China

Qing Liu

Sun Yat-sen University (SYSU)

135, Xingang Xi Road
Haizhu District
Guangzhou, Guangdong 510275
China

Lvhua Wang

Chinese Academy of Medical Sciences - National Cancer Center

Beijing
China

Shixiu Wu (Contact Author)

Hangzhou Cancer Hospital - Hangzhou Cancer Institute ( email )

Hangzhou, 310002
China