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.
Highlights
Esophageal cancer (EC) has a very high incidence and mortality rate worldwide
The optimal radiation dose for locally advanced EC was subsequently explored by the INT-0123 randomized controlled trial (RCT) [4] and their analysis showed no benefit in the high dose (HD) treatment arm (64.8 Gy) as compared to the standard dose of 50.4 Gy
Five studies reported the occurrence of locoregional failure (LRF) and 4 studies reported that of distant metastasis failure (DMF) in high dose (HD) and low dose (LD) groups
Summary
Esophageal cancer (EC) has a very high incidence and mortality rate worldwide. Approximately 75% of all cases occur in Asia with China bearing the largest burden, accounting for about 50% of the total cases and cancer specific deaths [1]. For patients with localized and locally advanced inoperable disease, the worldwide consensus standard treatment recommendation, as sturdily supported by the RTOG 85–01 trial, is definitive concurrent chemoradiotherapy (CCRT) [3]. The optimal radiation dose for locally advanced EC was subsequently explored by the INT-0123 randomized controlled trial (RCT) ( known as RTOG 94-05) [4] and their analysis showed no benefit in the high dose (HD) treatment arm (64.8 Gy) as compared to the standard dose of 50.4 Gy. Since a dose of 50.4 Gy has been recommended as the standard dose for locally advanced EC in the American guidelines as “evidence-based”. A dose of 50.4 Gy has been recommended as the standard dose for locally advanced EC in the American guidelines as “evidence-based” Additional data supporting this dose is lacking despite debates about its clinical validity [5]. Since several studies have successfully administered a radiation dose above 50 Gy without significant untoward effects, and a dose–response relationship has been observed with increasing doses above 50 Gy, a further dose escalation might be justifiable on its potential merits [7]
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