Patient characteristics
Table 1 presents the patient characteristics. In total, 69 patients were analyzed in this study. Of these, 35 patients were in the elderly group with a median age of 74 (range, 70–84). The younger group consisted of 34 patients with a median age of 63 (range, 44–69). There was no significant difference in PS between the two groups (p = 0.054). Esophageal stricture was the most common symptom, found in 21 (60.0%) patients in the elderly group and 21 (61.7%) patients in the younger group (p = 1.000). Most of the lesions in both groups were T4b, with tracheal or bronchial invasion in 28 (80.0%) patients in the elderly group and 27 (79.4%) patients in the younger group (p = 0.766). The median total dose of RT was 60 Gy in both groups (p = 0.572). A significant difference was not observed in the irradiation delivery between the two groups (p = 0.195). CTx was administered concurrently with RT in 82.9% of patients in the elderly group and 94.1% of patients in the younger group (p = 0.477). Of the patients who did not receive CTx in the elderly group, five patients were not indicated due to complications, and one patient refused the CTx. In the younger group, there was one case of off-label treatment due to complications and one case of refusal. In the elderly group, 26 (89.7%) patients received CF and 3 (10.3%) patients received FOLFOX out of 29 CTx treatments. A median of 2 (range, 1–8) cycles of CF (n = 16) and a median of 3 (range, 1–3) cycles of FOLFOX (n = 3) were administered as ACTx in the elderly group. In the elderly group, all patients received CF. A median of 2 (range, 1–10) cycles of CF were administered as ACTx in the younger group. Of the patients who did not receive ACTx in the elderly group, six patients received RT alone in the initial treatment, four received off-label treatment due to their general condition, two refused ACTx, two had early recurrence, and one died early. In the younger group, two received RT alone in the initial treatment, one received off-label treatment due to general condition, one refused ACTx, three had early recurrence, one died early, and one underwent salvage surgery.
Survivals
Figure 1 shows the OS of the elderly and younger groups. At the time of analysis, 48 patients had died. Overall mortality in the elderly and younger groups was 24 and 24, respectively, with 17 and 24 deaths from the primary disease (p = 0.087), respectively. The median survival time (MST) of the elderly group was 21.5 months, and the 1-, 3-, and 5-year OS rates were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group was 12.5 months, and the 1-, 3-, and 5-year OS rates were 52.2%, 29.4%, and 29.4%, respectively. Significant differences were not observed in OS between the two groups (p = 0.767).
Figure 2 shows the PFS of the elderly and younger groups. The median PFS time of the elderly group was 17.5 months, and the 1-, 3-, and 5-year PFS rates were 61.3%, 19.4%, and 9.7%, respectively. The median PFS time in the younger group was 12.1 months, and the 1-, 3-, and 5-year PFS rates were 52.2%, 24.6%, and 20.5%, respectively. Significant differences were not observed in PFS between the two groups (p = 0.926). The first recurrence in the elderly group was local recurrence of the primary tumor in 2 cases, regional lymph node recurrence in 3 cases, primary tumor and regional lymph node in 1 case, and distant metastasis in 14 cases. In the younger group, there were 7 cases of local recurrence of the primary tumor, 2 cases of regional lymph node recurrence, 2 cases of primary tumor and regional lymph node recurrence, 8 cases of distant metastasis, and 1 case of primary tumor and distant metastasis.
Table 2 shows the results of the analysis of OS predictors in all patients. In the univariate analysis, ACTx and CR of the primary tumor were significant predictors (p < 0.001 and < 0.001, respectively). In multivariate analysis, ACTx and CR were also significant predictors, with hazard ratios (HR) of 0.20 [95% confidence interval (CI) 0.09–0.42] (p < 0.001) and 0.20 (95% CI 0.08–0.44) (p < 0.001), respectively. Figure 3(a) shows the OS of all patients with and without ACTx. The MST in the ACTx group (n = 47) was 22.8 months, and the 1-, 3-, and 5-year OS rates were 71.3%, 42.6%, and 37.8%, respectively. The MST in the non-ACTx group (n = 22) was 6.4 months, and the 1-, 3-, and 5-year OS rates were 29.2%, 5.8%, and 0%, respectively. The OS was significantly better in the ACT group (p < 0.001). Figure 3(b) shows the OS of all patients with and without CR of the primary tumor, The MST in the CR group was 63.8 months, and the 1-, 3-, and 5-year OS rates were 89.4%, 68.9%, and 51.6%, respectively. The MST in the non-CR group was 9.3 months, and the 1-, 3-, and 5-year OS rates were 45.2%, 17.1%, and 14.3%, respectively. The OS was significantly better in the ACT group (p < 0.001).
Table 3 shows the results of the analysis of OS predictors in elderly patients. In the univariate analysis, ACTx was a significant OS predictor (p = 0.001). In multivariate analysis, ACTx and CR were significant predictors, with HRs of 0.14 (95% CI 0.37–0.53) (p = 0.004) and 0.22 (95% CI 0.06–0.78) (p = 0.019), respectively. Figure 4(a) shows the OS of elderly patients with and without ACTx. The MST in the ACTx group was 25.7 months, and the 1-, 3-, and 5-year OS rates were 85.5%, 47.0%, and 31.3%, respectively. The MST in the non-ACTx group was 9.0 months, and the 1-, 3-, and 5-year OS rates were 31.4%, 7.9%, and 0%, respectively. OS was significantly better in the ACTx group (p < 0.001). Figure 4(b) shows the OS of elderly patients with and without CR of the primary tumor. The MST in the CR group was 38.5 months, and the 1-, 3-, and 5-year OS rates were 92.3%, 57.0%, and 0%, respectively. The MST in the non-CR group was 10.7 months, and the 1-, 3-, and 5-year OS rates were 47.1%, 17.9%, and 12.0%, respectively. Significant differences in OS were not observed between the CR and non-CR groups (p = 0.051)
Toxicities
Table 4 summarizes the toxicities. In the elderly group, grade 3 or more hematologic toxicities of leukopenia, neutropenia, lymphopenia, hemoglobinopenia, and thrombocytopenia were observed in 11 (31.4%), 11 (31.4%), 1 (2.9%), 3 (8.6%), and 3 (8.6%) patients, respectively. In the younger group, grade 3 or more leukopenia, neutropenia, lymphopenia, hemoglobinopenia, and thrombocytopenia were observed in 8 (22.9%), 4 (11.4%), 4 (11.4%), 5 (14.3%), and 1 (2.9%) patients, respectively. The frequency of thrombocytopenia was significantly higher in the elderly group (p = 0.012). In terms of nonhematologic toxicities, in the elderly group, grade 3 or more hyponatremia, hypokalemia, esophagitis, esophageal fistula, and congestive heart failure were observed in 5 (14.3%), 5 (14.3%), 3 (8.6%), 1 (2.9%), and 1 (2.9%) patients, respectively. In the younger group, grade 3 or more hyponatremia, hypokalemia, esophagitis, dermatitis, nausea, esophageal stricture, and esophageal fistula were observed in 3 (8.8%), 2 (5.9%), 1 (2.9%), 1 (2.9%), 1 (2.9%), 2 (5.9%), and 7 (20.6%) patients, respectively. The frequency of esophageal fistula was significantly higher in the younger group (p = 0.022). Esophageal fistula was not associated with pretreatment stricture symptoms and tracheal/bronchial invasion (p = 0.136 and 1.000, respectively). Other nonhematologic toxicities were not significantly different between the two groups. There were 2 (5.7%) and 5 (14.7%) deaths due to massive hematemesis after initiation of treatment in the elderly and younger groups, respectively (p = 0.259).