Risk Factors Assessment And Prognostic Prediction Of ¹²⁵I Seed-Loaded Stent Placement For Advanced Esophageal Cancer

Part Ⅰ: Prognostic factors associated with the efficacy of ¹²⁵I seed-loaded stent placement for advanced esophageal cancerObjective: The efficacy of 125 iodine(¹²⁵I)seed-loaded stent placement has been proven for patients with unresectable advanced esophageal cancer.The aims of this study was to identify the risk factors related to the clinical prognosis in unresectable esophageal cancer patients treated with this irradiation stent placement,in order to provide reference for clinical practice.Methods: It’s a multicentre,retrospective study.From June,2012 to March,2016,esophageal cancer patients who underwent¹²⁵I seeds-loaded stent placement were retrospectively reviewed in five hospitals in China.Data were collected from the medical records,combined with follow up.Overall survival was estimated using Kaplan-Meier method.The log-rank tests were performed to compare differences between groups.The Cox regression models adjusted for stratification factors were used,and a stepwise multivariate analysis was performed to predict overall survival and relief of dysphagia on the basis of pretreatment clinical characteristics,respectively.The Wilcoxon signed-rank test was used to compare the changes of the life activity（Barthel Index score）before and after stent placement.The primary endpoint was independent risk factor associated with overall survival,and the secondary end point were factors related to the relief of dysphagia and the changes of daily life after ¹²⁵I seeds-loaded stent placement.Results: A total of 245 esophageal cancer patients who underwent ¹²⁵I seed-loaded stent placement were reviewed,and 44 patients were excluded.Finally,201 patients（73% males,n =147）were included in this study.The median age at the time of procedure was 71 years（IQR: 62–80）.The overall median survival time was 157 days.The main findings are as follows:（1）Three independent prognostic factors were identified for the overall survival: histology of tumour（squamous-cell carcinoma vs.adenocarcinoma;HR,1.45;P = 0.046）,ECOG score（< 2 vs.≥ 2;HR,1.51;P = 0.013）,and serum total protein（TP）（≥ 66 g/L vs.< 66 g/L;HR,0.67;P = 0.023）.The median survival was 176 days（95%CI:128–194）for patients with squamous cell carcinoma versus 138 days（95%CI: 117–169）for those with adenocarcinoma,183 days（95%CI:147–208）with TP ≥ 66 g/L versus 125 days（95%CI: 107–171）with TP < 66 g/L,and178 days（95%CI: 157–199）with ECOG-PS < 2 versus 101 days（95% CI: 77–125）with ECOG-PS ≥ 2.（2）Four factors,including age（≥ 71 years vs.< 71 years;OR,2.01;P = 0.029）,tumor location（superior vs.inferior;OR,0.49;P = 0.049）,TNM classification（IV vs.II;OR,3.19;P = 0.025）and T stage（T4 vs.T3;OR,0.27;P =0.003）,were significantly associated with the relief of dysphagia.（3）Despite a significant difference of the Barthel index scores（mean±SD,78.83±13.10 vs.74.67±10.03,P< 0.001）between pre-and post-stent placement,there was no statistical difference in the grade of patients’ self-care ability before and after ¹²⁵I seeds-loaded stent placement（P =1.000）.Conclusions:（1）For unresectable or post-operative recurrent esophageal cancer patients who underwent ¹²⁵I seed-loaded stent placement,squamous cell carcinoma,ECOG-PS < 2,and higher TP（≥ 66 g/L）are favourable prognostic factors for overall survival.（2）Younger patients（< 71 years）,T3 stage,tumour located in the inferior segment,and TNM stage II or III demonstrate better relief of dysphagia after this treatment.（3）There was no effect on the self-care ability of patients after this irradiation stent placement.PART Ⅱ: Risk prediction of complications for ¹²⁵I seed-loaded stent placement in patients with advanced esophageal cancerObjective: Stent-related complications seriously affect the clinical efficacy of esophageal stent placement.The results of previous studies showed that there was no difference in the incidence of complications between ¹²⁵I seeds-loaded stents and traditional self-expandable stent.The purpose of this study was to identify the predictors of adverse events after ¹²⁵I seed-loaded stent placement in patients with esophageal cancer,and to develop a predictive model for these patients.Methods: From June,2012 to March,2016,esophageal cancer patients who underwent¹²⁵I seeds-loaded stent placementwere retrospectively reviewed in five hospitals in China.Data were collected from the medical records,combined with follow up.Logistic regression was used to analyze the correlation between potential risk factors and overall complications.The logistic regression coefficient was used to verify the pridictive model and the ROC curve was used to evaluate the effect of the model by comparing the simulation results with the real results.To reduce the impact of treatment selection bias and potential confounding in an observational study,significant differences in patient characteristics,disease status,and symptom burden were rigorously adjusted using stabilised inverse-probability-of-treatment weighting（s IPTW）between groups.The primary end point was risk factors associated with stent-related complications.The secondary end-point were predictive model for haemorrhage and the incidence of complications between different diameter stents.Results: A total of 245 esophageal cancer patients underwent ¹²⁵I seed-loaded stent insertion were retrospectively reviewed and 44 patients were excluded,201 patients included in this analysis.The main findings are as follows:（1）The incidence of major complications was 27.4%（55 / 201）.Univariate and multivariate logistic regression analysis showed that patients age > 60 years（OR,0.335;P = 0.013）,TP < 60 g / L（OR,2.700;P = 0.012）and albumin（ALB）< 40g/L（OR,0.335;P = 0.008）were significantly associated with the incidence of overall complications.A significant difference was observed in tumour location [superior segment（1/20）vs.middle segment（1/108）vs.inferior segment（9/73）,P = 0.004].In 55 patients with stent related complications,the ALB level decreased significantly after stenting（mean ±SD:36.11 ±5.57 vs.35.20 ±4.67,P = 0.033）.（2）The rate of haemorrhage was 13.4% in157 patients with esophageal squamous cell carcinoma.Prior chemoradiotherapy（HR:3.948,95%CI: 1.237-12.598,P = 0.020）and tumour location（HR: 2.337,95%CI:1.018-5.553,P = 0.045）were independent risk factors of the stent related haemorrhage.The ROC value of internal validation for this model was 0.686（95%CI:0.569-0.802,P < 0.05）.（3）After s IPTW adjustment for baseline characteristics,the relief of dysphagia was not statistically different between the two groups（18mm vs.20 mm,P >0.05,both at one week after stent placement and at one week before death）.Comparable rates were found in haemorrhage（8.7% vs.9.6%,P = 0.843）,pneumonia（16.2% vs.9.4%,P = 0.247）,fistula formation（7.7% vs.5.8%,P = 0.658）,recurrent dysphagia（8.7% vs.7.5%,P = 0.538）,and stent migration（4.8% vs.5.86%,P =0.534）between the two groups.There were significantly fewer severe retrosternal pain incidents in the 18 mm group（15.4% vs.32.7%,P =0.013）in the weighted analysis,and the percentages of severest chest pain episodes（NRS ≥7）were significantly different between the two groups（1.9% vs.9.3%,P =0.010）.Conclusions:（1）Age > 60 years old,TP < 60 g / L and ALB < 40g/L were independent risk factors for overall complications after¹²⁵I seeds-loaded stent placement.The incidence of stent migration was higher in patients with lower esophageal lesions.ALB decreased significantly in patients with complications after stent placement.（2）Prior chemoradiotherapy and tumour location at the inferior segment are independent risk factors for haemorrhage in patients with advanced esophageal squamous cell carcinoma after ¹²⁵I-seed-loaded stent placement.（3）¹²⁵I seed-loaded stent placement with 18 mm diameter showed similar function on dysphagia relief to stent with 20 mm diameter,but nearly halved the incidence of severe chest pain.