The Predictive Factors And Influence On Prognosis Of Radiation Pneumonia In Patients With Esophageal Cancer Receiving Radiotherapy

Part 1 The Predictive Factors of Radiation Pneumonia before Radiotherapy in Patients with Esophageal Cancer Receiving Radiotherapy Objective: It is hard to reverse once radiation pneumonia(RP)occurs,so prevention is more important than treatment.This study aims to analyze the predictive factors of RP before radiotherapy in patients with esophageal cancer(EC)receiving radiotherapy(RT),hoping to identify the high-risk factors before radiotherapy,avoid formulate radiotherapy plan which easy to lead to RP,and reduce the incidence of RP in patients with EC receiving radiotherapy Methods and Materials: All data were retrospectively collected from 131 newly diagnosed EC who underwent radiotherapy enrolled from April 2014 to December 2018.Univariate analyses were used to find the potential predictors of symptomatic radiation pneumonitis(grade ?2 RP)and severe acute radiation pneumonitis (grade ? 3 RP).Multivariate analysis was used to find the independent predictors.Results: The incidences of symptomatic RP and severe acute RP were23.7%(31/131)and 9.9%(13/131)respectively.The factors that significantly correlated to symptomatic RP were mean lung dose(MLD,P=0.021),V5(P=0.011),V10(P=0.007),V15(P=0.028),V20(P=0.028).The further multivariate analysis indicated that V10 was independent predictors of symptomatic RP.The factors that significantly correlated to severe acute RP were emphysema(P = 0.006),V5(P=0.028),V10(P=0.022),V15(P=0.022),V20(P=0.024).The further multivariate analysis indicated that V10 was independent predictors of severe acute RP.Conclusion: V10 was independent predictor of symptomatic RP and severe acute RP.The risk of symptomatic RP and severe acute RP in high V10 group is significantly higher than that in low V10 group.When evaluating the radiotherapy plan of esophageal cancer,we not only pay attention to the MLD,V20 and V30,but also the V10.Part 2 The Predictive Factors of Radiation Pneumonia during Radiotherapy in Patients with Esophageal Cancer Receiving RadiotherapyObjective: This study aims to analyze the predictive factors of RP during radiotherapy in patients with esophageal cancer(EC)receiving radiotherapy(RT),hoping to predict the occurrence and severity of radiation pneumonitis effectively in the earliest time.Methods and Materials: All data were retrospectively collected from 131 newly diagnosed EC who underwent radiotherapy enrolled from April 2014 to December 2018.The hematological index was obtained at three different time points: pretreatment,at 3-week to 4-week during RT,at the end of RT.The PLR,NLR,LMR and SII were calculated,as follows: PLR = P/L;NLR = N/L;LMR = L/M;SII = P × N/L(neutrophil count [N],lymphocyte count [L],platelet count [P] and monocyte count [M]).Univariate analyses were used to find the potential predictors of symptomatic RP(grade ?2 RP)and severe acute RP (grade ? 3 RP)during the RT.Multivariate analysis was used to find the independent predictors.Results: The factors that significantly correlated to symptomatic RP during the RT were albumin(P<0.001)and pre-albumin(P<0.001)at the end of the RT,the pre/end ratio of albumin(P<0.001)and pre-albumin,PLR,LMR and SII during the RT,and the NLR,PLR,LMR,SII and D-dimer at the end of RT.The further multivariate analysis indicated that the pre/end ratio of pre-albumin,PLR during the RT,and NLR at the end of RT were independent predictors of symptomatic RP.The AUC of the three parameters combined was 0.806(95% CI: 0.716-0.896,P=0.000),evidently improving the prediction ability.The factors that significantly correlated to severe acute RP during the RT were albumin(P=0.033)and prealbumin(P=0.044)of pretreatment,albumin(P<0.001)and pre-albumin(P<0.001)at the end of the RT,the pre/end ratio of albumin(P<0.001),the PLR,LMR and SII during the RT,and the NLR,PLR,LMR,SII and D-dimer at the end of RT.The further multivariate analysis indicated that pre-albumin(P=0.007)of pretreatment,pre-albumin(P=0.015)at the end of the RT,the pre/end ratio of prealbumin(P=0.003),the SII during the RT(P=0.017),and the LMR at the end of RT(P=0.005)were independent predictors of severe acute RP.The AUC of the five parameters combined was 0.938(95%CI: 0.846~1.000,P=0.000),evidently improving the prediction ability.Conclusion: Monitoring the changes of inflammatory and nutritional indexes during radiotherapy may be able to predict the occurrence and severity of radiation pneumonia in the early stage.Whether reducing the inflammatory reaction and improving the nutritional status of patients can reduce the incidence of RP remains to be further studied.Part 3 Establishment and verification of a prediction model for symptomatic radiation pneumonitis in patients with esophageal cancer receiving radiotherapyObjective: This study aims to evaluate the value of the significant index before and during radiotherapy in predicting symptomatic radiation pneumonitis(RP)in esophageal cancer patients,establish a nomogram prediction model according to independent prediction factors,and verify the established model.Methods: A total of 163 patients with esophageal cancer were enrolled in our hospital.These patients were divided into two groups: model group(131 cases)and validation group(32 cases).According to the logistic regression analysis,the independent predictors for symptomatic RP were obtained,and the nomogram prediction model was established according to these independent predictors.The consistency index(C-index)and calibration curve were used to evaluate the accuracy of the model,and the prediction ability of the model was verified in the validation group.Recursive partitioning analysis(RPA)was used for the risk stratification analysis.Results: The ratio of change regarding the pre-albumin at the end of treatment(the pre/end ratio of pre-albumin,P=0.001),PLR during treatment(P=0.027),and NLR at the end of treatment(P=0.001)were the independent predictors for symptomatic RP.The C-index of the nomogram model was 0.811(95% CI: 0.723-0.900).The area under the ROC curve of the nomogram model was 0.811.The Calibration curves indicated favorable consistency between the nomogram prediction and actual outcomes.According to the risk stratification of RPA,the whole group was divided into three groups: low risk group,intermedium risk group,and high risk group.The incidence of symptomatic RP in these three groups was 0,16.9% and 57.6%,respectively.The calibration chart also revealed that the nomogram model has good accuracy in the validation group.Conclusion: The developed nomogram and corresponding risk classification system with superior prediction ability for symptomatic RP could predict the occurrence of RP in the early stage.Part 4 The Effect of Radiation Pneumonia on the Prognosis of NonOperative Esophageal CancerObjective: This study aims to analyze the influence of radiation pneumonitis on the prognosis of patients with esophageal cancer who cannot be resected surgically,comprehend the harm of radiation pneumonitis on patients with esophageal cancer,and arouse the attention of clinicians on the prevention and treatment of radiation pneumonitis.Methods and Materials: All data were retrospectively collected from 131 newly diagnosed EC who underwent radiotherapy enrolled from April 2014 to December 2018.univariate analysis was used to analyze the relationship between the clinicopathological features,inflammatory index,nutritional status,radiation pneumonitis and the overall survival rate(OS)of EC.According to the results of univariate analysis,factors with P < 0.05 were further included in multivariate logistic regression model to find independent prognostic factors.Results: The OS of the whole group was 61% in one year and 31% in two years.Univariate analysis showed that potential predictors which were significantly correlated with OS were gender(P = 0.044),NLR(P=0.023),albumin(P=0.000),BMI(P=0.002)before radiotherapy,NLR(P=0.000),PLR(P=0.000),LMR(P=0.001),SII(P=0.000)albumin(P=0.002),pre albumin(P=0.012)during radiotherapy,albumin(P = 0.000),pre albumin(P=0.019),BMI(P = 0.000)at the end of radiotherapy,the occurrence of symptomatic RP(P= 0.000)and the occurrence of severe acute RP(P=0.002).Multivariate analysis showed that gender,albumin before radiotherapy,NLR and pre albumin during radiotherapy,BMI at the end of radiotherapy were independent predictors for OS.Conclusions: Radiation pneumonitis was significantly related to the OS,but it was not an independent prognostic factor. gender,albumin before radiotherapy,NLR and pre albumin during radiotherapy,BMI at the end of radiotherapy were potential valuable markers in predicting OS of EC.