| Objective: To observe the short-term effect, acute toxicity,local control and survival rates in patients with esophageal cancer receiving intensity modulated radiation therapy concurrent with chemotherapy. To explore the influence on acute toxicity of different nutrition status and different inflammation index. And to explore prognostic factors on local control and survival rates.Methods: From April 2006 to April 2014, a total of 338 cases of esophageal cancer patients were eligible for retrospectively analysing. The median age was 61 years old(range 42-75 years), including 243(71.9%) males, 95(28.1%) females; Non-operative staging for all the patients : 29(8.58%) patients with stage Ⅰ, 170(50.30%) with stage Ⅱ,139(41.12%) with stage Ⅲ; 330 cases(97.6%) with squamous carcinoma, 4 cases(1.2%) with adenocarcinoma, 2(0.6%) cases with the gland spine cell carcinoma, 2 cases(0.6%) with the small cell carcinoma; 27 cases with cervical esophageal carcinoma, 115 cases with upper-thoracic esophageal carcinoma, 162 cases with middle-thoracic esophageal carcinoma, 34 cases with lower-thoracic esophageal cancer. All the patients received intensity modulated radiation therapy and the prescribed dose of GTV was 45~66Gy(median, 60Gy), 1.8~2.2Gy/F, 5F/W. All the patients received concurrent chemotherapy: 271 cases with FP regimen, 51 cases with TP regimen, 3 cases with DP regimen, 2 cases with EP regimen, 4 cases with single drug cis-platinum, 3 cases with single drug S-1, 2 cases with single drug fluorouracil, 2 cases with single drug paclitaxel. We evaluated the short-term effect, acute toxicity and 1-, 3-, 5- year local control and survival rates, analyzed the influence of clinical characteristic factors(gender, age, tumor location, tumor length measured by barium meal, the largest diameter of lesion in CT image, GTV volume, T stage, N stage and clinical stage), radiotherapy related factors(radiation dose, SIB(simulataneously integrated boost) or conventional fractionated radiotherapy and radiation continue time), chemotherapy related factors(chemotherapy regimens, chemotherapy cycles concurrent with radiotherapy, consolidation chemotherapy or not and total chemotherapy cycles), evaluation of short-term effect, nutrition status(BMI(body mass index) levels, ALB(albumin) levels, TLC(total lymphocyte count) levels and anemia or not), different systemic inflammation indexes(NLR(nertrophil lymphocyte ratio) levels and PLR(platelet lymphocyte ratio) levels) on local control and survival rates. The influence on acute toxicity of different nutrition status and different systemic inflammation status were also analyzed.Results: 1 The short-term curative effect: the complete remission(CR) rate was 29.3%(99/338), the partial remission(PR) rate was 69.2%(234/338), the non-remission(NR) rate was 1.5%(5/338) and the total efficiency(CR+PR) was 98.5%. The overall incidence of bone marrow suppression was 82.24%(278/338), the acute radiation esophagitis occurrence rate was 66.0%(223/338), and acute radiation pneumonitis occurrence rate was 32.5%(110/338). 1-, 2-, 3- and 5-year local control and overall survival rates were 77.3%, 67.4%, 62.0%, 55.6% and 73.5%, 53.1%, 41.6%, 26.1%, respectively, and the median survival time was 24 months. A total of 228 dead patients died of local recurrence or not control in 76 cases(33.3%), 58 cases(25.4%) of distant metastasis, and 31 cases(13.6%) of local treatment faliure combined with distant metastasis.2 The subgroup analysis of local control and overall survival rates showed that:Clicinal charactristic factors: ⑴ The 1-, 3-, 5-year local control and survival rates of female were higher than that of male(χ2=4.338, P=0.037 and χ2=5.581, P=0.018).(2) Patients were divided into <65 ages and ≥65 ages groups, and the 1-, 3-, 5-year local control and survival rates between two groups had no significant difference(χ2=0.000, P=0.986 and χ2=1.044, P=0.307).(3) The 1-, 3-, 5-year local control rate among cervical, upper, middle and lower thoracic segments had no significant difference(χ2=2.437, P=0.487), but 1-, 3-, 5-year survival rate had significant difference(χ2=10.884, P=0.012).(4) Patients were divided into <5.0 cm and ≥5.0 cm groups according to the tumor length measured by barium meal, the 1-, 3-, 5-year local control and survival rates between two groups had no significant difference(χ2=0.349, P=0.554 and χ2=2.037, P=0.153).(5) Patients were divided into <4.0 cm and ≥4.0 cm groups according to the largest diameter of lesion in CT image, the 1-, 3-, 5-year local control and survival rates between two groups had no significant difference(χ2=1.494, P=0.222 and χ2=2.299, P=0.129).(6) Patients were divided into <48.5 cm3 and ≥48.5 cm3 groups according to the median GTV volume, the 1-, 3-, 5-year local control and survival rates in <48.5 cm3 group were higher than those in ≥48.5 cm3 group(χ2=4.603, P=0.032 and χ2=6.911, P=0.009).(7) The 1-, 3-, 5-year local control and survival rates among T1, T2, T3, T4 had significant difference(χ2=8.656, P=0.034 and χ2=15.185, P=0.002).(8) The 1-, 3-, 5-year local control rate among N0, N1, N3 had no significant difference(χ2=3.050, P=0.218), but 1-, 3-, 5-year survival rate had significant difference(χ2=8.262, P=0.016).(9) The 1-, 3-, 5-year local control rate among clinical stage Ⅰ, stage Ⅱ, stage Ⅲ had no significant difference(χ2=5.317, P=0.070), but 1-, 3-, 5-year survival rate had significant difference(χ2=15.331, P=0.000).Radiotherapy related factors:(1) The 1-, 3-, 5-year local control and survival rates in dose ≥ 60 Gy group were higher than those in dose <60 Gy group(χ2=7.522, P=0.006 and χ2=6.132, P=0.013).(2) The 1-, 3-, 5-year local control and survival rates between SIB-IMRT group and conventional fractionated group had no significant difference(χ2=0.014, P=0.907 and χ2=0.014, P=0.905).(3) The patients were divided into <45 days and ≥45 days groups according to radiation continue time, the 1-, 3-, 5-year local control rate between two groups had no significant difference(χ2=0.133, P=0.715), but 1-, 3-, 5-year survival rate had significant difference(χ2=6.008, P=0.014).Chemotherapy related factors:(1) The 1-, 3-, 5-year local control and survival rates between FP regimen group and TP regimen group had no significant difference(χ2=0.243, P=0.622 and χ2=0.391, P=0.532).(2) The patients were divided into one cycle and two cycles groups according to cycles of chemotherapy concurrent with radiotherapy, the 1-, 3-, 5-year local control and survival rates between two groups had no significant difference(χ2=0.275, P=0.600 and χ2=0.868, P=0.352).(3) The 1-, 3-, 5-year local control and survival rates between consolidation group and without consolidation group had no significant difference(χ2=0.738, P=0.390 and χ2=1.017, P=0.313).(4) The 1-, 3-, 5-year local control and survival rates of patients receiving chemotherapy of ≥ 4 cycles were higher than those receiving chemotherapy of <4 cycles(χ2=4.885, P=0.027 and χ2=14.940, P=0.000).Short-term effects: The 1-, 3- and 5-year local control rate between CR and PR groups had no significant difference(χ2=0.787, P=0.375), but 1-, 3-, 5-year survival rate had significant difference(χ2=3.961, P=0.047).Different nutrition status:(1) The patients were divided into normal group and lower group according to BMI levels, the 1-, 3- and 5-year local control and survival rates of normal group were higher than lower group(χ2=9.233, P=0.002 and χ2=6.378, P=0.012).(2) The patients were divided into normal group and lower group according to ALB levels, the 1-, 3- and 5-year local control and survival rates of normal group were higher then lower group(χ2=20.159, P=0.000 and χ2=15.140, P=0.000).(3) The patients were divided into normal group, mildly lower group, moderately lower group and severely lower group according to TLC levels, the 1-, 3- and 5-year local control and survival rates among those groups had no significant difference(χ2=4.126, P=0.248 and χ2=1.124, P=0.771).(4) The 1-, 3- and 5-year local control and survival rates between anemia group and non-anemia group had no significant difference(χ2=0.658, P=0.417 and χ2=3.076, P=0.079).Different systemic inflammation indexes:(1) The patients were divided into higher group and lower group according to the median NLR level, the 1-, 3- and 5-year local control and survival rates between two groups had no significant difference(χ2=1.482, P=0.224 and χ2=0.023, P=0.880).(2) The patients were divided into higher group and lower group according to the median PLR levels, the 1-, 3- and 5-year local control and survival rates between two groups had no significant difference(χ2=0.380, P=0.508 and χ2=0.000, P=0.983).3 The subgroup analysis of acute toxicity showed that:Different nutrition status:(1) The incidence of bone marrow suppression, acute radiation esophagitis and acute radiation pneumonitis between different BMI levels had no significant difference(χ2=3.544, P=0.471, χ2=5.059, P=0.281 and χ2=4.557, P=0.027).(2) The incidence of acute radiation esophagitis between different ALB levels had significant difference(χ2=9.712, P=0.046), the incidence of bone marrow suppression and acute radiation pneumonitis had no significant difference(χ2=4.679, P=0.322, χ2=4.084, P=0.395).(3) The incidence of bone marrow suppression and acute radiation pneumonitis among different TLC levels had significant difference(χ2=30.157, P=0.003, χ2=39.495, P=0.000), the incidence of acute radiation esophagitis had no significant difference(χ2=10.091, P=0.608).(4) The incidence of acute radiation esophagitis between anemia group and non-anemia group had significant difference(χ2=17.558, P=0.002), the incidence of bone marrow suppression and acute radiation pneumonitis had no significant difference(χ2=5.184, P=0.269 and χ2=4.507, P=0.342).Different systemic inflammation indexes:(1) The incidence of acute radiation esophagitis between different NLR levels had closely significant difference(χ2=9.168, P=0.057), the incidence of bone marrow suppression and acute radiation pneumonitis had no significant difference(χ2=1.653, P=0.799 and χ2=4.771, P=0.312).(2) The incidence of acute radiation esophagitis between different PLR levels had significant difference(χ2=11.260, P=0.024), the incidence of bone marrow suppression and acute radiation pneumonitis had no significant difference(χ2=7.332, P=0.119 and χ2=2.489, P=0.647).4 Prognostic factors of local control and survival rates and influence factors of acute toxicity analysis:BMI level and ALB level were independent factors for local control; gender, tumor location, total cycles of chemotherapy were independent factors for overall survival. The incidence of acute radiation esophagitis of different ALB levels, different Hb levels and different PLR levels had significant difference; the incidence of acute radiation esophagitis between different NLR levels had closely significant difference; The incidence of bone marrow suppression and acute radiation pneumonitis among different TLC levels had significant difference.Conclusions:1 The effect is definitely in patients with esophageal cancer received IMRT concurrent with chemotherapy, and its acute toxicity is in the tolerable range for patients.2 Patients with tumor located in cervical and upper thoracic segments have higher survival rate than those in middle and lower thoracic segments. The local control and survival advantage is obvious in the patients whose GTV volume<48.5cm3 than that whose GTV volume ≥ 48.5cm3. Patients with shorter tumor length measured by barium meal and smaller largest diameter in CT image have local control and survival advantage.Patients with clinical stage Ⅰ~Ⅱ have higher survival rate than those with clinical stage Ⅲ.3 The local control and survival rates are higher in the patients whose radiation dose ≥60 Gy than those whose radiation dose < 60 Gy, The survival rate is higher in radiation continue time ≥45 days group than radiation continue time <45 days. Radiation dose ≥60 Gy and reducing unnecessary treatment interruption are recommended.4 The total cycle of chemotherapy ≥4 is recommended for esophageal cancer receiving chemoradiotherapy. The local control and survival rates in FP and TP groups have no significant difference, meanwihile, different cycles of chemotherapy concurrent with radiotherapy and consolidated chemotherapy after concurrent chemoradiotherapy or not show no significant difference.5 The local control and survival rates of BMI in normal level and ALB in normal level are higher. The acute radiation esophagitis occurrence rate of ALB in lower level is higher. the bone marrow suppression and acute radiation pneumonitis occurrence rate of TLC in lower level are higher. The acute radiation esophagitis occurrence rate of NLR and PLR in higher level before chemoradiotherapy are higher.6 BMI level and ALB level were independent factors for local control; gender, tumor location, total cycles of chemotherapy were independent factors for overall survival. |
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