The Analysis Of Radiation Dose And Radiotherapy Technology For Patients With Esophageal Squamous Cell Carcinoma

Part1 The efficiency of dose escalation in esophageal squamous cell carcinoma patients receiving 3-dimension radiotherapyObjective To evaluate the effect of dose escalation 3-dimension radiotherapy on overall survival（OS）for patients with esophageal squamous cell carcinoma（ESCC）.Methods The clinical data of 2344 ESCC patients treated with definitive radiotherapy（RT）alone or chemoradiotherapy from 2002 to 2016 in 10 hospitals was collected and analyzed retrospectively.After the propensity score matching（PSM）（1:2 ratio）,the patients were divided into low-dose group（EQD₂<60Gy）（n=303）and high-dose group（EQD₂≥60Gy）（n=606）based on the radiation dose.The 1-,3-and 5-year OS and progression-free survival（PFS）were compared between groups.The prognostic factors were also identified and analyzed.The Kaplan-Meier method was used for survival analysis.The log-rang test was used for survival comparison univariate prognostic analysis.Cox model was used for multivariate prognostic analysis.Results The median follow-up time was 59.6 months.After the PSM method,the 1-,3-and 5-year OS rates were 66.5%、34.7%、27.2%in low-dose group,72.9%、41.7%、34.7%in the high-dose group,respectively（P=0.018）.The 1-,3-and 5-year PFS rates were 52.2%、27.2%、23.1%in the low-dose group,58.3%、38.1%、33.9%in the high-dose group,respectively（P=0.001）.The patients in the high-dose group had significantly better OS and PFS rates compared those in the low-dose group.The outcomes of univariate analysis showed that cervical/upper esophagus location,early（II）AJCC clinical stage,node negative status,tumor length≤5cm,receiving IMRT,receiving concurrent chemotherapy and EQD₂≥60Gy were closely associated with improved OS.Multivariable analysis demonstrated that tumor location,N stage,concurrent chemotherapy and EQD₂ were the independent prognostic factors for OS.Conclusions Our results suggest radiation dose of≥60Gy yields more favorable survival outcomes for ESCC patients receiving definitive RT by modern techniques.Part 2 The efficacy and safety of intensity-modulated radiotherapy in reducing radiation dose in CTV in locally advanced esophageal squamous cell carcinomaObjective To compare the clinical efficacy and treatment-related toxicity between simultaneous integrated dose reduction in clinical target volume（CTV）with intensitymodulated radiotherapy（SIR-IMRT）and conventional IMRT（C-IMRT）in the treatment of ESCC.Methods From March 2010 to September 2016,the clinical data of 257 patients with ESCC who received definitive IMRT in the Tianjin Medical University Cancer Institute and Hospital were collected and retrospectively analyzed.Among these patients,137 patients received C-IMRT with a prescribed dose of 60 Gy in 30 fractions for planning target volume（PTV）,while 120 patients received SIR-IMRT with a prescribed dose of 60 Gy in 30 fractions for the planning GTV（PGTV）and a prescribed dose of 54 Gy in 30 fractions for PTV.All of the patients received definitive IMRT with elective nodal irradiation.Locoregional control,survival,treatment toxicity and dose to organs at risk（OAR）were compared between the groups.The survival outcomes were assessed with the Kaplan-Meier method and curves were compared with log-rank tests.Chi-square test was used for comparing dichotomous data between groups.Continuous variables were compared by using the Mann-Whitney U test.Results Patients who received SIB-IMRT showed a similar locoregional failure rate compared to with the C-IMRT group（27.5% versus 29.9%,P=0.668）.The 1-,2-and 3-year OS rates were 71.5%,44.3%,44.3% versus 77.9%,52.1%,32.9% in the CIMRT and SIR-IMRT groups（P=0.825）,respectively.The 1-,2-and 3-year PFS rates were 57.1%,34.1%,34.1% versus 57.3%,41.8%,28.5%（P=0.880）,and the 1-,2-and 3-year locoregional recurrence-free survival（LRRFS）were 80.8%、60.0%、55.4% versus 80.8%、57.0%、41.8%（P=0.216）in the C-IMRT and SIR-IMRT groups（P=0.825）,respectively.There were no statistically significant differences were observed regarding OS,PFS and LRRFS between the two groups.The dose of lung V30 and the maximum dose of spinal cord in the C-IMRT group were significantly higher than those in the SIR-IMRT group（P=0.013,P=0.047）.The incidence of acute radiation esophagitis was significantly lower in the SIR-IMRT group（P=0.046）,although no statistical difference was observed in the incidence of acute severe adverse events between the two groups.Conclusions SIR-IMRT offers an effective and safe option for patients with unresectable ESCC who receive definitive RT.Further prospective and larger sample size studies are warranted to confirm our results.