This study evaluated the survival outcome and toxicity of different re-irradiation doses combined with or without chemotherapy in the treatment of LRESCC. A recent study showed that, a radiotherapy dose of >59.4Gy after standard concurrent chemoradiotherapy (50.4 Gy) led to the achievement of complete response in patients with ESCC. The dose significantly improved local control, 5-year recurrence-free survival rate and 5-year OS rate . Previously, some studies have indicated that the survival rate of LRESCC can be significantly prolonged with a > 50 Gy dose of re-irradiation [2, 13, 14]. For instance, Kobayashi et al. demonstrated that 60 Gy was an appropriate salvage dose for LRESCC, after surgery . Besides, another study pointed out that patients with LRESCC with a radiation history should be given higher doses of radiotherapy . These studies suggest that increasing the dose of radiotherapy for recurrent esophageal cancer may prolong the overall patient survival.
Here, we compared the effects of 50 Gy and 60 Gy median re-irradiation dose on the survival of patients with LRESCC with radiation history. Our data showed that 54.4% (68/125) of the patients experienced recurrence within 2 years following initial (chemo) radiotherapy, which was consistent with previous reports [2, 13, 18, 19]. In their studies, Xu et al. reported that the 2-year survival rate and median survival time of LRESCC patients receiving ≥ 50 Gy re-radiotherapy was 37.5% and 18 months respectively . Whereas this outcome was better than the whole cohort of our study, it was similar to our survival results in the HD group. In this study, the 2-year survival rate and median survival time for the whole cohort was 29.6% and 14 months respectively. The 1-,2-, or 3-year survival rate and median survival time was 61.2%, 34.3% or 19.4% and 18 months in the HD group, and 48.3%, 24.1% or 10.3% and 11 months in the LD group, respectively. As demonstrated by our multivariate analyses, the dose of radiotherapy was an important factor in defining survival. The median survival time of patients receiving radiation alone in the HD group was 15 months, which was significantly higher than the 9 months in the LD group. Our results showed better outcome compared with previous studies [2, 13, 17]. The higher doses of radiation might have been more beneficial for tumor control. Therefore, we recommend higher doses of re-radiation for patients with recurrent ESCC after radiotherapy.
Besides, local control is a vital factor affecting patient survival outcome . To date, few studies have reported the rate of local control in patients with LRESCC following re-irradiation therapy. Previous studies reported that increasing the radiation dose can significantly improve the local control rate of esophageal cancer, and survival outcome [21, 22]. Here, the 3-year locoregional control rate in the LD group and that in the HD group was 3.4% and 14.9%, respectively. The outcome was discouraging probably because the lymphatic drainage was not included in the treatment field.
Many studies have demonstrated positive effect of chemotherapy in the initial treatment of ESCC . However, data on the role of chemotherapy in the re-irradiation therapy of ESCC remains very scant. Few studies have shown the role of chemotherapy in re-radiotherapy for recurrent ESCC. Chen et al. reported that the 1-, 2- or 3-year survival rate of 36 LRESCC patients receiving re-irradiation with concurrent chemotherapy (paclitaxel + cisplatin) was 51.7%, 21.4% or 12.2%, respectively . In addition, Katano et al. reported that the median survival time for 6 patients who underwent concurrent chemotherapy (nedaplatin and tegafur) with re-radiotherapy was 13.6 months . In a stratified analysis, our data demonstrated that chemotherapy coupled with radiotherapy could increase survival rate. In the LD group, the median survival time for chemoradiotherapy was 14 months, which was consistent with the results reported by Katano et al. . However, in the HD group, chemoradiotherapy did not show better survival benefit compared to the radiotherapy alone. Our results suggest that chemotherapy can increase the survival rate of LRESCC patients with re-radiotherapy, when patients are exposed to lower radiation doses.
Our data showed that acute radiation esophagitis was the most common toxicity in the whole cohort. Whereas the incidence of esophagitis in the HD group was higher than in the LD group (68.7% vs 58.6%), the difference was not significant. A previous study showed that the incidence of severe acute radiation esophagitis in patients with thoracic radiotherapy was 15–25% . Similarly, grade ≥ 3 acute esophagitis was rare in both groups in this study. Besides, hematological toxicity and gastrointestinal reactions were also common, but only hematologic toxicity was significant between the two groups. More than two-thirds of patients with hematological toxicity or gastrointestinal reaction received chemoradiotherapy. In this study, the incidence of radiation pneumonitis was lower than that shown in previous studies . In addition, grade 1-2 radiation pneumonitis occurred in six (10.3%) and eight (11.9%) patients in the LD and HD groups, respectively, with controllable symptoms. Severe complications occurred mainly within 3 months following re-irradiation. A total of 11 patients had severe treatment-related toxicity, such as bleeding, esophageal perforation, and esophageal fistula, eight of which were in the LD group. This may be related to the TR of ≤ 24 months in most patients (36/58, 62.1%) in the LD group. Severe late complications; esophageal stenosis, and the dysphagia were effectively relieved after esophageal dilation. Therefore, higher re-irradiation dose may be a safe treatment option for the patients.