J Cancer 2020; 11(15):4605-4613. doi:10.7150/jca.44447 This issue

Research Paper

Do Higher Radiation Doses with Concurrent Chemotherapy in the Definitive Treatment of Esophageal Cancer Improve Outcomes? A Meta-Analysis and Systematic Review

Linlin Xiao1#, Brian G. Czito2#, Qingsong Pang3, Zhouguang Hui4, Shaowu Jing1, Baoen Shan1*, Jun Wang1✉

1. Department of Radiotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
2. Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
3. Department of Radiotherapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
4. Department of Radiotherapy, Cancer Institute & Hospital, Peking Union Medical College, & Chinese Academy of Medical Sciences, Beijing, China.
#: These authors contributed equally to this work.
*: These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Xiao L, Czito BG, Pang Q, Hui Z, Jing S, Shan B, Wang J. Do Higher Radiation Doses with Concurrent Chemotherapy in the Definitive Treatment of Esophageal Cancer Improve Outcomes? A Meta-Analysis and Systematic Review. J Cancer 2020; 11(15):4605-4613. doi:10.7150/jca.44447. Available from https://www.jcancer.org/v11p4605.htm

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Background: To investigate the effects and safety profile of radiation dose escalation utilizing computerized tomography (CT) based radiotherapy techniques (including 3-Dimensional conformal radiotherapy, intensity-modulated radiotherapy and proton therapy) in the definitive treatment of patients with esophageal carcinoma (EC) with definitive concurrent chemoradiotherapy (dCCRT).

Methods: All relevant studies utilizing CT-based radiation planning, comparing high-dose (≥ 60 Gy) versus standard-dose (50.4 Gy) radiation for patients with EC were analyzed for this meta-analysis.

Results: Eleven studies including 4946 patients met the inclusion criteria, with 96.5% of patients diagnosed with esophageal squamous cell carcinoma (ESCC). The high-dose group demonstrated a significant improvement in local-regional failure (LRF) (OR 2.199, 95% CI 1.487-3.253; P<0.001), two-year local-regional control (LRC) (OR 0.478, 95% CI 0.309-0.740; P=0.001), two-year overall survival (OS) (HR 0.744, 95% CI 0.657-0.843; P<0.001) and five-year OS (HR 0.683, 95% CI 0.561-0.831; P<0.001) rates relative to the standard-dose group. In addition, there was no difference in grade ≥ 3 radiation-related toxicities and treatment-related deaths between the groups.

Conclusion: Under the premise of controlling the rate of toxicities, doses of ≥ 60 Gy in CT-based dCCRT of ESCC patients might improve locoregional control and ultimate survival compared to the standard-dose dCCRT. While our review supports a dose-escalation approach in these patients, multiple ongoing randomized trial initial and final reports are awaited to evaluate the effectiveness of this strategy.

Keywords: definitive concurrent chemoradiotherapy, dose escalation, esophageal cancer, esophageal squamous cell carcinoma, radiation dose