Objective To study the effect of three dimensional conformal intensity modulated radiotherapy and prognostic factors for postoperative local recurrent esophageal squamous cell carcinomas.Methods A total of 468 patieuts with postoperative local recurrent esophageal squamous cell carcinomas were retrospectively analyzed.The median interval between surgery and recurrence was 14.95 months (2-252 months).There were 45 patients with supraclavicular lympy node relapse,291 with mediastinal lymph node relapse,4 with abdominal lymph node relapse,15 with anastomosis relapse,89 with supraclavicular and mediastinal lymph node relapse,11 with anastomosis and mediastinal lymph node relapse,7 with mediastinal and abdominal lymph node relapse,1 with supraclavicular and anastomosis relapse,2 with supraclavicular and abdominal lymph node relapse,3 with anastomosis,mediastinal and supraclavicular lymph node relapse.There were 224 patients who received three-dimensional conformal radiation therapy,and the other 244 patients of intensity-modulated radiation therapy,with a median dose of 59.4 Gy (40-70 Gy).A total of 166 patients received adjuvant chemotherapy.Kaplan-Meier method was used to calculate the survival rate;Log-rank test was used for univariate prognostic analysis;Cox regression test was used for multivariate prognostic analysis.Results The follow-up rate was 95.3％.The recent curative effect in the effective rate was 81.6％,with 41.2％ CR rate.The overall 1,2,3,4 years of survival rates after radiotherapy were 61％,32％,21％,14％ respectively and the median survival time was 17.6 months.Univariate analysis showed that age,.pathologic stage,the number of positive lymph node cleaning,the recurrence area,single or multiple lesions,the size of the lesion,overall response rate,radiation dose,and chemotherapy (x2 =4.814-247.322,P ＜ 0.05) were associated with prognosis.Multivariate analysis showed that age,pathologic stage,the recurrence area,single or multiple lesions,the size of the lesion,overall response rate,radiation dose,and chemotherapy (P ＜0.05) were independent prognostic factors.A total of 370 patients had progressive diseases after radiotherapy,176 had local failure 47.57％ (176/370),148 had distant metastasis 40.00％ (148/370) and 16 had both local and distant failures 4.32％ (16/370).One case died of pneumonia;2 cases died of acute myocardial infarction;1 case died of cerebral hemorrhage;26 cases died of unknown cause (including lost to follow-up).Lung was the most common distant metastatic site.Conclusions Radiotherapy may improve the survival of esophageal squamous cell carcinoma patients with postoperative recurrence.Patients with less than 70 years old,early postoperative stage,single recurrent lesion,initial small lesions,response to radiotherapy,radiation dose of higher than 59.4 Gy,chemoradiation might have better prognosis.

Objective To compare the dosimetric difference among TomoDirect (TD) radiotherapy,Helical Tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in the treatment of upper thoracic esophageal carcinoma.Methods A total of 15 patients with cT2-4 N0-1 M0 upper thoracic esophageal squamous cell carcinoma were enrolled.Three plans were generated using the same dose objective for each patient:TD,HT and VMAT.Dose-volume histogram (DVH),homogeneity index (HI),conformal index (CI),dose at organ at risk (OAR),delivery time and monitor unit (MU) were compared among different plans.Results The D2 and D values in the HT and TD plans were significantly lower than those in the VMAT plans.The D98 value in the TD was similar to that in the HT,but lower than that in the VMAT.The HI of HT was significantly better than those of TD and VMAT (F =81.603,P ＜ 0.05).For the CI,there was no significant difference among the three techniques (P ＞ 0.05).For the V15 of lung,HT was significantly higher than TD (t =-2.626,P ＜0.05) and VMAT (t=3.547,P ＜ 0.05).The V20 of lung in TD was similar to that in HT,but higher than that in VMAT (t =2.824,3.052,P ＜ 0.05).The Dmax of spinal cord showed no significant difference among the three techniques.VMAT had a significantly shorter delivery time and lower MU compared with HT and TD (t =21.617,15.693,10.018,7.802,P ＜ 0.05).Conclusions HT and TD could gain a better planning target volume (PTV) coverage and HI than VMAT in the treatment of upper thoracic esophageal carcinoma.However,VMAT achieved the lowest lung V20,the least Mus and the shortest delivery time.HT achieved a better PTV coverage compared with TD,but TD had a lower lung V15 Mus and shorter delivery time compared with HT.

Objective:To investigate the efficacy of different types of neoadjuvant therapy for esophageal cancer.Methods:The clinical data of 542 patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant therapy in Anyang Tumor Hospital of Science and Technology from January 2015 to May 2022 were retrospectively analyzed. These patients, consisting of 198 females and 344 males, with 289 cases aging ≤ 65 and 253 cases aging >65, were divided into a neoadjuvant chemoradiotherapy (NCRT) group (137 cases), a neoadjuvant chemotherapy (NCT) group (241 cases), and a neoadjuvant immunotherapy plus chemotherapy (NICT) group (164 cases). In this study, primary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, and secondary endpoints comprised overall survival (OS), progression-free survival (PFS), and safety. Survival analysis was performed using the Kaplan-Meier method, and inter-group comparisons were made using the Log-rank test. Furthermore, prognostic factors were analyzed based on the Cox proportional hazards regression model.Results:The NCRT, NCT, and NICT groups exhibited MPR and pCR rates of 66.4% (91/137) and 35.3% (85/241), 63.4% (104/164) and 35.8% (49/137), and 6.6% (16/241) and 31.1% (51/164), respectively ( χ2=1.67, P < 0.001). These groups displayed 1-, 2-, and 3-year OS rates of 89.8%, 85.9%, and 91.9%; 82.3%, 71.4%, and 81.5%; and 72.3%, 61.4%, and 77.8%, respectively, with significant differences ( χ2=9.20, P < 0.01). Furthermore, they exhibited 1-, 2-, and 3-year PFS rates of 81.5%, 75.9%, and 80.1%; 67.9%, 61.0%, and 65.5%; and 66.6%, 53.5%, and 65.3%, respectively, with significant differences ( χ2=4.62, P < 0.05). Multivariate analysis showed that therapeutic modality, T stage, and N stage were independent prognostic factors for OS ( P < 0.05). Additionally, there was no difference in adverse reactions and postoperative complications among the three groups. Conclusions:Compared to NCT, NICT and NCRT feature higher pCR and MPR rates, along with more survival benefits. Therefore, neoadjuvant immunotherapy has the potential to serve as a preoperative therapeutic modality for esophageal cancer, yet large-scale randomized controlled trials are still required for confirmation.

Objective:To evaluate the efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC).Methods:A retrospective analysis was conducted on the data of 75 patients with R/M ESCC treated with sintilimab at Anyang Tumor Hospital from January 2020 to October 2021. The patients were divided into the radiotherapy (RT) group ( n=37) and non-radiotherapy (NRT) group ( n=38) based on whether they received radiotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse effects were compared between two groups. Count data were expressed as composition ratios and analyzed using Chi-square test or Fisher's exact test. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:There was no statistically significant difference in ORR and DCR between the RT and NRT groups (70% vs. 61%, P=0.375; 95% vs. 89%, P=0.414). However, the complete response (CR) rate in the RT group was higher compared to that in the NRT group (19% vs. 3%, P=0.022). The median follow-up duration was 25.4 months. There was no statistically significant difference in the median PFS and OS between the RT and NRT groups (13.8 months vs. 9.9 months, P=0.221; 20.2 months vs. 18.9 months, P=0.214). Subgroup analysis demonstrated that among patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes, there was no statistically significant difference in the median PFS between the RT and NRT groups (15.1 months vs. 8.4 months, P=0.115), but the median OS in the RT group was better than that in the NRT group (not reached vs. 12.3 months, P=0.036). Compared to the NRT group, besides an increase in grade 1-2 pneumonitis (41% vs. 18%, P=0.035), no significant increase in treatment-related toxicity was observed in the RT group. Conclusion:Immunotherapy combined with radiotherapy is safe in patients with R/M ESCC, and shows survival benefit in patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes.

Objective:To explore the biomarkers of radiochemotherapy sensitivity and potential mechanisms in esophageal squamous cell carcinoma (ESCC), and validate the screened biomarkers at human tissue, animal and cellular levels.Methods:Based on bioinformatics system, clinical and transcriptome data of ESCC were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. HUB genes related to chemoradiotherapy sensitivity were identified by weighted correlation network analysis (WGCNA) and cytoscape software and survival differences were analyzed. CellMiner database was used to predict and screen drugs with strong correlation with HUB genes. The expression levels of HUB genes in clinical tissues was detected by real-time reverse transcription PCR (qRT-PCR). Then, oe-AKR1C1 mouse model, cisplatin-resistant cells and radiation-resistant cells were constructed, and the effects of HUB genes on tumor size and mass, and cell proliferation ability were analyzed.Results:A total of 5 HUB genes were identified, among which NAD(P)H quinone dehydrogenase 1 (NQO1), AKR1C1 and NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) were significantly correlated with ESCC survival (all P<0.05). Dacarbazine, alectinib and obatoclax were the anti-tumor drugs predicted to have a strong correlation with HUB genes in this study. Human tissue test results showed that the expression levels of NQO1, AKR1C1 and NDUFS2 were up-regulated in patients with chemoradiotherapy resistance, and AKR1C1 and NDUFS2 had statistical significance (both P<0.05). The results of mouse tumor bearing experiment showed that the tumor volume and mass of oe-AKR1C1 mice after radiotherapy and chemotherapy were significantly higher than those in the control group (both P<0.05). The cell experiment results showed that the expression levels of AKR1C1 and NDUFS2 in radiation-resistant cells and cisplatin-resistant cells were significantly higher than those in control cells ( P<0.05), while there was no statistically significant difference in the relative expression level of NQO1. Conclusion:NQO1, AKR1C1 and NDUFS2 are HUB genes significantly related to the survival of ESCC, which can be used as important therapeutic tumor targets for ESCC.