What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis

Abstract

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose–response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

High vs. Low Radiation Dose of Concurrent Chemoradiotherapy for Esophageal Carcinoma With Modern Radiotherapy Techniques: A Meta-Analysis

“…The different results between the two subgroup analyses can be partially explained by the theory that 45 to 50-Gy radiation dose can be used to control microscopic tumors of SCC or AC, and at least 60 Gy is required aiming to control gross tumor ( 29 – 31 ). Our analysis is also in accordance with some nearly published studies ( 26 , 32 ). The results suggest that when the dose of radiotherapy is raised within a certain range below the 60 Gy dose threshold, it would not improve the OS and local–regional control of esophageal carcinoma patients.…”

“…For patients with esophageal cancer receiving CCRT, the recommended radiation dose remains controversial. Although several meta-analyses were published regarding the optimal radiotherapy dose of CCRT for esophageal carcinoma ( 26 – 28 ), the robustness of their findings was inadequate due to the limited sample size. Moreover, some outdated radiation techniques, including the improper multiple field technique, cobalt-60 equipment, and 2D-CRT, were included in these studies, introducing more heterogeneity.…”

Effect of modern high-dose versus standard-dose radiation in definitive concurrent chemo-radiotherapy on outcome of esophageal squamous cell cancer: a meta-analysis

“…In this present study, we defined a radiation dose of > = 60 Gy as HD-RT and < 60 Gy as SD-RT. Furthermore, only those studies using 60Gy as a threshold value for high dose and standard dose were included in our meta-analysis, and we have found that high radiation dose of > = 60 Gy was associated with better OS, PFS and LRFS, which is consistent with Chen’s study and Song’s study [8, 21]. However, how high radiation dose is appropriate for ESCC patients?…”

“…However, this review was a compilation of single treatment arm, with only 3 included studies containing both a HD-RT (≥ 60 Gy) arm and SD-RT arm. Another meta-analysis has indicated that patients who received ≥60 Gy radiation had a significantly better prognosis as compared with < 60 Gy [21]. The studies including patients received < 50 Gy radiation and the studies including patients diagnosed as esophageal adenocarcinoma were included in the meta-analysis.…”

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

“…A meta-analyses by Song et al in 2015 included 55 articles and concluded that high-dose radiation increased treatment response and 5-year OS rates while decreasing LRF and distant failure rates with without additional toxicity, notably for ESCC patients [31] . Another study by Chen et al analyzed 18 articles and also found that a dose of ≥ 60 Gy appeared to improve OS and LRC, notably in Asian patients [32] . Luo et al reached a similar conclusion [33] .…”