| Background and purpose:Esophageal cancer is one of the most common malignant tumors in humans,especially in China,where its incidence ranks first in the world.Esophageal cancer has the characteristics of high incidence and high mortality,and its prognosis is poor.Radiotherapy is one of the most important treatment methods for patients with esophageal cancer.Patients with esophageal cancer of the same stage were given the same treatment plan,but their prognosis may be different,which may be related to the difference in immune function and nutritional status between individuals.Immune function may be related to the prognosis and treatment response of esophageal cancer patients.Lymphocytes are important human immune cells and can reflect the immune status of patients.Lymphocytes are very sensitive to radiation,and lymphopenia caused by radiotherapy has been confirmed to be related to the prognosis of many malignant tumors,including esophageal cancer.With the development of radiotherapy technology,such as intensity-modulated radiotherapy,proton radiotherapy and other technologies,compared with traditional two-dimensional and three-dimensional radiotherapy,their radiation time is significantly shortened,the dose distribution in the field is more uniform,and the radiation dose to normal organs is reduced.At present,there are few studies on the physical factors of intensity-modulated radiotherapy causing lymphopenia in esophageal cancer.In addition to immune function,the nutritional status of cancer patients also plays an important role in prognosis.The typical clinical manifestation of patients with esophageal cancer is difficulty in progressive blocking,so most patients have different degrees of malnutrition.The incidence of malnutrition in esophageal cancer patients is the highest in all the malignant tumors.Many previous studies have confirmed that malnutrition can weaken the immune system of tumor patients and reduce the response to treatment,thus leading to a poor prognosis.Hemoglobin,serum albumin,and serum prealbumin are currently the most common factors that indicate human nutritional status.At present,there are few reports on whether there is a correlation between the nutritional factors of patients with esophageal squamous cell carcinoma such as albumin and the changes of lymphocytes during intensity-modulated radiotherapy.Therefore,based on the above research,we further discover the effect of intensity-modulated radiotherapy on the total number of peripheral blood lymphocytes in patients with esophageal cancer and explore the effect of these changes on short-term efficacy,side effects and survival prediction.Methods:The patients with esophageal squamous cell carcinoma who underwent intensity-modulated radiotherapy in the radiotherapy department of Qianfoshan Hospital were collected through the medical record system of Qianfoshan Hospital of Shandong Province.At the same time,healthy people who performed physical examinations in the physical examination center of our hospital were collected as healthy control groups.Select appropriate patients with esophageal squamous cell carcinoma according to the enrollment criteria,record the clinical data of each patient,and regularly follow-up and record the data.The blood routine and liver function and other clinical indicators of patients with esophageal cancer were collected within half a month before the start of radiotherapy.The time point was defined as T1.The minimum value during radiotherapy was defined as the lowest value and expressed as Min.The blood indicators of patients with esophageal cancer were collected again within 1 month after the end of radiotherapy,and the time point was defined as T2.The blood routine and liver function indexes of the healthy control group were collected and recorded.The Varian system is used to delineate the tumor target area and the spleen,lungs,heart and other endangered organs,and the dose-volume histogram is used to collect the following dose parameters such as planned target volume(PTV)prescription dose,PTV average dose,PTV volume,heart V5,V10,V20,V30,average heart dose,maximum heart dose,average body dose,body V5,V10,V20,V30,machine beats,average spleen radiation dose,spleen V5,V10,V20,V30,average double Lung radiation dose,double lung V5,V10,V20,V30 and other indicators and record and record such indicators.Statistical methods were used to analyze the difference between lymphocytes in patients with esophageal cancer before treatment and those in healthy controls,to study the correlation between lymphocyte changes and overall survival in patients with esophageal cancer during IMRT,and to analyze the nutrition factors and physical dosimetric factors that may cause lymphopenia.We also studied the relationship between the lowest value of lymphocytes during radiotherapy and the side effects and short-term effects of radiotherapy.Results:1.From February 2013 to May 2020,a total of 122 patients with esophageal cancer were enrolled in this study.The last follow-up time was August 2020.The median prescription dose of PTV for patients with esophageal cancer receiving intensity-modulated radiotherapy is 6000cGy,and the range is(4140-6996)cGy.During radiotherapy,12 cases had the lowest value of lymphocytes of grade 1-2,accounting for 9.8%,and 110 people had lymphopenia of 3-4,accounting for 90.2%of the total patients.In all patients,the incidence of lymphocyte nadir G1,G2,G3,and G4 during radiotherapy accounted for 0.82%,9.02%,63.11%and27.05%,respectively.At the same time,87 healthy people who were examined in the health examination center of our hospital were collected as the control group.The total number of lymphocytes,the percentage of lymphocytes,hemoglobin and albumin in the peripheral blood of the esophageal cancer group pre-radiotherapy were significantly lower than the blood parameters of the healthy population(P<0.05),but the white blood cells of the esophageal cancer patients were significantly higher than in the healthy control group(P<0.05).2.The hemoglobin of esophageal cancer patients with lymphopenia group before treatment was significantly lower than that of the esophageal cancer patients without lymphopenia group before treatment(P=0.032).3.During radiotherapy,there was no significant difference in the minimal value of lymphocytes between the two groups of concurrent radiotherapy and chemotherapy compared with radiotherapy alone.The white blood cells of the concurrent chemo-radiotherapy group were significantly lower than those of the single radiotherapy group(P=0.004).Among all concurrent chemotherapy patients,the MinALC of patients without fluorouracil chemotherapy was lower than that of patients with fluorouracil chemotherapy.The MinALC of patients with platinum-based chemotherapy was significantly lower than that of patients without platinum-based chemotherapy.The MinALC and Min WBC of the dual-agent chemotherapy group were significantly lower than those of the single-agent chemotherapy patients.4.White blood cells,total number of lymphocytes,hemoglobin and albumin,and serum prealbumin were significantly decreased during radiotherapy than before radiotherapy(P<0.001).After treatment,all peripheral blood parameters were still significantly lower than those before treatment(P<0.001).5.KM survival analysis showed that the overall survival time of the group of white blood cells>8.24×109/L before treatment was significantly shorter than that of patients in the white blood cell ≤8.24×109/L group(P<0.001).6.The patients were divided into two groups according to whether they had concurrent chemotherapy.There was no significant difference in OS between the two groups in KM survival analysis(P=0.26).The survival time of patients in stage Ⅰ-Ⅱgroup was significantly longer than that of patients in stage Ⅲ-Ⅳ group(P=0.032).According to patients’ death status as the endpoint,ROC curve analysis found the cut-off value of the lowest lymphocyte value during radiotherapy(MinALC≤0.43×109/L)and divided into two groups.KM survival analysis showed that survival time in patients with the MinALC≤0.43×109/L was significantly lower than that in the patients with MinALC>0.43×109/L(P=0.047).7.COX univariate analysis showed that clinical stage,T1 WBC(>8.24×109/L vs≤8.24×109/L),MinPA(<200 vs≥200mg/L)had predictive significance for overall survival(P<0.05).COX multivariate analysis showed that clinical stage(Ⅰ-Ⅱ vsⅢ-Ⅳ),T1 WBC(>8.24×1 09/Lvs≤8.24×109/L),MinALC(≤0.43×109/Lvs>0.43×109/L)were three factors that can predict overall survival of patients(P<0.05).8.T1ALC and MinHb in the MinALC≤0.43×109/L group were significantly lower than that in the MinALC>0.43×109/L group.At the same time,the mean lung radiation dose and the mean body radiation dose of the patients in the MinALC≤0.43×109/L group were significantly higher than those of the esophageal cancer patients in the Min>0.43×109/L group(P<0.05).9.There were no significant differences in bone marrow suppression,radiation pneumonitis,radiation esophagitis and short-term effective rates between the two groups in MinALC(≤0.43×109/L vs>0.43×109/L,P>0.05).10.ROC curve analysis showed that T1ALC,MinHb,mean body dose,bodyV30,V10,V5 exposure volume,mean double lung dose,double lung V30,V20,V10,V5 exposure volume were predictive factors for MinALC≤0.43×109/L.Among them,the AUC areas of T1ALC,the mean doses in double lungs,and double lungs V10 is greater than 0.7,which may be relatively more accurate in predicting the lowest lymphocyte value≤0.43 x 109/L during radiotherapy.11.Pearson bivariate analysis showed that MinHb/T1Hb,MinAlb/T1Alb,MinPA/t1PA with MinALC/T1ALC all showed a significant positive correlation(P<0.05).12.Pearson analysis showed that the degree of reduction of MinALC/T1ALC was significantly negatively correlated with the following radiotherapy dose factors:the exposure volume of heart V30,heart V20,heart V10,heart V5,body V30,body V20,body V10,body V5,and lungs V10,and mean heart dose,maximum heart dose,mean spleen dose,mean body exposure dose,and mean double lung dose.13.Pearson analysis showed that MUs was negatively correlated with the minimum value of lymphocytes.Although the P value(P=0.056)was greater than 0.05,the scatter plot showed a negative correlation trend.There was a negative correlation between MUs and(lymphocyte minimum/T1ALC)(P=0.134),and there was no statistical significance.Divide all patients into two groups,with MUs>1009 as the control group and MUs≤1009 as the experimental group.The mean value of MinALC in the control group was significantly lower than that in the experimental group,while MinALC/T1ALC and T1ALC and T2ALC were in the two groups had no statistical differences14.Set G4 MinALC to 1,and set the level 3 and below to 0.ROC curve analysis showed that the AUC areas of heart V30,heart V5,body V10,body V5,double lungs V10,the average body dose,the average lung dose and MUs were 0.584,0.591,0.651,0.647,0.599,0.655,0.625,0.613,respectively.15.ROC curve analysis shows that MinALC can predict the occurrence of grade 3-4 pneumonia,but it has poor predictive value for the occurrence of grade 3-4 esophagitis.Conclusion:The total number of lymphocytes,the percentage of lymphocytes,hemoglobin and albumin in the peripheral blood of patients with esophageal cancer before treatment are significantly lower than those of the healthy controls,but the white blood cells of patients with esophageal cancer are significantly higher than those of the healthy control group.Intensity-modulated radiotherapy will reduce the total number of lymphocytes in patients with esophageal cancer,and lymphocytes will be improved to a certain extent after radiotherapy,lymphocytes will improve to a certain extent after radiation,but they are still lower than the level before radiotherapy in the short term.The presence or absence of concurrent chemotherapy with radiotherapy has no significant correlation with the changes of lymphocytes in patients with esophageal cancer.Lymphopenia during radiotherapy is one of the predictors of overall survival for patients with esophageal cancer.Radiometric factors and nutritional factors such as hemoglobin,albumin,prealbumin,etc.will all have different effects on the decrease of lymphocytes in esophageal cancer.Therefore,optimizing the radiotherapy plan to reduce the radiation dose to normal organs,and strengthening the nutritional support treatment for patients with esophageal cancer during radiotherapy can reduce the impact of radiotherapy on lymphocytes,thereby reducing the impact on the immune function,which may beneficial to the prognosis of patients with esophageal cancer.Research significance and innovation:We studied the correlation between lymphocyte reduction caused by radiotherapy and acute side effects and short-term effective rate,to provide reference for clinical treatment.We study the correlation between the decrease of lymphocytes caused by radiotherapy and the physical factors of radiation.In view of these factors,the radiation plan is optimized to provide a reference for reducing the impact of radiotherapy on lymphocytes.The study of the correlation between nutritional factors and lymphocyte changes provides a reference for clinical strengthening of nutritional support treatment.The innovations of this study are 1.Taking Machine Unit(Mus)as an independent variable,and analyzing the linear correlation between it and the decrease of lymphocytes during radiotherapy.2.Analyze the correlation between the indicators of the body’s nutritional status such as albumin,serum albumin,hemoglobin and the degree of lymphocyte decrease caused by radiotherapy.3.Comprehensive analysis of the spleen,heart,lungs,body radiation dose factors and the size of the correlation with the degree of lymphocyte reduction.4.The value of the lowest lymphocyte value caused by intensity-modulated radiotherapy in predicting the side effects of radiotherapy such as severe radiation esophagitis and radiation pneumonia was also studied. |
PDF Full Text Request